ESSENTIALS

ESSENTIALS

SECTION 24  Neurological disorders 5802 Neuromuscular transmission disorders Myasthenia gravis and Lambert–​Eaton myasthenic syndrome are diagnosed by single-​fibre EMG (see previously) or repeti- tive stimulation of motor nerve. The studies are carried out pref- erentially in proximal nerves such as the accessory nerve or the musculocutaneous nerve. Care is mandatory to reduce the effect of movement artefacts. At single stimulation the compound muscle ac- tion potential amplitudes are usually normal in myasthenia gravis but reduced in Lambert–​Eaton myasthenic syndrome. At slow rates of stimulation of 2–​5 Hz, decrements of the compound muscle ac- tion potential occur in both disorders. At high rates of stimulation of 20–​50 Hz or after a maximal voluntary contraction, the com- pound muscle action potential is greatly increased (facilitation) in Lambert–​Eaton myasthenic syndrome. FURTHER READING Albers JW, Kelly JJ (1989). Acquired inflammatory demyelinating polyneuropathies:  clinical and electrodiagnostic features. Muscle Nerve, 12, 435–​51. Binnie CD, et al. (1995). EMG, nerve conduction and evoked poten- tials. In:  Osselton JW (ed) Clinical neurophysiology, pp. 43–​321. Butterworth-​Heinemann Ltd, Oxford. Bouche P et al. (1999). Electrophysiological diagnosis of motor neuron disease and pure motor neuropathy. J Neurol, 246, 520–​25. Brown WF, Bolton CF (eds) (1993). Clinical electromyography I,
2nd edition. Butterworth-​Heinemann, Boston, MA. Buchthal F (1957). An introduction to electromyography. Scandinavian University Books, Copenhagen. Buchthal F (1985). Electromyography in the evaluation of muscle disease: symposium in electrodiagnosis. Neurol Clinics, 3, 573–​98. Buchthal F, Kamieniecka Z (1982). The diagnostic yield of quantified electromyography and quantified muscle biopsy in neuromuscular disorders. Muscle Nerve, 5, 265–​80. Chiappa KH (ed) (1997). Evoked potentials in clinical medicine, 2nd edition. Lippincott-​Raven, Philadelphia, PA. Crone C, Krarup C (2013). Neurophysiological approach to periph- eral nerve disorders. In: Said G, Krarup C (Vol. 115, eds 3rd series); Aminoff M, Boller F, Swaab D (series eds) Peripheral nerve disorders, handbook of clinical neurology, pp. 81–​114. Elsevier, Waltham. Fuglsang-​Frederiksen A (1981). Electrical activity and force during voluntary contraction of normal and diseased muscle. Munksgaard, Copenhagen. Fuglsang-​Frederiksen A (2000). The utility of interference pattern ana- lysis. Muscle Nerve, 23, 18–​36. Ho TW et al. (1997). Patterns of recovery in the Guillain–​Barré syn- dromes. Neurology, 48, 695–​700. Kimura J (1989). Electrodiagnosis in diseases of nerve and muscle:
principles and practice, 2nd edition. FA Davis Co., Philadelphia, PA. Krarup C (1999). Pitfalls in electrodiagnosis. J Neurol, 246, 1115–​26. Magistris MR, et al. (1998). Transcranial stimulation excites virtually all motor neurons supplying the target muscle: a demonstration and a method improving the study of motor evoked potentials. Brain, 121, 437–​50. Mauguière F (1995). Evoked potentials. In: Osselton JW (ed) Clinical Neurophysiology, pp. 325–​572. Butterworth-​Heinemann, Oxford. Niedermeyer E, Lopes da Silva F (eds) (1993). Electroencephalography: basic principles, clinical applications, and related fields, 3rd edition. Williams & Wilkins, Baltimore, MA. Nuwer MR (1999). Spinal cord monitoring. Muscle Nerve, 22, 1620–​30. Sandberg A, Hansson B, Stålberg E (1999). Comparison between con- centric needle EMG and macro EMG in patients with a history of polio. Clin Neurophysiol, 110, 1900–​8. Simonetti S, Nikolic M, Krarup C (1999). Electrophysiology of the motor unit. In:  Younger DS (ed) Textbook of motor disorders,
pp. 45–​60. Lippincott Williams & Wilkins, Philadelphia, PA. Stålberg E, Trontelj JV. (1979). Single fibre electromyography. Mirvalle Press, Old Woking, Surrey. 24.3.3  Imaging in neurological diseases Andrew J. Molyneux, Shelley Renowden,
and Marcus Bradley ESSENTIALS Computed tomography and magnetic resonance imaging are the most important imaging techniques in the diagnosis of neurological disease. Computed tomography During exposure to a series of narrow X-​ray beams, a detector array spins around the patient and measures the absorption coefficients of tissues within the beam, the different coefficients providing image contrast. Modern helical multidetector computed tomography acquires data from large volumes of tissue simultaneously with the patient moving continuously through the machine. This enables very rapid scanning and the ability to acquire angiographic (computed tomography angi- ography and venography) and functional information (computed tom- ography perfusion). The volume data set is acquired and multiplanar reconstructions can be obtained in the sagittal, coronal, and oblique planes, as required. Iodinated contrast agents, as employed in general vascular imaging, are commonly used for image enhancement. Magnetic resonance imaging When the body is placed in a magnetic field, a small number of the tissue protons align themselves with the main magnetic field. They are subsequently displaced from their alignment by application of a radiofrequency gradient, and when this radiofrequency pulse termin- ates, the protons realign themselves with the main magnetic field, re- leasing a small pulse of energy as a radio signal that can be detected, localized, and processed by a computer to produce a cross-​sectional anatomic image. Many different and complex radiopulse sequences are used in magnetic resonance imaging, each of which is designed and used to answer particular clinical questions. They detect different aspects of tissue properties known as the ‘relaxation times’ of the pro- tons; times that will vary according to the proton-​containing tissue and the relative mobility of the protons. These are called T1 and T2 relaxation times. Gadolinium-​labelled compounds, which shorten the T1 relaxation time, are commonly used for image enhancement.

24.3.3  Imaging in neurological diseases 5803 Choice of imaging modality The choice between computed tomography or magnetic reson- ance imaging depends on several factors. Computed tomography is usually more readily available, is quicker to do, and is used in most acute situations, particularly in stroke and subarachnoid haemor- rhage, intracranial infection, trauma, and suspected intracranial masses. Magnetic resonance imaging is the imaging modality of choice in suspected spinal pathology and also in the detailed in- vestigation of cranial neurological diseases, particularly those af- fecting the white matter, epilepsy, stroke, tumours, and congenital anomalies. Introduction The modern imaging techniques of computed tomography (CT) and magnetic resonance imaging (MRI) for the demonstration of structural neurological disease have developed rapidly since their first introduction in the 1970s and 1980s, respectively. They have undergone further technological evolution, particularly in the last 10 years, and continue to do so. A variety of both CT-​ and MRI-​based techniques can provide anatomical, angiographic, and functional information. In addition, biochemical data may be obtained using magnetic resonance (MR) spectroscopy (MRS) and microstructural information can be obtained using diffusion tensor imaging. Historical perspective CT CT was developed by the British scientist and engineer Godfrey Hounsfield during the early 1970s and was the first technique to provide non​invasive and cross-​sectional images of the brain. It was introduced into clinical practice at the Atkinson Morley Hospital in Wimbledon, London in 1972, and the first results were published in 1973. Before this, invasive techniques such as angiography and air encephalography were required to diagnose neurological disease. CT was the beginning of a complete revolution in radiological imaging, for which Hounsfield received the Nobel Prize for medicine in 1979. CT rapidly became the imaging modality of choice in the diagnosis of structural brain disease until the advent of MRI, developed by British scientists in Nottingham and Aberdeen, and at a similar time in California during the early 1980s. It was introduced into wide- spread clinical use during the late 1980s and early 1990s. However, CT still remains an essential tool, particularly in the acute situation, when MRI is contraindicated, and in countries and regions where the availability cost of MRI systems is prohibitively expensive. CT produces a series of cross-​sectional images, usually in the axial plane. During exposure to an X-​ray beam, a detector array spins around the patient and measures the absorption coefficients of tissues within the beam. It is the different coefficients that pro- vide image contrast. Early machines measured a single slice at a time but the development of helical and multidetector CT now rou- tinely produce 256 slices and more, with the patient moving con- tinuously through the machine. The most modern scanners now acquire a volume data set rather than slices. This has enabled very rapid scanning with subsecond scan times and time-​resolved data, and the ability to acquire angiographic (CT angiography and venog- raphy data) and functional information (CT perfusion). MRI MRI is fundamentally very different from CT. No ionizing radiation is involved. It is based on the ability of a small number of protons within the body to absorb and emit radiowave energy when the body is placed within a strong magnetic field. Different tissues absorb and release radiowave energy at different rates. When the body is placed in a magnetic field, a small number of the tissue protons (hydrogen ions) align themselves with the main magnetic field. They are subsequently displaced from their alignment by application of a radiofrequency gradient. When this radiofrequency pulse terminates, the protons realign themselves with the main magnetic field, releasing a small pulse of energy as a radio signal that is detected, localized, and processed by a com- puter to produce a cross-​sectional anatomical image. Many different and complex radiopulse sequences are used in MRI and are determined by the way the radiofrequency pulses are timed. They are designed and used to answer certain clinical ques- tions in a variety of neurological circumstances. They detect dif- ferent aspects of tissue properties known as ‘the relaxation times of the protons’—​times that will vary according to the proton-​ containing tissue and the relative mobility of the protons. The most basic and most commonly used sequences are termed ‘T1-​weighted’ and ‘T2-​weighted’ sequences. The appearance of these scans is quite different, for example, fluid structures such as cerebrospinal fluid are white (high signal) on T2-​weighted and dark (low signal) on T1-​weighted images (Fig. 24.3.3.1b, c). Some tissues such as fat (unless suppressed by a specific sequence) and some blood breakdown products (e.g. methaemoglobin) will appear bright on T1-​ and T2-​weighted images. Flowing blood is usually markedly hypointense (black) on both sequences (‘a signal void’), as are cortical bone and air. Specific MR sequences have also been designed to produce non-​ invasive angiographic information and usually do not require an in- jection of a contrast agent (MR angiography and MR venography). Perfusion-​weighted MRI (PWI) can assess cerebral perfusion and diffusion-​weighted MRI (DWI), by assessing Brownian motion of mobile protons, is useful in diagnosis of hyperacute and acute is- chaemic stroke and may be also used to differentiate malignant tu- mour from an abscess (see later). A more sophisticated variant of DWI called diffusion tensor imaging gives a more detailed direc- tional analysis of the changes in diffusion and provides microstruc- tural information about the orientation of white matter tracts, useful in surgical planning. This is called tractography. MRS may provide useful biochemical information and may be used to grade brain tu- mours, differentiate malignant tumour from radiation necrosis, and malignant tumour from abscess. Functional MRI (fMRI) may lo- calize specific brain functions (e.g. motor function, sensory func- tion, and language, and can be useful for surgical planning where mass lesions are close to or involve eloquent cortex). The resolution of modern MR scanners is submillimetre, most are 1.5 T (15 000 G) and increasingly 3-​T scanners are being introduced. This higher field strength (measured in tesla (T): 1 tesla = 104 gauss (G)) allows faster scanning and higher resolution.

SECTION 24  Neurological disorders 5804 The sensitivity of MR for the detection of intracranial anatomy and pathology is extremely high and its multiplanar capacity is an additional advantage. MRI might be contraindicated in patients with certain metallic implants, especially cardiac pacemakers (although MRI-​compatible cardiac pacemakers are now available), some heart valves, older an- eurysm clips, and metallic foreign bodies in the orbit. It is also opti- mally avoided if possible in the first trimester of pregnancy. Contrast enhancement in brain imaging Intravenous contrast in brain imaging is frequently used to enhance conspicuity of pathology, to determine the vascularity of structures, leakiness of the blood-​brain barrier, and to improve the demonstra- tion of the blood vessels. In practice, it usually adds little to the spe- cific diagnosis. It will show the extent and pattern of enhancement in tumours, abscesses, and inflammatory lesions. For CT, the same iodinated contrast agents employed in general vascular imaging are used. In MRI, gadolinium-​labelled compounds, which shorten the T1 relaxation time, are used and show the same patterns of enhance- ment as iodinated contrast media used in CT. The sensitivity of MRI contrast agents is significantly greater in the detection of metastatic lesions and the extent of tumour spread. Gadolinium enhancement is particularly useful in the assessment of meningeal disease. An add- itional advantage of MRI is that blood vessels can be labelled using (a) (b) (d) (c) Fig. 24.3.3.1  Normal computed tomography (CT) and magnetic resonance (MR) scans of the brain at the level of the ventricles. (a) Normal axial CT image at the level of the lateral ventricles. (b) Normal axial T2-​weighted image of a brain at the level of the ventricular system. Note that the cerebrospinal fluid (CSF) is white, the white matter is dark, and the grey matter is lighter than the white matter. This is the most commonly used MRI sequence and it is usually the most sensitive in the detection of pathological processes. (c) Axial, T1-​weighted, unenhanced MR image, showing the cerebrospinal fluid to be dark (low signal) and the white matter lighter than the grey matter. (d) Coronal FLAIR (fluid-​attenuated inversion recovery) MRI: these are T2-​weighted images but normal cerebrospinal fluid is dark on this sequence. This improves the visibility of lesions in the brain, especially adjacent to the ventricles. The mild asymmetry of the bodies of the lateral ventricles seen on this scan is within the normal range.

24.3.3  Imaging in neurological diseases 5805 specific imaging sequences without actually administering contrast. Examples of these techniques include time-​of-​flight imaging, phase contrast imaging, and arterial spin labelling. Cerebral angiography In the last five years, CT angiography (CTA) and MR angiog- raphy (MRA) have largely replaced diagnostic, transfemoral, intra-​ arterial, digital subtraction angiography (DSA) for demonstration of the intra-​ and extracerebral vessels. Transfemoral angiography involves the selective catheterization of the carotid and/​or vertebral arteries via the femoral artery and direct injection of iodinated con- trast media into these arteries. It is used primarily for investigation of intracranial haemorrhage (ICH), where CTA has not demon- strated the cause, and in the investigation and assessment of com- plex neurovascular disorders (e.g. arteriovenous malformations). The basic techniques of DSA are used for endovascular therapy in the treatment of cerebral aneurysms, arteriovenous malformations, fistulae, and thrombectomy for acute ischaemic stroke. In the investigation of a transient ischaemic attack (TIA) and minor stroke caused by suspected extracranial carotid or vertebral stenosis, Doppler ultrasonography of the neck vessels is usually the main screening test. CTA or MRA is an alternative technique and useful where carotid intervention to relieve stenosis (usually carotid endarterectomy) is planned. This has been shown to be of substan- tial benefit in patients with critical stenoses to prevent recurrent stroke. In contrast, patients with intracranial stenosis do not benefit from endovascular intervention to open up stenotic vessels. Myelography This has largely been superseded by spinal MRI. It involves a lumbar puncture and injection of water-​soluble contrast into the lumbar subarachnoid space, followed by radiography to demonstrate the lumbar and cervical nerve roots and the spinal cord in patients with radiculopathy, suspected cauda equina compression, and myelop- athy, when MRI cannot be performed. Imaging of common neurological diseases Cerebrovascular disease and stroke The most frequent neurological presentation is acute stroke. Patients presenting with sudden onset of neurological deficit should be deemed to have suffered a vascular event until proved otherwise. In practice the clinical diagnosis of stroke is very accurate, provided that an adequate history is available. However, clinical differenti- ation of haemorrhage from infarction is not possible. The primary role of imaging is to identify whether the acute stroke is ischaemic or haemorrhagic and, when there is diagnostic doubt, whether a stroke has occurred. CT is the most reliable way of excluding primary intracerebral haemorrhage as a cause of acute stroke, provided that it is performed within about a week of onset. In ischaemic stroke, depending on the extent and location of infarct and timing of the examination relative to the onset of neurological deficit, it will only variably detect acute infarction. Within hours of the ictus, CT may show a vague area of low density, loss of grey/​white differentiation, or slight swelling and ef- facement of the sulci in the area of infarction, or it may be normal (Fig.  24.3.3.2a). In the latter especially, in hyperacute ischaemic stroke, when thrombolysis or clot extraction is contemplated, CT perfusion (CTP) (Fig.  24.3.3.2b) and CTA (Fig.  24.3.3.2c) are useful additional techniques and can be performed very quickly in a multislice CT scanner to provide information about the site and (a) (c) (b) Fig. 24.3.3.2  (a) CT scan showing an acute right middle cerebral territory infarction within a few hours of onset of the neurological deficit with a left hemiplegia. Note the subtle loss of differentiation between the grey and white matter on the right side, the slight but definite reduction in attenuation, and the effacement of the Sylvian fissure and cortical sulci. (b) CT perfusion image obtained with a 64-​slice multidetector CT scanner showing widespread reduced perfusion and area of penumbra (blue) on the right side. (c) CT angiogram showing acute thrombus at right middle cerebral artery bifurcation.

SECTION 24  Neurological disorders 5806 extent of arterial occlusion, and extent and location of the infarcted brain but, most important, the extent of ischaemic but potentially viable brain. Standard MRI may also be normal within the first 3 h on fluid-​ attenuated inversion recovery (FLAIR) images and up to 8 h on T2W (except that the occluded vessel may show absence of flow void) but DWI can demonstrate decreased diffusion in the ischaemic/​ infarcted brain within minutes of the ictus. PWI will also provide in- formation to discriminate between ischaemic and viable brain from infarcted brain. MRA will demonstrate the site of vascular occlu- sion. CT techniques are of more practical value in the evaluation of hyperacute ischaemic stroke, in the United Kingdom at least. Over the next 24 h or so, there is progressive development of a low-​density area on CT involving the cortex and white matter, in a vascular distribution and with mild mass effect. Swelling increases from day 3 to day 7, and the area of infarction is progressively better defined. Loss of volume in the damaged area occurs over time from about 4 weeks (Fig. 24.3.3.3). On MRI, an area of high T2 signal is demonstrated, in the area of infarction, involving cortex and white matter (Fig. 24.3.3.4). In the acute phase, there may also be some swelling around the area, representing oedema with effacement of sulci and ventricles but, with time, volume loss occurs. There was a change in the evidence base for treatment of hyperacute ischaemic stroke in 2015 when several major randomized control trials published in quick succession showed that endovascular neurointervention (mechanical thrombectomy) leads to improved clinical outcomes for selected patients with anterior circulation large vessel (internal carotid artery and proximal middle cerebral artery) occlusion compared to intravenous thrombolysis. Additional ran- domized control trials confirmed that the time window for suc- cessful thrombectomy in large vessel occlusion could be substantially increased dependent upon perfusion imaging with CT, defining sal- vageable ischaemic but potentially viable brain. Transient ischaemic attacks and minor stroke During the 1990s it was shown in the in two large randomized trials, the North American Carotid Surgery Trial and the European Carotid Surgery Trial, that carotid endarterectomy significantly reduced the risk of disabling stroke or death in patients with severe Fig. 24.3.3.3  CT showing mature left middle cerebral infarction. Note the large area of very low attenuation, with loss of volume on that side. (a) (c) (b) Fig. 24.3.3.4  (a) T2-​weighted axial MRI showing an acute middle cerebral territory infarct affecting the right perisylvian region. (b) MRI showing acute infarct (bright) on diffusion-​weighted MR image. (c) Diffusion-​weighted MRI showing the apparent diffusion coefficient (ADC map) and restricted diffusion (dark).

24.3.3  Imaging in neurological diseases 5807 carotid stenosis who had suffered a minor stroke or TIA. Recent work has shown that the risk of recurrent major stroke after a TIA or minor stroke is very high in the early period (two weeks, par- ticularly in the first few days after the ictus). Recent guidance from the National Institute for Health and Clinical Excellence (NICE) in the United Kingdom recommends that patients with these symp- toms need urgent specialist assessment (within 24 hours for those with a high ABCD2 score), including brain and carotid imaging to detect those with significant carotid stenosis. The goal is to iden- tify patients with treatable stenosis and urgently treat other risk factors. Non​invasive imaging using Doppler ultrasonography, MRI and MRA, and CT and CTA are all used to identify these pa- tients. MRI with DWI has the advantage of identifying with much greater sensitivity areas of acute ischaemia or small infarcts that will not be detected on CT and or on standard MRI sequences (Fig. 24.3.3.5a, b). Intracranial haemorrhage Acute primary intracranial bleeding (ICH) into the brain paren- chyma is easily detected on CT. Fresh blood appears as an area of high density (Fig. 24.3.3.6a). Blood generally remains hyperdense for 2 weeks but, as the clot gets broken down, it becomes the same density as brain tissue at 2 to 4 weeks, and then is of lower density than brain after 4 weeks. The speed of resolution depends on the size of the clot. After an ICH, a decision must be made whether to investigate patients in more detail for the presence of an underlying lesion re- sponsible for the haemorrhage, such as an intracranial aneurysm, (b) (a) (d) (c) Fig. 24.3.3.5  (a) CT scan of a patient with a primary intracerebral haemorrhage in the right parietal lobe. High-​attenuation area represents the acute clot. (b) CT scan of a patient with an acute subarachnoid haemorrhage from a ruptured basilar termination aneurysm, with clot in the prepontine cistern and around the brainstem, showing a white (as opposed to dark) cerebrospinal fluid. (c) Lateral internal carotid angiogram showing large internal carotid aneurysm at the origin of the posterior communicating artery. (d) Angiogram after placement of detachable platinum coils to occlude the aneurysm.

SECTION 24  Neurological disorders 5808 vascular malformation, or occasionally a tumour. If the distribution of ICH suggests that the cause may be aneurysmal, then prompt angiographic evaluation is necessary. Otherwise, selection of which patients should undergo cerebral angiography is sometimes difficult and largely depends on the intention to treat if an underlying le- sion is found. This will depend on patient’s age, clinical state, loca- tion of haematoma, and patient’s comorbidities. Cerebral amyloid angiopathy may account for a significant fraction of ICH in older patients. Where there is a decision to investigate and treat, cranial MRI may also be useful. It will diagnose haemorrhage related to tu- mour, anatomically localize an arteriovenous malformation and is necessary to exclude cavernous angiomas, a rarer cause of haemor- rhage that is angiographically occult. Blood in the subarachnoid space after a haemorrhage (SAH) may be visible around the base of the brain as a white layer, in contrast to the normal dark outline of cerebrospinal fluid in the basal cisterns. Cranial CT performed within 24 h of a SAH is about 90–​95% sensitive (see Fig. 24.3.3.5b) with some reports suggesting that sensitivity approaches 100% at less than six hours. Its sensi- tivity diminishes with time, depending on the extent of haemor- rhage. With a large SAH, the scan will remain positive for three to four days (see Fig. 24.3.3.5b). Lack of visible blood on CT does not exclude the diagnosis of SAH, and lumbar puncture to look for red blood cells is essential if this diagnosis is suspected clinically and CT scan is negative or equivocal. Lumbar puncture should be per- formed by an experienced operator to lessen the risk of a traumatic tap which may make exclusion of SAH impossible and ultimately lead to unnecessary cerebral angiography with its inherent risk of stroke. It is, however, very important not to miss a very small SAH, un- detectable on CT, which may have resulted from rupture of an intra- cranial aneurysm. Aneurysmal SAH is potentially life threatening because re-​rupture of the aneurysm is common. All patients who survive an SAH and are in good clinical con- dition should undergo urgent imaging of the cerebral vessels by either CTA or DSA to detect the presence of a berry aneurysm that may be responsible for the haemorrhage. If CTA is negative, formal intra-​arterial DSA is usually performed. Around 15% of patients with proven subarachnoid haemorrhage will not have an aneurysm. Recently ruptured aneurysms have a high likelihood of rebleeding, as high as 30% in the first four weeks after the haemor- rhage. Without treatment there is a 50% mortality rate at six months. Aneurysms should be detected and treated as soon as possible, either by endovascular techniques using detachable platinum coils (see Fig. 24.3.3.5c, d) or by neurosurgical clipping. A large multicentre randomized trial, the International Subarachnoid Aneurysm Trial, has reported improved clinical outcomes at one year after coil em- bolization compared with surgical clipping, an advantage main- tained over many years of follow-​up. Other cerebrovascular diseases Cerebral venous sinus thrombosis This uncommon, potentially fatal, condition presents non-​ specifically with headache, confusion, variable neurological deficits including coma, and sometimes seizures. Cranial CT may be normal or may demonstrate generalized or local cerebral swelling and/​or haemorrhagic venous infarction. Dense thrombus may be seen in the occluded sinuses and veins. The diagnosis is usually made by MRI when it is suspected, where lack of flow void is seen on some sequences (T2 weighted) and high-​signal methaemoglobin on T1-​weighted sequences are seen in thrombosed dural sinuses. Flow-​sensitive MRI sequences (MR venography) demonstrate the obstructed sinus well and are some- times useful because the signal returned by clot varies according to age of clot, and the particular sequence and field strength of the scanner (Fig. 24.3.3.7). CT venography on multislice scanners is an excellent alternative technique, readily demonstrating the extent of thrombosis. (a) (b) Fig. 24.3.3.6  (a) Diffusion-​weighted MRI showing restricted diffusion, in a patient with a recent transient ischaemic attack (TIA), as a bright area in the left basal ganglia. (b) CT angiogram obtained on 64-​slice multidetector CT (MDCT), with workstation reconstructions showing tight stenosis at the origin of the internal carotid artery.

24.3.3  Imaging in neurological diseases 5809 Anticoagulation is urgently required because progression of the thrombosis can lead to ICH and fatal venous infarction. Local pharmacomechanical thrombolysis/thrombectomy may be indicated where there is clinical deterioration despite adequate anticoagulation. Inflammatory diseases of the nervous system Multiple sclerosis One of the most common neurological diseases after stroke in western countries is multiple sclerosis (MS). Imaging plays a cru- cial role in the diagnosis, but it is important to understand the MR appearances are not pathognomonic. Clinical presentation, history, and neurological examination are crucial. The typical MS plaque is a well-​defined, ovoid, periventricular, white matter lesion with a long axis perpendicular to the ventricle and long axis of the brain, reflecting the perivenular inflammatory process (Fig.  24.3.3.8a). Sometimes, they enhance, may cavitate, and may be associated with oedema, and can be confused with tumours. When patients present with symptoms of spinal cord disease (myelopathy), MRI of both the spine and brain is indicated. The entire spinal cord is imaged to exclude spinal cord compression. (a) (c) (b) Fig. 24.3.3.7  (a) Sagittal T1W MRI showing extensive sagittal sinus thrombus; there is intermediate signal in the sagittal sinus, but normally there would be a black flow void in this T1-​weighted sequence. (b) Sagittal T2-​weighted sequence showing clot in the superior sagittal sinus. (c) Coronal MR venogram showing lack of filling in the sagittal sinus and the left transverse sinus. (a) (b) Fig. 24.3.3.8  (a) T2W axial MR image demonstrates a typical ovoid-​shaped white matter plaque in the deep white matter of the right hemisphere. (b) Cervical spine T2 sagittal MR image showing a demyelinating (multiple sclerosis) plaque in the cord with swollen cervical cord and diffuse high signal. The differential is between an inflammatory process and a spinal cord tumour. History will help to clarify.

SECTION 24  Neurological disorders 5810 An inflammatory plaque may be seen in the spinal cord, often in the cervical cord (Fig. 24.3.3.8b), although failure to identify such a lesion does not mean that one is not present. If MS-​type le- sions are also demonstrated in the brain the chance of that patient developing clinical MS within the next 10 years is high, around 80%. The difficulty comes in older patients aged over 45  years, where, increasingly, incidental small white matter lesions may be seen normally in the brain presumably due to age-​related vascular pathology. Neoplasms Primary intracranial tumours The neuroimaging appearances of individual brain tumours are rarely specific. The imaging tumour differential diagnosis takes not only tumour location into account but also patient age. Primary intracranial tumours can be broadly divided into those arising outside the brain (extrinsic, extra-​axial, parasellar, pineal region, cerebellopontine angle, and so on.) and those arising in the cerebral substance (intrinsic, intra-​axial). The range of path- ology of the locations is fundamentally different, as often is the prognosis. Differentiation between intrinsic and extrinsic lesions is usually easier on MRI than on CT because of the multiplanar capability of MRI (Fig. 24.3.3.9). Extrinsic intracranial tumours The most common tumours arising from structures outside the brain are meningiomas and vestibular schwannomas (often called ‘acoustics’) arising from cranial nerve VIII. Both are usually benign and present with symptoms of local pressure: cranial nerve VIII tu- mours can produce sensorineural deafness and/​or sometimes diz- ziness, whereas meningiomas may be incidental, and may cause seizures and/​or a wide variety of deficits according to location. The imaging characteristics of meningiomas and vestibular schwannomas are similar. CT scans usually show a slightly hyperdense mass causing local displacement of cerebral tissue. They generally enhance uniformly after the administration of intravenous contrast, although they may occasionally con- tain areas of low density representing necrosis or occasionally cyst formation within the tumour (Fig. 24.3.3.10a). On MRI, these lesions return a uniform intermediate signal on T1-​ and T2-​weighted sequences and both show intense gadolinium enhancement (Fig. 24.3.3.10b). Intrinsic cerebral tumours Most intrinsic tumours arise from glial cells and are classi- fied as gliomas. There are various types (e.g. astrocytoma, Fig. 24.3.3.9  Axial MRI T2-​weighted image showing typical lesions adjacent to the ventricles and in the white matter. (a) (b) Fig. 24.3.3.10  (a) Enhanced CT scan showing left frontal convexity meningioma. (b) Coronal T1W MR image after intravenous contrast: convexity meningioma showing broad dural origin (different patient).

24.3.3  Imaging in neurological diseases 5811 oligodendroglioma, oligoastrocytoma, ependymoma). The ma- jority are malignant, but low-​grade lesions may appear stable over many years and grow very slowly. They are all mass lesions and most are seen as areas of low density on CT, low signal on T1-​weighted MRI, and high signal on T2-​weighted MRI, with dis- tortion of normal structures. They may show abnormal enhance- ment following intravenous contrast. The presence or absence of haemorrhagic changes, necrosis, calcification, and extent of contrast enhancement will vary among tumours of different but also similar histological type. However, in general, high-​grade tu- mours are more likely to be heterogeneous with foci of necrosis, areas of haemorrhage, heterogeneous contrast enhancement, and oedema (Fig. 24.3.3.11a). Low-​grade tumours are more likely to be homogeneous and without haemorrhage or oedema. MRS (spectroscopy) may enable demonstration of character- istic biochemical patterns in some cerebral tumours, enabling the distinction of more aggressive tumours and differentiating nec- rotic tumours from abscesses, and distinguishing radiation ne- crosis from tumour recurrence. DWI may also help differentiate malignant glioma from abscess and primary cerebral lymphoma. Perfusion MRI may demonstrate foci of neovascularity more typ- ical of malignant tumours. The current role of imaging is primarily not to provide a precise histological diagnosis (that is the role of the neuropathologist) but rather to make the correct diagnosis of a ‘brain tumour’ and differentiate it from other mass lesions: acute or subacute infarcts, focal cortical dysplasias (congenital), abscesses, and inflammatory lesions such as acute MS plaques. This is not al- ways straightforward. Imaging is also important for precise tumour (a) (c) (b) (d) Fig. 24.3.3.11  (a) Contrast-​enhanced CT scan showing a large, deeply situated necrotic mass in the left hemisphere, with considerable enhancement, and appearances typical of a glioblastoma multiforme.
(b) T2-​weighted axial MRI showing diffuse infiltrating necrotic glioblastoma deeply situated in the left hemisphere and extending into the splenium of the corpus callosum; this a typical pattern of spread in this type of tumour. (c) Contrast-​enhanced, axial T1-​weighted MR image of glioblastoma, showing marked irregular contrast enhancement of the margins of the tumour, with lack of central enhancement, reflecting the extensive necrosis that is often a feature of these tumours. (d) Sagittal T1-​weighted image without contrast, showing the marked enlargement of the splenium of the corpus callosum depicted in the same patient.

SECTION 24  Neurological disorders 5812 localization and determination of the relationship to eloquent cortex and, therefore, is necessary for surgical planning and follow-​ up for assessment of surgical resection, radiotherapy, and chemo- therapy treatment. Imaging may also suggest the most appropriate site for biopsy. After brain tumours have been treated with surgery and chemoradiotherapy, it can be difficult to distinguish radiation necrosis from tumour recurrence. Both MRS and perfusion MR may be helpful in these circumstances. Oligodendroglioma These tumours are the most benign of the intrinsic cerebral tu- mours. They often present with seizures rather than neurological deficit. Their radiological hallmark is calcification, best detected on CT. Calcification may be invisible on MRI, but they are also more likely to appear heterogenous. The time course of these tumours may be very long, often evolving over 10–​20 years. Oligodendrogliomas may remain static for long periods (Fig. 24.3.3.12). Posterior fossa tumours Intrinsic posterior fossa tumours are the most common intracranial tumours in children. The most common lesion is a medulloblastoma, which usually arises in the roof of the fourth ventricle and accounts for about 30% of posterior fossa tumours in children. Other tu- mours commonly encountered are ependymomas, and fibrillary and pilocytic astrocytomas, both of which have a better prognosis than medulloblastomas. Medulloblastomas and ependymomas commonly metastasize down the spinal canal, producing what are known as ‘drop metastases’ to the lumbar or sacral region. Other intracranial tumours Colloid cyst This is a very characteristic benign lesion that arises at the foramen of Munro, between the lateral and third ventricles, and presents with obstructive hydrocephalus. Colloid cysts are usually readily detectable on CT and MRI, and although density and signal charac- teristics can vary quite widely, the location is absolutely character- istic (Fig. 24.3.3.13). They never enhance. Pituitary region tumours MRI is the investigation of choice for suspected pituitary/​parasellar lesions. Parasellar tumours, which arise outside the brain itself, are asso- ciated with a characteristic range of pathology. The most common Fig. 24.3.3.12  Axial T2-​weighted MRI showing a diffuse homogenous high-​signal lesion in the frontal lobe with a diffuse mass effect and sulcal effacement. These appearances are typical for a lower-​grade glioma. (a) (b) Fig. 24.3.3.13  (a) CT scan showing typical appearance of a colloid cyst (bright), but can be of any density. The location of this lesion at the foramen of Munro is absolutely characteristic and there is not really a differential diagnosis. (b) Coronal T2W MRI showing colloid cyst in characteristic location at the foramen of Munro at the junction of the lateral and third ventricles.

24.3.3  Imaging in neurological diseases 5813 lesion is a non​functioning pituitary adenoma, followed by hor­ monally active tumours (diagnosed initially not by MRI but by biochemical assay techniques), namely ACTH-​producing tumours (Cushing’s disease), prolactinomas, and growth-​hormone-​secreting tumours (acromegaly). All these have similar imaging character- istics, but their size varies widely: ACTH-​secreting adenomas are usually very small and may not be detectable even on high-​quality MRI. Non​functioning macroadenomas tend to present late, often with visual loss and/​or pituitary failure due to the large size and optic chiasmal compression (Fig. 24.3.3.14). Lesions invading the ­cavernous sinus may result in ophthalmoplegia. Meningiomas may also occur in the parasellar region and appear very similar. Craniopharyngioma This benign tumour arises in the hypothalamic region from rem- nants of Rathke’s cleft, usually in young patients, and presents with visual loss and/​or pituitary failure. The characteristic finding on CT is calcification. There is almost invariably a cystic as well as a solid component to the lesion. Brainstem gliomas These relatively uncommon tumours occur at a relatively young age. However, because of their location there is no prospect of any surgical approach and, if any treatment is appropriate, it is usually radiotherapy. Brainstem gliomas may vary widely in their aggres- siveness, from rapidly progressive lesions to indolent lesions that may remain static for many years. Secondary cerebral tumours These are among the most common intracranial tumours in adults and may be the presenting feature in some patients. Lung, breast, renal, and gastrointestinal tumours, as well as melanomas, metasta- size especially to the brain. Secondary tumours may be solitary or multiple and are fairly characteristic on the imaging, with intracranial masses (solid or cystic) surrounded by oedema and frequently with enhancement after intravenous contrast (Figs. 24.3.3.15 and 24.3.3.16). The dif- ferential diagnosis of multiple ring-​enhancing lesions in the brain is between cerebral metastases, abscesses, and inflammatory lesions. DWI may help to differentiate abscesses, which show decreased diffusion. Malignant meningeal deposits of the central nervous system (CNS) or systemic tumours are relatively uncommon, but they do occur and may be difficult to detect on non-​contrast-​enhanced imaging. MRI with gadolinium enhancement is the most sensitive detection method and is more sensitive than cerebrospinal fluid cytology. Intracranial infections Although intracranial infections are less common in Western coun- tries than tumours, it is vital that they are detected as urgent and (a) (b) Fig. 24.3.3.14  (a) Sagittal T1W MRI of pituitary adenoma with considerable suprasellar extension. (b) Coronal T1W MRI of pituitary adenoma invading the left cavernous sinus. Fig. 24.3.3.15  T1-​weighted enhanced MRI showing two secondary deposits (ring-​enhancing lesions with oedema) in the superior of the right frontal and parietal lobes.

SECTION 24  Neurological disorders 5814 definitive diagnosis and treatment are essential to their effective management. Bacterial infections Bacterial meningitis is the most common bacterial intracranial in- fection. Cranial CT is usually normal in uncomplicated cases but may show meningeal enhancement and/​or mild hydrocephalus. A  patient who is neurologically intact and has a Glasgow Coma Scale score of 15 does not require cranial CT before lumbar punc- ture. Note that mild communicating hydrocephalus is not a contra- indication to lumbar puncture (see next). In a patient with suspected meningitis, cranial CT is important, but antibiotics must not be de- layed by imaging. Cranial CT is often useful in diagnosing some of the compli- cations associated with bacterial meningitis (e.g. hydrocephalus, ventriculitis, cerebral oedema, cerebral abscess, subdural empyema, cerebral infarction, and venous sinus thrombosis). Cerebral abscess Pyogenic brain abscesses are usually single but may be multiple. In the early stage they may not be particularly well defined and begin as an area of cerebritis, which then evolves into an abscess—​a character- istic ring-​enhancing mass surrounded by oedema (Fig. 24.3.3.17). MRI is particularly useful in the specific diagnosis of an abscess and its differentiation from a malignant tumour. Abscesses show de- creased diffusion on DWI and have characteristic MR spectra. If a pyogenic abscess is suspected, then burr-​hole aspiration is mandatory to establish the diagnosis and drain the abscess. Abscesses may be seen at various stages of evolution if associated with a septicaemic illness. The source is either blood spread or direct spread from the infection in the paranasal sinuses or the mastoid. Subdural empyema This is a rare, but important, intracranial infection often caused by spread from a paranasal sinus infection. Pus accumulates in the subdural space, causing a spreading cortical thrombophlebitis. Empyema is usually due to the anaerobic bacterium Streptococcus milleri. Such abscesses are rapidly fatal if they are not treated aggressively with antibiotics and neurosurgical drainage. CT findings are subtle. The most obvious sign may be that of sulcal effacement due to cortical swelling and contrast enhancement may emphasize the thin subdural collection of fluid, which spreads over the brain surface, often alongside the falx. MRI is more sensitive in the detection of the small subdural collec- tions, but it is unnecessary if the diagnosis is clear on CT scans (Fig. 24.3.3.18). The underlying brain appears swollen and tight with the sulci obliterated; it will show moderate meningeal enhancement after intravenous contrast. Tuberculosis This most often manifests as tuberculous meningitis, a basal men- ingitis, and less often as either abscesses or granulomas in the brain. Fig. 24.3.3.16  T1-​weighted axial enhanced MRI showing metastases in the ventricular wall reflecting spread of disease in the subarachnoid space. (a) (b) Fig. 24.3.3.17  (a) T2-​weighted axial MRI showing large brain abscess near the left lateral ventricle—​a cystic lesion with oedema. (b) T1-​weighted axial MRI with contrast showing typical regular enhancement of the capsule of the abscess with surrounding oedema.

24.3.3  Imaging in neurological diseases 5815 If the meninges are involved there is almost invariably a degree of hydrocephalus. The basal meningitis may take a while to evolve on imaging. Viral encephalitis and HIV The most common cerebral viral infection is herpes simplex en- cephalitis (HSE). The imaging findings are often fairly typical, al- though CT scan changes may be very subtle during the early phase. Cranial CT shows a mild swelling with diffuse low density in the anterior and medial temporal lobes and insular cortex, often bi- lateral. MRI is much more sensitive and can be fairly specific (Fig. 24.3.3.19). Later, similar changes are seen in the cingulate gyri. Classically, there is sparing of the basal ganglia. A detailed description of HIV-​related cerebral imaging find- ings is beyond the scope of this textbook. The incidence of HIV encephalitis and the other more commonly associated oppor- tunistic infections has decreased since HAART (highly active retroviral therapy) became available in 1996, with the exception of progressive multifocal leucencephalopathy (PML). HAART has increased the survival of those infected with the JC virus that causes PML. In HIV encephalitis, the white matter is damaged and MR dem- onstrates high signal in the deep white matter bilaterally. There is also volume loss. The white matter changes are optimally demon- strated on MRI and are not well appreciated on CT. Toxoplasmosis produces multiple enhancing solid or cavitating nodules with oedema not distinguishable from other bacterial or fungal infections. Cryptococcal infection causes meningitis and imaging may be normal or enlargement of the perivascular spaces may be seen be- cause this fungus produces a mucoid material. Choroid plexitis sometimes occurs. PML invades oligodendrocytes and causes demyelination, classically in the parieto-​occipital white matter. MRI detects the disease more accurately and earlier, and is the investigation of choice. Dementia imaging This is an area of increasing interest due to the ageing population. The purpose of imaging is twofold; firstly, to identify any intracra- nial pathology that may mimic a dementing illness, and secondly, to assist with distinguishing different neurodegenerative processes that lead to dementia. Some patients present with cognitive impairment without a focal neurological deficit, but have pathology readily identified with imaging. Some examples include a large frontal meningioma, or an infiltrating primary brain tumour, or chronic subdural haematoma, or obstructive hydrocephalus. There are many forms of dementia and, in specialist clinics, imaging is used to help make a diagnosis when clinical features Fig. 24.3.3.18  Left frontal subdural empyema: a contrast-​enhanced axial CT scan showing a collection of fluid in the left frontal subdural
or extradural space in a patient with a large subdural empyema. Note that there is considerable soft-​tissue swelling over the frontal region.
The paranasal sinuses are often the source and show opacification
(not visible on this image). (a) (b) Fig. 24.3.3.19  (a) Axial T2-​weighted MRI of patient with herpes simplex encephalitis (HSE) shows bilateral hippocampal involvement with high T2 signal, much worse on the left, and extending into the anterior part of the temporal lobe. (b) Axial T2-​weighted MRI of patient with HSE showing high T2 signal in the left insular cortex of the temporal lobe.

SECTION 24  Neurological disorders 5816 are uncertain or when treatment options may be radically dif- ferent. Cross-​sectional imaging with CT and MR can be used to identify patterns of volume loss. Alzheimer’s disease may show preferential volume loss in the temporal lobes. Other forms of dementia may show less specific structural change. Radionuclide investigations such as brain perfusion SPECT (single-​photon emission computed tomography), DAT (dopamine active trans- porter), and brain PET (positron emission tomography) can show patterns of alteration in blood flow (in the case of SPECT), glu- cose metabolism (in the case of PET), or dopamine transporters (for DAT). These may be used to distinguish Alzheimer’s disease, frontotemporal dementias, and diffuse cortical Lewy body dis- ease, among others. Hydrocephalus An understanding of hydrocephalus and its two main types is im- portant, knowing whether it is ‘safe to carry out a lumbar puncture’ in a patient or not. ‘Obstructive or non​communicating hydrocephalus’ is the term given to enlargement of the ventricles caused by an obstruction, usually a mass lesion in the cerebrospinal fluid pathways within the brain (i.e. between where the cerebrospinal fluid is produced from the choroid plexus in the lateral ventricles and the out- flow from the fourth ventricle). It is usually caused by a tumour pressing on the ventricles or aqueduct. (Fig. 24.3.3.13a shows a colloid cyst causing obstructive hydrocephalus.) Communicating hydrocephalus If cerebrospinal fluid escapes from the fourth ventricle, but there is disturbance of flow around the basal cisterns or over the cortex, or there is a failure of absorption of cerebrospinal fluid, this is termed ‘communicating hydrocephalus’ or ‘cerebrospinal fluid absorption failure hydrocephalus’. Communicating hydrocephalus occurs most commonly after an SAH or meningitis. It may require temporary ventricular or lumbar drainage. However, because cerebrospinal fluid escapes from the fourth ventricle and circulates round the spinal cerebrospinal fluid spaces, it means that it is safe to perform a lumbar puncture to measure and, if appropriate, lower cerebrospinal fluid pressure. Seizures MRI is the imaging modality of choice in patients presenting with a seizure, and especially so in those with seizures refrac- tory to medication. An MRI scan should optimally be performed within four weeks in a patient presenting with an unprovoked seizure to exclude mass lesions, vascular malformations, strokes, and so on, although the diagnostic pick-​up rate here is low. By contrast, in refractory seizures—​often focal and most often temporal—​the pick-​up rate is much higher, and MRI (particu- larly 3T, providing enhanced signal-​to-​noise ratio and better resolution) is important to diagnose those lesions responsible because surgical excision may either cure the epilepsy or signifi- cantly reduce the frequency of seizures. Hippocampal sclerosis and dysplastic lesions are optimally demonstrated using MR (see Fig. 24.3.3.20). Congenital anomalies and paediatric imaging Any detailed discussion of this subject is beyond the scope of this chapter, and the reader is directed to specialist texts (see also Chapter 24.17). Where available, MRI is the investigation of choice in infants and children presenting with suspected congenital anomalies of the brain. It provides the most information and avoids exposure of young patients to ionizing radiation. The main drawback in this age group is the need for sedation or general anaesthesia. The most common indication for imaging in such patients is developmental delay or seizure disorders. It also plays a vital role in the imaging of a suspected, neonatal, hypoxic ischaemic insult, and in elucidating the cause of cerebral palsy. CT is a reasonable alternative, but cannot be relied on to detect all relevant pathology, particularly in hypoxic ischaemic injury. A wide variety of congenital anomalies is possible, ranging from minor abnormalities of neuronal migration, or localized areas of dysplastic cortex, to major anomalies of the whole brain and encephaloceles, in which there is an associated defect of the skull or spine such as a spina bifida. The most frequent is the Chiari 1 mal- formation of the posterior fossa associated with cerebellar ectopia. The cerebellar tonsils, classically peg-​shaped, extend below the for- amen magnum a distance of at least 5 mm. There may be associated syringomyelia. Summary and possible future developments Modern imaging techniques have revolutionized the diagnosis of neurological disease in the last 30 years. The techniques are likely to become even more sophisticated and accurate with further ex- tension into functional imaging and spectroscopic techniques, both with MR and nuclear medicine’s single-​photon emission CT (SPECT) and PET. The contribution of these techniques to the efficient and effective diagnosis of intracranial and spinal pathology, together with the ability to effectively exclude structural disease, has had a huge im- pact on neurological and neurosurgical clinical practice. In addition, the development of endovascular interventional neuroradiological techniques for the treatment of vascular diseases of the brain Fig. 24.3.3.20  Coronal T2W MR image in a patient with refractory right temporal lobe seizures, demonstrates a small high T2 signal scarred right hippocampus.