Chapter 22 Neurological disease
Neurology is a large and diverse subject which covers many conditions that require long-term coordinated care and have serious effects on the daily lives of patients and their families. Neurology includes conditions as diverse as cognitive disorders involving higher level mental functioning through to disorders of peripheral nerve and skeletal muscle. It is a specialty requiring good clinical skills and examination technique which cannot be replaced with investigations or imaging techniques alone (Table 22.1).
|Conditions||Events per 100 000/year|
Shingles (herpes zoster) and postherpetic neuralgia
Diabetic and other neuropathies
Severe brain injury and subdural haematoma
All CNS tumours
Presenile dementia (below 65 years)
Myasthenia, all muscle and motor neurone disease
Pattern recognition in neurology – interpretation of history, symptoms and examination – is very reliable. Practical experience is vital. There are three critical questions in formulating a clinical diagnosis:
Common gait abnormalities
Spasticity (p. 1082), more pronounced in extensor muscles, with or without weakness, causes stiff and jerky walking. Toes of shoes become scuffed, catching level ground. Pace shortens; a narrow base is maintained. Clonus – involuntary extensor rhythmic leg jerking – may occur.
There is muscular rigidity (p. 1118) throughout extensors and flexors. Power is preserved; the pace shortens, and slows to a shuffle; its base remains narrow. A stoop and diminished arm swinging become apparent. Gait becomes festinant (hurried) with short rapid steps. There is difficulty turning quickly and initiating movement, sometimes with falls. Retropulsion means small backward steps, taken involuntarily when a patient is halted.
In lateral cerebellar lobe disease (p. 1083) stance becomes broad-based, unstable and tremulous. Ataxia describes this incoordination. When walking, the person tends to veer to the side of the affected cerebellar lobe.
Peripheral sensory lesions (e.g. polyneuropathy, p. 1145) cause ataxia because of loss of proprioception (position sense). Broad-based, high-stepping, stamping gait develops. This form of ataxia is exacerbated by removal of sensory input (e.g. vision) and worse in the dark. Romberg’s test, first described in sensory ataxia of tabes dorsalis (p. 1129), becomes positive.
When weakness is distal, each foot must be lifted over obstacles. When ankle dorsiflexors are weak, e.g. in a common peroneal nerve palsy (p. 1144), the sole returns to the ground with an audible slap.
With frontal lobe disease (e.g. tumour, hydrocephalus, infarction), acquired walking skills become disorganized. Leg movement is normal when sitting or lying but initiation and organization of walking fail. Shuffling small steps (marche à petits pas), gait ignition failure or undue hesitancy may predominate. Urinary incontinence and dementia are often present.
Falls in the elderly are a major cause of hospital admission, e.g. following fractures. Often no precise cause can be found. A multidisciplinary approach is essential, e.g. reviewing risk factors such as rugs, stairs, footwear and home circumstances.
Dizziness covers many complaints, from a vague feeling of unsteadiness to severe, acute vertigo. It is frequently used to describe light-headedness, panic, anxiety, palpitations and chronic ill-health. The real nature of this symptom must be determined.
Vertigo (p. 1078) means the illusion of movement, a sensation of rotation or tipping. The patient feels the surroundings are spinning or moving. This is distressing and often accompanied by nausea or vomiting.
Blackout, like dizziness, is simply descriptive, implying either altered consciousness, visual disturbance or falling. Epilepsy (p. 1112) and syncope are mentioned in detail (p. 1116); hypoglycaemia and anaemia must be considered. Commonly no sinister cause is found. A careful history is essential.
Following a short or detailed examination, relevant findings are summarized in a brief formulation – the basis for investigation, transfer of information and management (Practical Boxes 22.1, 22.2 and Table 22.2).
Practical Box 22.1
Five-part short neurological examination
Practical Box 22.2
10-part neurological examination
Active movement against gravity and resistance
Active movement against gravity
Active movement with gravity eliminated
Flicker of contraction
The neurone is the functional unit of the entire nervous system (Fig. 22.1). Its cell body and axon terminate in a synapse. Size and type of each group of neurones vary. A thoracic spinal cord α-motor neurone has an axonal length of >1 metre and innervates between several hundred and 2000 muscle fibres in one leg – a motor unit. By contrast, some spinal or intracerebral interneurones have axons under 100 µm long, terminating on one neuronal cell body.
Figure 22.1 The functional unit: neurone and neurotransmitters. (a) The action potential, i.e. nerve impulse, travels down the axon. Microtubules carry neurotransmitters to nerve endings. (b) Action potential I depolarizes the synaptic membrane, opening voltage-gated calcium channels. (c) Influx of calcium ions cause vesicles to fuse with the membrane allowing neurotransmitter binding to receptors (i) and activation of secondary messengers that modulate gene transcription and also open ligand-gated channels (ii). This allows ions to enter, depolarize the membrane and initiate action potential II.
Neurotransmitters are excitatory (acetylcholine, noradrenaline, adrenaline, 5-hydroxytryptamine, dopamine, glutamate and aspartate) or inhibitory (γ-aminobutyric acid (GABA), histamine and glycine). Neuropeptides, e.g. vasopressin, ACTH, substance P and opioid peptides, as well as the purines (ATP and AMP) are both excitatory and inhibitory.
Synaptic transmission is mediated by neurotransmitters released by action potentials passing down an axon. Neurotransmitters activate postsynaptic receptors and are removed by transporter proteins. The neurotransmitter-receptor reaction increases ionic permeability and propagates a further action potential. Axonal electrical activity and synaptic chemical release is the basis of neurological function.
This subject causes unnecessary difficulty. Work on neuronal networks, functional imaging and plasticity questions the traditional views of highly specific localization of cortical function. The following paragraphs summarize areas of clinical relevance.
The concept of cerebral dominance arose from a simple observation: right-handed stroke patients with acquired language disorders had destructive lesions within the left hemisphere. Right-handed (and 70% of left-handed) people have language function on the left.
Damage in the left frontal lobe causes reduced speech fluency with relatively preserved comprehension. The patient makes great efforts to initiate language, which becomes reduced to a few disjointed words with failure to construct sentences. Patients who recover say they knew what they wanted to say, but could not get the words out.
Left temporo-parietal damage leaves fluency of language but words are muddled. This varies from insertion of a few incorrect or non-existent words into speech to a profuse outpouring of jargon (i.e. rubbish with wholly non-existent words). Severe jargon aphasia is bizarre and often mistaken for psychotic behaviour.
Patients who recover from Wernicke’s aphasia say that they found speech, both their own and others’, like an unintelligible foreign language, i.e. incomprehensible, but they could neither stop speaking nor understand speech.
This means the combination of the expressive problems of Broca’s aphasia and the loss of comprehension of Wernicke’s with loss of both language production and understanding. This is due to widespread damage to speech areas and is the commonest aphasia after a severe left hemisphere infarct. Writing and reading are also affected.
Dysarthria is disordered articulation – slurred speech. Language is intact. Paralysis, slowing or incoordination of muscles of articulation or local discomfort causes various patterns of dysarthria. Examples are the gravelly speech of pseudobulbar palsy (p. 1080), the jerky, ataxic speech of cerebellar lesions, the monotone of Parkinson’s, and speech in myasthenia that fatigues and dies away. Many aphasic patients are also dysarthric.
Disorders in right-handed patients with right hemisphere lesions are often difficult to recognize. There are abnormalities of perception of internal and external space. Examples are losing the way in familiar surroundings, failing to put on clothing correctly (dressing apraxia), or failure to draw simple shapes – constructional apraxia.
Disorders of memory follow damage to the medial surfaces of both temporal lobes and their brainstem connections – the hippocampi, fornices and mammillary bodies. Bilateral lesions are necessary to cause amnesia. In all organic memory disorders recent events are recalled poorly, in contrast to the relative preservation of distant memories.
Causes of an amnestic syndrome
This sensory nerve arises from olfactory (smell) receptors within nasal mucosa. Branches pierce the cribriform plate and synapse in the olfactory bulb. The olfactory tract passes to the olfactory cortex.
|Number||Name||Main clinical action|
Vision, fields, afferent light reflex
Eyelid elevation, eye elevation, ADduction, depression in ABduction, efferent (pupil)
Eye intorsion, depression in ADduction
Facial (and corneal) sensation, mastication muscles
Facial movement, taste fibres
Balance and hearing
Sensation – soft palate, taste fibres
Cough, palatal and vocal cord movements
Head turning, shoulder shrugging
Anosmia (loss of sense of smell) is caused by head injury (shearing of olfactory neurones as they pass through the cribriform plate at the skull base) or tumours of the olfactory groove (e.g. meningioma). Olfaction is temporarily (occasionally permanently) lost or diminished after upper respiratory infections and with local disorders of the nose. Many patients with gradual onset anosmia over many years may be unaware of the deficit, e.g. in Parkinson’s disease where anosmia precedes motor symptoms by many years but is often not noticed by the patient.
Detailed smell testing is difficult in routine clinical practice and rarely performed. Adequate testing requires use of commercially available kits such as scratch and sniff cards or odour filled pens with forced multiple choice identification.
Light regulated by the pupillary aperture is converted into action potentials by retinal rod, cone and ganglion cells (see page 1055). The lens, under control of the ciliary muscle, produces the image (inverted) on the retina. Axons in the optic nerve (1) decussate at the optic chiasm (2), fibres from the nasal retina cross and join with uncrossed fibres originating in the temporal retina to form the optic tract (3). Each optic tract thus carries information from the contralateral visual hemifield.
Figure 22.4 The visual pathway. 1. Mononuclear field loss – complete optic nerve lesion. 2. Bitemporal hemianopia – chiasmal lesion. 3. Homonymous hemianopia – optic tract lesion. 4. Homonymous quadrantanopia – temporal lesion. 5. Homonymous quadrantanopia – parietal lesion. 6. Homonymous hemianopia with macular sparing – occipital cortex or optic radiation. 7. Homonymous hemianopia (hemiscotoma) – occipital pole lesion.
From the lateral geniculate body, fibres pass in the optic radiation through the parietal and temporal lobes (4 and 5) to reach the visual cortex of the occipital lobe (6 and 7), which is somatotopically organized with macular vision located at the occipital pole (see Fig. 22.4).
Beyond the visual cortex visual information is further processed by neighbouring visual association areas to detect lines, orientation, shapes, movement, colour and depth; there is even a distinct area responsible for face recognition.
This is assessed in each eye with a Snellen chart and/or Near Vision Reading Types, corrected for refractive errors with lenses or a pinhole. The patient should stand 6 metres from a well-lit chart. Acuity is recorded as distance in metres from the chart over distance at which the line should be legible, e.g. 6/6 indicates ‘normal’ acuity and 6/60 very poor acuity.
Visual fields are assessed at the bedside by confrontation – comparing the examiner’s and patient’s fields, one eye at a time and quadrant by quadrant. Patience and good technique are required to get reliable results. White and red targets (traditionally hatpins) are used to assess peripheral and central fields respectively although in practice a fingertip is often substituted as a cruder screening test. More detailed quantification of fields may be obtained using Goldmann (manual) or Humphrey (automated) perimetry testing.
Field defects are described as hemianopic when half the field is affected and quadrantanopic when a quadrant is affected. Lesions posterior to the optic chiasm produce homonymous field defects, indicating involvement of the same part of the visual field in both eyes as information from the two visual hemifields is separated beyond this point. Lesions damaging decussating nasal fibres at the optic chiasm cause bitemporal defects.
Unilateral visual loss, commencing with a central or paracentral (off-centre) scotoma, is the hallmark of an optic nerve lesion. Because most fibres in the optic nerve subserve macular vision, lesions within the nerve disproportionately affect central vision and colour vision. A total optic nerve lesion causes unilateral blindness with loss of pupillary light reflex. Examination findings in optic neuropathy:
Causes of optic neuropathy
Papilloedema means swelling of the optic disc. Causes are shown in Box 22.4. The earliest signs of swelling are disc pinkness, with blurring and heaping up of disc margins, nasal first. There is loss of spontaneous pulsation of retinal veins within the disc. The physiological cup becomes obliterated, the disc engorged with dilated vessels. Small haemorrhages often surround the disc.
Causes of optic disc swelling
Various conditions simulate true disc swelling. Marked hypermetropic (long-sighted) refractive errors make a disc appear pink, distant and ill-defined. Myelinated nerve fibres at disc margins and hyaline bodies (drusen, p. 1064) can be mistaken for disc swelling.
Papilloedema produces few if any visual symptoms other than momentary visual obscurations with changes in posture. The underlying disease is the source of the patient’s symptoms. The blind spot is enlarged but this is not noticed by the patient. However, over time progressive and permanent constriction of visual fields occurs, ultimately culminating in optic atrophy.
Optic neuritis is one of the most common causes of subacute visual loss. Symptoms may vary from a mild fogging of central vision with colour desaturation to a dense central scotoma, but very rarely complete blindness. Pain on eye movements is almost universal. The optic disc usually appears normal despite severe visual loss (unless the inflammation is at the optic nerve head in which case the disc may appear swollen in the acute phase).
A plaque of demyelination within the optic nerve is the most common cause in Western populations. Dedicated MRI imaging of the optic nerves may show the inflammatory plaque and imaging of the brain may show additional inflammatory lesions which confer a higher risk of developing multiple sclerosis (MS). Approximately 50% of patients go on to develop MS with prolonged follow-up (see p. 1123). Recovery of visual acuity to 6/9 or better occurs in 95% of cases over months, with recovery time improved by high-dose i.v. steroids given acutely.
The anterior part of the optic nerve is supplied by the posterior ciliary arteries, occlusion or hypoperfusion of which leads to infarction of all or part of the optic nerve head. There is sudden or stuttering altitudinal visual loss (typically the lower half of the visual field) with disc swelling, later replaced by optic atrophy. The other eye is later affected in one-third of cases.
Optic tract lesions (rare) cause a homonymous hemianopia (loss of the contralateral visual field in both eyes). Optic radiation lesions cause homonymous quadrantanopic defects. Temporal lobe lesions (e.g. tumour, infarction) cause upper quadrantic defects, and parietal lobe, lower.
Widespread bilateral occipital lobe damage by infarction (‘top of the basilar’ syndrome), trauma or coning causes cortical blindness (Anton’s syndrome). The patient cannot see but characteristically lacks insight into this; he or she may even deny it. Pupillary responses remain normal (p. 1101).
A slight difference between the size of each pupil (up to 1 mm) is common (physiological anisocoria) and does not vary with differing light levels. The pupil tends to become smaller and irregular in old age (senile miosis); anisocoria is more pronounced. Convergence becomes sluggish with ageing.
Figure 22.5 Pupillary light reflex. Afferent pathway: (1) Light activates optic nerve axons. (2) Axons (some decussating at the chiasm) pass through each lateral geniculate body, and (3) synapse at pretectal nuclei. Efferent pathway: (4) Action potentials pass to Edinger–Westphal nuclei of IIIrd nerve, then, (5) via parasympathetic neurones in IIIrd nerves to cause (6) pupil constriction.
The consensual reflex (constriction of the right pupil when the left is illuminated) is absent. Conversely, the left pupil constricts when light is shone in the intact right eye, i.e. the consensual reflex of the right eye remains intact.
Relative afferent pupillary defect (RAPD). This occurs with incomplete damage to one optic nerve relative to the other. An RAPD is a sensitive sign of optic nerve pathology and can provide evidence of an optic nerve lesion even after recovery of vision. For a left RAPD:
When the light is swung from one eye to the other, the left pupil dilates slightly when illuminated and constricts slightly when the right eye is illuminated (the consensual reflex is stronger than the direct).
The sympathetic nervous supply to the eye is a three neurone pathway originating in the hypothalamus and descending by way of the brainstem and cervical cord to T1 nerve root, paravertebral sympathetic chain and, on via the carotid artery wall, to the eye. Damage to any part of the pathway results in Horner’s syndrome. This is significant not only because it affects vision but also because it may indicate a serious underlying pathology.
Causes of Horner’s syndrome
This is a dilated, often irregular, pupil, more frequent in women; it is common and usually unilateral. There is no (or very slow) reaction to bright light and also incomplete constriction to convergence. This is due to denervation in the ciliary ganglion, of unknown cause, and has no other pathological significance. A myotonic pupil is sometimes associated with diminished or absent tendon reflexes.
These cranial nerves supply the extraocular muscles and disorders commonly result in abnormal eye movements and diplopia (double vision) due to breakdown of conjugate (yoked) eye movements. Diplopia may also occur with local orbital lesions or myasthenia gravis.
Pursuit (slow) eye movements and saccadic eye movements are tested separately. The examiner assesses the range of eye movements in all directions and asks the patient to report double vision. Jerky pursuit movements with saccadic intrusion (i.e. brief fast saccades interspersed with slower pursuit movements), overshoot on saccadic movements and nystagmus may indicate cerebellar or brainstem pathology.
Fast voluntary eye movements originate in the frontal lobes. Fibres descend and cross in the pons to end in the centre for lateral gaze (paramedian pontine reticular formation – PPRF), close to the VIth nerve nucleus. Each PPRF also receives input from:
Conjugate lateral eye movements are coordinated from each PPRF via the medial longitudinal fasciculus (MLF, Fig. 22.6). Fibres from the PPRF pass both to the ipsilateral VIth nerve nucleus (lateral rectus) and, having crossed the midline, to the opposite IIIrd nerve nucleus (medial rectus and other muscles) via the MLF, thus linking the eyes for lateral gaze.
Figure 22.6 PPRF and INO. Impulses from PPRF pass via ipsilateral VIth nerve nucleus to lateral rectus muscle (ABduction) and via medial longitudinal fasciculus to opposite IIIrd nerve nucleus and thus to opposite medial rectus muscle (ADduction). A lesion of the MLF (X) causes failure of or slow ADduction in the right eye and nystagmus in the left eye with left lateral gaze. PPRF, para-median pontine reticular formation; INO, internuclear ophthalmoplegia; MLF, medial longitudinal fasciculus.
A destructive lesion on one side allows the eyes to be driven by the intact opposite pathway. A left frontal destructive lesion (e.g. an infarct) leads to failure of conjugate lateral gaze to the right. In an acute lesion the eyes are often deviated to the side of the lesion, past the midline and therefore look towards the left (normal) limbs; there is usually a contralateral (i.e. right) hemiparesis.
In the brainstem a unilateral destructive lesion involving the PPRF leads to failure of conjugate lateral gaze towards that side. There is usually a contralateral hemiparesis and lateral gaze is deviated towards the side of the paralysed limbs.
Damage to one MLF causes internuclear ophthalmoplegia (INO), a common complex brainstem eye movement disorder seen frequently in MS. In a right INO there is a lesion of the right MLF (Fig. 22.6). On attempted left lateral gaze the right eye fails to ADduct. The left eye develops nystagmus in ABduction. The side of the lesion is on the side of impaired ADduction, not on the side of the (obvious, unilateral) nystagmus. When present bilaterally, INO is almost pathognomonic of MS.
Pontine infarction involving the PPRF, VIth nerve nucleus and MLF on one side results in an ipsilateral horizontal gaze palsy and an INO so that abduction of the opposite eye (with nystagmus) is the only horizontal eye movement possible. Vertical gaze and convergence are preserved as they have distinct neural control mechanisms.
Failure of up-gaze may be caused by dorsal midbrain lesions, e.g. pinealoma or infarcts. When the pupillary light reflex fails in addition, this is called Parinaud’s syndrome. Defective up-gaze also develops in certain degenerative disorders (e.g. progressive supranuclear palsy). Some impairment of up-gaze occurs as part of normal ageing.
Nystagmus is rhythmic oscillation of eye movement, and a sign of disease of the retina, cerebellum and/or vestibular systems and their connections. Nystagmus is either jerk or pendular. Nystagmus must be sustained within binocular gaze to be of diagnostic value – a few beats at the extremes of gaze are normal.
Jerk nystagmus (usual in neurological disease) is a fast/slow oscillation. This is seen in vestibular, VIIIth nerve, brainstem, cerebellar lesions. Direction of nystagmus is decided by the fast component, a reflex attempt to correct the slower, primary movement.
The nucleus of the IIIrd nerve lies ventral to the aqueduct in the midbrain. It supplies four external ocular muscles (superior, inferior and medial recti, and inferior oblique), levator palpebrae superioris (which lifts the eyelid) and parasympathetic constriction of the pupil. Causes of a IIIrd nerve lesion are listed in Box 22.6.
Some causes of a IIIrd nerve lesion
Patients do not complain of diplopia as the ptosis effectively covers the eye. Sparing of the pupil indicates parasympathetic fibres are undamaged; these run in a discrete bundle on the surface of the nerve, thus the pupil is of normal size and reacts normally. Diabetic IIIrd nerve infarction is usually painless and pupil sparing, unlike compression by a posterior communicating artery aneurysm.