Chapter 33: Neurological dilemmas

In general practice there are many neurological problems that present a diagnostic dilemma, with some being true masquerades for the non-neurologist. This applies particularly to various seizure disorders, spaceoccupying lesions in the cerebrum and the cerebellum, demyelinating disorders, motor neurone disorders and peripheral neuropathies.

The most common pitfall that occurs with neurological disorders is misdiagnosis, and the most common reason for misdiagnosis is an inadequate history. Failure to appreciate the neurological meaning of points elicited during the history is another reason for misdiagnosis.

Some very important neurological disorders are presented in this section: Parkinson disease, which is common and can be easily misdiagnosed, especially when the classic ‘pill rolling’ tremor is absent or mild; multiple sclerosis (MS), because it is difficult to diagnose initially; and acute idiopathic demyelinating polyneuropathy (Guillain–Barré syndrome), because it can be rapidly fatal if misdiagnosed. MS can masquerade as almost anything—‘If you don’t know what it is, think of MS.’

Another brain teaser for the family doctor is to diagnose accurately the various types of epilepsy. The most commonly misdiagnosed seizure disorders are complex partial seizures or atypical generalised tonic–clonic seizures (see CHAPTER 54).¹ Even more difficult is the differentiation of real seizures from pseudo- or non-epileptic seizures. As a rule neurological conditions should be referred early for specialist management.

The onset of diplopia (double vision) in adults is often acute, very distressing and invariably easy to diagnose. It is invariably binocular, which usually results from extraocular muscular imbalance or weakness. The type of binocular diplopia—vertical, horizontal or oblique—provides clues in identifying the affected muscle. Monocular diplopia is double vision that occurs in one eye when the other is covered. It arises from the eye itself.

The diagnostic strategy model is outlined in TABLE 33.1.

Diagnosis

Diplopia should be differentiated from blurred vision, which is like ‘ghosting’ on a TV screen.

Office tests

Test for double vision with each eye occluded. If diplopia persists, it is uniocular. If, however, double vision disappears when either eye is covered, there is a defect of one of the muscles moving the eyeball. Determine whether diplopia occurs in any particular direction of gaze. It is most marked when moved in the direction of action of the weak muscle. Ask patient to follow your finger, red pin or penlight with both eyes and move it in an H pattern.

• 3rd nerve—eye turned out: divergent squint

• 6th nerve—failure to abduct: convergent squint (See FIG. 33.1).

Key investigations

• Nil for most cases

• First line: urinalysis, blood sugar, FBE, ESR/CRP (? arteritis)

• Consider: TFTs, imaging if indicated (refer)

• ESR (consider arteritis)

  Note:

• Exclude 3rd and 6th nerve palsies as they may be secondary to life-threatening conditions.

• Refer urgently if diplopia is binocular, of recent onset and persistent

Muscle weakness is a common feature of many disorders ranging from neurogenic and myogenic disorders to metabolic and psychiatric. It is very important clinically to be able to differentiate upper motor neurone (UMN) signs from lower motor neurone (LMN) signs (see TABLE 33.2).

Upper motor neurone lesions

UMN signs occur when a lesion has interrupted a neural pathway at a level above the anterior horn cell.² Examples include lesions in motor pathways in the cerebral cortex, internal capsule, brain stem or spinal cord.

Clinical examples include stroke (thrombosis, embolism or haemorrhage in the brain), tumours of the various pathways, demyelinating disease (e.g. multiple sclerosis) and infection (e.g. HIV).

Lower motor neurone lesions

LMN signs occur when a lesion interrupts peripheral neural pathways from the anterior horn cell, that is, the spinal reflex arc.

Clinical examples include peripheral neuropathy, Guillain–Barré syndrome, poliomyelitis and a thickened peripheral nerve (e.g. leprosy).

Note: A spinal cord lesion causes LMN signs at the level of the lesion and UMN signs below that level.

Neurogenic and myogenic muscle weakness

It is also important to distinguish between weakness caused by neurological conditions, especially those causing LMN lesions and muscular disorders. The features are compared in TABLE 33.3. Myotonia is muscle stiffness with difficulty in relaxation after voluntary contraction, e.g. dystrophia myotonica (myotonic dystrophy) (see TABLE 33.7).

Motor neurone disease (MND)

MND is a progressive neuromuscular disorder resulting in muscular limb and bulbar weakness due to death of motor neurones in the brain, brain stem and spinal cord. The sensory system is not involved, nor the cranial nerves to the eye muscles. Five to 10% of MND is inherited with an autosomal dominant pattern; the rest is sporadic. The three main patterns are:

1. amyotrophic lateral sclerosis (Lou Gehrig disease)—combined LMN muscle atrophy plus UMN hyper-reflexia, leading to progressive spasticity. This is the most common type.

2. progressive muscle atrophy—wasting beginning in the distal muscles; widespread fasciculation

3. progressive bulbar (LMN) palsy and pseudobulbar palsy (LMN lesions in the brainstem motor nuclei). Results in wasted fibrillating tongue, weakness of chewing and swallowing, and of facial muscles.

Symptoms and signs

• Weakness or muscle wasting—first noticed in hands (weak grip) or feet

• Stumbling (spastic gait, foot drop)

• Difficulty with swallowing

• Difficulty with speech, for example, slurring, hoarseness

• Fasciculation (twitching) of skeletal muscles and fibrillating tongue

• Cramps

• Emotional instability, depression

• ± Muscle pain

The diagnosis is clinical. There are no diagnostic tests, but neurophysiological tests and MRI of the brain and cord help differentiate from other conditions.

MND is incurable and progresses to death usually within 3–5 years from ventilatory failure/aspiration pneumonia.

No treatment is proven to influence outcome although riluzole, a sodium channel blocker, appears to slow progression slightly. Baclofen 10 mg bd may help symptoms of cramp. Botulinum toxin may help spasticity and propantheline or amitriptyline for drooling. Multidisciplinary care is essential.

Tremor is an important symptom to evaluate correctly. The diagnostic model, including causes is presented in TABLE 33.4. A common pitfall in patients presenting with tremor is for Parkinson disease (PD) to be diagnosed as benign essential tremor and for benign essential tremor to be diagnosed as PD, but the clinical distinction is not always easy and it must be remembered that as many as 20% will experience both concurrently.

Resting tremor—Parkinsonian

The tremor of PD is present at rest. The hand tremor is most marked with the arms supported on the lap and during walking. The characteristic movement is ‘pill-rolling’ where movement of the fingers at the metacarpophalangeal joints is combined with movements of the thumb. The resting tremor decreases on finger–nose testing. The best way to evoke the tremor is to distract the patient, such as focusing attention on the left hand with a view to ‘examining’ the right hand or by asking the patient to turn the head from side to side.

Action or postural tremor

This fine tremor is noted by examining the patient with the arms outstretched and the fingers apart. The tremor may be rendered more obvious if a sheet of paper is placed over the dorsum of the hands. The tremor is present throughout movement, being accentuated by voluntary contraction.

Causes

• Essential tremor (also called familial tremor or benign essential tremor)

• Senile tremor

• Physiological

• Anxiety/emotional

• Hyperthyroidism

• Alcohol

• Drugs, for example, drug withdrawal (e.g. heroin, cocaine, alcohol), amphetamines, lithium, sympathomimetics (bronchodilators), sodium valproate, heavy metals (e.g. mercury), caffeine, amiodarone

• Phaeochromocytoma

Intention tremor (cerebellar disease)

This coarse oscillating tremor is absent at rest but exacerbated by action and increases as the target is approached. It is tested by ‘finger–nose–finger’ touching or running the heel down the opposite shin, and past pointing of the nose is a feature. It occurs in cerebellar lobe disease and with lesions of cerebellar connections.

Flapping (metabolic tremor)

A flapping or ‘wing-beating’ tremor is observed when the arms are extended with hyperextension of the wrists. It involves slow, coarse and jerky movements of flexion and extension at the wrists.

Note: Flapping (asterixis) is not strictly a tremor.

Causes

• Wilson syndrome

• Hepatic encephalopathy

• Uraemia

• Respiratory failure

• Lesions of the red nucleus of the midbrain (the classic cause of a flap)

Essential tremor

Essential tremor, which is probably the most common movement disorder (2–5% prevalence), has been variously called benign, familial, senile or juvenile tremor.

Clinical features

• Autosomal dominant disorder (variable penetrance)

• Often begins in early adult life, even adolescence

• Usually begins with a slight tremor in both hands

• May involve head (titubation), chin and tongue and rarely trunk and legs

• Interferes with writing (not micrographic), handling cups of tea and spoons, etc.

• Tremor most marked when arms held out (postural tremor); less evident at rest

• Tremor exacerbated by anxiety

• May affect speech if it involves bulbar musculature

• Relieved by alcohol

• Can swing arm and gait normal

Triad of features

• Positive family history

• Tremor with little disability

• Normal gait

Distinguishing essential tremor from Parkinson disease

This is not always easy as a postural tremor can be present in PD although the hand tremor is most marked at rest with the arms supported on the lap. Parkinsonian tremor is slower at 4–6 Hz while essential tremor is much faster at around 8–13 Hz. Imaging is unnecessary.

A most useful way to differentiate the two causes is to observe the gait. It is normal in essential tremor but in PD there may be loss of arm swing and the step is usually shortened with stooped posture and shuffling gait.

Management

Most patients do not need treatment and all that is required is an appropriate explanation.¹ If necessary, use propranolol (first choice) or primidone 62.5 mg nocte (up to 250 mg).³ A typical starting dose of propranolol is 10–20 mg bd; many require 120–240 mg/day.³ If the tremor is only intrusive at times of increased emotional stress, intermittent use of benzodiazepines (e.g. lorazepam 1 mg) 30 minutes before exposure to the stress may be all that is required. Modest alcohol intake (e.g. a glass of whisky) is very effective. A standard drink of alcohol often alleviates the tremor. Larger doses of alcohol have no additional effect. If drugs fail, deep brain stimulation to the thalamus can be used.

Parkinson disease

Parkinson disease (PD) is a disorder of the automatic processor of the brain which relies on dopamine to maintain movements at a selected size and speed. Loss of dopamine causes movements to become smaller and slower. The pathological features are loss of dopamine-producing neurones from the substantia nigra in the brain stem together with Lewy bodies in the neurones.⁴ Genetic factors occur in 5% of individuals.

One of the most important clinical aspects of PD, which has a slow and insidious onset, is the ability to make an early diagnosis. Sometimes this can be very difficult, especially when the tremor is absent or mild, as occurs with the atherosclerotic degenerative type of Parkinsonism. The lack of any specific abnormality on special investigation leaves the responsibility for a diagnosis based on the history and examination. As a general rule of thumb the diagnosis of PD is restricted to those who respond to levodopa (L-dopa)—the rest are termed Parkinsonism or ‘Parkinson plus’.

The classic quintet of PD

1. tremor (at rest)

2. rigidity

3. bradykinesia

4. postural instability

5. gait freezing

   ≥2 signs = Parkinson disease

Key facts and checkpoints

• PD is a most common and disabling chronic neurological disorder. About 90% are idiopathic.

• The prevalence in Australia is 120–150 per 100 000.⁵ Lifetime risk is 1 in 40.

• The mean age of onset is between 58 and 62 years.⁵

• The incidence rises sharply over 70 years of age (peak 65 years).⁵

• The diagnosis is based on the history and examination.

• Always think of PD in an older person presenting with falls.

• A reduced sense of smell is one of the first symptoms. Others that may precede PD include constipation, REM sleep disorders and orthostatic hypotension.

• Non-motor automatic dysfunctions: cognition, behaviour, mood.

• Hemi-Parkinsonism can occur; all the signs are confined to one side and thus must be differentiated from hemiparesis. In fact, most cases of PD start unilaterally.

• Always consider drug-induced Parkinsonism. The usual drugs are phenothiazines, butyrophenones and reserpine. Tremor is uncommon but rigidity and bradykinesia may be severe.

• Other causes include vascular (atherosclerosis) and normal pressure hydrocephalus.

Refer to TABLE 33.5.

Signs

• Power, reflexes and sensation are usually normal.

• The earliest abnormal physical signs to appear are loss of dexterity of rapid alternating movements and absence of arm swing, in addition to increased tone with distraction.

• Positive frontal lobe signs, such as grasp and glabellar taps (only allow three blinks), are more common with Parkinsonism.

Note: There is no laboratory test for PD—it is a clinical diagnosis. Hypothyroidism and depression, which also cause slowness of movement, may cause confusion with diagnosis.

Note: The Steele–Richardson–Olszewksi syndrome (also known as progressive supranuclear palsy—PSP parkinsonism, mild dementia and vertical gaze dysfunction) is worth considering.

Principles of management

• Provide appropriate explanation and education.

• Explain that PD is slowly progressive and is improved but not cured by treatment. It is associated with increased mortality (RR death compared with general population ranges 1.6 to 3). The question of whether treatment reduces mortality remains controversial.⁷

• Refer to a specialist for shared care—from outset.

• Support systems are necessary for advanced PD.

• Walking sticks (which spread the centre of gravity) with appropriate education into their use may be necessary to help prevent falls, and constant care is required, so that admission to a nursing home for end-stage disease may be appropriate.

• Correct dopamine deficiency and/or block cholinergic excess in the brain.

Management (pharmacological)^8,9

Avoid postponing treatment. It should be commenced as soon as symptoms interfere with working capacity or the patient’s enjoyment of life. This will be apparent only if the correct questions are asked as the patient may accept impaired enjoyment without appreciating that it is due to PD. Start low—L-dopa 100/25 (½ tab bd) and go slow. There is usually no difference between the L-dopa preparations. The dosage should be tailored so that the patient neither develops side effects nor is on an inadequate dose of medication without significant therapeutic benefit (see TABLE 33.6). The dose usually progresses to 1 tab bd, then consider add-on therapy.

The older drugs, such as anticholinergics and amantadine, still have a place in modern management but L-dopa, which basically counters bradykinesia, is the best drug and the baseline of treatment. With the onset of disability (motor disturbances) L-dopa in combination with a decarboxylase inhibitor (carbidopa or benserazide) in a 4:1 ratio should be introduced. L-dopa therapy does not significantly improve tremor but improves rigidity, dyskinesia and gait disorder. Consider benzhexol or benztropine if tremor is the feature, especially in young patients.

The new non-ergot derivative dopamine agonists can be used in treatment, especially with the L-dopa ‘on–off’ phenomenon (fluctuations throughout the day). They are preferred to the ergot derivatives because of a superior adverse effect profile. They appear to be most effective when used in combination. The ergot derivatives can have serious adverse effects, including cardiac valve damage, and are no longer recommended. Selegiline is an effective second-line drug, especially in combination with Sinemet. If there is associated pain, depression or insomnia, the tricyclic agents (e.g. amitriptyline) can be effective.

Entacapone has the potential to increase ‘on time’ and reduce motor fluctuations in L-dopa treated patients who are beginning to experience end-of-dose failure. The initial dose is 200 mg and best used when combined with L-dopa.

Treatment strategy^8,9

Mild (minimal disability):

• L-dopa preparation (low dose), e.g. L-dopa 100 mg + carbidopa 25 mg (½ tab bd—increase gradually as necessary to 1 tab (o) tds)

  or

• amantadine 100 mg (o) daily may help the young or the elderly for up to 12 months—if inadequate response

• selegiline up to 5 mg bd can be added to L-dopa if necessary

Moderate (independent but disabled, e.g. writing, movements, gait):

• L-dopa preparation

• selegiline 1 mg bd

  and/or

• Add if necessary—non-ergot dopamine agent

  • – pramipexole start with 0.25 mg transdermally daily

  • – rotigotine start with 2 mg daily

Severe (disabled, dependent on others):

• L-dopa (to maximum tolerated dose) + non-ergot dopamine agent

• Add entacapone 200 mg (o) with each dose of L-dopa, e.g. Stalevo

• Consider antidepressants

An example of a practical treatment algorithm is presented in FIGURE 33.4.

Long-term problems

After 3–5 years of L-dopa treatment, side effects may appear in about one-half of patients:⁵

• involuntary movements—dyskinesia

• end-of-dose failure (reduced duration of effect to 2–3 hours only)—consider entacapone

• ‘on–off’ phenomenon (sudden inability to move, with recovery in 30–90 minutes)

• early morning dystonia, such as clawing of toes (due to disease—not a side effect)

Specialist advice is appropriate.

Advanced disease⁸

Under consultant and good home/nursing care:

• Apomorphine can be used for severe akinesia not responsive to L-dopa

• For nausea and vomiting side effects: domperidone 20 mg (o) tds 24 hours prior to apomorphine

• Better control may also be achieved with: amantadine 100 mg (o) bd

• Duodopa—levodopa into jejunum

Contraindicated drugs

• Phenothiazines and other older antipsychotics

• Butyrophenones

Multidisciplinary care

This important strategy includes physiotherapy, occupational therapy, physical therapy, e.g. tai chi, and psychiatry/psychology, e.g. CBT, mindfulness.

Treatment (surgical)

The preferred method is high-frequency deep brain stimulation via electrodes into the subthalamic nucleus, which may benefit all major features of the disease. The indication for surgery such as thalamotomy is erratic and disabling responses to prolonged L-dopa therapy, especially for annoying dyskinesias. It is considered more appropriate for younger patients with a unilateral tremor.⁸

When to refer

If the diagnosis is unclear at the time of initial presentation, it is appropriate either to review the patient at a later date or to refer the patient for more neurological assessment.

Once diagnosed or highly suspected it is best to refer to establish the diagnosis and to seek advice on initiation of treatment. Patients and families usually prefer this approach. In the initial years before motor fluctuations develop, management could be performed by the GP according to an overall plan developed in liaison with a neurological colleague. When fluctuations develop and end-stage diseases manifest (e.g. gait disorders), specialist supervision is appropriate.¹

Cognitive impairment with Parkinson disease^4,11

This may be due to multiple factors including Parkinson associated dementia, Lewy body dementia, Alzheimer disease and medication, all of which can induce psychosis, but L-dopa is the least likely. Neuropsychiatric symptoms, which can be varied and bizarre and usually worse in the evening, can occur. Factors contributing to psychosis are illustrated in FIGURE 33.5. Management is based on monotherapy with gradual build-up of L-dopa to maximum tolerated dose, for example, 450–600 mg/day.

Management (psychotic problems)

• Treat as an inpatient

• Exclude and treat comorbidities, e.g. UTI

• Eliminate and wean off worst drugs

• Increase L-dopa slowly to 150 mg tds or qid

• Give quetiapine or olanzapine at night-time

Paraesthesia and numbness

The diagnostic strategy model for paraesthesia and numbness is presented in TABLE 33.7.

Multiple sclerosis

Multiple sclerosis (MS) is the most common cause of progressive neurological disability in the 20–50 year age group.¹⁰ It is generally accepted that MS is an autoimmune disorder. Genetic and environmental factors are believed to play a role.¹² Early diagnosis is difficult because MS is characterised by widespread neurologic lesions that cannot be explained by a single anatomical lesion, and the various symptoms and signs are subject to irregular exacerbations and remissions. The lesions are ‘separated in time and space’. The most important issue in diagnosis is the need for a high index of suspicion. The use of MRI has revolutionised the diagnosis of MS.

MS is a primary demyelinating disorder with demyelination occurring in plaques throughout the white and grey matter of the brain, brain stem, spinal cord and optic nerves. The clinical features depend on their location. There is a loss of brain volume.

There is a variety of types of MS—relapsing remitting (most common), secondary progressive, progressive relapsing and primary progressive—together with ‘benign’ and ‘malignant’ forms.

Clinical features

See FIGURE 33.6.

• More common in females (3:1)

• Peak age of onset is in the fourth decade

• Transient motor and sensory disturbances

• UMN signs

• Symptoms develop over several days but can be sudden

• Monosymptomatic initially in about 80%

• Only 20% have a benign disease

• Multiple symptoms initially in about 20%

• Common initial symptoms include:

  • – visual disturbances of optic neuritis (blurred vision or loss of vision in one eye—sometimes both); central scotoma with pain on eye movement (looks like unilateral papilloedema)

  • – diplopia (brain-stem lesion)

  • – weakness in one or both legs, paraparesis or monoparesis

  • – sensory impairment in the lower limbs and trunk: numbness, paraesthesia; band-like sensations; clumsiness of limb (loss of position sense); feeling as though walking on cotton wool

  • – vertigo (brain-stem lesion)

• Subsequent remissions and exacerbations that vary from one individual to another

• 80% have a relapsing remitting disease

• There is a progressive form, esp. in women around 50 years

• Anxiety, depression and other mood disorders are common

Symptoms causing diagnostic confusion

• Bladder disturbances, including retention of urine and urgency

• ‘Useless hand’ due to loss of position sense

• Facial palsy

• Trigeminal neuralgia

• Psychiatric symptoms

In established disease, common symptoms are fatigue, impotence and bladder disturbances.

Examination (neurological)

The findings depend on the site of the lesion or lesions and include optic atrophy, weakness, hyper-reflexia, extensor plantar responses, nystagmus (two types—cerebellar or ataxic), ataxia, incoordination and regional impairment of sensation.

Diagnosis

The diagnosis is clinical along with the MRI and depends on the following determinants:

• Lesions are invariably UMN.

• >1 part of CNS is involved, although not necessarily at time of presentation.

• Episodes are separated in time and space.

• Practically MS can only be diagnosed after a second relapse or when the MRI shows new lesions.¹⁰

• An early diagnosis requires evidence of contrast-enhancing lesions or new T2 lesions on the MRI indicating dissemination in time.

• The diagnostic criteria is based on the internationally accepted 2010 McDonald criteria (refer to www.nice.org.uk)^12,13

Other neurological disorders such as infections (e.g. encephalitis), malignancies, spinal cord compression, spinocerebellar degeneration and others must be excluded.

Investigation

• Lumbar puncture: oligoclonal IgG detected in CSF in 90% of cases¹⁴ (only if necessary)

• Visual evoked potentials: abnormal in about 90% of cases

• MRI scan: usually abnormal, demonstrating MS lesions in about 90% of cases¹⁴

Course and prognosis

• The course is variable and difficult to predict. An early onset (<30 years) is usually ‘benign’ while a late onset (≥50 years) is often ‘malignant’.

• MS follows a classic history of relapses and remissions in 80–85% of patients.¹⁴

• The rate of relapse is about once in 2 years.

• About 20% have a progressive course from the onset with a progressive spastic paraparesis (applies mainly to late-age onset).

• The average duration of MS is about 40 years from diagnosis to death.¹⁴

• A ‘benign’ course occurs in about 30% of patients with 10–20% never suffering major disability.

• The median time to needing a walking aid is 15 years.⁸

• The likelihood of developing MS after a single episode of optic neuritis is about 60%.

Management principles

• All patients should be referred to a neurologist for confirmation of the diagnosis, which must be accurate.

• Explanation about the disorder and its natural history should be given.

• Acute relapses require treatment if causing significant disability.

• Depression and anxiety, which are common, require early treatment, e.g. paroxetine.

• CBT or mindfulness-based interventions.

Treatment (relapses)

Mild relapses

Mild symptoms, such as numbness and tingling, require only confirmation, rest and reassurance.

Moderate relapses

• Prednisolone—in outpatient setting

Severe relapses or attacks^8,15

These attacks include optic neuritis, paraplegia or brain-stem signs. Admit to hospital for IV therapy:

• methylprednisolone 1 g in 200 mL saline by slow IV infusion (1 hour) daily for 3 days

  Plasma exchange may be used.

  Observe carefully for cardiac arrhythmias.

Drugs to prevent relapses¹⁶

Currently first-line immunomodulators are the interferons, glatiramer acetate and the monoclonal antibodies natalizumab and alemtuzumab.

Interferon beta-1b (SC injection) and beta-1a (IM injection) appear to be effective (but expensive) for those with frequent and severe attacks.

New agents being evaluated include teriflunamide, daclizumab, ocrelizumab and Biotin.

Treatment (symptoms)^7,16

Spasticity

• Physiotherapy

• Baclofen 10–25 mg (o) nocte

• For continuous drug therapy: baclofen 5 mg (o) tds, increasing to 25 mg (o) tds + diazepam 2–10 mg (o) tds

• An alternative is dantrolene

Paroxysmal (e.g. neuralgias)

• Carbamazepine or gabapentin

Cannabis

The reported efficacy of the cannabis-based medicine Stativex for relaxation, pain and bladder function is still being debated. One RCT showed a positive effect on detrusor activity.¹⁸

See references 8 and 16 for treatment of other symptoms.

Peripheral neuropathy

Peripheral neuropathy (PN) refers to all conditions causing nerve damage outside the central nervous system. It can be a mononeuropathy, such as carpal tunnel syndrome; mononeuropathy multiplex involving multiple single nerves in an asymmetric pattern (as in vasculitides); or a polyneuropathy, which is a diffuse symmetric disorder best referred to as PN. It can be classified according to clinical progression as acute, subacute or chronic. The manifestations can be sensory, motor, autonomic or mixed (sensorimotor).

• Sensory symptoms: tingling, burning, numbness in extremities, unsteady gait (loss of position sense)

• Motor symptoms (LMN): weakness or clumsiness in hands, foot/wrist drop

• Signs: may be classic ‘glove and stocking’ sensory loss, sensory ataxia, LMN signs—distal muscle wasting, muscle weakness, reflexes absent or depressed, fasciculations

Causes

• Mostly sensory: diabetes mellitus, vitamin deficiency (folate, B1, B6, B12), alcohol, various neurotoxic drugs, leprosy, uraemia (CKF), amyloidosis, malignancy

• Mostly motor: lead poisoning, porphyria, various neurotoxic drugs, Charcot–Marie–Tooth syndrome (peroneal muscle atrophy), acquired inflammatory polyneuropathies—acute (Guillain–Barré syndrome) and chronic (chronic inflammatory demyelinating polyneuropathy)

Note: In many instances no cause is found despite a full history and examination.

Management

Refer to a suitably qualified consultant for diagnosis particularly via electrophysiology.

Acute inflammatory polyradiculoneuropathy (Guillain–Barré syndrome)

Guillain–Barré syndrome, which is a rapidly progressive and treatable cause of PN or ascending radiculopathy, is potentially fatal. Early diagnosis of this serious disease by the family doctor is crucial as respiratory paralysis may lead to death. The underlying pathology is segmental demyelination of the peripheral nerves and nerve roots.

Clinical features

• Weakness in the limbs (usually symmetrical)

• Paraesthesia or pain in the limbs (less common)

• Both proximal and distal muscles affected, usually starts peripherally and moves proximally

• Facial and bulbar paralysis (rare)

• Weakness of extraocular muscles (rarely)

• Reflexes depressed or absent

• Variable sensory loss but rare

Within 3–4 weeks the motor neuropathy, which is the main feature, progresses to a maximum disability, possibly with complete quadriparesis and respiratory paralysis.¹⁹

Investigation

• CSF protein is elevated; cells are usually normal.

• Motor nerve conduction studies are abnormal.

Management

• Admit to hospital.

• Respiratory function (vital capacity) should be measured regularly (2–4 hours at first).

• Tracheostomy and artificial ventilation may be necessary.

• Physiotherapy to prevent foot and wrist drop and other general care should be provided.

• Treatment is with plasma exchange or IV immunoglobulin (0.4 g/kg/day for 5 days), which may need to be continued monthly.⁸

• Corticosteroids are not generally recommended.

Outcome

About 80% of patients recover without significant disability. Approximately 5% relapse.¹⁹

Chronic inflammatory demyelinating polyneuropathy^8,20

This acquired immunological disorder is similar to Guillain–Barré syndrome except that it has a slower and more protracted course. Diagnosis is by nerve studies and treatment is with corticosteroids, plasmapheresis or IV immunoglobin.

Charcot–Marie–Tooth syndrome

This is an inherited autosomal dominant polyneuropathy with an insidious onset from puberty. Clinical features include weakness in the legs, variable distal sensory loss and muscle atrophy giving the ‘inverted champagne bottle’ appearance of the legs. The features vary according to the various subgroups. Refer for electrodiagnostic studies and specific genetic testing.

Familial periodic paralysis

An autosomal dominant skeletal muscle disorder. Clinical features:

• young patient (usually adolescent)

• day after vigorous exercise awakens with weakness in limbs (for 4–24 hours)

• flaccid paralysis/loss of deep tendon reflexes

Related to potassium levels—measure during symptoms. Classify as high, low or normal.

Myasthenia gravis

Myasthenia gravis (MG) is an acquired autoimmune disorder that usually affects muscle strength. Patients have fluctuating symptoms and variable distribution of muscle weakness. All degrees of severity, ranging from occasional mild ptosis to fulminant quadriplegia and respiratory arrest, can occur²¹ (see TABLE 33.8). It is associated with thymic tumour and other autoimmune diseases, for example, RA, SLE, thyroid and pernicious anaemia.

Clinical features

• Painless fatigue with exercise

• Weakness also precipitated by emotional stress, pregnancy, infection, surgery

• Variable distribution of weakness:

  • – ocular: ptosis (60%) and diplopia (see FIG. 33.7); ocular myasthenia only remains in about 10%

  • – bulbar: weakness of chewing, swallowing, speech (ask to count to 100), whistling and head lolling

  • – limbs (proximal and distal)

  • – generalised

  • – respiratory: breathlessness, ventilatory failure

Note: The classic MG image is ‘the thinker’—the hand used to hold the mouth closed and the head up.

Diagnosis

• Serum anti-acetylcholine receptor antibodies

• Electrophysiological tests if antibody test negative

• CT scan to detect thymoma

• Edrophonium test still useful but potentially dangerous (atropine is the antidote)

Management principles^8,21

• Refer for consultant management.

• Detect possible presence of thymoma with CT or MR scan of thorax. If present, removal is recommended.

• Thymectomy is recommended early for generalised myasthenia, especially in all younger patients with hyperplasia of the thymus, even if not confirmed preoperatively.

• Plasmapheresis is useful for acute crisis or where temporary improvement is required or patients are resistant to treatment.

• Avoid drugs that are relatively contraindicated.

• Pharmacological agents:

  • – anticholinesterase inhibitor drugs (e.g. pyridostigmine, neostigmine or distigmine) should be used only for mild-to-moderate symptoms

  • – corticosteroids are useful for all grades of MG (should be introduced slowly).

It is worth remembering that the four major causes of ptosis are:

1. 3rd cranial nerve palsy—ptosis, eye facing ‘down and out’, dilated pupil, sluggish light reflex

2. Horner syndrome—ptosis, miosis (constricted pupil), ipsilateral loss of sweating

3. Mitochondrial myopathy—progressive external ophthalmoplegia or limb weakness, induced by activity—no pupil involvement

4. Myasthenia gravis—ptosis and diplopia, no pupil involvement

Dystonia

Dystonias are sustained or intermittent abnormal repetitive movements or postures resulting from alterations in muscle tone. The dystonic spasms may affect one (focal) or more (segmental) parts of the body or the whole body (generalised).

Key facts and checkpoints

• Misdiagnosis is common as transient symptoms may be mistaken for an emotional or psychiatric disorder. Many cases take years to diagnose.

• Dystonias are often regarded as nervous tics.

• The cause is thought to be disorders of the basal ganglia of the brain, but mainly there is no known specific cause.

• Neuroleptic and dopamine receptor blocking agents (e.g. L-dopa, metoclopramide) can induce a severe generalised dystonia (e.g. oculogyric crisis) which is treated with benztropine 1–2 mg IM or IV.⁸ However, L-dopa is the drug of choice in some L-dopa responsive dystonias.

Focal dystonias

• Blepharospasm is a focal dystonia of the muscles around the eye resulting in uncontrolled blinking, especially in bright light. This is best treated with botulinum toxin, type A.

• Oromandibular dystonia affects the jaw, tongue and mouth, resulting in jaw grinding movements and grimacing. Proper speech and swallowing may be disrupted.

• Meige syndrome is a combination of blepharospasm and oromandibular dystonia.

Note: It must be differentiated from the buccallingual-facial movements of tardive dyskinesia.

• Hemifacial spasm involves involuntary, irregular muscle contractions and spasms affecting one side of the face. It usually starts with twitching around the eye and then spreads to involve all the facial muscles on one side. It is usually due to irritation of the facial nerve in its intracranial course and surgical intervention may alleviate this problem.

• Writer’s cramp, typist’s cramp, pianist’s cramp, golfer’s cramp are all occupational focal dystonias of the hand and/or forearm initiated by performing these skilled acts.

• Cervical dystonia or spasmodic torticollis is a focal dystonia of the unilateral cervical muscles. It usually begins with a pulling sensation followed by twisting or jerking of the head, leading to deviation of the head and neck to one side. In early stages patients can voluntarily overcome the dystonia.

• Laryngeal or spastic dystonia is a focal dystonia of the laryngeal muscles resulting in a strained, hoarse or creaking voice. It may lead to inability to speak in more than a whisper.

Treatment

The current treatment for focal or segmental (spread to an adjacent body region) dystonias is localised injection of purified botulinum A toxin into the affected muscle groups. The dosage is highly individualised and needs to be repeated at intervals of 3 and 6 months. The injections have to be given with great caution, ideally by a registered injector.

Tics

Motor and vocal tics are a feature of Tourette disorder. If socially disabling treat with:

• haloperidol 0.25 mg (o) nocte, very gradually increasing to 2 g (max.) daily⁷

  or

• clonidine 25 mcg (o) bd for 2 weeks, then 50–75 mcg bd

Facial nerve (Bell) palsy¹⁵

Facial (7th nerve palsy), which is an acute unilateral lower motor neurone paresis or paralysis, is the commonest cranial neuropathy. The classic type is Bell palsy, which is usually idiopathic although attributed to an inflammatory swelling involving the facial nerve in the bony facial canal. In Ramsay–Hunt syndrome, which is due to infection with herpes zoster causing facial nerve palsy, vesicles may be seen on the ipsilateral ear.

Associations:

• herpes simplex virus (postulated)

• diabetes mellitus

• hypertension

• thyroid disorder, e.g. hyperthyroidism

Clinical features

• Abrupt onset (can worsen over 2–5 days)

• Weakness in the face (complete or incomplete)

• Preceding pain in or behind the ear

• Impaired blinking

• Bell phenomenon—when closing the eye it turns up under the half-closed lid

Less common:

• Difficulty eating

• Loss of taste—anterior two-thirds of tongue

• Hyperacusis

Management

• prednisolone 1 mg/kg (o) (usually 60 mg) daily in the morning for 5 days (start within 48 hours of onset)

Note: This is controversial, but recent randomised trials and a Cochrane review support the use of prednis(ol)one. No good evidence for antiviral drugs.

• Patient education and reassurance

• Adhesive patch or tape over eye if corneal exposure (e.g. windy or dusty conditions, during sleep)

• Artificial tears if eye is dry and at bedtime

• Massage and facial exercises during recovery

Note:

• At least 70–80% achieve full spontaneous recovery; higher if mild.

• Electromyography and nerve excitability or conduction studies are a prognostic guide only.

• No evidence that nucleoside analogue, for example, aciclovir, is useful but should be used for Ramsay–Hunt syndrome.

• No evidence that surgical procedures to decompress the nerve are beneficial.¹⁵

Hand-out sheets from Murtagh’s Patient Education 7th edition:

• Bell palsy

• Tremor: essential tremor

• Parkinson disease

Parkinson disease <www.parkinsons.org.au>

Multiple sclerosis <www.msaustralia.org.au>

Amyotrophic lateral sclerosis <www.mnd.aust.asn.au>