This patient was diagnosed as having myasthenia gravis and was referred urgently to a neurologist. Myasthenia gravis is sometimes restricted to the ocular system and can present as a variable gaze palsy that is difficult to interpret in terms of individual muscles or cranial nerves. There is not always a history of fatiguability. Some of the many causes of diplopia are listed in Table 15.1.

Table 15.1 Causes of diplopia

Muscle/obstructive	Thyroid eye disease
	Orbital masses
	Orbital pseudotumour (ocular myositis)
	Myasthenia
	Latent squint (visible when tired)
Cranial nerves	Mass lesion in path of III, IV or VI nerves
	Mononeuritis multiplex
	False localising due to raised intracranial pressure
Central	Brainstem inflammation, demyelination, brainstem mass lesion, infarction, haemorrhage

Treatment

Treatment of myasthenia gravis includes oral anticholinesterases, e.g. neostigmine or pyridostigmine (dosage gradually increased), steroids, immunosuppression, and plasmapheresis. Restricted ocular myasthenia carries a better prognosis, as swallowing and the respiratory muscles may be permanently spared.

Thymectomy may be necessary, even in patients without a thymoma.

This woman remains well on pyridostigmine at regular intervals through the day but in view of the high doses required (>360 mg) she was put on immunosuppressive therapy (azathioprine and steroids). She got side effects of abdominal colic from the pyridostigmine and this was helped by oral propantheline.

Further reading

Chaudhuri A, Behan PO. Myasthenic crisis. QJM. 2009;102:97–107.

Case history (3)

A 30-year-old, 27-weeks pregnant woman complains of 4 weeks of headache, nausea, brief one-second episodes of visual loss and horizontal double vision that is worse on distance gaze.

On examination she is found to have bilateral papilloedema (Fig. 15.3) and bilateral restriction of lateral gaze consistent with sixth nerve palsies.

Figure 15.3 Papilloedema.

What action would you take?

• MR or CT scan of head.

In this case the ventricles were normal and therefore it was safe to proceed to a lumbar puncture. The opening pressure was recorded at 30 cm (normal pressure < 25 cm). A volume of CSF (usually around 20 mL) should be removed, so as to approximately halve the opening pressure.

Diagnosis.

This woman has idiopathic intracranial hypertension (IIH). This is most common in overweight females and rare in males.

Precipitating factors

• Vitamin A excess (including retinoids)

• Steroids.

Management

Repeated lumbar puncture and removal of CSF, e.g. every 1–2 weeks, has been widely used but is probably not helpful. Drugs such as acetazolamide can be helpful. Treatment is directed primarily at preventing visual loss due to uncorrected papilloedema and secondly for relief of headache/diplopia. The visual fields must be checked formally at intervals by screen perimetry to monitor any enlargement of the blind spots. If repeat puncture is unsuccessful in this usually self-limiting condition, optic nerve fenestration or even ventriculoperitoneal shunting may be necessary.

Remember

• There are a number of secondary causes of raised intracranial pressure without dilated ventricles or other space-occupying lesion, e.g. venous sinus thrombosis and meningeal disease

• MRI/MR venography and examination of CSF constituents is therefore mandatory.

Progress.

This patient’s condition improved post-partum.

Loss of vision

Case history (1)

A 64-year-old man presents in the A&E with visual loss in the right eye for 3 hours. He had a previous episode several months earlier. He describes the loss as a horizontal screen descending over his vision. You are called by the A&E officer to give an opinion. When you arrive the visual loss has recovered.

What is the most likely diagnosis?

Temporary monocular visual loss with a horizontal defect in this age group is very likely to be amaurosis fugax. This is often caused by thromboembolism in the ophthalmic artery and is a symptom of carotid stenosis.

Investigation and management

See pp. 175 and 176.

What is the differential diagnosis?

Transient ischaemic attacks (TIAs) are usually diagnosed clinically. Other causes of visual loss are shown in Table 15.2.

Table 15.2 Causes of acute or transient visual disturbance

Ophthalmological	Neurological
Glaucoma	Optic neuritis/demyelination
Amaurosis fugax	Compressive lesion of the optic nerve, chiasm, tract
Giant cell (temporal) arteritis	TIA/stroke of posterior cerebral circulation
Anterior ischaemic optic neuropathy	Migraine
Central retinal vessel occlusion	Occipital, temporal, parietal haemorrhage
Vitreous haemorrhage	Occipital, temporal, parietal space-occupying lesion
Retinal detachment	Temporal lobe epilepsy
Uveitis, keratitis	Raised intracranial pressure

Remember giant cell arteritis, which causes acute visual loss. It responds to steroids (see p. 182).

Abrupt and progressive visual loss over days is also seen in elderly hypertensives. There is often disc swelling and later disc pallor. This is due to an arteriopathy of the posterior ciliary artery resulting in ischaemia of the optic disc causing an anterior ischaemic optic neuropathy. Urgent management by a specialist is with heparin infusion and mannitol.

Progress.

This patient’s carotid doppler showed a 70% stenosis in the carotid artery and an internal carotid endarterectomy was performed. He has had no further episodes.

Case history (2)

A 24-year-old woman complains of several attacks of loss of vision, lasting up to 1 hour, in the right eye, accompanied by a left-sided pounding headache. Closer questioning reveals that the defect is in fact in the right visual field of both eyes.

Visual hemifield disturbance, sometimes with shimmering or jagged line scotomata, is a relatively common aura experienced by patients with migraine. Occasionally there is no headache.

If the symptoms are dramatic or atypical, or especially if there are any fixed symptoms or signs, an MRI scan should be performed to check for an underlying vascular lesion such as an arteriovenous malformation or underlying epileptogenic lesion, including occipital tumour.

Treatment

• Paracetamol 1 g, aspirin 900 mg (dispersible formulation) or an NSAID, e.g. ibuprofen 400–600 mg or naproxen 500 mg is given, as early as possible during an attack. Gastric emptying is reduced during the attack so dispersible formulations are preferred.

• Antiemetics (e.g. metoclopramide 10 mg or domperidone 10 mg).

• If these measures are ineffective, use a 5-hydroxytryptamine (5HT)_1B/_1D serotonin receptor agonist (triptan). These drugs relieve both the pain and the nausea. Triptans should be avoided in patients with vascular disease or uncontrolled/severe hypertension. Triptans should be given at the onset of the headache (e.g. during the aura phase). There are several triptans available with a spectrum of efficacy, e.g.:

• Sumatriptan 25–100 mg at onset of headache, repeat if necessary after at least 2 hours, max. 300 mg in 24 hours; SC 6 mg sumatriptan produces highest efficacy and most rapid response.

• Zolmitriptan 2.5 mg at onset, repeat if only partial response after 2 hours; 5 mg also available.

• Rizatriptan 10 mg at onset, repeat after 2 hours if only partial response.

• Oro-dispersible formulations exist for some triptans but absorption is slower.

• If there is no response to an initial dose, do not persist with subsequent doses during the same attack. However, the drug may be effective in subsequent attacks.

Progress.

This patient’s headache improved with paracetamol and sumatriptan. On subsequent episodes of migraine she was able to self-administer sumatriptan, an anti-emetic and paracetamol at the onset of her headaches. With this regimen her migraine has been manageable.

Further reading

Loder E. Triptan Therapy in Migraine. N Engl J Med. 2010;363:63–70. 2010

Bell’s palsy

Case History

You are called to see a 45-year-old man who woke up this morning with a ‘numb’ left face, a droopy left eyelid and drooling from the left side of his mouth.

On examination, it is apparent that his ‘numbness’ represents left facial weakness in the upper and lower distributions. There is no sensory loss and no lesions of the skin around or inside the ear (Ramsey Hunt Syndrome).

An acute VII nerve lesion, Bell’s palsy (Fig. 15.4) is usually due to a viral infection (often herpes simplex). It involves the VII facial nerve (motor only) with occasionally a loss of taste on the tongue and hyperacusis. There should be no sensory loss or other cranial nerve involvement.

Figure 15.4 Bell’s palsy.

Treatment is with steroids (60 mg prednisolone for a week) and tailing down over the subsequent 1–2 weeks, with an anti-viral, e.g. aciclovir given if diagnosed early. The patient should be reassured and the cornea protected if exposed. Sometimes recovery is incomplete and faulty reinnervation of the facial muscles or of the lacrimal gland may occur. Relapses are seen.

Bilateral or recurrent Bell’s palsy, or one that shows no recovery after several weeks, should be investigated with an MRI scan, possibly CSF analysis, and investigations for causes of mononeuritis multiplex.

Further reading

De Almeida JR, Al Khabori M, Guyatt GH, et al. Combined corticosteroid and antiviral treatment for Bell palsy: a systematic review and meta-analysis. JAMA. 2009;302:985–993.

Vertigo

Vertigo, the definite illusion of movement of the subject or surroundings, typically rotatory, indicates a disturbance of the vestibular nerve, brainstem or, very rarely cortical function. Deafness and tinnitus accompanying vertigo indicate involvement of the ear or cochlear nerve.

Case history (1)

An 85-year-old woman presented to A&E with a history of severe nausea, vomiting and dizziness, which started on waking one morning 2 weeks previously. She was confused and dehydrated. On rehydration she was able to give a clear history of true vertigo (the sensation of the environment spinning or rotating about her). The symptoms were precipitated by head movement, especially when she turned her head in bed.

On examination she has a normal eye movement. The rotational nystagmus in both eyes was brought on by sudden head movements (Hallpike’s manoeuvre).

What is the likely diagnosis?

This history is typical of vestibular neuronitis, the aetiology of which is uncertain. It occurs at any age. Recovery generally takes place to a large extent over 2–3 weeks, although complete recovery might take several months. Cinnarizine and other vestibular suppressants give symptomatic relief but are best avoided in the long term.

Peripheral vestibular lesions are characterised by positional vertigo, i.e. influenced – often in a stereotyped way – by head movement. This is manifest in the Hallpike’s test (Information box; Fig. 15.5), which characteristically reveals a rotational nystagmus.

Figure 15.5 Hallpike manoeuvre for diagnosis of Benign paroxysmal positional vertigo.

Information

Hallpike’s test

The patient is sat on a couch with her eyes open and facing the side of the lesion. The examiner swings the patient backwards so that she is supine and her head is below horizontal. Nystagmus following a latent interval of a few seconds is commonly noted if the test is positive.

A central vestibular lesion is sometimes also positional but generally fails to habituate (i.e. on Hallpike’s testing, continued repetition of the same movement results in no reduction in the unpleasantness or in the nystagmus).

The definitive investigation to differentiate the two sites and to lateralise the lesion is by caloric tests.

Remember

• If there is a suspicion of a central lesion, an MRI scan should be performed

• Always check for associated deafness, tinnitus, cranial nerve lesions or cerebellar disturbance for early identification of a cerebellopontine angle lesion, most commonly an VIII nerve Schwannoma (‘acoustic neuroma’).

What is the likely diagnosis?

Benign paroxysmal positional vertigo (BPPV). This is a relatively common disorder presenting with true vertigo, particularly on head movement. There are often vague ‘vestibular hypersensitivity’ symptoms, especially precipitated when there are conflicting visual inputs such as being stationary in a fast-moving visual field. Occasionally, the vertigo may be so sudden and dramatic as to present as a blackout.

Diagnosis

Largely clinical, although caloric testing may reveal mild dysfunction and MRI helps to exclude other conditions.

Management

Vestibular physiotherapy in the form of Cawthorne–Cooksey exercises (repetitive eye and head movements) and vestibular suppressants (e.g. β-histine). In some cases the cause is said to relate to fragments of calcification in the semicircular canals; some specialists perform the Epley manoeuvre; a gentle manipulation and rotation of the head, in an attempt to dislodge these fragments away from the receptors. Some severe cases may be successfully treated by surgical section of the nerve to the ampulla of the posterior semicircular canal.

Progress.

The patient has vestibular physiotherapy and was taught to continue the exercises at home. She continues to have dizziness in crowds but is better.

Case history (3)

A 70-year-old man presents with sudden onset of vertigo, vomiting, gait unsteadiness and left facial numbness.

On examination there is coarse unidirectional nystagmus, reduced left corneal reflex, left Horner’s syndrome, mild dysphagia and palatal deviation to the right, left-sided ataxia and impaired pin-prick on the right arm and leg.

This is a partial left lateral medullary syndrome due to a stroke in the territory of branches of the posterior or anterior inferior cerebellar arteries. The vertigo is usually not positional. Nystagmus of brainstem origin is often coarse, may be in any direction, often unidirectional and sometimes monocular.

Management

As for a stroke; see below.

Stroke

This is the sudden onset of focal neurological symptoms caused by interruption of the vascular supply to a region of the brain (ischaemic stroke) or intracerebral haemorrhage (haemorrhagic stroke). It is a common cause of mortality and physical disability.

Pathophysiology

Ischaemic stroke (infarction of central nervous tissue) results from cerebral infarction secondary to either arterial thromboembolism or emboli arising from the heart (e.g. in atrial fibrillation, mural thrombus after acute myocardial infarction, or rarely from vegetations in infective endocarditis).

Cerebral haemorrhage is often caused by microaneurysm rupture in small penetrating arteries in hypertensive patients. It can also occur by rupture of an aneurysm or arteriovenous malformation or by amyloid angiopathy in older patients. It accounts for ~15% of strokes.

Other causes of stroke in younger patients include arterial dissection, venous sinus thrombosis, thrombophilia, vasculitis and paradoxical embolisation through a patent foramen ovale.

Case history (1)

A 70-year-old man presents with a two and a half hour history of right-sided arm, leg and face weakness and loss of speech. He has no headache and is mildly confused. He has a history of ischaemic heart disease.

On examination he has a global dysphasia, full visual fields, upper motor neurone distribution right facial weakness and dense weakness (UMN distribution) of the right side with absent reflexes and an upgoing plantar response on that side. His pulse was regular.

A clinical diagnosis of left middle cerebral artery ischaemic stroke is made.

What immediate action would you take in this case (i.e. cerebral infarct)?

• Is thrombolysis to be considered? Yes. This stroke occurred less than 180 min ago, therefore immediate diffuse weighted MRI (more sensitive than CT) if available should be performed (Fig. 15.6). Unfortunately it was not available for this patient.

• CT will distinguish haemorrhage immediately but infarction cannot be seen early on (Fig. 15.6a).

Figure 15.6 a) CT of a Middle cerebral infarct performed in the early stages showing subtle changes in right MCA territory. b) MRI of same region done at the same time as the CT showing the full extent of the damage.

(Courtesy of Dr Paul Jarmon).

An early CT scan is also useful in stroke to check for subarachnoid or intracerebral haemorrhage and to help exclude other conditions that may masquerade as stroke, such as tumour, cerebral abscess and cerebral venous sinus thrombosis.

In this patient the CT showed no evidence of haemorrhage, therefore cerebral infarction was likely.

He was given IV tissue plasminogen activator (tPA) after ruling out contraindications and consenting the patient as soon as possible (MINUTES COUNT). Total dose 0.9 mg/kg; maximum 90 mg. Give 10% of total dose over 1 min and the remainder over 60 min by infusion (thrombolytic therapy is recommended by Cochrane reviews).

(If there had been a contraindication to the therapy or if thrombolysis is not available, he would have been given 300 mg aspirin.)

Remember

• If cerebral haemorrhage is shown on CT: do NOT give any therapy that might interfere with clotting, e.g. aspirin or heparin

• If posterior fossa haemorrhage: refer to neurosurgeons for possible emergency clot evacuation.

Further reading

Wechsler LR. Intravenous thrombolytic therapy for acute ischemic stroke. N Engl J Med. 2011;364:2138–2146.

Case history (2)

A 56-year-old man presents with weakness of the left hand and face lasting 3 hours and resolving gradually. He had a similar episode 3 months earlier with complete recovery. He is a type 2 diabetic and a smoker. A Doppler ultrasound reveals that he has a 90% stenosis at the origin of the right internal carotid artery. This is a transient ischaemic attack (TIA).

Transient ischaemic attack (TIA)

This is a transient episode of neurological dysfunction caused by focal brain, spinal cord or retinal ischaemia without acute infarction. The previous definition with its arbitrary 24-hour time scale is no longer used as the end point is now tissue injury.

Examples include:

• anterior circulation – sudden transient loss of vision in one eye (amaurosis fugax), aphasia, hemiparesis; or

• posterior circulation – diplopia, ataxia, hemisensory loss, dysarthria, transient global amnesia.

TIAs may herald the onset of stroke (one-quarter of patients developing stroke have had a TIA, usually within the previous week).

The ABCD² score can help to stratify stroke risk in the first 2 days.

• Age > 60 years	1 point
• BP > 140 mmHg systolic and/or > 90 mmHg diastolic	1 point
• Clinical features:
Unilateral weakness	2 points
Isolated speech disturbance	1 point
Other	0 points
• Duration of symptoms (min)
> 60	2 points
10–59	1 point
< 10	0 points
• Diabetes
Present	1 point
Absent	0 points