The brain is a wonderful organ. It starts working the moment you get up in the morning and does not stop until you get into the office.
Robert Frost (1874–1963)
This is a common chronic disease. Patients suffering from multiple sclerosis (MS) are readily available for the clinical examinations. They are mostly very well informed about, and interested in, their disease. MS usually begins in early adult life and is more common in women (2:1). The disease is much more common among people who lived as children in regions far from the equator. Exposure to Epstein-Barr virus infection at an older age increases risk and the condition is rare in sero-negative individuals. Numerous alleles associated with risk have been identified, but HLA-DRB1 has the strongest association.
The most common pattern of disease is called relapsing remitting multiple sclerosis (RRMS). In untreated patients the rate of relapse is 0.65 attacks a year. Episodes of fever or fatigue associated with a temporary worsening of symptoms are not considered to be relapses and are called pseudorelapses. In most cases complete or almost complete resolution of symptoms occurs in this phase of the disease. After 10 years up to 50% of patients begin to develop a progressive accumulation of disability – secondary progressive MS (SPMS). Eventually 80% of patients enter this stage.
The disease usually begins with an episode of acute neurological disturbance, which is called a clinically isolated syndrome. However, the clinical diagnosis requires at least two neurological events separated in time and place within the central nervous system (CNS). MS is primarily a clinical diagnosis, but the use of MRI scanning has led to the McDonald criteria for diagnosis. These allow for the diagnosis after a single neurological episode if the MRI shows a separate area typical of MS (see Table 12.1).
Sites of demyelinating lesions on MRI scanning
1. Ask about the presenting symptoms (listed here in approximate order of importance):
a. episodes of spastic paraparesis, hemiparesis or tetraparesis (may present as gradually progressive disease in late-onset MS)
b. episodes of limb paraesthesiae (owing to posterior column, medial lemniscus or internal capsule involvement)
c. episodes of visual disturbance – loss of acuity, pain on eye movement, loss of central visual field (optic neuritis), diplopia on lateral gaze
d. episodes of ataxia, dysarthria and tremor – Charcot’s triad (owing to cerebellar or posterior column involvement)
e. band sensations around trunk or limbs
f. less common symptoms, such as vertigo, symptoms of cranial nerve disorders (e.g. tic douloureux), urinary urgency, incontinence of faeces, impotence, depression, euphoria, dementia, seizures, bulbar dysfunction (pseudobulbar palsy).
2. Ask about precipitating factors, such as heat (hot baths, etc.), infection, fever, pregnancy and exercise. Disease activity tends to be less during pregnancy; relapse is common post-partum.
3. Ask about family history: MS is seven times more common in immediate relatives (sibling risk is 5%).
4. Ask about social disability – sexual function, ability to work, financial problems.
5. Ask about place of birth: MS is more common in subjects who spent their childhood in temperate latitudes than in tropical regions. Smoking is also a risk factor.
6. Find out what treatments have been tried and with what success and side-effects. Various unproven treatments are often tried by patients with this incurable disease. Ask whether any of these have been used.
1. The signs can be very variable. Look particularly for signs of spastic paraparesis and posterior column sensory loss, as well as cerebellar signs.
2. Examine the cranial nerves. Look carefully for loss of visual acuity, optic atrophy, papillitis and scotomata (usually central). Internuclear ophthalmoplegia is an important sign and is almost diagnostic in a young adult. It can also occur in patients with SLE or Sjögren’s syndrome who may have disease confined to the CNS, or with brain stem tumours or infarcts. Internuclear ophthalmoplegia is weakness of adduction in one eye as a result of damage to the ipsilateral medial longitudinal fasciculus; there is nystagmus in the abducting eye. In MS, internuclear ophthalmoplegia is often bilateral. Other cranial nerves may rarely be affected by lesions within the brain stem (III, IV, V, VI, VII, pseudobulbar palsy). Charcot’s triad consists of nystagmus, intention tremor and scanning speech, but occurs in only 10% of patients.
3. Look for Lhermitte’s sign (an electric shock-like sensation in the limbs or trunk following neck flexion). This can also be caused by other disorders of the cervical spine, such as subacute combined degeneration of the cord, cervical spondylosis, cervical cord tumour, foramen magnum tumours, nitrous oxide abuse and mantle irradiation.
4. Rarely, Devic’s disease, usually seen in children or young adults, is present (bilateral optic neuritis and transverse myelitis occurring within a few weeks of one another) and may be a variant of MS.
The differential diagnosis of multiple CNS lesions includes SLE, Sjögren’s syndrome, Behçet’s disease, small vessel ischaemia, acute disseminated encephalomyelitis, meningovascular syphilis, paraneoplastic effects of carcinoma, sarcoidosis, Lyme disease and multiple emboli from any source. It is important to distinguish MS affecting predominantly the spinal cord from other diseases – especially subacute combined degeneration of the cord (more common in the older population) and spinal cord compression presenting with root pain and persistent levels of sensory loss.
MS is essentially a clinical diagnosis, but the following tests may be helpful.
1. MRI is the imaging modality of choice (Fig 12.1). Table 12.1 lists the typical sites of changes. Typical changes are present in the great majority of patients with MS. Gadolinium contrast studies show leakage into the brain from blood vessels for up to months after the formation of a new lesion. T2-weighted images will show persisting changes probably owing to a combination of oedema, gliosis and inflammation. The extent of these abnormalities does not correlate well with the clinical picture, but T1-weighted images may show hypodense areas whose extent does correspond to the patient’s symptoms. These probably represent irreversible damage and axonal loss. CT scan may reveal low-density, sometimes contrast-enhancing, plaques in white matter (subcortical or periventricular, but only in 10–50% of cases). CT scanning is no longer in routine use for diagnosis of MS.
FIGURE 12.1 MRI of the brain of a patient with multiple sclerosis showing numerous plaques (white patches). Figure reproduced courtesy of The Canberra Hospital.
2. Visual-evoked responses are delayed in 80% of established cases and indicate previous optic neuritis (important if there is only one other clinically detectable lesion present). Auditory-evoked responses and somatosensory-evoked responses may be abnormal, but are not usually diagnostic.
3. Cerebrospinal fluid in chronic MS contains oligoclonal IgG bands (70%) and an altered IgG:albumin ratio. Myelin basic protein may be elevated in acute demyelination. There are usually fewer than 50 white cells per millilitre in the cerebrospinal fluid, but acute severe demyelination may result in a cell count exceeding 100/mL.
4. Antimyelin antibodies are of uncertain value.
A definite diagnosis is not possible without the presence of two or more CNS episodes, usually separated in time and place. The first may be a clinical abnormality and the second detected by MRI or visual-evoked responses (Macdonald criteria). These include objective CNS changes usually involving long tract signs and symptoms: pyramidal, cerebellar, optic nerve, posterior columns and medial longitudinal fasciculus. Gradual progression of symptoms may be used to make the diagnosis if typical cerebrospinal fluid abnormalities are present. The MRI should show four distinct areas of abnormality at least 3 mm in diameter. There should be no other explanation for the symptoms (see above).
There are two aspects to treatment of these patients: (1) supportive and symptomatic treatment; and (2) attempts to alter the disease progression. In addition, there are many support groups and organisations for patients with MS. These often give sensible advice to these distressed people and should be recommended to patients. It is most important, however, that the diagnosis is secure before patients are labelled with this condition with its numerous long-term implications.
1. The course of the disease:
a. relapsing–remitting MS: relapses with or without complete recovery, but stable between episodes. Offer disease-modifying therapy
b. secondary progressive MS: about half of the patients with relapsing– remitting MS develop secondary progressive MS within 10 years. They experience gradual progression of their symptoms without distinct episodes
c. primary progressive MS: these patients (10%) have increasing symptoms without distinct episodes from the start
d. progressive relapsing MS: in these patients there is gradual worsening with episodes of deterioration occurring later in the course of the illness.
2. General support is essential. During exacerbations, bed rest with meticulous nursing is vital. Treatment of bladder dysfunction, severe spasticity (e.g. with baclofen), urgency (e.g. with amitriptyline), tic douloureux and facial spasm (e.g. carbamazepine and physiotherapy) is important. Intention tremor can be treated with propranolol or clonazepam.
3. Drug treatment: immunomodulators and immunosuppresants.
a. Interferon beta 1a and interferon beta 1b have been shown to reduce the frequency of exacerbations by about one-third when used at an early stage of disease and to reduce the accumulation of CNS white matter lesions. They are more effective for the relapsing forms of the disease (see below). Remember the risk of hepatotoxicity and leucopenia; monitor blood tests.
b. Glatiramer acetate (subcutaneous) takes up to a year to provide benefit; the drug can induce non-cardiac chest pain. It is of similar efficacy to interferon. Bradycardia can be a problem.
c. Natalizumab (monoclonal antibody to alpha 4 integrin) is more effective than these agents, but its use is restricted to patients with very aggressive disease because 1 in 600 patients treated develop progressive multifocal leucoencephalopathy due to brain infection with the Jakob-Creuztfeld agent.
d. Fingolimod is an oral agent that has recently become available. It works via the sphingosine 1-phosphate receptor to prevent lymphocyte tracking through lymph nodes. It causes reversible lymphopenia. It has been shown to be more effective than interferon with relapse rates of 25% at 2 years. Side-effects include macular oedema and increased infection risk. It should not be given to people without varicella immunisation or known previous exposure and immunity.
e. Treatment for aggressive or unresponsive disease: methotrexate given in weekly doses of 7.5 mg reduces the progression of disability and the MRI signs of disease activity for up to 2 years. Azathioprine (2–3 mg/kg/day) is sometimes used for chronic progressive disease and appears to have a modest beneficial effect. Cyclophosphamide may slow progression in patients under the age of 40. Its side-effects make it difficult to use. Mitoxantrone has been used in rapidly progressive disease, but causes cardiac toxicity. Occasionally, autologous stem cell transplant has been used.
f. Acute relapses are treated with methylprednislone −1 gm/day for 3 doses. Plasmapheresis and intravenous gammaglobulin may help relapses when steroids fail. Treatment of relapses may hasten recovery but does not improve the long-term outlook or reduce the risk of further relapses.
At 15 years after the first episode, 80% of patients have significant symptoms that prevent them from working and require help with normal activities. If the initial episode is limited to a single abnormality and the MRI is normal, only 10% will go on to develop a second episode over the following 10 years. If the MRI is abnormal, up to 80% will experience further episodes.
As with all chronic and debilitating diseases a discussion about the patient’s expectations and prognosis and plans for the future is important.
This chronic auto-immune disease presents both diagnostic and management problems. Peak incidence in women is in the third decade of life, but in men it is in the seventh decade. Overall it is more common in women (2:1). Exacerbations and remissions (incomplete) are common.
1. Ask about symptoms at presentation:
a. ocular – diplopia (90%), drooping eyelids
b. bulbar – choking (weakness of pharyngeal muscles), dysarthria, difficulty (especially fatigue) when chewing or swallowing
c. limb girdle – proximal muscle weakness; there is fatigue on exertion and prompt partial recovery on resting.
2. Ask about a history of difficult anaesthesia (owing to prolonged weakness after muscle relaxation) and past episodes of pneumonia (as a result of bulbar and respiratory weakness).
3. Determine how the diagnosis was made, including whether electrodiagnostic studies were done and whether the patient had blood tests for acetylcholine receptor antibodies.
4. Ask about a history of thymectomy.
5. Enquire about other treatment – including drug dose and when the last dose was taken, plasma exchange or immunosuppressive therapy.
6. Ask about drug use, which may interfere with neuromuscular transmission (see below).
7. Ask about other organ-specific autoimmune disease associations (SLE, rheumatoid arthritis).
8. Enquire about the social history.
1. Examine for muscle fatigue, particularly the elevators of the eyelids and the oculomotor muscles (tested by sustained upward gaze), bulbar muscles (tested by counting or reading aloud) and the proximal limb girdles (tested by holding the arms above the head).
2. Look for the Peek sign (orbicularis oculi weakness – close the eyelids: within 30 seconds in myasthenia they will begin to separate and you will see the lower sclera).
3. Asking the patient to smile may produce a snarling expression. Speech on prolonged speaking may sound dysarthric or nasal because of weakness of the palate.
4. Weakness of neck flexion may be prominent.
5. Look for a thymectomy scar.
6. Reflexes are preserved, there is no sensory loss and muscle atrophy is usually minimal.
Tests for myasthenia gravis (Fig 12.2) include the following.
FIGURE 12.2 Myasthenia (face). The patient has bilateral asymmetrical ptosis and needs to use the frontalis muscle to elevate the eyelids. S R Hamilton. Albert and Jakobiec’s principles and practice of ophthalmology, 3rd edn. Elsevier, 2008, with permission.
1. Acetylcholine receptor antibodies (anti-AChR) – these occur in 80–90% of cases, with false-positive results being rare (but the frequency of positive tests is lower in pure ocular and inactive myasthenia gravis). The titre is not directly related to disease severity. Antistriated muscle antibody is detectable in 90% of patients with a thymoma, but is also common in elderly patients without a thymoma; muscle specific kinase antibodies (MuSK) are present in 40% of ‘seronegative’ (ACh antibody negative) patients.
2. Electromyogram (EMG) – in myasthenia gravis, repetitive stimulation at low frequencies causes an asymptotic reduction (there is progressively less reduction with each shock) in muscle action potential amplitudes if that particular muscle is affected. Needle examination of affected muscles shows motor unit potential variation and, sometimes, fibrillation potentials and myopathic change. Single-fibre EMG shows increased jitter and blocking.
3. Thymoma investigations – chest X-ray, thoracic CT scan or MRI.
4. Associated conditions – hyperthyroidism and autoimmune diseases (check thyroid function tests, rheumatoid factor and antinuclear antibodies).
5. Respiratory function tests – these patients may have severe respiratory impairment.
The prognosis of myasthenia gravis is good: 50% of patients have a remission, although 5–10% die from respiratory failure.
1. Anticholinesterases are the mainstay of treatment in mild cases. Pyridostigmine is the usual one prescribed. Potassium supplements and potassium-sparing diuretics (e.g. spironolactone) may give additional improvement, but are rarely used these days.
2. It is important to avoid drugs that interfere with neuromuscular transmission, including streptomycin, gentamicin, quinidine and procainamide.
3. Sudden worsening of the patient’s symptoms so as to be life-threatening (because of respiratory failure) is called a myasthenic crisis. It is often precipitated by infection, which must be treated aggressively with antibiotics (not aminoglycosides) and intensive respiratory support. Mechanical ventilation and a course of plasmapheresis may be required.
4. Sometimes the problem may be excessive anticholinesterase inhibitor treatment (cholinergic crisis). Temporary suspension of drug treatment and monitoring of muscle strength may be all that is required for these episodes.
1. Steroids are indicated for generalised severe disease when anticholinesterases are inadequate. They are then needed in the long term. They may aggravate disease initially (in the first week to 10 days), so all patients should be observed closely when treatment is commenced.
2. Failed steroid treatment in patients with severe disease is an indication for immunosuppressive drug therapy (e.g. azathioprine, cyclosporin, mycophenolate). Azathioprine has been shown to be effective as a steroid-sparing agent and to reduce relapses and prolong remissions. It should not be used as initial management or on its own. There is less evidence for other treatment, however.
3. Rituximab has been tried in desperate cases. This chimeric antibody attaches to the CD20 membrane site of B lymphocytes and attracts killer T cells and antibodies that destroy the lymphocytes which make the pathological antibodies. A course of treatment is very expensive.
4. Thymectomy is advisable early for many patients with generalised myasthenia gravis if they are ACh-antibody positive. The exceptions are elderly patients or those with an easily inducible remission. Thymomas occur in 10% of cases (and of these, 25% are malignant) and thymic hyperplasia occurs in 65%. Of such patients, after resection, 70% show improvement and 25% of those who improve undergo remission. Causes of failed response to thymectomy include incomplete removal, ectopic tissue and fulminant disease.
5. Plasmapheresis is useful in acute situations such as in myasthenic crisis, preparation for surgery or in the peripartum period. Very ill patients may need repeated treatments.
The differential diagnosis of proximal muscle weakness is important. The ocular muscle dystrophies also need to be considered. The Lambert-Eaton syndrome is occasionally confused with myasthenia gravis. This syndrome results from presynaptic failure of release of acetylcholine, caused by small cell carcinoma of the lung (in 50% of cases) or autoimmune disease. In the Lambert-Eaton syndrome:
• there is proximal muscle weakness and pain, and power may increase on repeated effort; reflexes are reduced or absent
• the ocular and bulbar muscles are usually spared
• the EMG is helpful (high-frequency stimulation causes an increment, whereas low-frequency stimulation causes a decrement and muscle action potential amplitudes are low).
Symptoms may be reduced by 3,4-diaminopyridine (DAP: safe and effective) or guanidine; steroids and plasma-exchange therapy can also be effective. Some patients with small cell carcinoma of the lung have a neurological remission if the tumour is completely removed. Treatment with d-penicillamine may cause a mild reversible form of myasthenia.
This disease is not uncommon in the examination, as patients may be in hospital for an extended period and present management difficulties. It is the most common acute polyneuropathy and can affect both sexes and all ages.
1. Ask about the presenting symptoms of ascending motor weakness, their time course and whether they are decreasing or increasing. The patient may report difficulty breathing. Other symptoms include paraesthesiae or sensory loss (sensory neuropathy is usually minimal) and symptoms of cranial nerve palsies, particularly bulbar lesions (all cranial nerves except I, II and VIII can be affected).
2. Ask about a preceding respiratory or gastrointestinal infection (which occurs in up to 50% of cases 1–3 weeks beforehand – Campylobacter, mycoplasma, EBV and influenza). Also enquire about other precipitating events, such as surgical operation, vaccination, intercurrent malignant disease (e.g. Hodgkin’s disease), SLE and HIV infection.
3. Ask about previous episodes of disease (in chronic relapsing polyneuropathy).
4. Ask about evidence of autonomic neuropathy, such as postural hypotension, labile blood pressure, difficult to control arrhythmias and, rarely, sphincter dysfunction (see Table 16.42).
5. Ask about neuropathic pain.
6. Enquire about the social history, family support, etc.
1. Predominantly, distal muscle weakness without atrophy is present, although 25% have more proximal than distal weakness. The upper limbs may be more affected than the lower limbs. Tendon reflexes are reduced or absent concomitant with the degree of weakness. Muscle tenderness is common (one-third of cases).
2. Signs of autonomic neuropathy (severe postural changes in blood pressure and cardiac arrhythmias) must be looked for.
3. Sensory loss is usually minimal, but if present affects the posterior columns (vibration and proprioception) more than the spinothalamic tracts.
4. Always measure forced expiratory time.
5. Look for pressure sores and signs of deep venous thrombosis in bed-bound patients.
Guillain-Barré syndrome is a clinical diagnosis. Helpful tests include the following:
1. immune stimulus – identify the immune stimulus by Monospot test, cold agglutinins, tests for cytomegalovirus, HIV or Campylobacter
2. cerebrospinal fluid examination – look for a raised protein level and the relative lack of white blood cells in 90% of cases; 10% have 10–50 mononuclear cells/mL
3. respiratory function tests (FEV1, FVC) – assess the progressive involvement of respiratory muscles; the patient can progress rapidly (even over hours) to respiratory failure requiring intubation and should be admitted to hospital, even if only mildly affected
4. nerve conduction and EMG studies – many nerves may have to be studied to find abnormalities because this disease is patchy, but abnormalities include slowed motor conduction, conduction blocks, increased distal motor latencies, reduced sensory action potentials and increased F wave latencies. EMG evidence of denervation takes 10 days to 3 weeks to appear and may indicate axonal involvement with a worse prognosis.
Prognosis is good – most patients make a complete recovery over time (up to a year), but 2% die (usually of respiratory complications, pulmonary emboli, cardiac arrhythmias) and 10% have a major residual deficit. If the deficit does not diminish in 3 weeks or the patient has autonomic neuropathy, a poorer prognosis is more likely.
1. Physiotherapy is used to prevent contractures. Respiratory support in an intensive care unit is essential if the vital capacity is less than 1 L.
2. Plasmapheresis or intravenous gammaglobulin shortens the time to recovery from respiratory paralysis and hastens the return of mobility. They are equally effective and combined treatment offers no additional benefit. Treatment should be begun as soon as possible. Rapid improvement is much more likely if treatment is begun within 2 weeks of the first symptoms. Relapses may occur and are more common after intravenous gammaglobulin than after plasmapheresis.
3. Steroids (and ACTH) are not beneficial.
Infections such as glandular fever, acute viral hepatitis, Mycoplasma pneumonia, Campylobacter jejuni and HIV can cause Guillain-Barré syndrome. Post-influenza vaccine disease is rare. The differential diagnosis of acute ascending motor paralysis includes diphtheria, polio, polyarteritis nodosa, acute intermittent porphyria, tick or snake bites and rhabdomyolysis, arsenic poisoning and botulism. Critical illnessmyopathy or polyneuropathy must not be missed. Remember that diphtheria, botulism and myasthenia gravis usually begin with bulbar symptoms.
The differential diagnosis of autonomic neuropathy includes diabetes mellitus, alcoholism, acute intermittent porphyria and amyloidosis.
Transient ischaemic attacks and ‘funny turns’
Patients presenting with a ‘funny turn’ can pose a difficult diagnostic problem as there are many possible explanations. The problem may be neurological, cardiac, endocrinological or psychiatric. A careful history and physical examination should enable the candidate to produce a sensible differential diagnosis and management plan. Treatment is usually fairly straightforward once the diagnosis is made.
1. It may be possible from the history to establish whether cerebrovascular disease and, in particular, transient ischaemic attacks (TIAs) explain the funny turns.
a. TIAs occur suddenly; there is focal neurological loss that is maximal at onset and does not spread or intensify. By definition, the symptoms must resolve within 24 hours. Specific enquiry should be made about unilateral weakness or clumsiness, difficulty understanding or expressing spoken language, altered sensation unilaterally, and partial or complete loss of vision in one eye or bilateral blindness.
b. Faintness, confusion, simultaneous bilateral weakness, slurred speech and spinning sensations are not localising symptoms and are less suggestive of a TIA.
2. Neurological deficits that have lasted for longer than 24 hours are consistent with the syndrome of a completed stroke.
a. The absence of focal symptoms in a patient with severe headache and vomiting suggests subarachnoid haemorrhage. Vomiting and focal symptoms may occur with intracerebral haemorrhage, but headache is present in less than 50% of these patients.
b. In ischaemic stroke, the symptoms typically begin abruptly, often during sleep, and are not usually associated with headache or vomiting.
3. Presyncope refers to a sense of impending loss of consciousness, manifest as faintness or light-headedness and is often associated with sweating, nausea, anxiety and visual dimming.
a. Causes of this condition can include cardiac arrhythmias, postural hypotension, cough syncope and micturition syncope.
b. Vasovagal syncope or presyncope can often be diagnosed clinically if the history is typical: an episode begins with clamminess, sweating and nausea and often occurs in a crowded room or after something upsetting has happened.
4. Epilepsy needs to be considered in the differential diagnosis.
a. Partial epilepsy is usually accompanied by an aura or a warning (e.g. flashing lights, twitching of the face or a limb, unilateral tingling or numbness, buzzing noises or humming).
b. Primary generalised epilepsy begins with loss of consciousness.
c. Eyewitness accounts are crucial in making a diagnosis. Tongue-biting and incontinence with tonic–clonic movements suggest primary generalised epilepsy.
d. Remember that seizure activity may accompany cerebral hypoxia of any cause (e.g. Stokes-Adams attacks). A long period of drowsiness often follows a major seizure.
5. Vertigo is the illusion of movement of the self or the environment. The sensation may be rotational. Often nausea, vomiting, imbalance and anxiety are associated.
a. Causes of this condition include vestibular neuronitis, acute labyrinthitis, benign positional vertigo, Ménière’s disease, vertebrobasilar insufficiency, posterior fossa neoplasms, cerebellar haemorrhage and MS.
b. Cerebellar haemorrhage characteristically causes severe associated nausea and vomiting, and is of sudden onset.
c. Ask whether the vertigo is related to the position of the head (e.g. made worse by turning over in bed or by looking up). This symptom suggests labyrinthine disease, most commonly benign positioning vertigo.
6. Unsteadiness of gait may be secondary to a number of disorders of the peripheral or central nervous system. Drug side-effects, neoplasms, cerebellar and extrapyramidal diseases can present in this way.
7. Hypoglycaemia is an important, albeit rare, cause of funny turns and must always be considered in the differential diagnosis of suspected cerebrovascular disease. It is associated with hunger, sweating, tremor and tachycardia (owing to catecholamine release), as well as neurological dysfunction. Causes of hypoglycaemia include: too much insulin or oral hypoglycaemic agent and not enough food; reactive or postprandial, usually among patients with gastric surgery; or fasting (especially among patients with hypopituitarism, adrenal insufficiency, cirrhosis, alcoholism or rarely an insulinoma).
8. There are a number of cardiac causes of funny turns or syncope.
a. A dizzy feeling related to standing up and without any component of true vertigo suggests postural hypotension. This can be a complication of antihypertensive treatment, especially with vasodilating drugs, and occasionally occurs in patients with single-chamber ventricular pacemakers (pacemaker syndrome).
b. Orthostatic hypotension is common in the elderly and in patients with autonomic neuropathy (e.g. secondary to diabetes mellitus).
c. Episodes of complete heart block may complicate ischaemic heart disease or be caused by degenerative disease of the conducting system. These patients describe syncope occurring without warning. Unless they have been injured by the fall they feel normal again immediately.
d. Ventricular and supraventricular tachyarrhythmias may cause dizziness or syncope, possibly associated with palpitations. Ventricular arrhythmias are more likely in patients with known structural heart disease (e.g. previous infarction). Remember that antiarrhythmic drugs can cause bradycardia and are associated in some cases with dangerous proarrhythmic effects.
e. Patients with severe aortic stenosis may present with exertional syncope, which is usually associated with ischaemic-like chest pain.
9. Other conditions that need to be considered include episodes of hyperventilation or panic attacks. Patients who sigh often because of anxiety are rarely aware of any abnormality of their breathing. Their dizziness is often accompanied by a sensation of swaying. Transient global amnesia sometimes presents as a funny turn involving temporary disorientation and loss of memory.
10. Find out about risk factors and associated symptoms.
a. If a TIA or stroke is suspected, enquire about risk factors for vascular disease (in particular, smoking, hypertension, diabetes and hyperlipidaemia).
b. Neck pain may indicate arterial dissection.
c. Symptoms of connective tissue disease or thrombotic episodes may be relevant.
d. Ask for a list of all the drugs the patient has been taking. Enquire about medications that increase the risk of vascular episodes, including oral contraceptives and some peripheral vasodilator drugs that can lower blood pressure. Also ask specifically about sedatives, hypoglycaemic agents, anticonvulsants and drugs affecting cardiac conduction.
A complete examination of the neurological and cardiovascular systems is essential, but must be guided by the symptoms.
1. The fundi should be carefully examined for evidence of emboli, hypertensive changes, diabetic changes and ischaemic retinopathy. Test the visual fields (e.g. left or right half visual field loss in a carotid territory stroke). Look for nystagmus.
2. Carotid bruits should be listened for, but their absence does not exclude tight carotid stenosis. Unfortunately, even if a bruit is present, this does not necessarily indicate tight common or internal carotid artery stenosis, because external carotid artery stenosis can also cause a bruit.
3. If indicated, perform the Hallpike test for benign paroxysmal positional (positioning) vertigo (BPPV).
4. Check all the pulses. Decide whether atrial fibrillation is present. Test the blood pressure lying and standing for postural hypotension. Listen for murmurs (e.g. as a result of aortic stenosis, infective endocarditis, rheumatic heart disease or a prosthetic valve). Examine for peripheral vascular disease. Note the presence of an electronic pacemaker.
5. Palpate over the temporal areas for the tenderness of giant cell arteritis.
1. In patients with a suspected, but not typical, TIA it is worthwhile checking a full blood count, ESR (elevated in temporal arteritis and in connective tissue disease), fasting plasma glucose (for evidence of diabetes or hypoglycaemia), cholesterol (for hypercholesterolaemia), urinalysis (for evidence of renovascular disease) and an ECG (for evidence of ischaemic heart disease, arrhythmia or heart block). Look for a long or short QT interval. Patients in sinus rhythm, but with bifascicular or trifascicular block, may be having episodes of complete heart block. Serological testing for tertiary syphilis (Treponema pallidumhaemoglutination test (TPHA)) is rarely indicated.
2. A CT or MRI scan of the head (see Figs 12.3 and 12.4) should be performed for all patients with a TIA or stroke, as 5% of TIAs are caused by structural lesions. A CT scan is also worth performing in patients with established stroke to exclude haemorrhage, as this may alter management.
FIGURE 12.3 MRI of the brain showing a metastatic cerebellar tumour (arrow). Figure reproduced courtesy of The Canberra Hospital.
FIGURE 12.4 MRI of the brain showing a cerebellar infarct (arrow). Figure reproduced courtesy of The Canberra Hospital.
3. A carotid ultrasound should be performed in patients who have carotid territory TIAs. Suggestive features of a carotid artery TIA include monocular visual loss, unilateral sensory disturbances or weakness, or aphasia. Vertebrobasilar TIAs, on the other hand, may cause bilateral visual loss, weakness or sensory disturbance, and crossed sensory and motor loss. If a greater than 70% stenosis of the origin of the internal carotid artery on the symptomatic side is found, carotid angiography should be considered with a view to endarterectomy or angioplasty, which is of value in otherwise fit patients.
4. Transoesophageal echocardiogram (TOE) should be considered in any stroke patient with abnormalities on examination of the heart or with abnormalities on the ECG (or chest X-ray). It is also recommended when no other cause has been found for the episode. A TOE with contrast injection may reveal a patent foramen ovale. This known cause of paradoxical embolism is present in up to 30% of people. Trials are underway to establish the benefits (if any) of catheter-based closure of these when they are detected in patients with otherwise unexplained stroke, but remember that stroke is an uncommon cause of syncope.
5. Patients with atrial fibrillation should have their thyroid function checked and an echocardiogram performed to look at left ventricular size – a predictor of risk of embolic events. Rarely an intracardiac mass (usually a left atrial myxoma) is discovered. It is a rare cause of stroke and is often associated with systemic symptoms. Resection is usually possible.
6. In relatively young patients with a TIA (<50 years of age), careful attention to the possibility of a connective tissue disease is worthwhile. Check an antinuclear antibody, anticardiolipin antibody (because of antiphospholipid antibody syndrome) and procoagulation profile.
This will, of course, depend on the diagnosis in the particular case. If a TIA is likely, you should plan to discuss vascular risk factor treatments, anti-platelet therapy and the role of carotid endarterectomy.
1. There is a direct relationship between high blood pressure, smoking and cholesterol level and an increased risk of ischaemic stroke as well as coronary artery disease. Therefore, management of risk factors by conservative means or with drugs is essential.
2. Anti-platelet therapy reduces the risk of stroke in patients prone to TIAs. Low-dose aspirin (between 75 and 100 mg per day) is a reasonable regimen to use. Clopidogrel is an adenosine diphosphate (ADP) inhibitor and an expensive alternative to aspirin. Recurrence of symptoms when patients are already taking aspirin is an indication for the combination of aspirin and dipyridamole. Aspirin and clopidogrel in combination have not been shown to be more effective than aspirin alone. At least 2 years of treatment is necessary after a TIA, but many would recommend the lifelong use of anti-platelet agents.
In those with atrial fibrillation not caused by rheumatic heart disease, aspirin reduces the risk of a recurrent event by one-fifth and warfarin reduces it by one-half. The risk of major haemorrhage with warfarin use is less than 2% per year, especially if the INR is kept below 2.5. Most cardiologists would recommend warfarin or anticoagulation with one of the newer direct thrombin inhibitors or anti-Xa drugs, to any patient in atrial fibrillation who has had a definite or even a possible embolic event and in patients with an elevated CHADS score (p. 79). In those who have rheumatic heart disease, mechanical prosthetic heart valves or other cardiac sources of emboli, long-term anticoagulation with warfarin is strongly recommended.
3. Carotid endarterectomy or angioplasty is worth considering in patients with a TIA in the carotid territory within the preceding 6 months who have documented severe (>70%) stenosis of the origin of the internal carotid artery on the symptomatic side. Surgery in such cases is definitely superior to medical therapy. A decision to operate should be based on the availability of surgical expertise and the complication (stroke) rate of a particular surgical unit.
4. Other treatment will depend on the final diagnosis and can range from anticonvulsants to pacemaker insertion. It is usually unwise to treat these patients without an established diagnosis.