Neurological disease



Neurological disease


J.P. Leach


R.J. Davenport



Clinical examination of the nervous system


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Neurology has long been misperceived as a specialty in which intricate clinical examination and numerous investigations are required to diagnose obscure and untreatable conditions. In fact, it requires careful history-taking with a lesser contribution from targeted examination and considered investigation. The development of specific, effective treatments has made accurate diagnosis essential.


The brain, spinal cord and peripheral nerves combine to allow us to perceive and react to the external world, while maintaining a stable internal environment. The brain provides a platform for processing information and forming a response and, in doing so, both forms and is affected by our personality and mental state. Nervous system disorders are common, accounting for around 10% of the UK’s general practice consultations, 20% of acute medical admissions, and most chronic physical disability. While pathological and anatomical localisation is important, skill is required to identify those neurological symptoms not associated with neurological disease, to differentiate patients requiring investigation and treatment from those who need reassurance.


Initially, it is important to exclude conditions that constitute neurological emergencies (Box 26.1). If the presentation is not an emergency, more time can be taken to reach a diagnosis. The history should provide a hypothesis for the site and nature of the potential pathology, which a focused examination may refine and inform what further investigation would be useful. A discussion with the patient about possible interventions and rehabilitation may then take place.



As Stroke has become a specific subspecialty in many centres, it is described in a separate chapter, although it is clearly a neurological condition. This chapter should be read with it, to help clarify how the presentation, diagnosis and management of stroke differ from other conditions.



Functional anatomy and physiology




Cells of the nervous system


The nervous system comprises billions of connections between billions of specialised cells, supplied by a complex network of specialised blood vessels. In addition to neurons, there are three types of glial cells. Astrocytes form the structural framework for neurons and control their biochemical environment. Astrocyte foot processes are intimately associated with blood vessels, forming the blood–brain barrier (Fig. 26.1). Oligodendrocytes are responsible for the formation and maintenance of the myelin sheath, which surrounds axons and is essential for the rapid transmission of action potentials by saltatory conduction. Microglial cells derive from monocytes/macrophages and play a role in fighting infection and removing damaged cells. Peripheral neurons have axons invested in myelin made by Schwann cells. Ependymal cells line the cerebral ventricles.




Generation and transmission of the nervous impulse


The role of the central nervous system (CNS) is to generate outputs in response to external stimuli and changes in internal conditions. Each neuron receives input by synaptic transmission from dendrites (branched projections of other neurons), which may sum to produce output in the form of an action potential. This is conducted down axons, with synaptic transmission to other neurons or, in the motor system, to muscle cells. These processes require the maintenance of an electrochemical gradient across neuron cell membranes by specialised membrane ion channels. Synaptic transmission involves the release of neurotransmitters that modulate the function of the target cell by interacting with structures on the cell surface, including ion channels and other cell surface receptors (Fig. 26.2). At least 20 different neurotransmitters are known to act at different sites in the nervous system, and all are potentially amenable to pharmacological manipulation.



The neuronal cell bodies may receive synaptic input from thousands of other neurons. The synapsing neuron terminals are also subject to feedback regulation via receptor sites on the pre-synaptic membrane, modifying the release of transmitter across the synaptic cleft. In addition to such acute effects, some neurotransmitters produce long-term modulation of metabolic function or gene expression. This effect probably underlies more complex processes in, for example, long-term memory.



Functional anatomy of the nervous system


Major components of the nervous system and their interrelationships are depicted in Figure 26.3.




Cerebral hemispheres


The cerebral hemispheres coordinate the highest level of nervous function, the anterior half dealing with executive (‘doing’) functions and the posterior half constructing a perception of the environment. Each cerebral hemisphere has four functionally specialised lobes (Fig. 26.4 and Box 26.2), but some functions are lateralised, and this depends on cerebral dominance (i.e. the hemisphere in which language is represented). Cerebral dominance aligns limb dominance with language function: in right-handed individuals the left hemisphere is almost always dominant, while around half of left-handers have a dominant right hemisphere.



image 26.2   Cortical lobar functions


















































Lobe Function Effects of damage
Cognitive/behavioural Associated physical signs Positive phenomena
Frontal Personality
Emotional control
Social behaviour
Contralateral motor control
Language
Micturition
Disinhibition
Lack of initiation
Antisocial behaviour
Impaired memory
Expressive dysphasia
Incontinence
Impaired smell
Contralateral hemiparesis
Frontal release signs1
Seizures – often nocturnal with motor activity
Versive head movements
Parietal: dominant Language
Calculation
Dysphasia
Acalculia
Dyslexia
Apraxia3
Agnosia5
Contralateral hemisensory loss
Astereognosis2
Agraphaesthesia4
Contralateral homonymous lower quadrantanopia
Asymmetry of optokinetic nystagmus (OKN)
Focal sensory seizures
Parietal: non-dominant Spatial orientation
Constructional skills
Neglect of contralateral side
Spatial disorientation
Constructional apraxia
Dressing apraxia
Contralateral hemisensory loss
Astereognosis2
Agraphaesthesia4
Contralateral homonymous lower quadrantanopia
Asymmetry of OKN
Focal sensory seizures
Temporal: dominant Auditory perception
Language
Verbal memory
Smell
Balance
Receptive aphasia
Dyslexia
Impaired verbal memory
Contralateral homonymous lower quadrantanopia Complex hallucinations (smell, sound, vision, memory)
Temporal: non-dominant Auditory perception
Melody/pitch perception
Non-verbal memory
Smell
Balance
Impaired non-verbal memory
Impaired musical skills (tonal perception)
Contralateral homonymous upper quadrantanopia Complex hallucinations (smell, sound, vision, memory)
Occipital Visual processing Visual inattention
Visual loss
Visual agnosia
Homonymous hemianopia (macular sparing) Simple visual hallucinations (e.g. phosphenes, zigzag lines)


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1Grasp reflex, palmomental response, pout response.


2Inability to determine three-dimensional shape by touch.


3Inability to perform complex movements in the presence of normal motor, sensory and cerebellar function.


4Inability to ‘read’ numbers or letters drawn on hand, with the eyes shut.


5Inability to recognise familiar objects, e.g. faces.




The frontal lobes are concerned with executive function, movement, behaviour and planning. In addition to the primary and supplementary motor cortex, there are specialised areas for the control of eye movements, speech (Broca’s area) and micturition.


The parietal lobes integrate sensory perception. The primary sensory cortex lies in the post-central gyrus of the parietal lobe. Much of the remainder is devoted to ‘association’ cortex, which processes and interprets input from the various sensory modalities. The supramarginal and angular gyri of the dominant parietal lobe form part of the language area (p. 1169). Close to these are regions dealing with numerical function. The non-dominant parietal lobe is concerned with spatial awareness and orientation.


The temporal lobes contain the primary auditory cortex and primary vestibular cortex. On the inner medial sides lie the olfactory cortex and the parahippocampal cortex, which is involved in memory function. The temporal lobes also contain much of the limbic system, including the hippocampus and the amygdala, which are involved in memory and emotional processing. The dominant temporal lobe also participates in language functions, particularly verbal comprehension (Wernicke’s area). Musical processing occurs across both temporal lobes, rhythm on the dominant side and melody/pitch on the non-dominant.


The occipital lobes are responsible for visual interpretation. The contralateral visual hemifield is represented in each primary visual cortex, with surrounding areas processing specific visual submodalities such as colour, movement or depth, and the analysis of more complex visual patterns such as faces.


Deep to the grey matter in the cortices, and the white matter (composed of neuronal axons), are collections of cells known as the basal ganglia that are concerned with motor control; the thalamus, which is responsible for the level of attention to sensory perception; the limbic system, concerned with emotion and memory; and the hypothalamus, responsible for homeostasis, such as temperature and appetite control. The cerebral ventricles contain cerebrospinal fluid (CSF), which cushions the brain during cranial movement.


CSF is formed in the lateral ventricles and protects and nourishes the CNS. The CSF flows from third to fourth ventricles and through foramina in the brainstem to dissipate over the surface of the CNS, eventually being reabsorbed into the cerebral venous system (see Fig. 26.41, p. 1217).









The motor system


A programme of movement formulated by the pre-motor cortex is converted into a series of signals in the motor cortex that are transmitted to the spinal cord in the pyramidal tract (Fig. 26.6). This passes through the internal capsule and the ventral brainstem before decussating in the medulla to enter the lateral columns of the spinal cord. The pyramidal tract ‘upper motor neurons’ synapse with the anterior horn cells of the spinal cord grey matter, which form the lower motor neurons.



Any movement necessitates changes in posture and muscle tone, sometimes in quite separate muscle groups to those involved in the actual movement. The motor system consists of a hierarchy of controls that maintain body posture and muscle tone, on which any movement is superimposed. In the grey matter of the spinal cord, the lowest order of the motor hierarchy controls reflex responses to stretch. Muscle spindles sense lengthening of the muscle; they provide the afferent side of the stretch reflex and initiate a monosynaptic reflex leading to protective or reactive muscle contraction. Inputs from the brainstem are largely inhibitory. Polysynaptic connections in the spinal cord grey matter control more complex reflex actions of flexion and extension of the limbs that form the basic building blocks of coordinated actions, but complete control requires input from the extrapyramidal system and the cerebellum.



Lower motor neurons

Lower motor neurons in the anterior horn of the spinal cord innervate a group of muscle fibres termed a ‘motor unit’. Loss of lower motor neurons causes loss of contraction within this unit, resulting in weakness and reduced muscle tone. Subsequently, denervated muscle fibres atrophy, causing muscle wasting, and depolarise spontaneously, causing ‘fibrillations’. Except in the tongue, these are usually only perceptible on electromyelography (EMG; p. 1152). With the passage of time, neighbouring intact neurons sprout to provide re-innervation, but the neuromuscular junctions of the enlarged motor units are unstable and depolarise spontaneously, causing fasciculations (which are large enough to be visible to the naked eye). Fasciculations therefore imply chronic partial denervation with re-innervation.



Upper motor neurons

Upper motor neurons have both inhibitory and excitatory influence on the function of anterior horn motor neurons. Lesions affecting the upper motor neuron result in increased tone, most evident in the strongest muscle groups (i.e. the extensors of the lower limbs and the flexors of the upper limbs). The weakness of upper motor neuron lesions is conversely more pronounced in the opposing muscle groups. Loss of inhibition will also lead to brisk reflexes and enhanced reflex patterns of movement, such as flexion withdrawal to noxious stimuli and spasms of extension. The increased tone is more apparent during rapid stretching (‘spastic catch’), but may suddenly give way with sustained tension (the ‘clasp-knife’ phenomenon). More primitive reflexes are also released, manifest as extensor plantar responses. Spasticity may not be present until some weeks after the onset of an upper motor neuron lesion. Chronic spasticity in a patient with a spinal cord lesion may also be exacerbated by increased sensory input – for example, from a pressure sore or urinary tract infection.




The cerebellum


The cerebellum fine-tunes and coordinates movements initiated by the motor cortex. It also participates in the planning and learning of skilled movements through reciprocal connections with the thalamus and cortex, and in articulation of speech. A lesion in a cerebellar hemisphere causes lack of coordination on the same side of the body. Cerebellar dysfunction impairs the smoothness of eye movements, causing nystagmus and renders speech dysarthric. In the limbs, the initial movement is normal, but as the target is approached, the accuracy of the movement deteriorates, producing an ‘intention tremor’. The distances of targets are misjudged (dysmetria), resulting in ‘past-pointing’. The ability to produce rapid, accurate, regularly alternating movements is also impaired (dysdiadochokinesis). The central vermis of the cerebellum is concerned with the coordination of gait and posture. Disorders of this therefore produce a characteristic ataxic gait (see below).



Vision


The neurological organisation of visual pathways is shown in Figure 26.7. Fibres from ganglion cells in the retina pass to the optic disc and then backwards through the lamina cribrosa to the optic nerve. Nasal optic nerve fibres (subserving the temporal visual field) cross at the chiasm, but temporal fibres do not. Hence, fibres in each optic tract and further posteriorly carry representation of contralateral visual space. From the lateral geniculate nucleus, lower fibres pass through the temporal lobes on their way to the primary visual area in the occipital cortex, while the upper fibres pass through the parietal lobe.



Normally, the eyes move conjugately (in unison), though horizontal convergence allows visual fusion of objects at different distances. The control of eye movements begins in the cerebral hemispheres, particularly within the frontal eye fields, and the pathway then descends to the brainstem with input from the visual cortex, superior colliculus and cerebellum. Horizontal and vertical gaze centres in the pons and mid-brain, respectively, coordinate output to the ocular motor nerve nuclei (3, 4 and 6), which are connected to each other by the medial longitudinal fasciculus (MLF) (Fig. 26.8). The MLF is particularly important in coordinating horizontal movements of the eyes. The extraocular muscles are then supplied by the oculomotor (3rd), trochlear (4th) and abducens (6th) cranial nerves.



The pupillary response to light is due to a combination of parasympathetic and sympathetic activity. Parasympathetic fibres originate in the Edinger–Westphal subnucleus of the 3rd nerve, and pass with the 3rd nerve to synapse in the ciliary ganglion before supplying the constrictor pupillae of the iris. Sympathetic fibres originate in the hypothalamus, pass down the brainstem and cervical spinal cord to emerge at T1, return up to the eye in association with the internal carotid artery, and supply the dilator pupillae.



Speech


Much of the cerebral cortex is involved in the process of forming and interpreting communicating sounds, especially in the dominant hemisphere (see Box 26.2, p. 1142). Decoding of speech sounds (phonemes) is carried out in the upper part of the posterior temporal lobe. The attribution of meaning, as well as the formulation of the language required for the expression of ideas and concepts, occurs predominantly in the lower parts of the anterior parietal lobe (the angular and supramarginal gyri). The temporal speech comprehension region is referred to as Wernicke’s area (Fig. 26.9). Other parts of the temporal lobe contribute to verbal memory, where lexicons of meaningful words are ‘stored’. Parts of the non-dominant parietal lobe appear to contribute to non-verbal aspects of language in recognising meaningful intonation patterns (prosody).



The frontal language area is in the posterior end of the dominant inferior frontal gyrus known as Broca’s area. This receives input from the temporal and parietal lobes via the arcuate fasciculus. The motor commands generated in Broca’s area pass to the cranial nerve nuclei in the pons and medulla, as well as to the anterior horn cells in the spinal cord. Nerve impulses to the lips, tongue, palate, pharynx, larynx and respiratory muscles result in the series of ordered sounds recognised as speech. The cerebellum also plays an important role in coordinating speech, and lesions of the cerebellum lead to dysarthria, where the problem lies in motor articulation of speech.



The somatosensory system


Sensory information from the limbs ascends the nervous system in two anatomically discrete systems (Fig. 26.10). Fibres from proprioceptive organs and those mediating well-localised touch (including vibration) enter the spinal cord at the posterior horn and pass without synapsing into the ipsilateral posterior columns. Neural fibres conveying pain and temperature sensory information (nociceptive neurons) synapse with second-order neurons that cross the midline in the spinal cord before ascending in the contralateral anterolateral spinothalamic tract to the brainstem.



The second-order neurons of the dorsal column sensory system cross the midline in the upper medulla to ascend through the brainstem. Here they lie just medial to the (already crossed) spinothalamic pathway. Brainstem lesions can therefore cause sensory loss affecting all modalities of the contralateral side of the body. Sensory loss on the face due to brainstem lesions is dependent on the anatomy of the trigeminal fibres within the brainstem. Fibres from the back of the face (near the ears) descend within the brainstem to the upper part of the spinal cord before synapsing, the second-order neurons crossing the midline and then ascending with the spinothalamic fibres. Fibres conveying sensation from progressively more forward areas of the face descend a shorter distance in the brainstem. Thus, sensory loss in the face from low brainstem lesions is in a ‘balaclava helmet’ distribution, as the longer descending trigeminal fibres are affected. Both the dorsal column and spinothalamic tracts end in the thalamus, relaying from there to the parietal cortex.



Pain

Pain is a complex percept that is only partly related to activity in nociceptor neurons (Fig. 26.11). In the posterior horn of the spinal cord, the second-order neuron of the spinothalamic tract is affected by a number of influences in addition to its synapse with the fibres from nociceptors. Branches from the larger mechanoceptor fibres destined for the posterior column also synapse with the second-order spinothalamic neurons and with interneurons of the grey matter of the posterior horn. The nociceptor neurons release neurotransmitters (such as substance P), in addition to excitatory transmitters, which influence the excitability of the spinothalamic neurons. Activity in the posterior horn neurons is modulated by fibres descending from the peri-aqueductal grey matter of the mid-brain and raphe nuclei of the medulla. Neurons of this ‘descending analgesia system’ are activated by endogenous opiate (endorphin) peptides. The spinal cord’s posterior horn is therefore much more than a relay station in pain transmission; its complexity allows it to ‘gate’ and modulate painful sensation before it ascends in the spinothalamic tract. In the diencephalon, the perception of pain is further influenced by the rich interconnections of the thalamus with the limbic system.




Sphincter control

The sympathetic supply to the bladder leaves from T11–L2 to synapse in the inferior hypogastric plexus, while the parasympathetic supply leaves from S2–4. In addition, a somatic supply to the external (voluntary) sphincter arises from S2–4, travelling via the pudendal nerves.


Storage of urine is maintained by inhibiting parasympathetic activity and thus relaxing the detrusor muscle of the bladder wall. Continence is maintained by simultaneous sympathetic and somatic (via the pudendal nerve) mediated tonic contraction of the urethral sphincters. Voiding is usually under conscious control, and triggered by relaxation of tonic inhibition on the pontine micturition centre from higher centres, leading to relaxation of the pelvic floor muscles and external and internal urethral sphincters, along with parasympathetic-mediated detrusor contraction.




Sleep


The function of sleep is unknown but it is required for good health. Sleep is controlled by the reticular activating system in the upper brainstem and diencephalon. It is composed of different stages that can be visualised on electroencephalography (EEG). As drowsiness occurs, normal EEG background alpha rhythm disappears and activity becomes dominated by deepening slow-wave activity. As sleep deepens and dreaming begins, the limbs become flaccid, movements are ‘blocked’ and EEG signs of rapid eye movements (REM) are superimposed on the slow wave. REM sleep persists for a short spell before another slow-wave spell starts, the cycle repeating several times throughout the night. REM periods become longer as the sleep period progresses. REM sleep seems to be the most important part of the sleep cycle for refreshing cognitive processes, and REM sleep deprivation causes tiredness, irritability and impaired judgement.



Localising lesions in the brainstem


After taking a history and examining the patient, the clinician should have an idea of the nature and site of any pathology. Given the density of tracts and nuclei in the brainstem (see Fig. 26.5), detailed localisation may be possible on the basis of history and examination alone, to be confirmed or refuted by investigation.


Brainstem lesions typically present with symptoms due to cranial nerve, cerebellar and upper motor neuron dysfunction and are most commonly caused by vascular disease. Since the anatomy of the brainstem is very precisely organised, it is usually possible to localise the site of a lesion on the basis of careful history and examination in order to determine exactly which tracts/nuclei are affected, usually invoking the fewest number of lesions.


For example, in a patient presenting with sudden onset of upper motor neuron features affecting the right face, arm and leg in association with a left 3rd nerve palsy, the lesion will be in the left cerebral peduncle in the brainstem and the pathology is likely to have been a small stroke, as the onset was sudden. This combination of signs is known as Weber’s syndrome, and is one of several well-described brainstem syndromes, which are listed in Box 26.3. The effects of individual cranial nerve deficits are discussed in the sections on eye movements (p. 1169) and on facial weakness, sensory loss in brainstem lesions, dysphonia and dysarthria, and bulbar symptoms (pp. 1163, 1165, 1168 and 1173).




Investigation of neurological disease


Experienced clinicians will make around 90% of neurological diagnoses on history alone, with a lesser contribution from examination and investigation. As investigations become more complex and more easily available, it is tempting to adopt a ‘scan first, think later’ approach to neurology. The frequency of ‘false-positive’ results, the wide range of normality and the unnecessary expense, inconvenience and worry caused to patients should encourage a more thoughtful approach. Investigation may include assessment of structure (imaging) and function (neurophysiology). Neurophysiological testing has become so complex that in many countries it constitutes a separate specialty focusing on electroencephalography, evoked potentials, nerve conduction studies and electromyography.



Neuroimaging


Neurological imaging has traditionally allowed assessment of structure only. Various techniques are available, including X-rays (plain X-rays, computed tomography (CT), CT angiography, myelography and angiography), magnetic resonance (MR imaging (MRI), MR angiography (MRA)) and ultrasound (Doppler imaging of blood vessels). The uses and limitations of each of these are shown in Box 26.4.



It is now possible to use imaging techniques to assess CNS function. Single photon emission clinical tomography (SPECT) scanning can use the lipid-soluble properties of radioactive tracers to mark cerebral blood flow at the time of injection. This can be useful in investigating dementia or epilepsy. SPECT can also be used in the diagnosis of movement disorders: for example, by examining dopamine activity to assess the function of the basal ganglia in patients with possible parkinsonism.


Functional MRI (fMRI) can be used to assess blood flow during specific tasks (e.g. speaking, remembering, calculation), which can provide ‘maps’ of cortical function that are accurate enough to help plan lesionectomy and epilepsy surgery. Similarly, MR spectroscopy is being developed to identify the chemical composition of specific regions, providing clues as to whether lesions are ischaemic, neoplastic or inflammatory.



Head and orbit


Plain skull X-rays are now largely restricted to the diagnosis of fractures and sinus disease. CT or MRI is needed for intracranial imaging. CT will show bone and calcification well, and will easily image collections of blood. It will also detect abnormalities of the brain and ventricles, such as atrophy, tumours, cysts, abscesses, vascular lesions and hydrocephalus. Diagnostic yield is often improved by the use of intravenous contrast and thinner slicing using spiral CT. Surrounding bone structures render posterior fossa CT images less useful, and CT is less sensitive to white matter changes than MRI.


MRI resolution is unaffected by bone and so is more useful in the investigation of posterior fossa disease. Its sensitivity to cortical and white matter changes makes it effective in picking up inflammatory conditions such as multiple sclerosis, and in investigating epilepsy. Different MRI techniques will increase sensitivity to acute ischaemic stroke and may allow detection of abnormalities by filtering signals from other tissues (e.g. adipose tissues in the orbits).


Examples of brain imaged by the various techniques are shown in Figure 26.12.




Cervical, thoracic and lumbar spine


Plain X-rays are useful in the investigation of trauma to vertebrae, but their value in providing information about non-bony tissues is limited, which makes them far less helpful in the assessment of inflammatory and degenerative conditions of the spine. MRI has transformed the investigation of these areas, since it can give information not only about the vertebrae and intervertebral discs, but also about their effects on the spinal cord and nerve roots. Myelography is an invasive technique involving injection of contrast into the lumbar theca. While the outline of the nerve roots and spinal cord provides information about abnormal structure, the accuracy and wide availability of MRI have reduced the need for this. Myelography may still be used for technical reasons or where MRI is unavailable, contraindicated, or precluded by the patient’s claustrophobia. Examples of the cervical spine imaged by plain X-rays, myelography and MRI are shown in Figure 26.13.





Neurophysiological testing


Electroencephalography


The electroencephalogram (EEG) is used to detect electrical activity arising in the cerebral cortex. The EEG involves placing electrodes on the scalp to record the amplitude and frequency of the resulting waveforms. With closed eyes, the normal background activity is 8–13 Hz (known as alpha rhythm), most prominent occipitally and suppressed on eye opening. Other frequency bands seen over different parts of the brain in different circumstances are beta (faster than 13/s), theta (4–8/s) and delta (slower than 4/s). Normal EEG changes evolve with age and with alertness; lower frequencies predominate in the very young and during sleep.


In recent years, digital technology has allowed longer, cleaner EEG recordings that can be analysed in a number of ways and recorded alongside contemporaneous video of any clinical ‘event’. Meanwhile, the development of intracranial recording allows more sensitive monitoring via surgically placed electrodes in and around lesions to help increase the efficacy and improve the safety of epilepsy surgery.


Abnormalities in the EEG result from a number of conditions. Examples include an increase in fast frequencies (beta) seen with sedating drugs such as benzodiazepines, or marked focal slowing noted over a structural lesion such as a tumour or an infarct. Improved quality and accessibility of imaging have made EEG redundant in lesion localisation, except in the specialist investigation of epilepsy (p. 1182). EEG remains useful in progressive and continuous disorders such as reduced consciousness (p. 1159), in encephalitis (p. 1205), and in certain dementias such as Creutzfeldt–Jakob disease (p. 1211).


Since sleep induces marked changes in cerebral activity, EEG can be useful in characterising those conditions where sleep patterns are disturbed. In paroxysmal disorders such as epilepsy, EEG is at its most useful when it captures activity during one of the events in question. Up to 5% of some normal populations may demonstrate epileptiform discharges on EEG which prevent its use as a screening test for epilepsy. Over 50% of patients with proven epilepsy will have a normal ‘routine’ EEG, and, conversely, the presence of epileptiform features does not of itself make a diagnosis (most notably in younger patients with a family history of epilepsy). In view of this, the EEG should not be used where epilepsy is merely ‘suspected’.


The EEG in epilepsy is predominantly used in its classification and prognosis, and in some patients to localise the seat of epileptiform discharges when surgery is being considered. During an epileptic seizure, high-voltage disturbances of background activity (‘discharges’) will often be noted. These may be generalised, as in the 3-Hz ‘spike and wave’ of childhood absence epilepsy, or more focal, as in localisation-related epilepsies (Fig. 26.14). Techniques such as hyperventilation or photic stimulation can be used to increase the yield of epileptiform changes, particularly in the generalised epilepsy syndromes. While some argue that it is possible to detect ‘spikes’ and ‘sharp waves’ to lend support to a clinical diagnosis, these are non-specific and therefore not diagnostic.




Nerve conduction studies


Electrical stimulation of a nerve causes an impulse to travel both efferently and afferently along the underlying axons. Nerve conduction studies (NCS) make use of this, recording action potentials as they pass along peripheral nerves and (with motor nerves) as they pass into the muscle belly. Digital recording has enhanced sensitivity and reproducibility of these tiny potentials. By measuring the time taken to traverse a known distance, it is possible to calculate nerve conduction velocities (NCVs). Healthy nerves at room temperature will conduct at a speed of 40–50 m/s. If the recorded potential is smaller than expected, this provides evidence of a reduction in the overall number of functioning axons. Significant slowing of conduction velocity, in contrast, suggests impaired saltatory conduction due to peripheral nerve demyelination. Such changes in NCS may be diffuse (as in a hereditary demyelinating peripheral neuropathy, p. 1223), focal (as in pressure palsies, p. 1224) or multifocal (e.g. Guillain–Barré syndrome, p. 1224; mononeuritis multiplex, p. 1224). The information gained can allow the disease responsible for peripheral nerve dysfunction to be better deduced (see Box 26.99, p. 1223).


Stimulation of motor nerves allows for the recording of compound muscle action potentials (CMAPs) over muscles (Fig. 26.15). These are around 500 times larger than sensory nerve potentials, typically around 1–20 millivolts. Since a proportion of stimulated impulses in motor nerves will ‘reflect’ back to the anterior horn cell body (forming the ‘F’ wave), it is also possible to obtain some information about the condition of nerve roots.



Repetitive nerve stimulation (RNS) at 3–15/s provides consistent CMAPs in healthy muscle. In myasthenia gravis (p. 1226), where there is partial blockage of acetylcholine receptors, however, there is a diagnostic fall (decrement) in CMAP amplitude. In contrast, an increasing CMAP with high-frequency RNS is seen in Lambert–Eaton myasthenic syndrome (p. 1227).



Electromyography


Electromyography (EMG) is usually performed with NCS, and involves needle recording of muscle electrical potential during rest and contraction. At rest, muscle is electrically silent but loss of nerve supply causes muscle membrane to become unstable, manifest as fibrillations, positive sharp waves (‘spontaneous activity’) or fasciculations. During muscle contraction, motor unit action potentials are recorded. Axonal loss or destruction will result in fewer motor units. Resultant sprouting of remaining units will lead to increasing size of each individual unit on EMG. Myopathy, in contrast, will cause muscle fibre splitting, which will result in a large number of smaller units on EMG. Other abnormal activity, such as myotonic discharges, may signify abnormal ion channel conduction, as in myotonic dystrophy or myotonia congenita.


Specialised single fibre EMG (SFEMG) can be used to investigate neuromuscular junction transmission. Measuring ‘jitter’ and ‘blocking’ can identify the effect of antibodies in reducing the action of acetylcholine on the receptor.



Evoked potentials


The cortical response to visual, auditory or electrical stimulation can be measured on an EEG as an evoked potential (EP). If a stimulus is provided – for example, to the eye – the tiny EEG response can be discerned when averaging 100–1000 repeated stimuli. Assessing the latency (the time delay) and amplitude can give information about the integrity of the relevant pathway. MRI now provides more information about CNS pathways, thus reducing reliance on EPs. In practice, visual evoked potentials (VEPs) are most commonly used to help differentiate CNS demyelination from small-vessel white-matter changes (Fig. 26.16).


Apr 9, 2017 | Posted by in GENERAL SURGERY | Comments Off on Neurological disease
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