# 01 - 4 Neuropsychiatry

# 4 Neuropsychiatry

121
Neuropsychiatry
A brief history of neuropsychiatry  122
What is neuropsychiatry?  124
Psychiatric presentations of organic illness  126
Neurological examination in psychiatry  128
Neurological investigations in psychiatry  130
Movement disorders in psychiatry  132
Functional neurological symptoms  134
Neurodevelopmental disorders in adulthood  136
Psychiatric aspects of epilepsy 1  138
Psychiatric aspects of epilepsy 2  140
Parkinson’s disease and related syndromes  142
Neuropsychiatric aspects of central nervous system 
infections  144
HIV/​AIDS and psychiatry 1  146
HIV/​AIDS and psychiatry 2: clinical presentations  148
Autoimmune and connective tissue disorders  150
Dementia: general overview  152
Reversible causes of cognitive impairment  154
Alzheimer’s disease 1  156
Alzheimer’s disease 2: pharmacological treatments  158
Fronto-​temporal dementia  160
Dementia with Lewy bodies  162
Vascular dementia (vascular neurocognitive disorder)  164
Other specific neurodegenerative conditions  166
Prion diseases  168
Amnestic disorders  170
Psychiatric aspects of brain injury  172
Mild traumatic brain injury (concussion)  174
Psychiatric sequelae of stroke  176
Chapter 4

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Chapter 4  Neuropsychiatry
A brief history of neuropsychiatry
‘ . . . from nothing else but the brain come joys, delights, laughter and 
sports, and sorrows, griefs, despondency, and lamentations . . . And by 
the same organ we become mad and delirious, and fears and terrors 
assail us . . . ’
From ‘On the Sacred Disease’ Hippocrates (c.400 BC)
Wilhelm Griesinger (1817–​1868) is often referred to as the ‘founding father 
of neuropsychiatry’ (perhaps more accurately the first ‘biological psych­
iatrist’). It is to him that the (apocryphal) quotation has been attributed that 
all mental diseases are just diseases of the brain.1 Griesinger was a phys­
ician (the concept of psychiatrist did not exist at the time), and there is no 
doubt that his textbook Pathologie und Therapie der Psychischen Krankheiten 
[Textbook of Mental Pathology and Therapeutics] (1845) was hugely influen­
tial. He established the journal Archiv für Psychiatrie und Nervenkrankheiten 
[Archives of Psychiatry and Nervous Diseases], which, in the hands of 
Meyer and Wetsphal, became the leading research journal in psychiatry 
internationally.
The philosophical roots of modern neuropsychiatry are to be found in the 
earlier new materialism of the nineteenth century. Étienne-​Jean George2 
(1795–​1828), a disciple of Pinel and Esquirol, emphasized the organic aeti­
ology of mental disorder. Antoine Laurent Bayle (1799–​1858) challenged 
the dualist view of the time with a unitary view of general paralysis—​that 
dementia and mental disorder are both features of the same disease. 
However, it was Griesinger’s works that had the greatest influence on many 
European neuropsychiatrists, including Meyer, Meynert, Liepmann, Pick, 
Oppenheim, Charcot, Korsakoff, von Monakow, Babinski, Janet, Freud, 
Jackson, Bleuler, Kraepelin, Bonhoeffer, and Alzheimer.
In the UK, the most important psychiatrist at the time Henry Maudsley 
(1835–​1918) had views very close to those of Griesinger.3 It was Meynert’s 
disciple Karl Wernicke (1848–​1905)4 who further advanced Griesinger’s 
ideas, proposing: a model to encompass all brain-​related diseases (whether 
so-​called psychiatric or neurological); the development of a pathophysio­
logical model to mediate between the brain and behaviour; and the 
1  Griesinger’s ideas were a reaction to gross German materialism. He was keen on emerging physio­
logical ideas of the time, and it was in this new ambiguous space that he located mental disorders 
(i.e. not neuroanatomically). His related view that many psychological events occur in non-​conscious 
spaces has led some to consider him a ‘pioneer’ of psychodynamic psychiatry.
2  Georget introduced the still popular ‘technology alibi’ that, although all mental disorders are 
caused by changes in the brain, in some cases, we cannot yet demonstrate this due to a lack of 
appropriate technology. (Caveat lector: this is not a scientific hypothesis, but rather a hypothetical 
syllogism based upon a foundational claim that the mind is represented in the brain).
3  In The Physiology and Pathology of Mind (1867), Maudsley states: ‘Mental disorders are neither more 
nor less than nervous diseases in which mental symptoms predominate’.
4  Wernicke is one of the most important psychiatrists of the late nineteenth century, and had he 
not died young, psychiatry might now be a ‘Wernickian world’, as his views on classification, mental 
symptoms, and the relationship between brain and behaviour could have superseded Kraepelin’s.

A brief history of neuropsychiatry
introduction of the first ‘neuropsychological approach’ to mental symp­
toms. Other important figures include Jackson (1834–​1911), von Monakow 
(1853–​1930), Goldstein (1878–​1965), and Guiraud (1882–​1974). In the 
early 1900s, neuropsychiatry was an emerging discipline in the German-​ and 
French-​speaking world, and to an extent in the USA.
All was to change when the rise of psychodynamic thinking led many 
psychiatrists to embrace a new ‘mentalistic’ approach, and a separ­
ation from neurology began. There was resistance. Notably, Sir Charles 
Symonds (1890–​1978), the doyen of British neurologists, fought to prevent 
psychiatry’s drift away from neurology and neuroscience.5 However, after 
World War II, the division between neurology and psychiatry widened, 
symbolized by The Archives of Neurology and Psychiatry (first published in 
1919)  separating into two journals. In many countries, separate depart­
ments of neurology and psychiatry were formed, with separate training 
programmes.
However, from the mid-​twentieth century onwards, developments in 
neuropsychopharmacology led to the emergence of what has been called 
the ‘second biological psychiatry’. There was a real explosion of research in 
neurosciences, a ‘remedicalization’ of psychiatry, and a decline in the dom­
inance of psychodynamism. By the 1980s, even the nosology of psychiatry 
was changing, with the publication of ICD-​9 (1978) and DSM-​III (1980), 
when the neuroses were rejected in favour of a biological medical model. 
With the development of functional imaging techniques, including CT, MRI, 
and PET/​SPECT, and rapid advances in molecular genetics, research of 
neurologists, psychiatrists, psychologists, and cognitive neuroscientists in­
creasingly overlapped. In the UK, the British Neuropsychiatry Association 
(BNPA) was founded in October 1987, chaired by Professor Lishman,6 and 
all clinical neuroscience professionals were welcome to join. In the USA, the 
American Neuropsychiatric Association (ANPA) was founded in 1988 and 
the first joint meeting with the BNPA was in 1991.
At the turn of the millennium, there were calls for a rapprochement of 
neurology and psychiatry.7 The Royal College of Psychiatrists established a 
Special Interest Group in Neuropsychiatry in 2001, and this led to a Section 
of Neuropsychiatry in 2008 and a Faculty of Neuropsychiatry in 2014, with 
emphasis on training, standards, service development, and academic/​re­
search links. It is likely that over the next decade, we will see the disciplines 
of neurology and psychiatry becoming closer still. Early signs are in pro­
posals for ICD-​11 where ‘Dissociative neurological symptom (previously 
conversion) disorders’ may be listed with other ‘Diseases of the nervous 
system’.8
5  Lishman WA (1992) What is neuropsychiatry? J Neurol Neurosurg Psychiatry 55:983–​5.
6  There is no doubt that WA Lishman (1931–​) has been a major influence in the field of neuropsych­
iatry, both as a teacher and trainer of generations of neuropsychiatrists at the Institute of Psychiatry/​
Maudsley and through his textbook Organic Psychiatry: The Psychological Consequences of Cerebral 
Disorder’ (1978, 1987, 1997, and multi-​author 2012).
7  Martin JB (2002) The integration of neurology, psychiatry, and neuroscience in the 21st century. 
Am J Psychiatry 159:695–​704.
8  Stone J, Hallett M, Carson A, Bergen D, Shakir R (2014) Functional disorders in the Neurology 
section of ICD-​11. A landmark opportunity. Neurology 83:2299–​301.

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Chapter 4  Neuropsychiatry
What is neuropsychiatry?
‘Psychiatry is a protean discipline and neuropsychiatry is one of its 
incarnations.’
Berrios and Markova (2002)9
To many psychiatrists, neuropsychiatry is synonymous with psychiatry as both 
are concerned with ‘the functional or organic disturbances of the central 
nervous system that give rise to, contribute to, or are associated with mental 
and emotional disorders.’10 The history of (neuro)psychiatry (E A brief his­
tory of neuropsychiatry, p. 122) is populated by figures like Emil Kraepelin 
(1856–​1926) and Alois Alzheimer (1864–​1915) who practised psychiatry 
but hoped to discover the basis of psychiatric diseases through histological 
and neuropathological research. These days, the term neuropsychiatry can 
be applied in many ways. In the scientific field, neuropsychiatry may refer 
broadly to any endeavour by a scientist, educator, clinician, policymaker, or 
individual who seeks to advance our understanding of the neurological basis 
of psychiatric disorders, the psychiatric manifestations of neurological dis­
orders, and the evaluation and care of those with neurologically based be­
havioural disturbances. When referring specifically to a medical subspecialty, 
it may mean one or the other of two parallel, but historically distinct, clinical 
disciplines: behavioural neurology and neuropsychiatry.
Behavioural neurology (also known as behavioural neuroscience and 
brain sciences) is essentially a branch of neurology that links normal and 
abnormal behaviours to functioning of specific areas or functional networks 
of the brain. The origins of this approach arise in research and early localiza­
tion theories of Franz Gall (1758 –​1828),11 followed in the mid-​nineteenth 
century by neuroanatomical lesion studies in aphasias by Paul Broca (1824–​
1880) and Carl Wernicke (1848–​1905). Research in this area peaked in the 
late nineteenth and early twentieth centuries, with work extending into the 
clinical descriptions of dementias by Alzheimer and Arnold Pick (1851–​
1924). It was not until 1972 that the ‘father of behavioural neurology’ 
Norman Geschwind (1926–​1984) coined the name at a meeting of the 
American Academy of Neurology, and in 1982, the Behavioural Neurology 
Society was founded (now the Society for Behaviour and Cognitive 
Neurology).12 In the USA, Geschwind and colleagues were responsible for 
a renaissance of behavioural neuroscience, not only because of their work 
on disconnection syndromes, aphasia, and behavioural syndromes of limbic 
epilepsy (the eponymous Geschwind syndrome), but also the legacy of 
training generations of behavioural neurologists (including such luminaries 
9  Berrios GE, Markova IS (2002) The concept of neuropsychiatry: a historical overview. J Psychosom 
Res 53:629–​38.
10  ‘Neuropsychiatry’, as defined in Campbell’s Psychiatric Dictionary, 9th edn (2009), Oxford 
University Press.
11  Claimed as the founder of phrenology, Gall’s ideas that a person’s personality could be deter­
mined from the shape of their skull, although controversial and repeatedly disproven, did promote 
the idea of functional localization within the brain—​an idea originally put forward by French naturalist 
and philosopher Charles Bonnet (1720–​1793) over 60 years earlier.
12  Society for Behavioral and Cognitive Neurology. M http://​the-​sbcn.org/​ [accessed 30 
May 2018].

What is neuropsychiatry?
as Kenneth Heilman13 and Antonio Damasio14). With the advent of in vivo 
neuroimaging from the 1980s onwards, the cognitive neurosciences have 
capitalized on having new tools to explore lesion, structural, and functional 
correlations with behavioural dysfunction in living people.
The interwoven history of neuropsychiatry is outlined briefly on 
E pp. 122–​123. It is worth noting that historically neuropsychiatry is a dis­
tinct discipline from biological psychiatry, which emerged along with bio­
logical treatments of psychiatric disorders in the late 1930s to early 1950s. 
The term biological psychiatry was coined in 1946 after a meeting on ‘the 
biological basis of behaviour’, organized by Johannes M Nielsen (1890–​1969), 
Professor of Neurology at the University of Southern California, and George 
N Thompson (1909–​), Chief Psychiatrist at the Los Angeles General Hospital. 
From this meeting arose the Society of Biological Psychiatry, the membership 
of which comprised many of the elite of the American neuroscience estab­
lishment. Neilsen and Thompson published the first textbook of biological 
psychiatry The Engrammes of Psychiatry in 1947. Biological psychiatry devel­
oped to encompass the expanding fields of brain biochemistry, neuroendo­
crinology, cellular and molecular medicine, and genetics, as they applied to 
mental disorders. Due to the cross-​fertilization of the neurosciences over 
the last 70 years, it has become increasingly difficult to distinguish biological 
psychiatry from other clinical and academic neurosciences. Indeed the term 
is sometimes used in a pejorative way to suggest overly reductive thinking. 
The same allegations have been levelled at neuropsychiatry. Developments 
in our understanding of the interaction between genes and the environment, 
together with the rise of biological psychology, neuropsychology, and more 
recently cognitive neuropsychiatry,15 also mean that if we are ever to have a 
more complete understanding of how the brain functions in health and dis­
ease, then further integration is vital. In clinical practice, ignoring psychological 
and social aspects is at best inconsiderate and at worst negligent.
The current practice of both neuropsychiatry and behavioural neurology 
is focused on better understanding the links between neuroscience and 
behaviour, with an emphasis on the care of individuals with neurologically 
based behavioural disturbances. Whether trained primarily in psychiatry, 
neurology, or both, practitioners require specific experience in the evalu­
ation, differential diagnosis, prognosis, pharmacological treatment, psy­
chosocial management, and neurorehabilitation of persons with complex 
neuropsychiatric and neurobehavioural conditions.
13  Professor of Neurology and Health Psychology, Director of University of Florida Memory 
Disorders Clinic, Center for Neuropsychological Studies, and the Behavioral Neurology-​
Neuropsychiatry Fellowship Program. M http://​neurology.ufl.edu/​divisions-​2/​memory-​and-​
cognitive-​disorders/​memory-​and-​cognitive-​faculty/​kenneth-​heilman-​m-​d/​ [accessed 30 May 2018].
14  Professor of Neuroscience and Director of the Brain and Creativity Institute at the University of 
Southern California and an Adjunct Professor at the Salk Institute. He has written a number of books, 
including Descartes’ Error: Emotion, Reason and the Human Brain (1994), which is regarded as one of 
the most influential popular science books of the twentieth century. M https://​dornsife.usc.edu/​cf/​
faculty-​and-​staff/​faculty.cfm?pid=1008328 [accessed 30 May 2018].
15  First proposed in 1993 by Anthony S David, now Professor of Cognitive Neuropsychiatry at 
King’s College London (David AS (1993) Cognitive neuropsychiatry? Psychol Med 23:1–​5) as ‘a sys­
tematic and theoretically driven approach to explain clinical psychopathologies in terms of deficits 
to normal cognitive mechanisms’. (For an overview, see: Halligan PW, David AS (2001) Cognitive 
neuropsychiatry: towards a scientific psychopathology. Nature Rev Neurosci 2:209–​15). M http://​
psych.cf.ac.uk/​home2/​halligan/​halligan_​david%202001.pdf [accessed 30 May 2018].)

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Chapter 4  Neuropsychiatry
Psychiatric presentations of organic 
illness
All psychiatric illnesses are, by their nature, organic, i.e. they involve abnor­
malities of normal brain structure or function. The term ‘organic illness’ in 
modern psychiatric classification, however, refers to those conditions with 
demonstrable aetiology in central nervous system (CNS) pathology. Organic 
disorders related to substance misuse are dealt with in E Chapter 14. This 
chapter deals with those disorders that are caused by degenerative, trau­
matic, inflammatory, infective, autoimmune, and metabolic conditions.
Organic illnesses are included in the lists of differential diagnoses for most 
psychiatric syndromes. For this reason, most patients presenting with psy­
chiatric symptomatology merit a thorough physical examination (including 
neurological examination and, in some cases, special investigations) before 
a diagnosis of primary psychiatric illness is made. While psychiatrists do not 
have to be expert neurologists, a sound knowledge of those conditions that 
bridge neurology and psychiatry is essential.
Listed here are common organic causes of psychiatric syndromes (de­
lirium, dementia, and amnestic disorders are discussed later).
Organic causes of psychosis
 • Neurological [encephalitis, e.g. herpes simplex virus (HSV); epilepsy; 
dementia; brain injury; brain tumour; HIV; neurosyphilis; intracerebral 
abscess; stroke).
 • Endocrine (hyper-​/​hypothyroidism; Cushing’s; hyperparathyroidism; 
Addison’s disease).
 • Metabolic (uraemia; sodium imbalance; porphyria).
 • Autoimmune (systemic lupus erythematosus (SLE) (‘lupus psychosis’); 
autoimmune encephalitis).
 • Medications [steroids; levodopa (L-​dopa); isoniazid; anticholinergics; 
antihypertensives; anticonvulsants; methylphenidate].
 • Drugs of abuse [novel psychoactive substances (NPS); amphetamines; 
cocaine; LSD; cannabis; phencyclidine (PCP); opioids].
 • Toxins.
Organic causes of depression
 • Neurological [stroke; epilepsy; Parkinson’s disease; brain tumour; 
dementia; multiple sclerosis (MS); Huntington’s disease; brain injury]. 
Cerebellar disease is associated with a cognitive-​affective syndrome with 
depressed mood or labile affect.
 • Infectious [HIV; Epstein–​Barr virus (EBV)/​infectious mononucleosis; 
brucellosis).
 • Endocrine and metabolic [hypothyroidism; Cushing’s; Addison’s disease; 
parathyroid disease; vitamin deficiency (B12 and folate); porphyria].
 • Cardiac disease [myocardial infarction (MI); congestive cardiac failure 
(CCF)].
 • SLE.
 • Rheumatoid arthritis.
 • Cancer.

Psychiatric presentations of organic illness
 • Medications [analgesics; antihypertensives; levodopa; anticonvulsants; 
antibiotics; steroids; combined oral contraceptive (OCP); cytotoxics; 
cimetidine; salbutamol).
 • Drugs of abuse [alcohol; benzodiazepines (BDZs); cannabis; cocaine; 
opioids].
 • Toxins.
Organic causes of mania
 • Neurological (stroke; epilepsy; brain tumour; brain injury; MS).
 • Endocrine (hyperthyroidism).
 • Medications (steroids; antidepressants; mefloquine; interferon, isoniazid; 
cytotoxics).
 • Drugs of abuse (cannabis; cocaine; amphetamines).
 • Toxins.
Organic causes of anxiety
 • Neurological (TLE; dementia; brain injury; stroke; brain tumour; MS; 
Parkinson’s disease].
 • Pulmonary [chronic obstructive airways disease (COAD)].
 • Cardiac (arrhythmias; CCF; angina; mitral valve prolapse).
 • Endocrine (hyperthyroidism; phaeochromocytoma).
 • Medications (antidepressants; antihypertensives; flumazenil; yohimbine; 
fenfluramine).
 • Drugs of abuse [alcohol (withdrawal); BDZs (withdrawal); caffeine; 
cannabis; cocaine; LSD; MDMA (ecstasy); amphetamines, NPS].

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Chapter 4  Neuropsychiatry
Neurological examination in psychiatry
A neurological examination should ideally be performed in all patients pre­
senting with psychiatric symptoms—​urgently where there is suspicion of 
an ‘organic’ disorder. With practice, the feeling of ‘normal’ (tone, reflexes, 
optic discs, tandem gait) becomes more firmly established and it becomes 
possible to pick up minor abnormalities which may be diagnostically helpful.
Examination routine
 • General observation—​of the patient walking into the examination room 
(or lying in bed) gives an impression of the conscious level, demeanour, 
mood, gait, and the presence of movement disorders (E Movement 
disorders in psychiatry, p. 132).
 • Gait Ask the patient to walk to the end of the room and turn round.
 • Tandem gait—​ask the patient to walk heel-​to-​toe across the room.
 • Romberg’s sign—​with the examiner’s hands on either side and ready to 
support the patient, should they lose balance, ask the patient to stand 
with their feet together and eyes closed. The test is positive, suggesting 
impaired proprioception, if the patient loses balance.
 • Cranial nerves—​with the patient seated on a chair or an examination 
couch, cranial nerves I–​XII may be quickly assessed using this routine:
 •​ I: not routinely clinically tested, but ask about the sense of smell—​
often lost (anosmia) after brain injury and in Parkinson’s disease.
 •​ II: test visual acuity using the Snellen chart; visual fields with a ‘wiggling 
finger’ or a red pin; and optic discs via fundoscopy. Test pupillary 
reactions to light and accommodation.
 •​ III, IV, and VI: test eye movements and observe any ptosis.
 •​ V: test facial sensation in all three branches of the trigeminal nerve, 
using cotton wool. Test jaw clench.
 •​ VII: test facial movements, asking the patient to copy the examiner—​
raise the eyebrows, close the eyes, and bare the teeth.
 •​ VIII: test hearing by whispering in each ear.
 •​ IX: gag reflex—​not routinely tested.
 •​ X: ask the patient to swallow and cough.
 •​ XI: ask the patient to elevate their shoulders and to turn their head 
left and right against resistance.
 •​ XII: ask the patient to stick out their tongue.
 • Muscle tone—​with the patient seated or reclined on the examination 
couch, test muscle tone in upper and lower limbs. If i tone is suspected, 
test for ankle clonus by rapidly dorsiflexing the foot at the ankle.
 • Muscle power—​test power in upper and lower limbs.
 • Reflexes—​test deep tendon reflexes at the knees, ankles, and elbows. 
The plantar reflex (Babinski) rewards the inconvenience of removing 
shoes with the reassurance that there is no significant upper motor 
neuron lesion.
 • Sensation—​finally, an attempt at sensory examination may be made using 
cotton wool (light touch), a tuning fork (temperature and vibration), and 
proprietary sensory-​testing sharps (e.g. ‘Neurotip™’); note that sensory 
testing relies entirely on the patient’s subjective report.

Neurological examination in psychiatry
Examination findings in neuropsychiatric conditions
Some or all of the following signs may be observed or elicited on examin­
ation, aiding diagnosis.
 • Vascular neurocognitive disorder (vascular dementia)—​pyramidal weakness 
with i tone and brisk reflexes, dysphasia, hurried shuffling gait (marche 
à petit pas).
 • Parkinson’s disease—​shuffling gait with stooped posture, bradykinesia, 
asymmetrical pill-​rolling tremor, cogwheel rigidity, dysdiadochokinesia, 
positive glabellar tap test.
 • Drug-​induced Parkinsonism—​similar to Parkinson’s disease, but posture 
less stooped and rigidity and tremor are symmetrical.
 • Functional neurological disorders—​Hoover’s sign, intermittent ‘give way’ 
weakness, tight-​roping (excessive, successfully corrected overbalancing) 
on tandem gait, non-​anatomical sensory loss, tubular visual field defect, 
tremor ‘entrains’ to rhythm of repeated voluntary movements in 
another limb.
 • Raised intracranial pressure—​papilloedema, drowsiness. There may be 
signs of a localizing lesion (e.g. hemiparesis or aphasia due to tumour). 
Idiopathic intracranial hypertension is associated with papilloedema and 
most common in obese young women.
 • Normal pressure hydrocephalus (NPH)—​hypokinetic gait—​the patient 
looks ‘glued to the floor’. Ataxia.
 • Advanced dementia—​long tract signs, including brisk reflexes and upgoing 
plantars, may be present. Primitive reflexes are less specific.
 • Amyotrophic lateral sclerosis (ALS)/​motor neuron disease (MND)—​muscle 
wasting, fasciculation, dysarthria.
 • Progressive supranuclear palsy—​characteristic loss of downgaze, followed 
by loss of upgaze. Unsteady gait, dysarthria.
 • Creutzfeldt–​Jakob disease (CJD)—​ataxia, myoclonus, visual impairment 
(blurred vision, visual agnosia, or cortical blindness).
 • Wilson’s disease—​Kayser–​Fleischer rings, ataxia, masked facial 
appearance, dysarthria, late dystonia, rigidity, spasticity, and flexion 
contractures.
 • Subacute combined degeneration of the cord—​(caused by B12 deficiency 
and associated with a dementia syndrome) Spasticity in the legs with 
extensor plantars, but hyporeflexia at the knees and ankles. Peripheral 
sensory loss (especially to pain and temperature) and optic atrophy 
(pale discs).
 • Neurosyphilis—​ataxia, signs of stroke, reduced visual acuity, optic 
atrophy, Argyll Robertson pupils (small; accommodate but do not 
react), hearing loss, hypotonia and hyporeflexia, loss of proprioception 
and vibration sense, positive Romberg’s test.

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Chapter 4  Neuropsychiatry
Neurological investigations in psychiatry
Basic observations and blood tests to exclude reversible causes or comorbid 
physical illness should be routinely performed in all new presentations of 
psychiatric illness.
Standard blood tests in psychiatric practice
 • FBC, U&Es, LFTs [including gamma glutamyl transferase (GGT) which 
is sensitive to alcohol excess], inflammatory marker [C-​reactive protein 
(CRP) or erythrocyte sedimentation rate (ESR)], thyroid function, bone 
profile (calcium, phosphate).
 • B12 and folate.
 • Tests for relevant infections: HIV ( + viral hepatitis) where risk factors; HIV 
and syphilis in subacute dementia.
 • Blood or urine toxicology.
In certain circumstances, more invasive and/​or expensive investigations 
may be useful, as follows.
Additional blood tests
 • Autoimmune encephalitis antibodies —​aypical psychosis (e.g. with alteration 
of consciousness or cognition, seizures, or movement disorder).
 • Genetic tests for specific mutations—​consider where history of early-​
onset and strong family history of dementia, e.g. dementia of the 
Alzheimer type (DAT) (E Alzheimer’s disease 1, p. 156), fronto-​
temporal disease (FTD) (E Fronto-​temporal dementia, p. 160). Note 
ethical issues in testing for Huntington’s disease, which has implications 
for other family members (E Huntington’s disease, p. 166).
Imaging
 • CT brain—​is usually performed in the investigation of cognitive 
impairment, in order to exclude tumour/​space-​occupying lesion (SOL) 
or NPH and to assess the extent of cerebrovascular disease and global 
and focal areas of atrophy.
 • MRI brain—​may be suggested to allow abnormalities on CT to be 
assessed in higher resolution or where the CT scan appears normal, but 
abnormalities are suspected. Changes after brain injury, in encephalitis, 
and after stroke may be evident on MRI, but not CT. Pacemakers and 
other metal implants are contraindications to MRI.
 • PET/​SPECT/​dopamine active transporter (DAT)—​radioisotope scans can 
be used to assess function. SPECT is helpful in discriminating DAT from 
FTD, and DAT can help with early diagnosis of Parkinson’s disease and 
Lewy body dementia.

Neurological investigations in psychiatry
Electroencephalography16
 • Interictal EEG—​in general, has a limited role in the differential 
diagnosis of epilepsy. A normal EEG does not exclude epilepsy, and 
epileptiform discharges are found in 1% of the general population 
and between 10% and 30% of people with other cerebral pathology 
or on psychotropic medication. In conditions other than epilepsy, the 
EEG is often non-​specific—​showing similar patterns in most types of 
encephalopathy. However, there are notable exceptions where the 
EEG is distinctive: non-​convulsive status epilepticus, CJD, and subacute 
sclerosing panencephalitis (SSPE). EEG can be useful in distinguishing 
functional/​psychogenic coma from organic causes of unconsciousness.
 • Video EEG/​video telemetry—​can aid the diagnosis of epilepsy and 
dissociative (non-​epileptic) seizures by recording a typical event, but 
only if an event is captured during recording.
Cerebrospinal fluid sampling (lumbar puncture)
 • LP and analysis of cerebrospinal fluid (CSF) for protein, blood, and 
cytology should be considered where encephalitis (infective or 
autoimmune) is suspected.
 • Oligoclonal bands in CSF which are not matched in the plasma (unpaired 
oligoclonal bands) suggest CNS inflammation.
 • Test for CSF 14-​3-​3 protein in suspected CJD.
16  Smith SJM (2005) EEG in neurological conditions other than epilepsy: when does it help, what 
does it add? J Neurol Neurosurg Psychiatry 76(Suppl 2):ii8–​12.

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Chapter 4  Neuropsychiatry
Movement disorders in psychiatry
Movement 
disorders 
occur 
in 
three 
contexts 
within 
psych­
iatry:  neurodegenerative disorders with psychiatric symptoms (e.g. 
Parkinson’s disease), psychiatric disorders with abnormal movements 
(stereotypies, tics), and medication-​induced movement disorders (e.g. 
EPSEs).
Pathophysiology
Movement disorders commonly involve a disequilibrium of neurotransmit­
ters, such as dopamine (DA), acetylcholine (ACh), and gamma-​aminobutyric 
acid (GABA), within the circuits of the basal ganglia. Levels of DA and ACh 
tend to be inversely related. For example, in Parkinsonism, there is dDA 
with iACh; conversely, chorea is characterized by iDA and dACh.
Parkinsonism
A syndrome characterized by four core symptoms: slow, ‘pill-​rolling’ tremor 
(4Hz); rigidity; bradykinesia; and postural abnormalities.
Aetiology
 • Degenerative diseases—​idiopathic Parkinson’s disease (85% cases) 
and Lewy body dementia; progressive supranuclear palsy (PSNP); 
multisystem atrophy (MSA); corticobasal degeneration (CBD).
 • Medication—​antipsychotics; metoclopramide; domperidone.
 • Toxins—​cobalt; manganese; magnesium; organophosphates.
 • Infections—​encephalitis lethargica (post-​influenza); CJD.
 • Miscellaneous—​cerebrovascular disease involving the basal ganglia; 
trauma of the basal ganglia; NPH; neoplasia of the basal ganglia; 
dementia pugilistica (punch-​drunk syndrome).
Tic disorders
Tics are spontaneous, repetitive, rhythmic movements that can be motor or 
vocal and usually involve iDA in the basal ganglia. They are semi-​voluntary 
and can only be resisted for a short time with difficulty. Tics are classified as 
primary or secondary and occur in:
 • Tourette’s syndrome—​multiple motor, and at least one vocal, tics many 
times per day for >1yr (E Tic disorders, p. 676).
 • Chronic tic disorder—​motor or vocal tics, but not both.
 • Provisional tic disorder—​childhood tics present for <1yr.
 • Infection—​CJD; Sydenham’s chorea; encephalitis.
 • Drugs—​levodopa; methylphenidate; cocaine; amphetamines.
 • Other—​carbon monoxide (CO) poisoning; stroke/​trauma (rare).
Tremor
 • Exaggerated physiological tremor—​(8–​12Hz); occurs at rest and with 
action; causes: stress, anxiety, caffeine, medications.
 • Essential tremor—​(6–​12Hz); at rest, with action and postural; most 
noticeable symmetrically in upper limbs.
 • Extra-​pyramidal—​(4Hz); resting tremor; e.g. Parkinsonism.
 • Cerebellar, midbrain, or red nucleus—​(4–​6Hz); intention tremor; 
causes: trauma, vascular, MS, tumour.

Movement disorders in psychiatry
Catatonia
(E The catatonic patient, p. 1054)
 • A motor syndrome with several causes, diagnosed (DSM-​5) by the 
presence of three or more of the following:
 •​ Stupor (no psychomotor activity).
 •​ Catalepsy (passive induction of a posture held against gravity).
 •​ ‘Waxy flexibility’.
 •​ Mutism.
 •​ Negativism (opposition/​no response to instructions or stimuli).
 •​ Posturing (active maintenance of postures against gravity).
 •​ Mannerism.
 •​ Stereotypy.
 •​ Agitation (motor excitement not influenced by external stimuli).
 •​ Echolalia and echopraxia.
 • Treatment—​BDZs, ECT.
Chorea
Brief, irregular, ‘dance’-​like, unpredictable movements, which, in mild 
cases, may appear voluntary. There are many causes, including preg­
nancy, Sydenham’s chorea, drugs (antipsychotics, levodopa, OCP), and 
Huntington’s disease. Treatment—​antipsychotics, BDZs, or tetrabenazine 
have been tried.
Hemiballismus
A rare and dramatic movement disorder. An extreme version of chorea 
in which a structural lesion or metabolic damage to the subthalamic nu­
cleus causes involuntary flailing, ballistic movements of the limbs. Causes—​
include stroke and non-​ketotic hyperglycaemia. Treatment—​antipsychotics 
or tetrabenazine may help.
Alien hand syndrome
A complex movement disorder associated with a sense of loss of limb 
ownership. The patient’s hand performs complex, meaningful move­
ments without being guided by the intention of the patient, who is unable 
to stop the hand from grasping objects. It occurs in 60% of patients with 
corticobasal degeneration17 and has also been described after stroke.
Encephalitis lethargica
Roughly 20yrs after the great influenza epidemic of the 1920s, large numbers 
of patients who had suffered from influenza encephalitis during the epidemic 
developed this disorder (also called post-​encephalitic Parkinsonism), now 
thought to be an autoimmune condition. Clinical findings—​Parkinsonism; 
oculogyric crises; pupillary abnormalities; psychosis. The disorder was the 
subject of the book (and film) by Oliver Sacks, entitled Awakenings.
17  Belfor N, Amici S, Boxer AL, et al. (2006) Clinical and neuropsychological features of corticobasal 
degeneration. Mech Ageing Dev 127:203–​7.

134
Chapter 4  Neuropsychiatry
Functional neurological symptoms
Epidemiology
Functional neurological symptoms (also historically called hysterical, con­
version, psychogenic, or medically unexplained) account, in whole or part, 
for up to 30% of presentations to neurology outpatient clinics.18 Patients 
experience similar levels of disability to those with conditions such as MS, 
but greater levels of psychiatric comorbidity and emotional distress; up 
to 70% have depression or anxiety disorders. Rates of misdiagnosis are 
low19 (see also E Medically unexplained symptoms 1: introduction, p. 858; 
E Medically unexplained symptoms 2: clinical presentations, p. 860; E 
Medically unexplained symptoms 3: management principles, p. 862).
Clinical features
Symptoms often have a sudden onset, which may or may not follow a recent 
traumatic event, injury, illness (migraine is a common trigger), medical inter­
vention, or anaesthetic. Symptoms may closely mimic those of neurological 
disease: weakness, sensory loss, dysphonia or dysarthria, muscle jerks, or 
seizures. Diagnosis requires positive clinical features of functional disorder 
(see Box 4.1). Aetiology is unclear; current research suggests that abnormal 
attentional focus may generate symptoms, and functional MRI (fMRI) studies 
show abnormal activation of the prefrontal cortex during attempted move­
ment; dissociative seizures may relate to panic (although most patients do 
not experience typical anxiety symptoms). A history of prior trauma is no 
longer required for diagnosis (DSM-​5); recent reviews suggest many, but 
importantly not all, patients have a history of stressful life events.
18  Carson AJ, Ringbauer B, Stone J, McKenzie L, Warlow C, Sharpe M (2000) Do medically unex­
plained symptoms matter? A prospective cohort study of 300 new referrals to neurology outpatient 
clinics. J Neurol Neurosurg Psychiatry 68:207–​10.
19  Stone J, Sharpe M, Rothwell PM, Warlow CP (2003) The 12 year prognosis of unilateral func­
tional weakness and sensory disturbance. J Neurol Neurosurg Psychiatry 74:591–​6.
Box 4.1  Positive clinical features of functional 
neurological disorder
 • Leg weakness and gait disturbance—​Hoover’s sign, marked 
inconsistency on examination (e.g. able to walk but unable to move 
the leg during examination).
 • Tremor—​‘entrains’ to a rhythm tapped with the opposite hand or 
with the foot; disappears when distracted.
 • Sensory symptoms—​sharply demarcated and non-​anatomical 
distribution of sensory loss, e.g. with a sharp midline boundary. 
Tubular visual field defect.
 • Dissociative seizures—​long duration, fluctuating course, asynchronous 
movements, side-​to-​side head and body movements, eyes closed, and 
ictal crying.
 • Cognitive symptoms—​detailed recall of ‘forgetting’ events; gross 
inconsistency in test performance vs observed or reported level of 
function; attending clinic alone.

Functional neurological symptoms
Prognostic factors
Symptoms with a short history and acute onset often get better within days 
or weeks; however, commonly, symptoms run a chronic course, with high 
levels of disability and distress ongoing after many years. Perpetuating fac­
tors may include: fear of neurological disease, avoidance of movement and 
normal activity, secondary anxiety or depression, and social adversity. As 
with most psychiatric and neurological conditions, litigation is the strongest 
predictor of poor outcome.
Investigations
Even in the presence of positive clinical evidence of a functional disorder, 
it is generally sensible to perform relevant investigations—​CT head, CT 
spine, neurophysiology—​to be sure no organic pathology has been missed 
and to reassure the patient that their concerns have been taken seriously. 
Where it is not possible to witness or obtain a good witness account of 
dissociative seizures, video EEG can be extremely helpful.
Management
 • Explanation: where the diagnosis is clear, it can and should be 
confidently explained that this is a positive diagnosis, and not one of 
exclusion, and that the condition is familiar, common in neurology clinics, 
and not a ‘medical mystery’.
 • The condition may be described as a disturbance of function, but 
not structure; some use the basic analogy of a ‘software’, rather than 
‘hardware’, problem; other patients may be able to engage with an 
explanation of abnormal attentional focus disturbing processes which 
are usually automatic.
 • If present, positive clinical signs, such as the Hoover’s sign or 
entrainment of tremor, can be positively used to demonstrate to the 
patient the unhelpful role of attention and therefore potential for 
recovery.20
 • For patients who do not improve after a clear explanation of diagnosis, 
physiotherapy (ideally from a therapist with interest or experience 
in functional disorders),21 or CBT may be effective. Treat comorbid 
depression or anxiety.
 • Follow-​up for those with widespread symptoms may help to prevent 
iatrogenic harm from over-​investigation or from treatments that are 
likely to be unhelpful. BDZs and opiates, in particular, can worsen 
symptoms of dissociation and fatigue.
20  Stone J, Edwards M (2012) Trick or treat? Showing patients with functional (psychogenic) motor 
symptoms their physical signs. Neurology 79:282–​4.
21  Nielsen G, Stone J, Matthews A, et al. (2015) Physiotherapy for functional motor disorders: a 
consensus recommendation. J Neurol Neurosurg Psychiatry 86:1113–​19.

136
Chapter 4  Neuropsychiatry
Neurodevelopmental disorders 
in adulthood
As the rates of diagnosis of neurodevelopmental disorders in children have 
i in recent years, there is increasing recognition of the lifelong impact of 
neurodevelopmental disorders (E Attention-​deficit/​hyperactivity dis­
order, pp. 668-​672). Individuals, often without a previous diagnosis, may 
present complaining of difficulties associated with core symptoms of these 
disorders or due to associated psychopathology and social difficulties. 
Parents may recognize their own symptoms and seek diagnosis following 
the diagnosis in a child.
Attention-​deficit/​hyperactivity disorder
Epidemiology
The estimated prevalence of ADHD in adults in the USA is 4.4%, and in the 
UK 2.3%. ♂:♀ 2:1. Some symptoms of childhood ADHD persist in adult­
hood in 50–​65%, with the full syndrome persisting in 15%.
Clinical features
Social problems as a result of inattentive and impulsive behaviours include:
 • Difficulty maintaining relationships and employment.
 • Poor engagement with medical care.
 • Criminal behaviours. ADHD is common in prisons and young offender 
institutions.
 • Substance misuse and addiction, particularly with stimulants, reflecting 
a combination of social disadvantage and self-​medication. It may 
be difficult to disentangle symptoms of ADHD from symptoms of 
intoxication, withdrawal, or complications such as drug-​induced 
psychosis.
Diagnosis
Symptoms of inattention and/​or hyperactivity-​impulsivity:
 • Impaired function.
 • Present in different settings (e.g. home and work).
 • Present from childhood, evidenced by collateral history from parent ± 
school reports.
 • Must not be explained by another mental disorder, although the 
presence of secondary mood, anxiety, or substance misuse disorders 
may make this difficult to establish.
Treatment
(See NICE guidelines, 2008.)22
 • Atomoxetine, methylphenidate, or dexamfetamine.
 • Full medical examination and history, including assessment of cardiac 
risk factors prior to treatment.
22  Kendall T, Taylor E, Perez A, Taylor C (2008) Guidelines: diagnosis and management of attention-​
deficit/​hyperactivity disorder in children, young people, and adults: summary of NICE guidance. 
BMJ 337:751–​3.

Neurodevelopmental disorders in adulthood
 • Atomoxetine may cause agitation, suicidality, and idiosyncratic liver 
reactions but is safest if there is a risk of diversion or misuse and is less 
likely to cause psychosis.
 • Monitor weight (risk of weight loss), blood pressure (BP), and pulse on 
all stimulants.
 • Offer CBT to those unable or unwilling to take medication.
Autism spectrum disorders
(See also E Pervasive developmental disorders, p. 820; E Autism spec­
trum disorders, p. 674.)
Clinical features
The core features are:
 • Deficits in reciprocal social interaction.
 • Restricted and repetitive behaviours and interests.
 • Communication impairments.
In adolescence and adulthood, communication skills often improve, but so­
cial deficits can be more problematic, perhaps reflecting the more complex 
demands of adult relationships.23 Adults without a prior diagnosis of ASD 
may present with secondary anxiety or mood disorders.
Diagnosis
Requires collateral history or supporting information (e.g. school reports) 
evidencing that deficits have been present since early childhood. The Autism 
Spectrum Quotient (AQ) questionnaire can be helpful as a screening tool.
Treatment
Supportive, including direction to available support agencies. Secondary 
mood disorders or anxiety disorders should be treated as for those without 
mood or anxiety disorders, including with psychological treatment where 
available.
23  Seltzer MM, Krauss MW, Shattuck PT, Orsmond G, Swe A, Lord C (2003) The symptoms of 
autism spectrum disorders in adolescence and adulthood. J Autism Dev Disord 33:565–​81.

138
Chapter 4  Neuropsychiatry
Psychiatric aspects of epilepsy 1
An epileptic seizure is a transient occurrence of signs and/​or symptoms 
due to abnormal excessive or synchronous neuronal activity in the brain. 
Epilepsy is a disease of the brain, characterized by an enduring predispos­
ition to epileptic seizures. The prevalence of active epilepsy in the UK is 
estimated to be 5–​10/​1000. The clinical manifestation of a seizure depends 
on: the cause of epilepsy, the location of the epileptic focus, and the spread 
of the epileptic discharge within the brain. Seizures are broadly classified 
as generalized when arising in diffuse bilateral networks or focal when 
arising from specific areas of the brain. Epilepsy carries significant disease 
burden and is associated with an i risk of psychiatric disorders, the most 
common being depression and anxiety which affect up to 30% of people 
with epilepsy.
Psychological consequences of diagnosis
People with epilepsy have a significantly poorer health-​related quality of life, 
when compared with the general population, associated with frequent seiz­
ures, medication side effects, social disability, and stigma, as well as cognitive 
and mood problems.
Neuropsychiatric effects of treatment
All antiepileptic drugs can induce psychiatric symptoms in people with epi­
lepsy. Mood disorders are the most prevalent, followed by behavioural 
disturbances and, rarely, psychosis. Patients with a previous psychiatric his­
tory are at higher risk of developing these side effects. Specifically, pheno­
barbital, vigabatrin, tiagabine, topiramate, levetiracetam and zonisamide 
have been reported to trigger symptoms of depression, and vigabatrin, 
tiagabine, topiramate, and levetiracetam have been associated with psych­
osis. Aggressive behaviour and irritability have also been reported as a side 
effect of some antiepileptic drugs, particularly levetiracetam, perampanel, 
and topiramate.
Cognitive problems
Cognitive problems are common with multifactorial aetiology, depending 
on the underlying epilepsy-​causing pathology, the frequency and localization 
of the seizures, the effects of medication, and psychiatric comorbidity. Early 
onset of seizures, long duration of epilepsy, and high frequency of seizures 
are associated with poorer cognitive outcome. Clinically, the most common 
presentation is of memory problems—​in general, the result of sedation 
and slower processing speed secondary to medication. However, in TLE, 
there is a primary problem of encoding and consolidating information due 
to brain pathology.
Psychiatric disorders directly attributed to epilepsy—​
independent of seizures
Interictal depression
Depression is the most common psychiatric comorbidity in people with 
epilepsy. Prevalence ranges from 10% in people with well-​controlled epi­
lepsy to 50% for those with refractory epilepsy and symptomatic focal

Psychiatric aspects of epilepsy 1
epilepsy (TLE). There is a bi-​directional relationship between depression 
and epilepsy—​people with a history of depression have a 7-​times risk of 
developing epilepsy, suggesting a possible common pathogenic mechanism. 
Diagnosis—​depression in people with epilepsy is often under-​recognized; 
atypical depressive symptoms are sometimes attributed to ‘interictal dys­
phoric disorder’, and typical symptoms of depression, including fatigue, 
weight changes, sleep difficulties, and poor concentration, overlap with 
common side effects of antiepileptic drugs and/​or the consequences of 
recurrent seizures. The Neurological Disorders Depression Inventory for 
Epilepsy (NDDI-​E)24 is a self-​rated six-​item questionnaire which has been 
validated to screen for depression in patients with epilepsy. Suicide rates 
in people with epilepsy are three times that of the general population, and 
suicide is the cause of up to 5% of all epilepsy deaths. Newly diagnosed pa­
tients are at higher risk of suicide. Treatment—​there is some evidence that 
CBT is helpful. Antidepressants, usually SSRIs (E Prescribing for patients 
with epilepsy, p. 1038), may also be effective.
Interical anxiety
The prevalence of anxiety in people with epilepsy is higher than in the gen­
eral population, with a significantly elevated risk of social phobias, general­
ized anxiety disorder (GAD), and agoraphobia. Anxiety is more common in 
people with focal epilepsy.
Interictal psychosis
The prevalence of psychosis among people with epilepsy is between 7% 
and 10%—​6–​10 times that of the general population. Risk factors include 
family history of psychosis, earlier age at onset of epilepsy, and low intel­
lectual ability. A schizophrenia-​like syndrome, characterized by an absence 
of negative symptoms and little deterioration of personality, has been de­
scribed. More recent studies have found no differences in psychotic symp­
toms between patients with schizophrenia with or those without epilepsy, 
although there is evidence that people with epilepsy may have a less severe 
course and a better response to antipsychotics. Treatment—​antipsychotic 
medication, usually haloperidol or sulpiride (E Prescribing for patients with 
epilepsy, p. 1038). There is little evidence for superiority of any particular 
medication, and choice represents a balance between effective treatment 
of psychosis and the risk of lowering the seizure threshold. In general, the 
chosen antipsychotic should be titrated slowly to the lowest effective dose. 
Most antipsychotics can cause non-​specific changes on the EEG in patients 
with or without epilepsy. Clozapine can produce epileptiform discharges on 
the EEG, but this does not predict the occurrence of seizures.
Forced normalization or alternating psychosis
A relatively rare situation in which the patient’s presentation alternates be­
tween periods of frequent seizures with a normal mental state and periods 
of improved seizure control and normalization of the EEG, but with the 
emergence of psychotic symptoms. This phenomenon has been observed 
following the introduction of anticonvulsants.
24  Gilliam FG, Barry JJ, Hermann BP, et al. (2006) Rapid detection of major depression in epilepsy: a 
multicentre study. Lancet Neurol 5:399–​405.

140
Chapter 4  Neuropsychiatry
Psychiatric aspects of epilepsy 2
Psychiatric disorders directly attributed to epilepsy—​
dependent on seizures
Pre-​ictal symptoms
People with epilepsy may experience mood changes during the days and 
hours leading up to the seizure. These include symptoms of irritability, emo­
tional lability, depression, anxiety, or (rarely) aggression, all of which subside 
after the seizure.
Ictal symptoms
Changes in mental state as a direct expression of the seizure activity begin 
abruptly, are short-​lasting and stereotyped, and are often accompanied by 
other ictal symptoms like motor automatisms. Ictal fear and anxiety are a 
common experience, particularly in patients with TLE. Psychotic-​like symp­
toms include brief experiences of visual, auditory, or gustatory hallucin­
ations, usually with preserved insight. In non-​convulsive status epilepticus, 
these psychotic-​like symptoms can persist and can be distinguished from a 
primary psychiatric disorder by the presence of confusion and other ictal 
features. Ictal aggression is very rare.
Post-​ictal symptoms
Post-​ictal confusion
Characterized by an altered state of consciousness following a seizure, 
resulting in agitated and confused behaviour, lasting between minutes to 
an hour. Aggressive behaviour may be a feature; however, it is often non-​
directed, unintentional, and brief.
Post–​ictal depression
The most commonly reported mood disturbance following a seizure. 
Depressive symptoms range from mild to moderate and are often accom­
panied by symptoms of anxiety. Some patients, particularly if they have a 
history of mental illness, will experience suicidal ideation. Post-​ictal depres­
sion symptoms often resolve within 24hrs, although they can at times last 
for several days after the seizure.
Post-​ictal psychosis
This affects 7–​10% of people with epilepsy. Risk factors include a >10yr 
history of seizures, bilateral ictal foci, structural brain abnormalities, and a 
previous history of psychiatric disorders. Episodes are often triggered by 
a cluster of, or a marked increase in, generalized seizures, followed by a 
24–​72hr period of normal mental state, after which psychotic symptoms 
develop. Psychotic symptoms include delusions (paranoid, persecutory, re­
ligious) and visual and auditory hallucinations. There is frequently a marked 
affective component and a degree of confusion or delirium. Symptoms 
resolve spontaneously within days or weeks, but during the acute phase, 
BZDs or antipsychotics may be required. In the long term, improving 
seizure control will reduce the chances of further episodes (see Box 4.2).

Psychiatric aspects of epilepsy 2
The ecstatic seizures of Prince Myshkin
He was thinking, incidentally, that there was a moment or two in his epi­
leptic condition almost before the fit itself (if it occurred in waking hours) 
when suddenly amid the sadness, spiritual darkness, and depression, his 
brain seemed to catch fire at brief moments . . . His sensation of being alive 
and his awareness increased tenfold at those moments which flashed by like 
lightning. His mind and heart were flooded by a dazzling light. All his agita­
tion, doubts, and worries seemed composed in a twinkling, culminating in a 
great calm, full of understanding . . . but these moments, these glimmerings 
were still but a premonition of that final second (never more than a second) 
with which the seizure itself began. That second was, of course, unbearable.
Dostoyevsky: The Idiot
M http://​www.gutenberg.org/​ebooks/​2638
Box 4.2  Post-​ictal psychosis diagnostic criteria
 • Episode of psychosis (often with confusion and delirium), developing 
within 1wk of a seizure or cluster of seizures.
 • Psychosis lasting at least 15hrs and <2mths.
 • Mental state characterized by delirium or delusions (e.g. paranoid, 
non-​paranoid, delusional, misidentifications) or hallucinations (e.g. 
auditory, visual, somatosensory, olfactory) in clear consciousness.
 • No evidence of:
 • A history of treatment with antipsychotic medications or psychosis 
within the past 3mths.
 • Antiepileptic drug toxicity.
 • An EEG demonstrating non-​convulsive status.
 • A recent history of head trauma or alcohol/​drug intoxication or 
withdrawal (other than BZDs used for epilepsy).
Reprinted from Logsdail SJ, Toone BK. Post-​ictal psychoses. A clinical and phenomeno-​logical 
description. Br J Psychiatry 1988;152 with permission from Cambridge University Press.

142
Chapter 4  Neuropsychiatry
Parkinson’s disease and related 
syndromes
Parkinson’s disease results in progressive impairment of voluntary initiation 
of movement, associated with dementia of variable severity, as well as psy­
chiatric morbidity. It is caused by a gradual loss of dopaminergic neurons 
in the substantia nigra (pars compacta). This results in dDA and iACh in 
the basal ganglia. The remaining cells of the substantia nigra contain Lewy 
bodies.
Epidemiology
Occurs in 20/​100,000 people; typically has its onset in the 50s and peaks 
during the 70s; ♂:♀ = 3:2; 5% of cases are familial; 25% of patients are dis­
abled or die within 5yrs and 760% within 10yrs; rare survival 720yrs.
Symptoms and signs of Parkinson’s disease
 • Tremor—​resting, ‘pill-​rolling’ tremor of 4Hz; this is an early sign that may 
start unilaterally and may be asymmetrical in intensity; tremor increases 
with excitement or fatigue and diminishes during sleep.
 • Rigidity—​‘lead-​pipe’ or ‘cog-​wheel’ rigidity, especially in flexor muscles.
 • Bradykinesia—​slowness; difficulty initiating movement; reduced facial 
expression and blinking; ‘mask facies’; reduced arm swing; ‘festinating 
gait’; reduced voluntary speech; micrographia; ‘freezing’ episodes.
 • Postural abnormalities—​flexed posture; postural instability, with 
frequent falls.
 • Autonomic instability—​postural hypotension; constipation; urinary 
retention; sweaty, greasy, seborrhoeic skin; hypersalivation with 
drooling.
 • Positive glabellar tap.
Differential diagnoses
 • MSA—​Parkinsonism; ataxia; vertical gaze palsies; pyramidal signs; 
autonomic abnormalities.
 • PSNP—​also known as Steele–​Richardson–​Olszewski syndrome; has its 
onset in the 50s and 60s and is characterized by a tetrad of: subcortical 
dementia, pseudobulbar palsy, supranuclear palsy, and dystonia (of the 
head and neck).
 • Dementia with Lewy bodies (DLB) (E Dementia with Lewy bodies, 
p. 162).
Dementia in Parkinson’s disease
Fifty to 80% of patients develop dementia. Risk of dementia increases with 
increasing age, increasing severity of symptoms, and coexisting cardiovas­
cular disease. Patients who do not develop dementia may develop subtle 
cognitive deficits such as rigidity and difficulty sequencing multi-​stage tasks.
Clinical features Usually a subcortical dementia with slowing, im­
paired executive function, personality change, and memory impairment. 
Hallucinations and paranoia are common, and the later picture is as in DLB 
(E Dementia with Lewy bodies, p. 162).
Pathology Indistinguishable from that of DLB.

Parkinson’s disease and related syndromes
Depression in Parkinson’s disease
Very common finding, with 40–​70% of patients affected. While depres­
sion may arise in the context of adjustment to diagnosis and worsening 
Parkinson’s disease symptoms, reduced levels of monoamines [DA, nor­
adrenaline (NA), 5-​hydroxytryptamine (5-​HT)]) and degeneration of 
subcortical pathways are likely to be important causative factors. Mood 
fluctuations are often noted in association with changes in plasma DA levels.
Treatment SSRIs; ECT (improves the depressive illness but can precipitate 
delirium).
Psychosis/​delirium in Parkinson’s disease
Psychosis occurs in some cases and is commonly due to medications used 
in Parkinson’s disease such as:
 • Anticholinergics—​delirium, agitation, hallucinations, etc.
 • levodopa and DA agonists can cause psychiatric complications, including 
delirium, psychosis, mania, and impulse-​control disorders (ICDs).
Treatment Removal or dose adjustment of causative agents; occasionally, 
atypical antipsychotics with a lower risk of EPSEs may be used cautiously.
Impulse-​control disorders
(E Impulse-​control disorders 1, p. 422; E Impulse-​control disorders 2, 
p. 424; E Impulse-​control disorders 3, p. 428.)
ICDs, in the form of pathological gambling, hypersexuality, compulsive 
eating, or compulsive shopping, are recognized complications of treatment 
with dopamine agonists and occur in 714% of patients with Parkinson’s dis­
ease (also in patients receiving treatment with dopamine agonists for other 
conditions such as restless legs syndrome, MS, and PSNP).
Treatment Patients must be warned of the risk of ICDs prior to com­
mencing treatment. Decrease or discontinue dopamine agonist if symptoms 
develop.
Dopamine dysregulation syndrome
Patients develop addictive behaviours towards prescribed dopamine 
agonist medication, taking doses in excess of those required to treat motor 
symptoms. Resulting dopaminergic excess can cause ‘punding’ (repetitive, 
purposeless, complex motor behaviours such as collecting or rearranging 
objects), ICDs, and psychosis.
Treatment Reduction and supervision of medication.

144
Chapter 4  Neuropsychiatry
Neuropsychiatric aspects of central 
nervous system infections
Viral encephalitis
 • Mumps, varicella-​zoster, arbovirus, rubella—​may cause encephalitis, 
resulting in behavioural problems, learning difficulties, and ADHD-​like 
symptoms in children.
 • HSV 1—​involves inferior frontal and anterior temporal lobes, resulting—​
in the acute phase—​in delirium, hallucinations, and TLE. Chronic 
outcomes include an isolated amnestic syndrome, dementia, and 
Klüver–​Bucy syndrome. EEG: slowing, with bursts of i slow wave in 
the temporal region. Treatment: early treatment with intravenous (IV) 
aciclovir (before diagnosis is confirmed) reduces long-​term disability.
 • Measles—​can cause both an acute viral encephalitis and rarely SSPE, 
a slow viral infection with onset of symptoms years after initial 
measles infection. Clinical features: behavioural problems, deteriorating 
intellectual function, movement disorders (ataxia, myoclonus), seizures, 
and, finally dementia and death. Pathology: white and grey matter 
changes to the occiput, cerebellum, and basal ganglia. EEG: periodic 
complexes.
Tuberculosis
 • TB meningitis—​in high-​prevalence areas most common in children, and in 
low-​prevalence areas more common in adults; caseating exudate covers 
the base of the skull, leading to vascular infarcts and hydrocephalus; 
cranial nerves may become involved. Psychiatric symptoms: apathy, 
withdrawal, insidious personality changes, delirium, hallucinations, 
chronic behavioural problems.
 • Tuberculoma—​presents with focal signs, seizures, raised intracranial 
pressure (ICP).
Neurosyphilis
Historically known as general paresis of the insane (GPI) or Cupid’s disease, 
neurosyphilis is a chronic outcome of spirochaetal infection of the brain 
parenchyma. It manifests roughly 15–​20yrs after infection. The spirochaetes 
have a predilection for frontal and parietal lobes, and the disease typically 
presents as a progressive frontal dementia.
Classic symptoms Grandiosity, euphoria, and mania with mood-​congruent 
delusions. Disinhibition, personality change, and memory impairment are 
also common.
Neurological features Argyll Robertson pupils, ‘trombone tongue’, 
tremor, ataxia, dysarthria, myoclonus, hyperreflexia, spasticity, and 
extra-​pyramidal signs.
Megalomania in general paralysis
Gentlemen,—​You have before you today a merchant, aged forty-​three, 
who sits down with a polite greeting, and answers questions fluently and 
easily . . . His illness began about two years ago. He became absent-​minded 
and forgetful, to such an extent at last that he was dismissed by the firm 
for whom he had worked. Then, a year ago, he became excited, made

145
NEUROPSYCHIATRIC ASPECTS OF CNS INFECTIONS
extensive purchases and plans, weeping now and then in the deepest des­
pair, so that he had to be taken into the hospital. On admission, he felt full 
of energy . . . and intended to write verses here, where he was particularly 
comfortable. He could write better than Goethe, Schiller, and Heine. The 
most fabulous megalomania quickly developed. He proposed to invent an 
enormous number of new machines, rebuild the hospital, build a cathedral 
higher than that at Cologne, and put a glass case over the asylum. He was 
a genius, spoke all the languages in the world, would cast a church of cast-​
steel, get us the highest order of merit from the Emperor, find a means of 
taming the madmen, and present the asylum library with 1000 volumes, 
principally philosophical works. He had quite godly thoughts . . . When at 
its height, the disease may present a great resemblance to maniacal states, 
but the physical examination and proof of the defective memory will save 
us from confusing it with them. So also will the senseless nature of the 
plans and the possibility of influencing them, and the feebleness and yielding 
character of the manifestations of the will, which are all greater in general 
paralysis.
Kraepelin E (1913) Lectures on Clinical Psychiatry, 3rd nglish edn. 
London: Baillière, Tindall and Cox

146
Chapter 4  Neuropsychiatry
HIV/​AIDS and psychiatry 1
Highly active antiretroviral rherapy (HAART) has, in many countries, re­
sulted in greatly i life expectancy for those living with HIV infection. 
Nevertheless, neuropsychiatric complications are not uncommon, particu­
larly in developing countries where rates of infection remain high, and in 
other circumstances where HIV/​AIDS remains undiagnosed, where treat­
ment is unavailable, or where treatment is available but social or psycho­
logical factors prevent compliance with treatment. In addition, a diagnosis 
of HIV and associated morbidity and mortality may have major conse­
quences for the psychological and social functioning of individuals, fam­
ilies, and communities. People with HIV/​AIDS are subject to prejudice and 
stigma as a result of the diagnosis, but also due to historical association with 
socially marginalized groups. Stigma contributes to the psychological burden 
of infected individuals and their families.
The responsibility of carers working with patients with HIV/​AIDS goes 
far beyond that of treating immediate physical problems. Holistic practice 
requires the healthcare professional to adopt a true biopsychosocial ap­
proach with appreciation of the emotional state of the patient, as well as 
the host of social, economic, spiritual, and ethical challenges accompanying 
the diagnosis with the disease.
Contexts in which psychiatric problems may arise
There are a number of contexts in which psychiatric problems may arise in 
relation to HIV/​AIDS:
 • Health anxiety in non-​infected individuals who may be concerned about 
being infected due to contact with HIV +ve individuals.
 • Pre-​test anxiety.
 • Post-​test stress may precipitate a psychiatric illness such as adjustment 
disorder, a major depressive episode, and suicidality.
 • Living with HIV/​AIDS often results in stressful life events (e.g. losing 
a job, becoming economically disadvantaged, experiencing social 
alienation).
 • In some cases, individuals with psychiatric needs (e.g. victims of abuse, 
patients with learning disabilities) may be more vulnerable to becoming 
infected with the virus.
 • HIV can directly infect neurons in the brain, causing neuropsychiatric 
symptoms.
 • HIV +ve individuals are susceptible to secondary opportunistic 
infections and/​or tumours of the CNS, which may manifest with 
neuropsychiatric symptoms.
 • Antiretroviral medications may cause psychiatric symptoms. Efavirenz 
can cause depression, anxiety, and suicidal ideation. Zidovudine (AZT 
[azidothymidine]) may precipitate both depression and mania, especially 
at high doses, while isoniazid prophylaxis has been known to precipitate 
a psychotic illness.

HIV/AIDS and psychiatry 1
Counselling HIV/​AIDS patients
 • Pre-​test counselling—​consider: meaning of a +ve result; what actions the 
individual will take; confidentiality issues; fears of the individual; high-​risk 
behaviours; reactions to stress; social and other implications of +ve 
result.
 • Post-​test counselling—​clarify distortions; assess emotions; decide who 
to tell; discuss the prevention of transmission; offer support to the 
individual and family.
Ethical issues
 • HIV testing—​issues of informed consent; only test without consent if a 
test result will significantly alter clinical management.
 • Confidentiality—​encourage the individual to tell their sexual partner and 
other medical personnel; if the individual refuses, one may be obliged to 
inform without consent.
 • Resource allocation—​e.g. availability of antiretroviral drugs.

148
Chapter 4  Neuropsychiatry
HIV/​AIDS and psychiatry 2: clinical 
presentations
Depression
At least 30–​50% of individuals suffer a major depressive episode at some 
time following diagnosis, and depression can contribute to treatment non-​
adherence. Depression in HIV often has multiple causes. Depressive illness 
should be differentiated from the physical effects of HIV-​related illness (e.g. 
weight loss, loss of energy) and from HIV-​associated dementia. Treatment—​
is as for individuals without HIV, although the choice of antidepressant may 
be influenced by HIV-​related comorbidities.
Suicide
Although suicide rates have declined since the introduction of HAART, 
there is still a nine times i risk of suicide in individuals living with HIV/​
AIDS. Risk factors include younger age, psychiatric illness, social isolation/​
alienation, and exposure to efavirenz.
Mania
Manic symptoms may develop in the context of HIV psychosis or as a 
result of treatment with antiretroviral agents such as zidovudine (AZT). 
Treatment—​lithium is preferable (beware risk of toxicity), since there 
is some evidence suggesting that sodium valproate may increase viral 
replication.
Anxiety
Infection with the virus is associated with an i risk of GAD, panic disorder, 
PTSD, and OCD.
Chronic pain
Up to 80% of patients experience chronic pain at some point, in particular 
chronic headache. This may lead some individuals to self-​medicate, putting 
them at risk of substance dependence.
Delirium
Delirium occurs in up to 30% of patients with advanced illness (AIDS). It can 
be caused by direct infection of the brain by the virus, secondary infections 
and/​or tumours, or substance withdrawal.
Psychosis
A psychotic illness characterized by fluctuating symptoms that may alter 
over hours to days may occur in the context of HIV infection. Atypical 
bizarre psychotic symptoms may give way to prominent mixed affective 
symptoms, which, in turn, may change to a withdrawn apathetic state.
Aetiological factors Include the effects of stress, medications, and sec­
ondary infections/​tumours, superimposed on the effects of direct infection 
of the brain by the virus. Psychosis is a common early manifestation of 
HIV-​associated dementia, and it is likely that mild cognitive deficits coexist 
with the psychotic illness.

HIV/AIDS and psychiatry 2: clinical presentations
Preferred treatment Low-​dose haloperidol or an atypical antipsychotic 
(e.g. olanzapine, quetiapine) due to i sensitivity to EPSEs. Antiretroviral 
agents, such as zidovudine (AZT), may also reduce psychotic symptoms.
HIV-​associated neurocognitive disorder (HAND)
HIV-​associated dementia (HAD; previously termed AIDS dementia com­
plex) is relatively common in advanced HIV (AIDS), although the incidence 
has declined significantly with HAART.
Epidemiology
Ninety per cent of AIDS patients have CNS changes post-​mortem; 70–​80% 
develop a cognitive disorder; 30% develop HAD. Mean survival after diag­
nosis with HAD is 6mths.
Pathology
Direct central nervous system infection
HIV is neurotropic, entering the brain through endothelial gaps; the virus 
attaches to group 120 on CD4 +ve sites of microglial cells; a cascade opens 
calcium channels, leading to excitotoxicity and causing neuronal death and 
i apoptosis in the basal ganglia and subcortical and limbic white matter.
Opportunistic infections/​tumours
Toxoplasmosis, papovavirus, cytomegalovirus (CMV), HSV, non-​Hodgkin’s 
lymphoma, and Kaposi’s sarcoma give rise to variable neuropathology, 
including encephalitis and focal necrosis.
Clinical presentation
Mild neurocognitive disorder
Asymptomatic HIV +ve patients may have very early CNS infection that 
is often discounted as stress. Symptoms include cognitive slowing and 
memory deficits, as well as motor slowing and subtle incoordination.
HIV-​associated dementia
With worsening of symptoms, the clinical picture constitutes a dementia 
syndrome and is an AIDS-​defining disorder. Clinical features are classified as 
cognitive (subcortical dementia, focal cognitive deficits, amnesia, mutism), 
motor (movement disorders, e.g. tremor, ataxia, choreo-​athetosis, spasti­
city, myoclonus), and affective (depression, apathy, agitation, disinhibition, 
mania). The HIV Dementia Scale (HDS)25 can be used to screen for HAD. 
Investigations—​CT/​MRI: atrophy, iT2 signal; CSF: opportunistic infection, 
cytology, enzyme-​linked immunosorbent assay (ELISA) +ve; EEG: general­
ized slowing. Treatment—​with HAART can slow progression.
25  Sacktor NC, Wong M, Nakasujia N, et al. (2005) The International HIV Dementia Scale: a new 
rapid screening test for HIV dementia. AIDS 19:1367–​74.

150
Chapter 4  Neuropsychiatry
Autoimmune and connective 
tissue disorders
Autoimmune (limbic) encephalitis
Over the last 10yrs, there has been a great increase in recognition, under­
standing, and detection of a range of neuropsychiatric conditions caused 
by auto-​antibodies to brain substrates. A case series of patients with anti-​
N-​methyl-​D-​aspartate (NMDA) encephalitis found that 4% of patients pre­
sented with isolated psychiatric symptoms, although most of these cases 
presented during a relapse and only a minority (0.8%) at disease onset.
Clinical features Vary between conditions and patients. Typically subacute 
or acute onset of anxiety, psychosis, cognitive impairment, seizures, and 
sometimes movement disorder.
Investigations Blood should be sent for testing in cases of acute/​subacute 
cognitive impairment ± anxiety or psychosis, especially with a history of 
seizures where alternative causes are not clear. Some would suggest testing 
all new presentations of psychosis, although resources may prevent this.
Clinical subtypes
 • Voltage-​gated potassium channel (VGKC) antibodies—​target the 
hippocampus, leading to pure amnestic deficit. Seizures are common, 
and neuromyotonia (writhing fasciculations), sleep disturbance, or 
autonomic disturbance may also be present.
 • NMDA receptor antibody encephalitis—​is more common in young women 
and often associated with ovarian teratoma (removal of which is 
associated with good prognosis). Symptoms: fluctuating anxiety, global 
cognitive impairment, psychosis, seizures.
 • Paraneoplastic encephalitis—​antibodies associated with small cell lung 
cancer (anti-​Hu), testicular cancer (anti-​Ma2), and thymoma (CRMPS) 
lead to varying patterns of neuropsychiatric symptoms.
 • Other antibodies—​other antibodies recently associated with autoimmune 
encephalitis include those to the AMPA (α-​amino-​3-​hydroxy-​5-​
methyl-​4-​isoxazolepropionic acid) receptor (limbic encephalitis), 
GABA B receptor (seizures and limbic encephalitis), and glutamic acid 
decarboxylase (GAD) (TLE with cognitive involvement).26
Systemic lupus erythematosus
This multisystem autoimmune disorder is most common in women in their 
30s. Neuropsychiatric symptoms are common and may be due to the ac­
tivity of auto-​antibodies (30%), cerebral microvasculopathy and thrombosis, 
disease activity in other systems (uraemia, hypertension, inflammatory me­
diators), or side effects of medication (e.g. steroids, isoniazid, hydralazine). 
Seizures, cranial nerve palsies, peripheral neuropathy, ‘spinal stroke’, and 
other focal signs may occur, in addition to the common dermatological, 
rheumatological, haematological, and cardiovascular manifestations of the 
disorder. Psychiatric symptoms occur in 60% of cases, and syndromes include:
26  Kayser MS, Titulaer MJ, Gresa-​Arribas N, Dalmau J (2013) Frequency and characteristics of iso­
lated psychiatric episodes in anti-​NMDA receptor encephalitis. JAMA Neurol 70:1133–​9.

Autoimmune and connective tissue disorders
 • Lupus psychosis—​transient psychotic episodes with a recurrent and 
fluctuating course. Relapses are frequent, and symptoms are variable 
with auditory and visual hallucinations, as well as paranoia, affective 
instability, and disturbed sensorium, characteristic of the illness. Severe 
prolonged cerebral vasculitis may result in vascular dementia.
 • Depression—​up to 30% of SLE patients experience clinically significant 
depressive illness.
 • Schizophrenia-​like psychosis—​a rare finding in SLE.
Polyarteritis nodosa
Most common in young men, polyarteritis nodosa (PAN) is an immune-​
mediated necrotizing vasculitis, characterized by saccular aneurysms and 
infarction. Neuropsychiatric findings include:  stroke, focal signs, seizures, 
‘spinal stroke’, delirium, and auditory and visual hallucinations.
Neurosarcoid
Sarcoidosis is a multisystem inflammatory disorder of unknown cause. 
Central or peripheral nerve involvement (neurosarcoid) is rare, but diffuse 
vasculopathy may cause delirium, dementia, or seizures, and granulomatous 
infiltration of the CNS may cause a range of neuropsychiatric symptoms.27,28
Investigations Lesions may be visible on MRI, and there may be elevated 
protein in the CSF. Histological diagnosis of an accessible lesion (e.g. skin, 
lung) reveals caseating granulomata.
Treatment Corticosteroids, methotrexate, or immunomodulators, e.g. 
infliximab.
27  Vincent A, Bien CG, Irani SR, Waters P (2011) Autoantibodies associated with diseases of the 
CNS: new developments and future challenges. Lancet Neurol 10:759–​72.
28  Hoitsma E, Faber CG, Drent M, Sharma OP (2004) Neurosarcoidosis: a clinical dilemma. Lancet 
Neurol 3:397–​407.

152
Chapter 4  Neuropsychiatry
Dementia: general overview
Essence
Dementia is a syndrome characterized by progressive, irreversible global 
cognitive deficits. Different patterns of deficits occur, depending on the 
underlying pathology. For a diagnosis to be made, there must be significant 
impairment of functioning and other possible diagnoses should be excluded 
(E Reversible causes of cognitive impairment, p. 154).
Causes
 • Parenchymal/​degenerative—​Alzheimer’s disease (50–​70%); Lewy body 
dementia (<5%) and dementia in Parkinson’s disease; FTD (5–​10%); MS; 
PSNP; corticobasal degeneration; MND; Huntington’s disease; Wilson’s 
disease.
 • Intracranial—​vascular dementia (20–​30%); NPH (reversible in some 
cases).
 • Infection—​CJD (prion disease); neurosyphilis; HAND; TB; SSPE.
 • Toxins—​prolonged alcohol misuse [alcohol-​related brain damage 
(ARBD)]; heavy metal poisoning.
Clinical features
(See Box 4.3.)
 • Cognitive impairment—​characteristic patterns of impairment occur 
in different types of dementia. Most typically, initial impairment of 
episodic (short-​term) memory progresses to more extensive memory 
impairment, apraxia, agnosia, and dysphasia.
 • History of personality change—​social withdrawal, disinhibition, 
diminished self-​care, apathy, deteriorating executive function.
 • Hallucinations and delusions—​often paranoid (20–​40%) and poorly 
systematized.
 • Anxiety and/​or depression—​in 50%.
 • Neurological features—​seizures, primitive reflexes, pseudobulbar palsy, 
long tract signs (e.g. hyperreflexia or upgoing plantars.
 • Emotional lability/​pseudobulbar affect—​(in stroke) (E Psychiatric 
sequelae of stroke, p. 176).
 • Sundowning syndrome—​as evening approaches, confusion and 
restlessness increase.
Differential diagnosis
Delirium; depression (pseudodementia; E Pseudodementia, p. 552); other 
reversible causes of cognitive impairment (E Reversible causes of cog­
nitive impairment, p.  154); amnestic disorders (E Amnestic disorders, 
p. 170); intellectual disability (ID); psychotic disorders; normal ageing (E 
Normal ageing, p. 544).
Investigations
FBC; LFT; U&Es; glucose; ESR; thyroid-​stimulating hormone (TSH); cal­
cium; phosphate; syphilis serology; HIV; vitamin B12 and folate; CRP; blood 
culture; LP; EEG; chest X-​ray (CXR); ECG; CT; MRI; SPECT.

Dementia: general overview
Principles of management
 • Assessment—​diagnostic, functional, and social.
 • Cognitive enhancement—​acetylcholinesterase inhibitors (donepezil, 
galantamine, rivastigmine); glutamate receptor antagonist (memantine).
 • Treat psychosis/​agitation—​consider antipsychotics.
 • Treat depression/​insomnia—​SSRIs; hypnotics.
 • Treat medical illness—​avoid drugs which may worsen cognitive 
impairment (e.g. opiates, BZDs, anticholinergics).
 • Psychological support—​to both patient and caregivers.
 • Functional management—​maximize mobility; encourage independence 
with self-​care, toilet, and feeding; aid communication.
 • Social management—​accommodation; activities; financial matters; legal 
matters (power of attorney, wills, and curatorship).
Box 4.3  Clinical syndromes of dementia
Dementias may be classified in terms of the primary site of pathology. 
Since the site of pathology in the brain correlates with neuropsychiatric 
symptomatology, this is a useful system of classification.
 • Cortical dementias Primarily involve the cortex:
 • bvFTD/​PPA (E Fronto-​temporal dementia, p. 160). Characterized 
in the frontal (behavioural) variant by prominent personality change, 
including either disinhibition and social indiscretion or profound 
apathy, and in temporal lobe variants by language impairments. 
A common cause of early-​onset dementia, it is often undiagnosed 
or mistaken for psychiatric illness. CT and MRI show fronto-​
temporal atrophy; SPECT shows fronto-​temporal hypoperfusion, 
and FDG-​PET shows reduced fronto-​temporal glucose metabolism.
 • Posterior–​parietal, e.g. Alzheimer’s disease (E Alzheimer’s 
disease 1, p. 156). Characterized by early memory loss and focal 
cognitive deficits. Personality changes are later manifestations. 
Language impairments involve problems with word-​finding (lexical 
anomia). CT shows thinning (<12mm) of the cortex of the medial 
temporal lobe.
 • Subcortical dementias Parkinson’s disease (E Parkinson’s disease and 
related syndromes, p. 142); Huntington’s disease (E Huntington’s 
disease, p. 166); Wilson’s disease (E Wilson’s disease, p. 166); 
Binswanger encephalopathy (E Vascular dementia (vascular 
neurocognitive disorder), p. 164); PSNP (E Progressive supranuclear 
palsy, p. 142); HIV-​associated dementia (E HIV-​associated neurocognitive 
disorder (HAND), p. 149); NPH (E Normal pressure hydrocephalus, 
p. 154). Clinical features: gross psychomotor slowing, depressed mood, 
movement disorders, mild amnesia, and personality changes.
 • Cortical–​subcortical dementias, e.g. Lewy body dementia (E Dementia 
with Lewy bodies, p. 162). Clinical features: cortical and subcortical 
symptoms.
 • Multifocal dementias, e.g. CJD and other prion diseases (E Prion 
diseases, p. 168). Clinical features: rapid onset and course; involves 
the cerebellum and subcortical structures.

154
Chapter 4  Neuropsychiatry
Reversible causes of cognitive 
impairment
An important aim of the assessment of a patient with suspected dementia is 
to exclude and treat any reversible causes of cognitive impairment. The dis­
orders listed below may be produced by a dementia-​like syndrome, which, 
in many cases, can be reversed with treatment.
Causes
 • Intracranial—​NPH; chronic subdural haematoma (SDH); posterior 
reversible encephalopathy syndrome; autoimmune encephalitis (E 
Autoimmune (limbic) encephalitis, p. 150).
 • Psychiatric/​functional—​depression (‘pseudodementia’); psychosis; 
functional or anxiety-​related cognitive impairment.
 • Infection—​HSV encephalitis; neurosyphilis; HAND (E HIV-​associated 
neurocognitive disorder (HAND), p. 149); TB.
 • Endocrine—​hypothyroidism; hyperparathyroidism; Cushing’s and 
Addison’s disease.
 • Metabolic—​uraemia; hepatic encephalopathy; hypoglycaemia; calcium 
imbalance; magnesium imbalance; electrolyte imbalance.
 • Vitamin deficiency—​B12; folate; pellagra (niacin); thiamine.
 • Drugs/​medications—​BZDs, opiates, and anticholinergic medications, 
in particular, cause a degree of cognitive impairment, which may be 
clinically significant in vulnerable individuals or those with comorbid 
dementia or brain injury.
 • Toxins—​prolonged alcohol misuse; heavy metal poisoning; CO 
poisoning.
Normal pressure hydrocephalus
A syndrome where there is dilatation of cerebral ventricles (especially third 
ventricle), but normal CSF pressure at LP. It typically presents with the triad 
of dementia, gait disorder, and urinary incontinence. Importantly, the de­
mentia is potentially reversible if NPH is treated promptly.
Aetiology Fifty per cent of cases are idiopathic; 50% are secondary to 
mechanical obstruction of CSF flow across the meninges (e.g. meningitis, 
subarachnoid haemorrhage, trauma; radiotherapy).
Clinical features There is progressive slowing of cognitive and motor func­
tioning, consistent with a pattern of subcortical dementia. Gait is broad-​
based, bradykinetic, and shuffling. Urinary incontinence is a late symptom.
Investigations CT scan shows isize of the lateral ventricles and thinning of 
the cortex; 24hr ICP monitoring shows abnormal pulsatility.
Treatment Abnormal pulsatility on 24hr CSF pressure monitoring, short 
duration of symptoms, improvement of symptoms after therapeutic re­
moval of 40–​50mL of CSF, and NPH secondary to an identified cause are 
predictors of good response to ventriculo-​peritoneal shunt.

Reversible causes of cognitive impairment
Chronic subdural haematoma
An insidious and fluctuating syndrome of cognitive and motor impairment 
may result from an undetected chronic SDH. An SDH results from rupture 
of the bridging veins between the dura and arachnoid mater and tends to 
occur over the frontal and/​or parietal cortices. In 30% of cases, there is bi­
lateral SDH. SDH should be suspected where there is a fluctuating pattern 
in cognitive function, especially if risk factors for SDH exist: elderly after a 
fall, infancy, cerebral atrophy (e.g. chronic alcoholism), clotting disorders, or 
anticoagulant treatment.
Clinical features An SDH may only manifest with symptoms months after it 
develops; therefore, there may be no history of recent trauma. Headache, 
altered level of consciousness, and amnesia may all occur, often with fluc­
tuations in severity. Typically, the mental state may be variable on different 
occasions, and there may be periods of unusual drowsiness, as well as both 
cognitive and physical slowness and sluggishness. Minor focal signs are 
sometimes detected. The general picture is of a subcortical dementia of 
relatively rapid onset.
Investigations CT scan during the first 3wks may not show the SDH, as it is 
isodense during the early phase. Therefore, contrast should be used. Later 
on, as the SDH liquefies, a low-​density convexity may be detected over the 
fronto-​parietal cortex.
Treatment Surgical drainage of SDH via burr holes. Steroids may be 
helpful for conservative treatment.

156
Chapter 4  Neuropsychiatry
Alzheimer’s disease 1
Also termed ‘dementia of the Alzheimer type’ (DAT), this is the most 
common cause (70%) of dementia in older people. It is a degenerative dis­
ease of the brain, with prominent cognitive and behavioural impairment that 
is sufficiently severe to interfere significantly with social and occupational func­
tion. It affects 7850,000 people in the UK and >46 million worldwide. As the 
percentage of the total population aged over 65 in the developed world con­
tinues to increase, the burden of DAT-​related healthcare is also increasing.
Epidemiology
Risk of DAT increases with age: 1% at age 60yrs; doubles every 5yrs; 40% of 
those aged 85yrs. Age-​specific incidence is the same for men and women—​ 
750% excess prevalence in women is explained by their longer lifespan. 
Mean survival from time of diagnosis is 4–​8 years; most will be fully de­
pendent within 4yrs.
 • Risk factors—​increasing age, Down’s syndrome, apolipoprotein E ε4 
allele, diabetes, smoking, hypertension in middle age.
 • Protective factors—​apolipoprotein E ε2 allele, higher level of premorbid 
education, higher level of physical activity in middle age, non-​steroidal 
anti-​inflammatory drugs (NSAIDs).
 • Genetics—​first-​degree relatives are at a slightly i risk. Carriers of the 
apolipoprotein E ε4 allele on chromosome 19 (15% of Europeans) 
are at further i risk; apolipoprotein E ε2 is protective. Single-​gene 
autosomal dominant inherited DAT is rare, affecting <1% of those 
with DAT and associated with early onset; identified mutations include 
amyloid precursor protein (APP) on chromosome 21 and the genes for 
presenilin 1 (PSEN1) and presenilin 2 (PSEN2).
Pathophysiology
 • Amyloid plaques—​insoluble β-​amyloid peptide deposits as senile plaques 
or β-​pleated sheets in the hippocampus, amygdala, and cerebral cortex. 
i density with advanced disease.
 • Neurofibrillary tangles (NFTs)—​consist of phosphorylated tau protein and 
are found in the cortex, hippocampus, and substantia nigra. Also found 
in normal ageing, Down’s syndrome, and PSNP.
 • The co-​occurrence of amyloid plaques and NFTs was described by Alois 
Alzheimer in his 1906 description of the disorder and is still accepted 
universally as a hallmark of the disease.
 • Up to 50% loss of neurons and synapses in the cortex and hippocampus.
 • Cholinergic hypothesis—​the pathological changes lead to degeneration 
of cholinergic nuclei in the basal forebrain (nucleus basalis of Meynert). 
This results in dcortical ACh.
Assessment
 • Detailed history—​including an informant history is essential. Informant 
rating scales, such as IQCODE, are helpful. Physical examination, 
including full neurological examination (E Neurological examination in 
psychiatry, p. 128), and blood tests (E Neurological investigations in 
psychiatry, p. 130) should be performed to rule out reversible causes 
(E Reversible causes of cognitive impairment, p. 154).

Alzheimer’s disease 1
 • Cognitive testing—​may begin with MMSE, MOCA, or ACE-​III.
 • Imaging—​CT: cortical atrophy, especially over parietal and temporal 
lobes, and ventricular enlargement. MRI: atrophy of grey matter 
(hippocampus, amygdala, and medial temporal lobe). Where diagnosis 
remains uncertain: SPECT shows temporal and posterior parietal 
hypoperfusion and fludeoxyglucose-​PET (FDG-​PET) shows reduced 
metabolism in temporal and posterior parietal lobes.
Clinical features
 • Early—​failing memory, disorientation in time, muddled efficiency 
with activities of daily living (ADLs), spatial dysfunction, and changes 
in behaviour (e.g. wandering and irritability). By the time the patient 
presents, cognitive deficits are usually apparent.
 • Middle—​global intellectual deterioration—​aphasia, apraxia, agnosia, 
impaired visuospatial skills, and executive dysfunction.
 • Late—​fully dependent. Physical deterioration, incontinence, gait 
abnormalities, spasticity, seizures (3%), tremor, weight loss, primitive 
reflexes, extra-​pyramidal signs.
 • Behavioural and psychological symptoms in dementia (BPSD)—​delusions 
(15%) usually of a paranoid nature. Auditory and/​or visual hallucinations 
(10–​15%). Depression in up to 20% of patients. Behavioural 
disturbances include aggression, wandering, explosive temper, sexual 
disinhibition, inappropriate toileting, excessive eating, and searching 
behaviour.
Clinical subtypes and overlapping syndromes
 • Posterior cortical atrophy—​an atypical variant of DAT in which the 
parietal, occipital, and occipito-​temporal cortices are first affected; 
memory and language are relatively preserved in early stages, but 
impairments of visuospatial function are prominent. Gerstmann’s 
syndrome (acalculia, agraphia, finger agnosia, left–​right disorientation) 
and/​or Balint’s syndrome (simultanagnosia, oculomotor apraxia, optic 
ataxia, environmental agnosia) may be present. Progresses to global 
impairment.
 • Logopenic aphasia—​a subtype of semantic dementia, with dverbal 
output, phonological errors with preserved grammar, and impaired 
sentence repetition. Most have DAT pathology.
Pray, do not mock me: I am a very foolish fond old man,
Fourscore and upward, not an hour more or less;
And, to deal plainly, I fear I am not in my perfect mind.
Methinks I should know you and know this man;
Yet I am doubtful: for I am mainly ignorant what place this is,
and all the skill I have remembers not these garments;
nor I know not where I did lodge last night.
Do not laugh at me;
For as I am a man, I think this lady to be my child Cordelia.
Shakespeare: King Lear, Act II Scene 7

158
Chapter 4  Neuropsychiatry
Alzheimer’s disease 
2: pharmacological treatments
There are as yet no truly disease-​modifying drugs available for DAT; 
available drugs provide mild symptomatic benefits in some patients. 
Acetylcholinesterase inhibitors (AChEIs) were the first drugs to be licensed 
for the treatment of DAT. They act by enhancing ACh at cholinergic syn­
apses in the CNS and, in this way, may cause mild clinical improvements in 
cognitive, functional, and behavioural symptoms, reducing time spent in full 
nursing care. They are recommended as first-​line agents in the treatment of 
mild to moderate DAT (see Box 4.4).
Acetylcholinesterase inhibitors
Similar efficacy over 6mths; long-​term efficacy unknown. Switching between 
agents is acceptable.
 • Donepezil—​piperidine derivative, developed in 1996; gastrointestinal 
tract (GIT) absorbed, with liver metabolism; long half-​life (70hrs); highly 
selective (acts centrally only); linear kinetics. Problems: GIT side effects 
at high dose; bradycardia; GIT bleed (rare); contraindicated in asthma. 
Benefits: selective, therefore dside effects; no liver toxicity; predictable 
kinetics; narrow dose range; 1× daily dosage. Dose: 5–​10mg/​day.
 • Rivastigmine—​developed in 1998; short half-​life (12hrs); inhibits 
acetylcholinesterase and butyrylcholinesterase in CNS. Problems: GIT 
Box 4.4  NICE guidance on donepezil, galantamine, 
rivastigmine, and memantine for the treatment 
of Alzheimer’s disease (TA217)
AChEIs—​donepezil, rivastigmine, or galantamine—​are recommended:
 • For managing mild to moderate Alzheimer’s disease.
Memantine is recommended:
 • For moderate Alzheimer’s disease in patients who are intolerant to, or 
have a contraindication to, AChEIs.
 • In severe Alzheimer’s disease.
For all of the above medications:
 • Treatment should be started on the advice of either a secondary 
care medical specialist (psychiatrist, geriatrician, and neurologist) or 
by another healthcare professional (e.g. GP, nurse specialist) with 
specialist expertise in diagnosing and treating Alzheimer’s disease.
 • Treatment should be continued only while it has a worthwhile effect 
on cognitive, global, functional, or behavioural symptoms.
Non-​Alzheimer dementias and mild cognitive impairment (MCI):
 • AChEIs and memantine should not be prescribed for VaD or MCI, 
except as part of properly constructed clinical research studies.
 • People with DLB who have non-​cognitive symptoms causing significant 
distress to the individual, or leading to behaviour that challenges, 
should be offered an AChEI.
Source: Data from M https://​www.nice.org.uk/​guidance/​ta217 [accessed 30 May 2018].

Alzheimer’s disease 2: pharmacological treatments
side effects; twice daily dosage. Benefits: not metabolized by the liver 
and least likely to cause drug–​drug interactions. Dose: start with 1.5mg 
twice daily (bd); increase to 3–​6mg bd—​now available in a modified-​
release once-​daily (od) form or 24hr patch [thought to be helpful in 
reducing gastrointestinal (GI) side effects].
 • Galantamine—​selectively inhibits acetylcholinesterase and acts as 
an allosteric ligand at nicotinic ACh receptors; metabolized in the 
liver; short half-​life (5hrs); selective. Problems: twice daily dosage. 
Dose: 4–​12mg bd.
Other drugs
 • Memantine—​a partial NMDA receptor antagonist that may protect 
neurons from glutamate-​mediated excitotoxicity. Trials show benefits 
of memantine augmentation of donepezil. A Cochrane review indicates 
mild benefit in moderate to severe DAT.29
Future treatment strategies?
Although only at experimental stages, there is some evidence for other 
approaches to DAT. These include: monoclonal antibodies to amyloid-​B 
(crenezumab; solanezumab); anti-​inflammatories; secretase inhibitors; 
drugs targeting insulin resistance; and vaccination against abnormal forms 
of tau protein.
Mild cognitive impairment
(See Box 4.5.)
29  McShane R, Sastre AA, Minakaran N (2006) Memantine for dementia. Cochrane Database Syst 
Rev M http://​onlinelibrary.wiley.com/​doi/​10.1002/​14651858.CD003154.pub5/​full [accessed 30 
May 2018].
Box 4.5  Mild cognitive impairment
The term mild cognitive impairment (MCI) is widely used in the dementia 
research community but does not translate well to clinical practice. MCI 
refers to patients with mild cognitive symptoms not severe enough to 
meet diagnostic criteria for dementia. Recent research suggests that the 
pathological changes of Alzheimer’s disease begin to appear many years 
before clinical symptoms develop. Researchers are keen to identify those 
with the earliest clinical manifestations, as ‘conversion’ to Alzheimer’s dis­
ease is therefore a key target for study and treatment. MCI (particularly 
amnestic MCI) is therefore currently used as a proxy measure to iden­
tify this ‘at-​risk’ group. However, in clinical practice, MCI is an imperfect 
construct, a description of symptoms, rather than a diagnosis, with the 
potential to cause great anxiety in patients and families. Although around 
10% of elderly individuals with MCI will progress to dementia each year, 
others will never develop dementia and some return to normal levels of 
cognition.

160
Chapter 4  Neuropsychiatry
Fronto-​temporal dementia
The FTDs are a set of overlapping clinical syndromes caused by disease 
primarily affecting the frontal and temporal lobes.30,31,32 FTDs account for 
720% of cases of early-​onset dementia. Personality change and social dis­
inhibition or language impairment often precede memory impairment (E 
Box 4.9, p. 171). Early disease is commonly mistaken for primary psychiatric 
disorder.
Pathology
Fronto-​temporal lobar degeneration (FTLD) refers to a range of underlying 
pathologies: neuronal loss, gliosis, and protein inclusions consisting of either 
tau (Pick bodies) in 40% (FTLD-​tau), TDP-​43 in 50% (FTLD-​TDP), and FUS 
in some cases (FTLD-​FUS).
Genetics
Forty per cent have a positive family history, 10% due to autosomal dom­
inant mutations—​the most common are MAPT, GRN, and C9ORF.
Clinical subtypes
 • Behavioural variant FTD (bvFTD) (Pick’s Disease)33—​most common 
subtype. Onset usually 45–​65yrs. Mean survival from diagnosis: 8yrs 
(range 2–​20).
 • Clinical features: disinhibition, loss of social empathy with tactlessness 
and breaches of etiquette, apathy, stereotypic behaviours (without 
anxiety, unlike OCD), changes in food preference (overeating and 
preference for sweet foods). Early cognitive symptoms of poor 
attention and executive dysfunction progress to include all cognitive 
domains.
 • Neurological: a minority have signs of MND (up to 15% with MND 
develop a bvFTD syndrome).
 • Investigations: imaging may be normal; or CT/​MRI: bilateral 
(asymmetrical) abnormalities of frontal/​temporal lobes; and 
SPECT: frontal and/​or temporal lobe abnormalities. EEG is normal.
 • Diagnosis: based on clinical criteria (see Box 4.6).
 • Primary progressive aphasia (PPA)—​initial symptoms are due to impaired 
language function, caused by temporal lobe disease, but symptoms of 
bvFTD may also be present or may develop as disease progresses.
 • Progressive non-​fluent aphasia (PNFA)—​non-​fluent, effortful speech with 
agrammatism. Pathology: atrophy in Broca’s area.
30  Rascovsky K, Hodges JR, Knopman D, et al. (2011) Sensitivity of revised diagnostic criteria for the 
behavioural variant of frontotemporal dementia. Brain 134:2456–​77.
31  Neary D, Snowden J, Mann D (2005) Frontotemporal dementia. Lancet Neurol 4:771–​80.
32  Seelaar H, Rohrer JD, Pijnenburg YA, Fox NC, van Swieten JC (2011) Clinical, genetic and patho­
logical heterogeneity of frontotemporal dementia: a review. J Neurol Neurosurg Psychiatry 82:476–​86.
33  Lanata SC, Miller BL (2016) The behavioural variant fronto-​temporal dementia (bvFTD) syn­
drome in psychiatry. J Neurol Neurosurg Psychiatry 87:501–​11.

Fronto-temporal dementia
 • Semantic dementia (SD)—​fluent speech with loss of concepts/​meaning. 
Pathology: left > right temporal lobe atrophy (sometimes called temporal 
variant or tvFTD).
 • Logopenic progressive aphasia (LPA)—​impaired sentence repetition. 
A variant of Alzheimer’s type dementia. Management: currently, no 
specific treatments; SSRIs of limited benefit for behavioural symptoms 
(disinhibition, overeating, and compulsions).
Box 4.6  International consensus criteria for bvFTD
There must be a progressive deterioration of behaviour and/​or cogni­
tion, and symptoms must not be better accounted for by a psychiatric, 
non-​degenerative neurological or medical disorder.
Possible bvFTD
Three of the following behavioural/​cognitive symptoms are persistent 
or recurrent:
 • Early behavioural disinhibition (one of: socially inappropriate 
behaviour; loss of manners or decorum; impulsive, rash or careless 
actions).
 • Early apathy or inertia.
 • Early loss of sympathy or empathy (one of: diminished response 
to other people’s needs and feelings; diminished social interest, 
interrelatedness, or personal warmth).
 • Early perseverative, stereotyped, or compulsive/​ritualistic behaviour 
(one of: simple repetitive movements; complex, compulsive, or 
ritualistic behaviours; stereotypy of speech).
 • Hyperorality and dietary changes (one of: altered food preferences; 
binge eating, i consumption of alcohol or cigarettes; oral exploration 
or consumption of inedible objects).
 • Neuropsychological profile: executive/​generation deficits with 
relative sparing of memory and visuospatial functions (all of: deficits in 
executive tasks; relative sparing of episodic memory; relative sparing 
of visuospatial skills).
Probable bvFTD
 • Meets criteria for possible bvFTD.
 • Exhibits significant functional decline (by caregiver report or rating 
scale).
 • Imaging consistent with bvFTD (one of: frontal and/​or temporal 
atrophy on MRI or CT; frontal and/​or temporal hypoperfusion or 
hypometabolism on PET or SPECT).
Definite bvFTD
 • Meets criteria for possible or probable bvFTD.
 • Histopathological evidence of FTLD on biopsy or at post-​mortem OR 
presence of a known pathogenic mutation.
Source: data from Lanata, S.C. and Miller, B.L. (2016) The behavioural variant fronto-​temporal 
dementia (bvFTD) syndrome in psychiatry. Journal of Neurology, Neurosurgery & Psychiatry, 
87:501–​11.

162
Chapter 4  Neuropsychiatry
Dementia with Lewy bodies34
Common form of dementia in the elderly (720% of new diagnoses of de­
mentia in hospital35 and 4% of new community cases) that lies on a clinical 
and pathological continuum with Parkinson’s disease.
Epidemiology
Age of onset: 50–​83yrs. Age at death: 68–​92yrs. ♂ > ♀.
Clinical features
Dementia with fluctuating cognitive performance and consciousness and 
early sparing of memory; Parkinsonism (70%: bradykinesia, rigidity, gait dis­
order, tremor); complex hallucinations—​visual (760%: often people and ani­
mals) and auditory (720%)—​with associated emotional responses varying 
from fear to amusement); significant depressive symptoms (740%); recur­
rent falls/​syncope (730%:  due to autonomic dysfunction), transient dis­
turbances of consciousness (mute and unresponsive for several minutes); 
antipsychotic sensitivity (760%). The mean survival time/​rate of cognitive 
decline is similar to Alzheimer’s disease (but rapid deterioration over 1–​2yrs 
does occur). See Box 4.7 for a summary of diagnostic criteria.
Pathological features
Eosinophilic A–​synuclein neuronal inclusions (Lewy bodies), with neuronal 
loss in brainstem nuclei (especially basal ganglia) and paralimbic and neo­
cortical structures. Associated neuronal loss. Lewy neurites—​distinctive pat­
tern of ubiquitin and A-​synuclein immunoreactive neuritic degeneration—​in 
the substantia nigra, hippocampal region (CA2/​3), dorsal vagal nucleus, 
basal nucleus basilis of Meynert, and transtentorial cortex. Alzheimer-​type 
changes—​senile plaques present in a similar density and distribution, fewer 
NFTs, less tau pathology. Vascular disease—​in 730%.
Differential diagnosis
Other dementia syndromes (especially DAT), delirium, Parkinson’s disease 
(in which motor symptoms appear ≥1yr prior to cognitive symptoms; 80% 
ultimately develop dementia which is pathologically equivalent to DLB), 
PSNP, MSA, CJD, psychiatric disorders (e.g. late-​onset delusional disorder, 
depressive psychosis, mania).
Investigations
 • CT/​MRI—​relative sparing of medial temporal lobes in most 
cases. Moderate increases in deep white matter lesions, frequent 
periventricular lucencies on MRI.
 • HMPAO SPECT scan—​(blood flow) Global (especially occipital), medial, 
temporal lobes relatively preserved.
 • FP-​CIT SPECT—​(presynaptic dopamine transporter) Reduced in the 
putamen, as in Parkinson’s disease.
34  Walker Z, Possin KL, Boeve BF, Aarsland D (2015) Lewy body dementias. Lancet 386:1683–​97.
35  Jones SV, O’Brien JT (2014) The prevalence and incidence of dementia with Lewy bodies: a sys­
tematic review of population and clinical studies. Psychol Med 44:673–​83.

163
DEMENTIA WITH LEWY BODIES
Management
 • Antipsychotics—​avoid/​use with great caution: severe sensitivity reactions 
(40–​50%), e.g. irreversible Parkinsonism, impairment of consciousness, 
neuroleptic malignant syndrome (NMS)-​like autonomic disturbances—​
2-​ to 3-​fold increase in mortality.
 • AChEIs—​recommended by national guidelines for treatment of non-​
cognitive symptoms (e.g. apathy/​psychosis/​agitation).
 • Other—​no clear evidence for antidepressants, anticonvulsants, or 
BDZs. Clonazepam may be useful for sleep disturbance (vivid dreams, 
muscle atonia, excessive jerking, and other complex movements). Anti-​
Parkinsonian medication—​use cautiously for clinically significant motor 
symptoms, but note the risk of exacerbating psychotic symptoms.
Box 4.7  Consensus criteria for the diagnosis of dementia 
with Lewy bodies
 • Central feature required for a diagnosis of DLB:
 • Progressive dementia severe enough to interfere with normal social 
or occupational function.
 • Deficits on tests of attention, executive function, and visuospatial 
ability might be especially prominent.
 • Two of the following core features are essential for a probable 
diagnosis of DLB; one is essential for a possible diagnosis of DLB.
 • Fluctuating cognition.
 • Recurrent visual hallucinations.
 • Spontaneous motor features of Parkinsonism.
 • Features supportive of the diagnosis are:
 • Repeated falls, syncope, transient unexplained LOC, severe 
autonomic dysfunction, non-​visual hallucinations, systematized 
delusions, depression, relative preservation of medial temporal lobe 
structures, generalized low uptake on SPECT or PET with reduced 
occipital activity, abnormal myocardial scintigraphy, prominent slow 
wave activity on EEG with temporal lobe transient sharp waves.
 • A diagnosis of DLB is less likely if:
 • Cerebrovascular disease accounts for part or all of the clinical signs 
and symptoms.
 • Parkinsonism does not appear until severe dementia.
Source: data from McKeith, I. G., et al. (2005). Diagnosis and management of dementia with 
Lewy bodies third report of the DLB consortium. Neurology 65: 1863–​1872.

164
Chapter 4  Neuropsychiatry
Vascular dementia (vascular 
neurocognitive disorder)
Vascular dementia (VaD) is the second most common cause of dementia 
after DAT,36 accounting for 20% of cases. It often coexists with DAT and 
results from thromboembolic or hypertensive infarction of small and 
medium-​sized vessels. Features that suggest a vascular cause of cognitive 
impairment include: sudden onset, stepwise deterioration, and risk factors 
for cardiovascular disease. Its presentation is variable, and three syndromes 
of vascular cognitive impairment are commonly recognized:37
 1. Cognitive deficits following a single stroke Not all strokes result in 
cognitive impairment, but when they do, the deficits depend upon 
the site of the infarct. Difficulties with language, praxis, or executive 
function are most common; isolated memory symptoms are unusual. 
Cognitive deficits may remain fixed or recover, either partially or 
completely.
 2. Cognitive deficits as a result of multiple strokes (multi-​infarct dementia) 
Multiple strokes lead to stepwise deterioration in cognitive function. 
Between strokes, there are periods of relative stability. There are often 
risk factors for cardiovascular disease.
 3. Progressive small-​vessel disease (Binswanger disease) Multiple 
microvascular infarcts of perforating vessels lead to progressive 
lacunar formation and white matter hyperintensities on MRI. This is 
a subcortical dementia with a clinical course characterized by gradual 
intellectual decline, generalized slowing, and motor problems (e.g. gait 
disturbance and dysarthria). Depression and pseudobulbar palsy are 
not uncommon.
Epidemiology
Most common onset: age 60–​70yrs; ♂ > ♀. Other risk factors include: family 
or personal history of cardiovascular disease, smoking, diabetes mellitus, 
hypertension, hyperlipidaemia, polycythaemia, coagulopathies, sickle-​cell 
anaemia, valvular disease, atrial myxoma, and carotid artery disease. There 
are rare familial cases with onset in the 40s—​cerebral autosomal dominant 
arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).
Clinical features
Onset may follow a stroke, with associated motor symptoms, and is more 
acute than DAT. Emotional, personality, language, and executive impair­
ments are common and often early; memory impairments occur later. 
Symptoms may fluctuate in severity. Depression and emotional lability are 
common, and catastrophic emotional reactions are sometimes reported. 
36  Calabrese V, Giordano J, Signorile A, et  al. (2016) Major pathogenic mechanisms in vascular 
dementia:  Roles of cellular stress response and hormesis in neuroprotection. J Neurosci Res 
94:1588–​603.
37  Rossor M, Brown J (1998) Vascular and other dementias. In: Butler R, Pitt B (eds). Seminars in Old 
Age Psychiatry, pp. 73–​86. London: Gaskell.

Vascular dementia (vascular neurocognitive disorder)
Physical signs include features of generalized vascular disease, together with 
neurological impairments (e.g. rigidity, akinesia, brisk reflexes, pseudobulbar 
palsy). Ten per cent have seizures at some point. Prognosis is poorer than in 
DAT, with an average lifespan of 5yrs from onset. Cause of death is usually 
ischaemic heart disease (50%), stroke, or renal failure.
Investigations
 • Routine ‘dementia screen’ (E Standard blood tests in psychiatric 
practice, p. 130).
 • Serum cholesterol, clotting screen, vasculitis screen [ESR, CRP, 
complement, anti-​nuclear factor (ANF), rheumatoid factor, anti-​DNA 
antibodies, antiphospholipid antibodies, etc.), and syphilis serology are 
additional tests in unusual cases (e.g. ‘young strokes’).
 • ECG, CXR, CT, and MRI are essential.
 • Other investigations may include: echocardiography (for cardiac/​
valvular defects or ventricular failure) and carotid artery Doppler 
ultrasound.
Management
 • Establish causative factors. Contributory medical or surgical conditions 
should be treated early.
 • There is no evidence that daily aspirin is effective in delaying the course 
of VaD, and it is associated with a risk of haemorrhage.
 • General health interventions include changing diet, stopping smoking, 
managing hypertension, optimizing diabetic control, and increasing 
exercise.

166
Chapter 4  Neuropsychiatry
Other specific 
neurodegenerative conditions
Huntington’s disease
A genetic disease characterized by a combination of dementia and 
worsening chorea. There is autosomal dominant inheritance with 100% 
penetrance; thus, 50% of a patient’s offspring will be affected. Genetic 
testing allows presymptomatic diagnosis, but as no treatment is available 
and a positive test has implications for other family members, there are 
ethical issues around presymptomatic testing.
Pathology The genetic defect is a trinucleotide repeat of CAG—​between 
37 and 120 repeats on chromosome 4. ddGABA neurons in the basal gan­
glia; this leads to i stimulation of the thalamus and cortex by the globus 
pallidus. Also increase in DA transmission.
Clinical features Chorea, dementia, and a family history of HD. Chorea is 
a movement disorder characterized by initial jerks, tics, gross involuntary 
movements of all parts of the body, grimacing, and dysarthria. There is i 
tone, with rigidity and stiffness, positive primitive reflexes, and abnormal 
eye movements.
Clinical course Onset usually during 30s and 40s; a small number of 
juvenile-​onset cases; deteriorating course to death within 10–​12yrs.
Psychiatric syndromes Occur in 60–​75% of patients with HD.
 • Anxiety and depression are common.
 • Psychosis is common and often occurs early.
 • Executive dysfunction with impulsivity and aggression.
 • Subcortical dementia—​slowing, apathy, and amnesia.
Investigations EEG:  slowing. CT/​MRI:  atrophy of the basal ganglia, with 
‘boxing’ of the caudate and dilatation of the ventricles. PET: dmetabolism 
in the basal ganglia.
Treatment No treatment arrests the course of the disease. Antipsychotic 
and antidepressant medications may provide symptomatic relief of psychi­
atric symptoms. Tetrabenazine, antipsychotics, and BDZs may help reduce 
abnormal movements.
Wilson’s disease
A rare genetic disease caused by a mutation of the APT7B gene on chromo­
some 13, which prevents normal hepatic excretion of excess copper into 
bile. Inheritance is autosomal recessive. Copper deposits in the liver cause 
cirrhosis and in the basal ganglia result in degeneration of the lentiform nu­
cleus (hepato-​lenticular degeneration).
Clinical features Onset in childhood or early adulthood. Liver cirrhosis. 
Extra-​pyramidal signs include: tremor, dystonia, i tone, flapping tremor of 
the wrists, wing-​beating tremor of the shoulders, risus sardonicus of the 
face, bulbar signs (dysphagia, dysarthria), and Kayser–​Fleischer rings (green-​
brown corneal deposits).

Other specific neurodegenerative conditions
Psychiatric syndromes
 • Mood disturbances—​common.
 • Subcortical dementia—​25%.
 • Psychosis—​rare.
Investigations iserum/​urine copper; dcaeruloplasmin.
Treatment Copper-​chelating agents: penicillamine or trientine.
Pantothenate kinase-​2-​associated 
neurodegeneration (PKAN)
One of a group of rare inherited conditions responsible for 
neurodegeneration with brain iron accumulation (NBIA),38 which are as­
sociated with abnormal accumulation of iron in the brain. PKAN (formerly 
Hallervorden–​Spatz syndrome)39 is an autosomal recessive disorder with 
onset typically in childhood or early adulthood.
Clinical features Symptoms include dystonia, Parkinsonism, spasticity, seiz­
ures, ID or dementia, optic atrophy, and pigmentary retinopathy.
Psychiatric syndromes
 • OCD.
 • Schizophrenia-​like psychosis.
 • Depression.
Investigations Characteristic ‘eye of the tiger’ sign on T2-​weighted MRI, 
caused by iron deposits in the basal ganglia. Genetic tests are available.
Treatment There is no treatment available to reverse the condition. Iron-​
chelating agents (e.g. desferrioxamine) may slow progression.
38  Schipper HM (2012) Neurodegeneration with brain iron accumulation—​clinical syndromes and 
neuroimaging. Biochim Biophys Acta 1822:350–​60.
39  The term pantothenate kinase neurodegeneration is now used in preference to Hallervorden–​
Spatz syndrome, because it is now known that Hugo Spatz and Julius Hallervorden (who described 
the syndrome in 1922) were members of the Nazi party who performed research using the brains of 
executed prisoners during World War II.

168
Chapter 4  Neuropsychiatry
Prion diseases
Prion diseases are rare, rapidly progressive dementing illnesses caused by 
the spread of deposits of abnormal prion protein (PRNP) throughout the 
brain as a result of either inherited genetic mutation, sporadic mutation, 
or infection. The typical pathological finding is spongy encephalopathy, and 
in terms of the nosology of the dementias, prion disease is considered a 
multifocal dementia. While prion diseases tend to respect the species bar­
rier (e.g. ‘scrapie’ is a prion disease limited to sheep), this is not always the 
case (e.g. vCJD).
Creutzfeldt–​Jakob disease
A rare disease of 50–​70yr olds, with equal sex distribution, resulting in 
around 100 UK deaths per year. Eighty-​five per cent of cases result from 
spontaneous mutation of PNRP, 10% from inherited mutations, and 5% re­
sulting from vCJD or iatrogenic transmission during transplant surgery of 
dura, corneal grafts, and pituitary growth hormone. The clinical picture is 
one of rapidly progressive dementia, cerebellar and extra-​pyramidal signs, 
myoclonus, and death within a year. EEG shows periodic complexes. CT 
atrophy of the cortex and cerebellum. Elevated levels of 14-​3-​3 protein are 
found in the CSF.
New variant CJD—​bovine spongiform encephalopathy
The rise of vCJD followed an epidemic of bovine spongiform encephal­
opathy (BSE) in cattle. BSE is a prion disease of cows that is thought to 
have been spread by cattle feeds that contained CNS material from infected 
cows. The disease in humans affects mainly young people in their 20s and is 
characterized by early anxiety and depressive symptoms, followed by per­
sonality changes, and finally a progressive dementia. Ataxia and myoclonus 
are prominent, and the typical course is 1–​2yrs until death. EEG changes are 
only seen late in disease.
Rare inherited prion diseases
 • Fatal familial insomnia (FFI)—​causes progressive and profound insomnia, 
anxiety, hallucinations, and ultimately rapidly progressive dementia. 
Inherited PRNP mutation.
 • Gerstmann–​Sträussler–​Scheinker syndrome (GSS)—​causes dysarthria, 
ataxia, memory problems, and rapidly progressive dementia. Inherited 
PRNP mutation.
Kuru
This was a rare disease of Papua New Guinea cannibals who ate the brains 
of their deceased relatives. The incubation period was prolonged—​up 
to 40yrs before disease onset, then progression was rapid and fatal (see 
Box 4.8).

Prion diseases
Box 4.8  A ‘cannibalism genotype’ protects against CJD
Researchers at University College London in 2003 suggested that canni­
balism was common and widespread in human ancestors. They analysed 
DNA from 30 elderly Fore women from Papua New Guinea who had 
participated in many cannibalistic feasts before they were banned by the 
Australian government in the 1950s. It was the practice of the Fore for 
women and children to consume the brains of dead kin in the belief that 
this act would ‘recycle’ the spirit of the dead within the living. At the 
peak of the epidemic (1920–​1950), kuru—​an acquired prion disease—​
killed up to 2% of the population annually. Most of the women survivors 
tested by researchers had a novel PrP variant G127V that was much less 
common in the younger population, indicating that it conferred substantial 
protection against the disease. At the time of publication in 2003, none 
of the patients who had, to date, contracted new vCJD in Britain carried 
the protective genotype. This suggests that this genotype is protective 
against prion diseases in humans. The researchers then examined DNA 
from various ethnic groups around the world and found that all, except 
the Japanese, carried the protective genotype to a similar degree. Genetic 
tests showed that this gene could not be there by chance but was a result 
of natural selection. This implies that ancestral human populations were 
exposed to some form of prion disease. Researchers concluded that fre­
quent epidemics of prion disease caused by cannibalism in human ances­
tors would explain the worldwide existence of the protective genotype 
in modern humans.
Source: data from Mead S, Stumpf MP, Whitfield J, et al. (2003) Balancing selection at the 
prion protein gene consistent with prehistoric kurulike epidemics. Science 300: 300, Issue 5619, 
pp. 640–​643.

170
Chapter 4  Neuropsychiatry
Amnestic disorders
Amnestic disorders are syndromes characterized by memory impairment 
(anterograde and/​or retrograde amnesia), which are caused by a gen­
eral medical condition or substance use and where delirium and dementia 
have been excluded as causative of the amnesia. Amnestic disorders may 
be transient or chronic (< or >1mth). Amnestic conditions usually involve 
some or all of the following neuroanatomical structures:  frontal cortex, 
hippocampus and amygdala, dorsomedial thalamus, mamillary bodies, and 
periaqueductal grey matter (PAG). In terms of neurochemistry, glutamate 
transmission at the NMDA receptor is often implicated in amnesia, mainly 
due to its role in memory storage in the limbic system—​long-​term potenti­
ation (LTP). A number of amnestic disorders are recognized:
Wernicke’s encephalopathy
An acute syndrome, with a classic triad of symptoms (ataxia, ophthalmo­
plegia/​nystagmus, and altered mental status), caused by thiamine depletion, 
usually related to alcohol abuse, and associated with pathological lesions in 
the mamillary bodies, PAG, thalamic nuclei, and the walls of the third ven­
tricle (E Wernicke–​Korsakoff syndrome, p. 606).
Korsakoff psychosis
Amnesia and confabulation with atrophy of the mamillary bodies, associ­
ated with alcohol excess and Wernicke’s encephalopathy (E Wernicke–​
Korsakoff syndrome, p. 606).
Vascular disease
Aneurysm of the anterior communicating artery may result in amnestic dis­
order, but amnesia due to stroke is rare.
Brain injury
An open or closed brain injury involving acceleration or deceleration forces 
may result in injury to the anterior temporal poles (as this structure col­
lides with the temporal bone). Anterograde post-​traumatic amnesia (PTA) 
is prominent, with retrograde amnesia relatively absent (E Traumatic brain 
injury, p. 172).
Herpes simplex virus encephalitis
Affects the medial temporal lobes and results in deficits in short-​term 
memory (STM) storage. Treatment with IV aciclovir where the condition is 
suspected may prevent deficits from becoming permanent.
Hypoxic brain damage
Hypoxia following asphyxia from CO poisoning, near drowning, etc. may 
damage sensitive CA1 and CA3 neurons in the hippocampus. This results in 
problems with STM storage.
Alcohol blackouts (‘palimpsest’)
Significant alcohol intoxication may lead to amnesia for the period of intoxi­
cation, usually in the context of chronic alcohol misuse.

Amnestic disorders
Electroconvulsive therapy
There may be a period of mild anterograde and/​or retrograde amnesia for 
a few hours following administration of ECT. In exceptional cases, there 
may be reported ongoing patchy memory loss for up to 6–​9mths (E Does 
ECT cause brain damage? p. 308).
Transient global amnesia (TGA)
This is a syndrome of amnesia and disorientation with repetitive questioning 
lasting 4–​10hrs. Age 40–​80. Aetiology remains unknown.
Transient epileptic amnesia (TEA)
Recurrent episodes of amnesia and disorientation lasting 30mins to 1hr, 
often occurring from sleep or on waking, due to medial temporal lobe seiz­
ures in epilepsy. Interictal EEG suggestive in 30%. Accelerated long-​term 
forgetting leads to lacunes in remote autobiographical memory.
Dissociative amnesia
Sudden retrograde autobiographical memory loss, ranging from hours 
to years. May be associated with depersonalization or derealization (E 
Dissociative (conversion) disorders, p. 869).
Other causes of amnesia
Substances (BDZs, anticholinergics); SOLs (e.g. tumours); hypoglycaemia. 
NMDA receptor antibody encephalitis. (See Box 4.9.)
Box 4.9  Patient HM
On 23 August 1953, patient HM underwent a bilateral medial temporal 
lobotomy in an attempt to control his epileptic seizures. This resulted in 
severe anterograde memory impairment that made HM one of the most 
studied patients in the history of cognitive psychology, up until his death 
in 2008.
HM’s syndrome was surprisingly isolated, with impairment mostly 
limited to his inability to register new facts into long-​term memory, des­
pite immediate memory being preserved for both verbal and non-​verbal 
tasks. Although his operation was performed when he was 27, his mem­
ories were intact until age 16, with an 11-​year retrograde amnesia.
His IQ was above average, with almost normal language production 
and comprehension—​he could understand and produce complex verbal 
material (but was impaired on tests of semantic and symbolic verbal flu­
ency). His perceptual abilities were normal, except for his sense of smell 
(secondary to damage of the olfactory tracts). Despite the fact that some 
of his spatial abilities were compromised, he did not have any attentional 
deficit.

172
Chapter 4  Neuropsychiatry
Psychiatric aspects of brain injury
Terminology
Acquired brain injury (ABI) can occur as a result of trauma [traumatic brain 
injury (TBI)], hypoxia/​ischaemia, stroke, toxic or metabolic insult, infec­
tion, or any pathological process causing sudden, irreversible, and non-​
progressive damage to the brain after the neonatal period.
Management of brain injury
 • The acute psychiatric effects of brain injury can be challenging to 
manage. Those who require psychiatric input after the acute period 
have emotional and cognitive symptoms ranging from subtle to severe.
 • There is strong evidence for benefits of early intensive 
neurorehabilitation after moderate and severe brain injury; after mild 
brain injury, patients benefit from information, advice, and follow-​up (E 
Mild traumatic brain injury, p. 174).
Traumatic brain injury
TBI is a common cause of death and lifelong disability (largely due to neuro­
psychiatric sequelae) in young adults. Common causes are road traffic ac­
cidents, falls, and assaults; ♂ > ♀; alcohol is often a contributory factor. 
Improved life expectancy has, however, led to an increase in TBI in the frail 
elderly in high-​income countries, shifting the age of peak incidence from 
20s to 40s.
Acute effects of traumatic brain injury
 • PTA (post-​traumatic delirium)—​extends from the time of the injury until 
normal memory resumes. PTA may end abruptly or merge gradually 
into persisting deficits.
 • Retrograde amnesia (RA)—​includes the period between the last clearly 
recalled memory prior to the injury and the injury itself. It is usually a 
dense amnesia, lasting seconds or minutes, but can be difficult to assess 
where there has been prolonged PTA.
Factors associated with poorer long-​term outcome after traumatic brain injury
 • Conscious level post-​injury (mild: GCS score 13–​15; moderate: GCS 
score 9–​12; severe: GCS score <8).
 • Duration of loss of consciousness.
 • i duration of PTA (>24hrs, poorer outcome).
 • Age (older—​poorer prognosis).
 • Pre-​injury educational or occupational level.
 • Reduced pre-​injury cognitive reserve, e.g. due to cerebrovascular 
disease or alcohol dependence.
Long-​term sequelae of moderate/​severe acquired 
brain injury
Memory Difficulties learning new information are common after brain 
injury, especially involving damage to frontal or temporal lobes. Bilateral 
hippocampal damage after hypoxic–​ischaemic injury (HII) can cause 
an amnestic syndrome. Treatment:  frequent orientation, cognitive 
rehabilitation.

Psychiatric aspects of brain injury
Executive dysfunction Diffuse or prefrontal lesions can cause a 
dysexecutive syndrome:  difficulties with planning, judgement, abstract 
thought, sustained attention, and social cognition, leading to impulsive, 
socially inappropriate behaviour, poor frustration tolerance with aggres­
sive outbursts, and disorganization. This can cause significant disability and 
family distress, even in the absence of significant memory impairment. 
Treatment:  aggression and irritability may respond to propranolol where 
there are no contraindications (e.g. asthma).
Perceptual problems Visuospatial neglect or agnosia, cortical blindness 
(especially after HII), or optic nerve damage may be missed as reasons for 
failure to progress with rehabilitation. Visual or auditory misinterpretations 
may be mistaken for psychosis. Treatment: occupational therapy (OT) input 
and adaptations.
Speech and language disorders Dysphasia, dysarthria.
Mood and anxiety disorders Depression occurs in 25% of individuals 
after TBI and should be considered where cognitive or behavioural symp­
toms worsen months or years after injury. Apathy or emotional lability 
due to damage to the prefrontal cortex or limbic lobe are less likely to re­
spond to treatment. Anxiety occurs commonly. Treatment: SSRIs; consider 
duloxetine if comorbid pain.
Psychosis Psychotic symptoms may appear as part of a post-​traumatic 
delirium following brain injury. A schizophrenia-​like psychotic disorder after 
brain injury occurs relatively rarely 1–​5yrs after injury and is associated with 
frontal and temporal damage. Premorbid psychosis is a risk factor for brain 
injury. Treatment: antipsychotics.
Sequelae in children
Less psychopathology after ABI due to i brain plasticity. Recovery may con­
tinue for up to 5yrs after injury (as opposed to 72yrs in adults). Problems 
may include aggression and ADHD-​like syndromes.
Complications associated 
with neuropsychiatric deterioration
 • Hydrocephalus—​can occur days to months after injury and is associated 
with deteriorating cognitive function, gait, incontinence, and depressed 
conscious level. Treatment: neurosurgical.
 • Post-​traumatic epilepsy—​occurs in 5% of closed and 30% of open 
head injuries, usually during the first year, and worsens prognosis. 
Treatment: antiepileptic medication.

174
Chapter 4  Neuropsychiatry
Mild traumatic brain injury (concussion)
Epidemiology
The majority of presentations to hospital after TBI are with mild TBI. 
Although in the majority, symptoms resolve within days to weeks; a mi­
nority are troubled by persistent symptoms and may seek psychiatric advice.
Definition (WHO)
 • GCS score of 13–​15 30mins post-​injury.
 • Loss of consciousness (LOC) 30mins or less.
 • PTA <24hrs.
 • Not due to alcohol, medications, penetrating craniocerebral injury, or 
treatment of other medical conditions or injuries.
Clinical course
Early (first 24hrs) Headache, blurred vision, dizziness, confusion, memory 
problems, fatigue, sleep disturbance. Depersonalization/​derealization may 
be described as dizziness or confusion.
First month after injury In most, all symptoms will resolve in the first days 
after mild TBI. Headache, dizziness [persisting dizziness should raise suspi­
cion of benign paroxysmal positional vertigo (BPPV), common after mild 
TBI and easily treatable], mild cognitive symptoms, and fatigue may persist 
in a few.
Symptoms persisting >3mths after injury Cognitive function usually returns 
to baseline within 3mths. A minority of patients develop persistent symp­
toms such as memory and concentration difficulties, fatigue, headaches, 
dizziness, and sleep disturbance. Psychological factors related to injury 
are likely to be important—​similar symptoms occur in non-​brain-​injured 
trauma patients. In many, the ‘post-​concussional syndrome’ (a term best 
discarded) can be considered a secondary functional neurological disorder.
Risk factors for persistent (‘post-​concussional’) symptoms
 • Alcohol excess—​alcohol excess is a risk factor for mild TBI; post-​injury 
memory and concentration problems, fatigue, headache, irritability, and 
sleep difficulties may reflect ongoing alcohol use, and alcohol is likely to 
underpin the apparent i risk of epilepsy after mild TBI.
 • Age—​older age is associated with persistent symptoms.
 • Social stressors—​may be premorbid or relate to circumstances of the 
injury (commonly assault) or to lost income due work absence.
 • Depression and anxiety—​psychological distress around the injury can give 
rise to specific or generalized anxiety, PTSD, or depression, all of which 
perpetuate fatigue and cognitive symptoms.
 • Unhelpful illness beliefs—​beliefs that the brain has been irreversibly 
damaged or that there is a high risk of dementia seem more common in 
those with persisting symptoms.
 • Litigation/​compensation issues—​ongoing litigation is strongly associated 
with persisting symptoms.

Mild traumatic brain injury (concussion)
Management
Clear, reassuring explanation and advice soon after mild TBI may help to 
prevent persistent symptoms.
Advice
(See also M http://​www.headinjurysymptoms.org)
 • Mild TBI has a good prognosis and rarely causes lasting problems.
 • Common symptoms occurring in the first few days—​headache, poor 
concentration, tiredness, or dizziness—​do not indicate ‘brain damage’.
 • The risk of developing serious complications is low. If ‘red flag’ 
symptoms (LOC, drowsiness, seizure, CSF leak, severe headache, 
or focal neurological symptoms) occur, return to the Emergency 
Department as soon as possible. Serious problems are rare beyond the 
first week.
 • Prolonged rest is likely to be unhelpful, and return as soon as is 
comfortable to normal activities should be recommended.
 • Severe disabling symptoms may benefit from CBT or graded exercise 
therapy (GET) where fatigue is prominent.
Chronic traumatic encephalopathy
(See Box 4.10.)
Box 4.10  Chronic traumatic encephalopathy
‘Punch drunk’ syndrome, or encephalitis pugilistica, was a condition of 
cognitive and neurological deterioration first noted in retired professional 
boxers in the early 1900s. Chronic traumatic encephalopathy (CTE) is a 
more recently described syndrome, in which neuropsychiatric symptoms 
(e.g. cognitive impairment, personality change, fatigue, depression, and 
suicidality) occur many years after mild TBI, particularly in retired profes­
sional sports people who have sustained multiple concussions. Although 
CTE has been the subject of extensive media attention, its definition 
and existence are not strongly supported by scientific evidence. There 
have been no prospective longitudinal studies. Retrospective studies, vul­
nerable to inclusion and recall bias, revealed multiple confounding risk 
factors, including strikingly high levels of drug and alcohol use in retired 
professional sports people. In fact, review of all pathologically described 
cases has cast doubt on the existence of CTE as a widespread problem 
in American footballers;* neuropathological findings overlap with many 
common neurodegenerative disorders, and there appears to be no i risk 
of dementia after mild TBI.** So while concussion is best avoided, patients 
can be assured that current evidence suggests that mild TBI does not in­
crease the risk of later-​life dementia.
* Maroon JC, Winkelman R, Bost J, Amos A, Mathyssek C, Miele V (2015) Chronic traumatic 
encephalopathy in contact sports: a systematic review of all reported pathological cases. PLoS 
One 10:e0117338.
** Godbolt AK, Cancelliere C, Hincapié CA, et al. (2014) Systematic review of the risk of 
dementia and chronic cognitive im-​pairment after mild traumatic brain injury: results of the 
International Collaboration on Mild Traumatic Brain Injury Prognosis. Arch Phys Med Rehabil 
95:S245–​56.

176
Chapter 4  Neuropsychiatry
Psychiatric sequelae of stroke
A range of psychiatric problems may occur following stroke. These include 
the following.
Cognitive disorders
 • Vascular neurocognitive disorder (E Vascular dementia (vascular 
neurocognitive disorder), p. 164).
 • Non-​progressive, e.g. after a single stroke.
 • Progressive—​also called VaD.
 • Amnestic disorder—​e.g. after ruptured anterior communicating artery 
(ACOM) aneurysm (E Amnestic disorders, p. 170).
Post-​stroke depression
Depressive illness is common, occurring in around a third of patients after 
stroke.40 Depression may occur early or late during stroke recovery and 
may be missed in the presence of cognitive or communication impairment, 
and it is associated with poor functional outcome and excess morbidity and 
mortality.41
Risk factors for post-​stroke depression
Physical disability, stroke severity, and cognitive impairment are the most 
consistent predictors of depression after stroke. Women are affected 
slightly more often than men.42 Lesion location does not influence depres­
sion risk.43 Treatment:  antidepressants are effective, especially for severe 
depression, although after stroke, they may bring a higher risk of adverse 
effects. SSRIs are most widely used and usually well tolerated.44
Personality changes and executive dysfunction
Damage to frontal lobes can cause a constriction in the range of interests, 
loss of intellectual flexibility, apathy and loss of volition, irritability, and loss 
of social sensitivity.
Pseudobulbar affect
Also called pathological emotionalism, emotional incontinence, or patho­
logical laughter/​crying. Present in up to 50% after stroke and in many other 
neurological disorders. Presentation involves emotional lability with unpro­
voked and uncontrollable crying or laughter, inconsistent with the patient’s 
subjective emotional state. May respond to treatment with an SSRI or 
amitriptyline.
40  Hackett ML, Yapa C, Parag V, Anderson CS (2005) Frequency of depression after stroke: a sys­
tematic review of observational studies. Stroke 36:1330–​40.
41  Pan A, Sun Q, Okereke OI, Rexrode KM, Hu FB (2011) Depression and risk of stroke: morbidity 
and mortality. JAMA 306:1241.
42  Hackett ML, Anderson CS (2005) Predictors of depression after stroke: a systematic review of 
observational studies. Stroke 36:2296–​301.
43  Carson AJ, MacHale S, Allen K, et al. (2000) Depression after stroke and lesion location: a sys­
tematic review. Lancet 356:122–​6.
44  Hackett ML, Anderson CS, House A, Xia J (2008) Interventions for treating depression after 
stroke. Cochrane Database Syst Rev 4:CD003437.

Psychiatric sequelae of stroke
Psychosis
Circumscribed delusions may arise in individuals with profound anosognosia 
or somatoparaphrenia (denial of ownership of a limb or half of one’s body), 
almost always due to right-​sided lesions. Schizophrenia-​like psychotic dis­
orders occur rarely and have also been associated with right-​sided lesions. 
Peduncular hallucinosis is a rare syndrome of complex visual hallucinations 
associated with infarcts involving the pons and the midbrain.