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

A score of < 4 is associated with a minimal risk, whereas > 6 is high risk for a stroke within 7 days of a TIA.

• If patients are at a high risk of a TIA, i.e. ABCD² score > 4, or have had two recent TIAs, especially within the same vascular territory, they should be admitted for investigation and treatment (see below).

• All patients should be referred to a TIA clinic and ideally seen within 24 hours. Investigation and treatment should be regarded as urgent and should be completed within 10 days.

Further reading

Brott G, Hobson RW 2nd, Howard G, et al. Stenting versus endarterectomy for treatment of carotid artery stenosis. N Engl J Med. 2010;363:11–23.

Rothwell PM, Algra A, Amarenco P. Medical treatment in acute and long-term secondary prevention after transient ischaemic attack and ischaemic stroke. Lancet. 2011;377:1681–1692.

Case history (3)

A 40-year-old man presents with a 1-week history of headache followed by loss of speech and a right hemiparesis. His weakness worsens over the next 24 h and he becomes confused. A CT scan is normal at this time. A subsequent MRI scan reveals an infarct in the left frontal lobe with small haemorrhages elsewhere in the hemispheres. His ESR and autoantibodies are normal. CSF analysis reveals 35 lymphocytes/mm³ but is otherwise normal. A right frontal brain biopsy reveals primary cerebral granulomatous angiitis (a rare necrotising inflammation with granulomatous vasculitis of the brain and meningeal vessels). He is treated with high-dose steroids and cyclophosphamide.

What are the causes of strokes in this young age group?

In the younger age group, other causes of stroke, such as vasculitis or structural cardiac lesions, occur. In many of these conditions, specific treatment is indicated. Cerebral vasculitis is difficult to diagnose because systemic inflammatory markers may be normal. The CSF and intra-arterial angiography are sometimes also normal. Even a cerebral/meningeal biopsy may miss involved vessels because the condition is often patchy.

Progress.

This patient was initially treated with high dose steroids and cyclophosphamide. The steroids were reduced gradually and oral cyclophosphamide continued for 6 months.

Further reading

Cramer SC. Brain Repair after Stroke. N Engl J Med. 2010;362:1827–1829.

Subdural haemorrhage

This is caused by venous bleeding in the subdural space from rupture of a vein. It usually follows a head injury, often trivial.

Case history

A 77-year-old woman was admitted 2 weeks previously with failure to manage at home alone. There had been a 2-year history of cognitive decline that seemed to have accelerated to precipitate the admission.

On examination, she was confused, unable to repeat a five-digit number, disorientated and had an upgoing left plantar. Her Glasgow Coma Score (GCS, p. 492) was 12.

Management

The management of subdural haematomas depends on their size and the severity of symptoms. Small ones may simply be managed conservatively with follow-up CT scanning. Larger or more acutely symptomatic subdurals should be surgically evacuated.

Progress.

This patient had an acute subdural haemorrhage which precipitated her deterioration. This was managed surgically with overall treatment in her cognitive state.

Parkinson’s disease

Parkinson’s disease is a neurodegenerative disorder affecting nigrostriatal dopaminergic cells, as well as other brain cells.

It causes a combination of tremor, rigidity and akinesia, developing slowly over many months or years.

Case history

A 75-year-old man with Parkinson’s disease presented with uncontrollable gyrating movements of his arms and legs. On obtaining a detailed history it transpired that he was on levodopa therapy. This had recently been increased to co-careldopa 50/200 (a mixture of carbidopa and levodopa) three tablets × 4 daily.

What is the problem?

This patient has dyskinesia – a common, late side effect of levodopa (LD) therapy for parkinsonism. About 10% of patients per year of therapy will develop such dyskinesias, involving uncontrollable choreoathetoid movements and dystonic posturing. At this stage in the illness, the severity of dyskinesia is dose dependent and so a balance has to be struck between ‘off’ symptoms of bradykinesia and rigidity and ‘on’ dyskinetic symptoms. In this case, the co-careldopa was prescribed at too high a dose.

When commencing levodopa therapy, patients are generally started on co-careldopa 25/100 or co-beneldopa (100 mg/25 mg tablets: a mixture of benserazide hydrochloride and levodopa in proportions of 1 : 4) × 3 daily. These drugs consist of a combination of levodopa and a peripheral DOPA decarboxylase inhibitor (DDI) to prevent inappropriate peripheral activation to dopamine. The dose of these drugs can be gradually increased in amount and frequency as the underlying disease worsens.

Alternatively, patients may receive a controlled-release preparation; co-careldopa 50/200 has nearly twice the bioavailable strength of straight careldopa but the co-beneldopa (25/1000) preparation is a more equivalent dose. The controlled release preparations may be given once at night to help with nocturnal or early morning ‘off’ symptoms, or may be given two to three times a day alone or in combination with straight levodopa in an effort to smoothen fluctuating symptoms.

Information

Some physicians start off with controlled release preparations. This is to minimise dose fluctuations that may result in dyskinesias later in the course of the disease, but there is no clear evidence for this protective effect.

Occasionally, dyskinesias occur in relation to dramatic fluctuations in levodopa levels rather than to high peak levels; the solution in this situation is to place the patient on a higher dose of longer-acting medication.

Other treatment available

• Exercise and physiotherapy are useful.

• Initiate pharmacological treatment when there is impairment/disability resulting from symptoms.

• Early treatment with monoamine oxidase B (MAOB) inhibitors (selegiline or rasagiline) may delay the need for more definitive dopamine replacement therapy by several months.

• Dopamine agonists (DAs) are used in patients below 70 years. Although they are less effective and less well tolerated than LD, they are also associated with fewer long-term motor complications.

• In older patients (i.e. more severely affected at diagnosis) start LD + DDI (co-beneldopa or co-careldopa) because of fewer side effects.

• Non-ergot DAs (pramipexole and ropinirole oral 3 times daily, or once daily with slow-release formulations, rotigotine via transdermal patch) are used in preference to ergot-derived drugs.

• All patients with PD will eventually require treatment with LD, often in combination with a DA. A typical starting dose is 50 mg of LD (e.g. co-careldopa 62.5 mg) 3 times daily, increasing after 1 week to 100 mg 3 times daily.

Progress.

This patient was put on a lower dose of co-careldopa and the dyskinesia settled.

Further reading

Lees AJ, Hardy J, Revesz T. Parkinson’s disease. Lancet. 2009;373:2055–2066.

Multiple sclerosis (MS)

MS is an autoimmune disease of unknown aetiology. It causes plaques of demyelination throughout the brain and spinal cord. Acute relapses are caused by focal inflammatory demyelination which causes a conduction block. These plaques can be demonstrated using an MRI scan (Fig. 15.8).

Figure 15.8 Multiple sclerosis – showing plaques in the posterior column and lateral corticospinal tracts.

(Courtesy of the late Ian MacDonald).

Case history (1)

A 28-year-old man presents with several days of pain and progressive loss of vision in one eye.

Examination showed diminished visual acuity 6/36 and disc swelling (papilloedema). He had previously had an episode of difficulty in walking and urinary incontinence which had recovered fully after several weeks.

What is the problem with his eyes?

The swelling of the disc, along with diminished visual acuity, suggests optic neuritis as other causes of papilloedema do not usually give visual disturbance. Optic neuritis is a common early presentation of multiple sclerosis (MS). The previous history suggesting an episode of transverse myelitis (inflammation of the cord) indicates dissociation in space and time, providing strong clinical support for the diagnosis of multiple sclerosis.

What action would you take?

• An MRI should be performed to look for demyelinating lesions of MS.

• CSF analysis for oligoclonal bands is usually unnecessary to further corroborate the diagnosis.

• Visual evoked potentials are likely to be delayed in the affected eye but may also reveal subclinical involvement of the other eye, providing evidence for dissociation in space.

• Medication. Recovery after an episode of optic neuritis is aided by intravenous methylprednisolone, e.g. 1 g/day for 3 days.

Progress.

This patient’s vision improved following his steroid therapy. However, the MRI showed demyelinating lesions of MS and he is being followed up in the Neurology Clinic.

Case history (2)

A previously well 25-year-old woman develops double vision, vertigo, unsteadiness, as well as speech and swallowing problems over 2 days. She is admitted to hospital where she rapidly deteriorates, becoming confused and hypoxic. She requires ventilatory support. An MRI scan reveals a number of small bilateral periventricular white matter lesions and lesions in the brainstem and cerebellar peduncles. She is given intravenous methylprednisolone and recovers well over the next 2 weeks apart from residual mild vertigo and intermittent diplopia.

Remember

Multiple sclerosis may sometimes present dramatically as a brainstem syndrome with central respiratory problems and rapid severe bulbar failure. Early supportive management and steroids is essential in such cases. There may be excellent recovery following the relapse. Patients with known MS who suffer a relapse involving bulbar function or dysarthria should similarly be carefully observed.

Case history (3)

A patient with known multiple sclerosis with frequent severe relapses, bladder instability and incontinence and painful leg spasms wonders if anything can be done for her incurable condition.

What would you suggest?

Many forms of treatment have been marketed, but none has been shown to improve outcome.

• Acute relapses. Short courses of steroids, such as IV methylprednisolone 1g/day for 3 days or high-dose oral steroids, are used widely in relapses and do sometimes reduce severity. They do not influence long-term outcome.

• Preventing relapse and disability. Beta-interferon (both INF β-1b and β-1a) by self-administered injection is used in relapsing and remitting disease. This is defined as at least two attacks of neurological dysfunction over the previous 2 or 3 years followed by a reasonable recovery. IFN β1b is also used for secondary progressive MS. Interferon certainly reduces relapse rate in some patients and prevents an increase in lesions seen on MRI. Unwanted effects are flu-like symptoms and irritation at injection sites. Beta-interferons are expensive.

• Glatiramer acetate, an immunomodulator, has been shown to reduce relapse frequency in ambulatory patients with relapsing remitting MS – similar to beta-interferon.

• Natalizumab is a monoclonal antibody which inhibits migration of leucocytes into the central nervous system by inhibitory α-4 integrins found on the surface of lymphocytes and monocytes. It is useful in severe, relapsing remitting MS that is unresponsive to other treatments. It is associated with a risk of progressive multifocal leucoencephalopathy (PML) and all patients need close surveillance for this and hypersensitivity reactions.

• Alemtuzumab, an anti-CD52 monoclonal antibody that destroys T- and B-cells, reduces disease activity.

• Mitoxantrone is used in primary progressive MS in specialist centres. It is potentially cardiotoxic and myelosuppressive.

• New oral disease modifying drugs, e.g. fingolimod, a sphingosine-1-phosphate receptor modulator, and cladribine (both given orally), an immunomodulator of lymphocytes, have shown benefit in ongoing trials.

Progress.

This patient was admitted for reassessment. She was treated with baclofen for her spasms and spasticity and gabapentin for neuropathic pain. An anti-muscarinic (oxybutin) was tried for her urinary problems but eventually she was taught to self-catheterise herself intermittently. The physiotherapists, occupational therapists and a social worker were asked to review her. Disease modifying therapy was thought to be inappropriate for her advanced condition.

Further reading

Chataway J, Miller DH. Multiple sclerosis – quenching the flames of inflammation. Lancet. 2011;378:1759–1760.

Frohman EM, Wingerchuk DM. Transverse Myelitis. N Engl J Med. 2010;363:564–572.

Pelletier D, Hafler DA. Fingolimod for multiple sclerosis. New Engl J Med. 2012;366:339–347.

Encephalitis

This is an inflammation of the brain parenchyma which is often due to a virus.

Case history (1)

A 45-year-old man presents with a one week history of malaise, followed by increasing confusion, headache, meningism and a seizure.

On examination he was confused, with a Glasgow Coma Score of 10. He had fever, neck stiffness and hyper-reflexia of the left arm and leg.

Diagnosis.

A tentative diagnosis of an encephalitis was made.

What action would you take?

• Supportive care: including respiratory support if necessary.

• Treatment of any seizures: ictal and post-ictal states are a reversible element of changes in conscious level.

• CT scan showed no space-occupying lesion.

• Lumbar puncture: there was a lymphocytosis.

• Serology and PCR: for likely aetiological agents (see below).

• If there is even a remote possibility that the cause is HSV1, start aciclovir immediately, intravenous 10 mg/kg × 3 daily. HSV is treatable; most other causes are not (Box 15.1). Patients have been known to relapse and respond to further treatment.

Remember

• Most cases of viral encephalitis present in the same way, the symptoms being milder than those for a bacterial meningitis. In many cases the viral cause can be worked out from the epidemiological pattern, e.g. from the geographical area where the disease was contracted and the season of the year.

• The term ‘encephalitis’ encompasses any acute febrile illness, perhaps with some meningeal involvement, that is accompanied by acute generalised or focal cerebral disturbance. Thus there is considerable overlap with meningitis.

Further investigations

• An MRI scan showed temporal oedema

• An EEG excluded generalised or complex partial status epilepticus

• If there is a possibility of immunosuppression (as a result of AIDS, lymphoproliferative disorders or iatrogenic) this should be investigated

Progress.

The MRI was highly suggestive of an HSV1 encephalitis and this was confirmed by serology and PCR. The patient was treated with IV aciclovir. Although he survived he was left with a significant residual deficit. He was sent for rehabilitation. He had problems with his memory, particularly common following HSV1 encephalitis.

Remember

• All cases of encephalitis in developed countries should be given aciclovir

• HSV is treatable; most other causes are not.

Case history (2)

A 25-year-old woman has an upper respiratory tract infection. Following recovery she becomes drowsy over a period of 48 h.

On examination she is apyrexial with a GCS of 9. She has abnormal eye movements and gaze-evoked nystagmus. There is marked spasticity in the limbs.

Investigations. CT shows effacement of cerebral sulci but it is safe to do a lumbar puncture. Lumbar puncture reveals 40 lymphocytes/mm³. She requires intubation to protect the airway.

A provisional diagnosis of HSV1 encephalitis is made.

Follow-on. A subsequent MRI scan reveals diffuse and confluent T2 hyperintensities in the periventricular white matter, in the brainstem and also within cerebral grey matter.

What is the diagnosis?

Acute disseminated encephalomyelitis (ADEM). This is considered to be a post-viral (sometimes post-mycoplasma), mainly white matter inflammatory condition, although the distinction from a direct viral encephalitis may be blurred. At the other end of the scale, the distinction from a severe initial attack of multiple sclerosis might also be unclear, although the latter attack is usually milder, more likely to be associated with CSF oligoclonal bands, and is characterised in retrospect with repeated attacks. However, treatment of both ADEM and multiple sclerosis attacks is similar, namely with high doses of steroids. Because of the nature of presentation of ADEM, anti-virals are usually also given.

Progress.

She is treated with intravenous methylprednisolone followed by a course of oral steroids and made a good recovery after several weeks, with some residual pyramidal gait difficulty.

Falls

Case history

A 70-year-old man presents with recurrent falls. On examination he has a rigid increase in tone, worse in the trunk than the limbs, marked bradykinesia and extreme mental slowness. He is unable to move his eyes vertical or laterally. He walks with a rather upright gait. He is thought to have Parkinson’s disease but has had a poor response to levodopa.

What is the diagnosis?

This man has progressive supranuclear palsy (PSP; also known as Steele–Richardson syndrome). Parkinson’s disease usually results in falls late on in the disease. Early falls should lead to suspicion of PSP or multisystem atrophy (which does not cause early cognitive problems).

Information

Steele–Richardson syndrome

• Parkinsonism

• Axial rigidity

• Dementia

• Defective upward-and-lateral gaze

Some common causes of falls are listed below. Some simply relate to stance or gait difficulties.

Causes of falls

Progress.

This patient continued to deteriorate and died of pneumonia 6 months later.

Case history

A 65-year-old woman is worried she has epilepsy. She suffers repeated falls when walking outside. There is no warning before falling, she tends to graze her knees and hands and recovers immediately in a state of embarrassment. If she loses consciousness at all, it could only be for a split second because she is certainly aware when she hits the ground.

There is no abnormality on examination.

What is the diagnosis?

The diagnosis is drop attacks. These are benign episodes that commonly occur in middle-aged to elderly women. There is no loss of consciousness and they are not considered epileptic (see p. 503). They are due to sudden changes in lower limb tone, presumably brainstem in origin.

Progress.

This patient was reassured that she did not have epilepsy and was helped by using a walking stick.

Further reading

Dykes PC, Carroll DL, Hurley A, et al. Fall prevention in acute care hospitals. JAMA. 2010;304(17):1912–1918.

Traumatic brain injury

Case history (1)

A 25-year-old man is knocked unconscious by a blow from a sledgehammer. He regains consciousness after a few minutes and attends A&E. He is nauseated and in pain but reasonably alert, with a Glasgow Coma Scale (GCS; Table 15.3) of 14. A skull X-ray shows a linear skull vault fracture. After being reasonably well for many hours his conscious level rapidly deteriorates to a GCS of 5. A subsequent CT scan reveals a large extradural blood collection that requires emergency drainage by craniotomy.

Table 15.3 The Glasgow Coma Scale (GCS)

	Score
Eye opening (E)
Spontaneous	4
To speech	3
To pain	2
No response	1
Motor response (M)
Obeys	6
Localises	5
Withdraws	4
Flexion	3
Extension	2
No response	1
Verbal response (V)
Orientated	5
Confused conversation	4
Inappropriate words	3
Incomprehensible sounds	2
No response	1

Glasgow Coma Scale = E + M + V (GCS minimum = 3; maximum = 15)

Extradural haemorrhage is a serious secondary effect of head injury. These bleeds occur into a tight space, resulting in a rather long lucid interval as the blood slowly accumulates. CT reveals a convex hyperdense collection in the acute phase. By contrast, subdural haemorrhages bleed more freely into a more easily opened space so the shape is concave on CT and there is little lucid interval.

Progress.

Following his craniotomy and drainage, he gradually recovered over the next few days. However, 2–3 weeks later he was still amnesic and needed constant attention. He is being followed up by the neurologists.

General management of traumatic injuries

Remember

• Always carefully monitor head injuries and record changes in GCS rather than simply considering one value in isolation

• The result of secondary swelling by haemorrhage or oedema (the latter is common in children) is raised intracranial pressure (ICP) leading to reduced perfusion pressure and coning.

What action would you take in a patient with a head injury?

• Attend first to any secondary or concomitant general problems, i.e. resuscitation, correct hypovolaemic shock, hypotension or compromised airway.

• Assess severity, using circumstances of injury and period of amnesia as a guide.

• Establish whether there is anterograde amnesia: the inability to form memories from the time of injury to the time of continuous normal memory, is the most accurate guide.

• Brainstem damage in head injury can affect central respiratory drive, bulbar function and pressor responses.

• Regular GCS measurements; below 5 at 24 h implies severe injury and 50% of such patients die.

• Do CT scan (see Box 15.2).

How would you manage the following problems?

• If the patient is deteriorating, or has evidence of raised ICP: consider insertion of a bolt, which is simply a tube into the ventricle through which ICP can be recorded.

• If ICP > 20 mmHg: need to treat; give enough mannitol IV to raise the plasma osmolality to 300 to decrease the intracranial pressure. However, the benefits of mannitol are still controversial. Mannitol also has poorly understood neuroprotective effects. Hyperventilation with IPPV will also lower the ICP.

• If the patient has haemorrhages: a craniotomy may be indicated.

Follow-up

Check for continued improvement in the weeks subsequent to the head injury. At 2–3 weeks post-injury, the development of hydrocephalus is a major complication.

Case history (2)

A 30-year-old man falls from a second-storey building and is immediately unconscious. He is admitted comatose, GCS 5, although he is breathing spontaneously. There are no external injuries and CT scan of the head is normal. He does not regain consciousness.

Diffuse axonal injury is the primary effect of traumatic brain injury and a common cause of vegetative state. There is usually immediate loss of consciousness followed by prolonged coma.

Milder axonal injury is reversible, e.g. in concussion. This damage occurs with brain accelerations or decelerations such as hitting the floor or wall, rather than by a direct blow to the head. The mechanism of damage is due to stretching of axons causing Ca²⁺ entry and neurofilament damage, interrupting axonal transport over the next 12 h. Certain areas are particularly vulnerable, such as the parasagittal white matter, internal capsule, cerebellar peduncles, posterior corpus callosum and dorsolateral midbrain.

Progress.

This patient was in a coma for a week and never recovered. Consent was obtained for his organs to be used for transplantation.

Severe brain injury

Case history (1)

Your patient has had a severe hypoxic cerebral episode following a cardiac arrest. He is currently stable from a cardiac point of view but comatose (GCS 5) and requiring ventilatory support on ITU. He has been given 24 hours of induced hypothermia 32–34°. The ITU staff and the patient’s relatives want an indication as to the likelihood of useful recovery.

What are your prognostic indicators?

There are some prognostic values, depending on the time after the initial cerebral insult. The following criteria indicate poor outcome:

• Absent or extensor plantar response 72 hours after cerebral insult.

• Absent pupillary or corneal reflexes 72 hours after cerebral insult.

In general, every case must be assessed on its merits, especially with regard to the nature of the original insult and whether it was a discrete event or likely to be resulting in ongoing brain injury.

Note: relatives should not be given conflicting or inaccurate information.

Beware

Determination of brain death is made only by the appropriate consultant specialists who assess – on separate occasions – the various brainstem reflexes and responses listed under ‘Aspects of examination’, above. The nature of the insult must be clear and remediable causes must be excluded. Because the criteria for brain death are heavily weighted towards brainstem function and, in the UK, EEG corroboration is not required, the locked-in syndrome (Table 15.4) should be excluded. In this state, a severe pontine lesion prevents access to or from the outside world. The only signs of relatively spared higher-level function may be preserved vertical optokinetic nystagmus or eye following, and preserved vertical doll’s eye reflexes.

Table 15.4 Differentiation diagnosis of the vegetative state

NB: EEG and measures of cerebral metabolism are not required to make these clinical diagnoses. EEG, electroencephalography; PET, positron emission tomography; E, eye opening; M, motor response; V, verbal response.

From: The vegetative state: guidance on diagnosis and management. Clinical Medicine 2003; 3: 251.

Meningitis

Case history (1)

A 55-year-old, a heavy alcohol user is brought to A&E with headache, confusion and a high fever.

On examination he is found to be photophobic and have neck stiffness. He is thought by the A&E staff to have meningitis and is immediately given IV benzylpenicillin because they were unclear about the most likely organism. You are called urgently to A&E.

Remember

Give immediate penicillin if meningococcal meningitis suspected.

What would you do?

You quickly check the neurological signs and agree this is meningitis. You also note that there is no purpuric rash of meningococcal septicaemia. You try and see his fundi but are unsure whether papilloedema is present. You are worried about doing a lumbar puncture because he is semi-conscious and you are concerned about the possibility of ‘coning’. You arrange an immediate CT scan, which is normal. You proceed with a lumbar puncture and the CSF, which is turbid, is sent urgently to the microbiologists.

What do you do next?

Investigations

• Blood culture

• CXR

This man has meningitis, presumably bacterial. You recheck for purpuric spots of meningococcal meningitis.

Information

Lumbar puncture

This should be performed with sterile measures. Check no papilloedema:

• Obtain patient consent

• Place patient in lateral decubitus position

• Identify L4–5 interspace (intersection of imaginary line between iliac crests and spine)

• Clean area with antiseptic, e.g. chlorhexidine

• Local anaesthetic (2% lidocaine) into skin and subcutaneous tissue

• Insert lumbar puncture spinal needle (bevel upwards) into skin over L4–5 interspace horizontally and slightly towards the head

• When needle penetrates the dura mater (slight decrease in resistance is felt), withdraw stylet and allow a few drops of CSF to escape

• Measure CSF pressure by connecting manometer to needle (normal CSF pressure is 60–150 mmH₂O); it rises and falls with respiration and heart beat

• Collect CSF in three sterile tubes (2 mL per tube)

• Send to laboratory. Note if clear, cloudy, yellow (xanthochromic) or red

• Remove needle and apply sterile dressing

• Patient should lie horizontal for 4 h to avoid headache. Analgesics might be required.

Indications and contraindications are shown in Table 15.5.

Table 15.5 Indications and contraindications for lumbar puncture

Indications	Contraindications
Diagnosis of meningitis, encephalitis and subarachnoid haemorrhage (sometimes)	Raised intracranial pressure
Measurement of CSF pressure, e.g. for idiopathic, intracranial hypertension (IIH)	Local infections at site of puncture area
Removal of CSF therapeutically (IIH)	Platelet count < 40 × 10⁹/L
Diagnosis of conditions, e.g. neoplastic involvement	Mass lesion in brain or spinal cord

The CSF results sent through are:

• Protein: 1.5 g/L (normal range 0.2–0.4 g/L)

• Glucose: 1.5 mmol/L

• Leucocytes: 500/mm³

• Pneumococcus is seen on Gram stain.

Diagnosis

Pneumococcal meningitis. You immediately start treatment with IV cefotaxime 8 g daily in four divided doses because there is a high incidence of penicillin-resistant pneumococcus (Table 15.6).

Table 15.6 Treatment regimens: antibiotics and acute bacterial meningitis

Organism	First choice	Alternative
Unknown	Cefotaxime	Benzylpenicillin and cefotaxime
Meningococcus	Benzylpenicillin	Cefotaxime
Pneumococcus	Cefotaxime	Penicillin if organism sensitive
Haemophilus	Cefotaxime	Chloramphenicol
Listeria	Amoxicillin + gentamicin

This table shows the value of cefotaxime in clinical practice.

Further reading

Thigpen MC, Whitney CG, Messonnier NE, et al. Bacterial meningitis in the United States, 1998–2007. N Engl J Med. 2011;364:2016–2025.

Causes of meningitis

• Staphylococcus aureus

• Mumps (meningoencephalitides).

• Subarachnoid haemorrhage

• Chemical meningitis.

• Recurrent:

• Nasal sinus fistula

• Traumatic CSF leak

• Epstein–Barr virus

• Sarcoidosis, Behçet’s

• Mollaret’s meningitis (HSV type 2).

• Pneumococcal meningitis most commonly occurs in the debilitated or in those with a chest or sinus infection, valvular disease, splenectomy or a fistula from the paranasal air sinuses to the brain.

• Meningococcal meningitis (see also p. 7) occurs in epidemics and is sometimes associated with a petechial or purpuric rash and has a very rapid evolution. It is seen in young adults. Nasopharyngeal swab culture is useful for typing meningococcus and haemophilus (see below).

• Staphylococcus aureus meningitis generally occurs in the context of systemic infection, abscesses or neurosurgical procedures.

• Pseudomonas and other Gram-negative enterobacillae are usually a consequence of surgical access to the CSF.

• Listeria meningitis is quite common. It should be treated with amoxicillin and gentamicin. It is also associated with an encephalitis.

• Haemophilus influenzae type B used to be extremely common but has been substantially reduced in many countries by immunisation (Hib vaccine) in children.

Progress.

This man made an excellent recovery from his pneumococcal meningitis.

Case history (2)

A 22-year-old Asian man is admitted from A&E with an insidious 2-week history of malaise, headaches and marked confusion. On examination he is pyrexial, drowsy, has neck stiffness and has upgoing plantar responses. A presumptive diagnosis of tuberculous meningitis is made.

What action would you take?

• Routine blood tests.

• CXR: may show evidence of TB.

• CT scan: an immediate scan is done because with his confusion and possible raised intracranial pressure coning is a possibility following lumbar puncture. CT scan normal.

• Lumbar puncture.

The CSF results (Table 15.7) sent back to your house officer are:

• Glucose 1.8 mmol/L (blood level 6.5, i.e. low glucose)

• Protein 2.3 g/L (very high protein)

• 250 white cells (70% lymphocytes).

Note: the CSF protein can be so high as to cause the formation of a fine clot (‘spider web’).

Table 15.7 Typical changes in the CSF in meningitis

* Some polymorph cells may be seen in the early stages of viral meningitis and encephalitis.

Reprinted from Kumar and Clark Clinical Medicine 8th edn, 2012, by permission of the publisher Elsevier.

Note: tubercle bacilli are only occasionally seen in the CSF and the CSF must be sent for culture, which takes 6 weeks.

How would you manage this case?

Start anti-TB chemotherapy on the basis of the clinical picture and high protein in the CSF, which strongly suggest tuberculous meningitis. Don’t wait for the culture! Start therapy (rifampicin, isoniazid and pyrazinamide, for 6 weeks until the culture and sensitivities come back. Three drugs should be given for 3 months, followed by rifampicin and isoniazid for 9 months, depending on sensitivities. Specialist advice should be sought for treatment, notification and contact tracing.

Progress.

This patient made a good recovery. Prednisolone was also given for the first 3 weeks

Further reading

van de Beek D, de Gans J, Tunkel AR, et al. Community-acquired bacterial meningitis in adults. New England Journal of Medicine. 2006;354:44–53s.

Fits and faints

Case history (1)

A 16-year-old young woman is referred with a suspected seizure. Earlier that day in her office she had felt unwell for about an hour. On getting up from her chair she suddenly lost consciousness without warning. She was incontinent of urine. She woke some minutes later, but had nausea and malaise for the rest of the day. Witnesses said that, when unconscious, she was flaccid, that her mouth, hands and feet were twitching and she was pale.

Is this a fit or a faint?

The patient has probably suffered a faint. Some factors are good at distinguishing a fit from faint (Table 15.8) whereas others are unreliable. In the above case, it is noted that faints, other than cardiac syncope, only occur on standing; the preceding symptoms are prolonged or ill defined. Twitching is not usually as violent as in a clonic seizure and the underlying muscle tone is not increased.

Table 15.8 Features of fits and faints

	Fit	Faint
Prodrome	None or characteristic brief aura	Short or prolonged. Blood draining, visual darkening, rushing noise. Cardiac syncope may have no prodrome
Posture at onset	Any	Standing unless cardiac
Injury	Common	Rarer. Protective reflexes may act
Incontinence	Sometimes	Sometimes
Skin colour	Normal, flushed or pale	Pale
Recovery	Slow return of consciousness	Rapid, more physical weakness with clear sensorium
Frequency	Rare to many a day	Not repeated attacks each day
EEG	May be abnormal	Normal

Investigations

In suspected cardiac syncope include:

• ECG

• 24-h ambulatory monitoring

• Echocardiogram

Vasovagal faints are generally idiopathic but there are often precipitating or predisposing factors.

Associations with faints

• Adolescent, young adult female

• Low blood pressure

• Postural hypotension

• Heavy periods

• Micturition with prostatic problems

• Hot, stuffy surroundings

• Fasting, hypoglycaemia

• Dehydration

• Vagal stimuli such as distress or nausea.

Vasovagal attacks must be distinguished from cardiac syncope (see p. 265). In the latter there is often no warning, there may be breathlessness and engorged jugular veins and the heart rate may be faster than 140 or slower than 40.

Progress.

This girl and her parents were reassured that she had had a simple faint.

Case history (2)

A 16-year-old boy presents with repeated brief falls. He does not seem to lose consciousness but has been seen in A&E several times with severe head and facial injuries resulting from these episodes. Recovery, apart from associated injury, is immediate.

What is the diagnosis?

This history is suggestive of atonic seizures. This seizure disorder usually presents in childhood, often as one aspect of a complex epileptic syndrome. Not all seizures resulting in falls are generalised tonic–clonic in nature.

The loss of tone is immediate and absolute so that no protective reflexes occur and injury can be severe. Some sufferers need to wear crash helmets.

Progress.

He was referred to the neurologists for management of his epilepsy.

Epilepsy

An epileptic seizure is a convulsion or transient abnormal event experienced by the subject as a result of a paroxysmal discharge of cerebral neurones. Epilepsy, by definition, is the continuing tendency to have such seizures. Recurrent seizures can be prevented in most cases by anti-convulsant drugs.

Case history (3)

A 28-year-old man is brought to A&E because he was found to be unconscious and shaking in the high street. You are called to see him urgently because he has had a further tonic/clonic generalised seizure.

How would you manage this situation?

Remember

Status epilepticus exists when seizures follow each other without recovery of consciousness.

General measures

• Secure the airway; remove any false teeth and insert oropharyngeal tube.

• Administer 60% oxygen.

• Secure venous access: many anti-convulsants cause phlebitis, so choose a large vein.

• Glucose, 50 mL of 20% IV if hypoglycaemia is a possibility (see p. 221).

• Thiamine, 250 mg by slow IV injection if patient is a chronic alcohol user.

Control seizures

Remember

Full ventilatory support must be available when treating status epilepticus.

• Lorazepam 0.1 mg/kg by slow (2 mg/min) intravenous injection. Give rectal diazepam (10–20 mg) or intramuscular midazolam (0.2 mg/kg) if intravenous access difficult.

• If seizures continue give IV phenytoin:

• Phenytoin: loading dose of 15 mg/kg at a rate not exceeding 50 mg/min. Give a further bolus up to total loading dose of 30 mg/kg if seizures persist. Continue with a maintenance dose of 100 mg IV at intervals of 6–8 h.

If seizures continue (despite phenytoin) use:

• Phenobarbital: 15 mg/kg at a rate not exceeding 100 mg/min and repeated at intervals of 6–8 h if necessary; IV clonazepam can also be used.

• If seizures continue despite these measures the patient is given a general anaesthetic, using thiopentone or propofol, and management is continued with full anaesthetic support.

Progress.

This patient had no further fits after being given phenytoin. He was known to have epilepsy and was referred back urgently to his normal consultant for management of his drug therapy.

Difficulty walking

Case history (1)

A 75-year-old man is referred with a 1-year history of progressive difficulty with his walking. He has hypertension which is well controlled with ramipril 5 mg daily. His wife says that his memory has been progressively getting worse.

On examination he has a mini mental score of 22, indicating a cognitive impairment. His grasp and snout (pursing of lips on lightly tapping the closed lips) reflexes are present, indicating frontal lobe disease. His legs are stiff and his walking is disorganised. This is an apraxic gait.

An apraxic gait is typical of frontal lobe pathology and can be regarded as a problem with high-level programming and execution of gait. This man has vascular dementia (multi-infarct dementia). Patients with cerebrovascular disease should always be imaged to exclude a frontal meningioma or other lesion.

Progress.

This patient was referred to the psychogeriatric department for full assessment. He was started on donepezil 5 mg daily (a reversal inhibitor of acetyl cholinesterase).

Case history (2)

A 70-year-old woman has a 3-week history of progressive difficulty in walking and loss of bladder function. For the last 6 months she has had problems with a stiff gait, numbness in the feet and pains down the left arm.

On examination she has wasting and weakness of the hands and brisk triceps reflexes. In the legs there are signs of an upper motor neurone lesion with brisk reflexes and an extensor plantar response. There is also a patchy sensory loss in both arms and feet.

What is the diagnosis?

Cervical myelopathy, which at this age is most commonly due to spondylitis. She requires an urgent MRI scan of her cervical spine with a view to early decompression because relatively acute deficits are more potentially reversible. The MRI showed cord compression at the level of C5–6 (Fig. 15.9).

Figure 15.9 MRI showing spinal cord compression. a) Multiple vertebral metastases (arrows); b) cervical compression caused by meningioma (arrow).

Walking difficulties with upper motor signs in the legs should always be investigated by cervical imaging. Thoracic compression is relatively much less common in the elderly age group.

Other common causes of difficulty in walking are:

Progress.

In view of this woman’s serious disability and bladder problems, decompressive surgery was performed. This stabilised her condition but without improvement in her bladder function.

Headaches

Case history (1)

A 35-year-old woman is admitted to the Medical Admission Unit (MAU) with very severe headache of explosive onset. She is slightly drowsy with a Glasgow Coma Scale of 13 and she has photophobia and meningism.

A CT scan shows blood in the subarachnoid space (this has a 95% sensitivity in the first 24 hours).

Diagnosis.

Subarachnoid haemorrhage.

• Arrange for cerebral MR angiography to identify the source of bleeding.

• If aneurysm found, refer to neurosurgeon for surgical treatment.

• Nimodipine (e.g. 60 mg orally 4-hourly for 2–3 weeks, or 1 mg/hour IV) can reduce arterial spasm and reduce further cerebral infarction.

• Avoid hypotension (it may worsen the ischaemic deficit). Treat hypertension if diastolic pressure is persistently > 130 mmHg. Aim for a very gradual decrease in BP with careful monitoring and frequent repeat neurological examination.

• Supportive measures include bed rest, analgesia and laxatives (avoid sudden rises in ICP or BP).

• Watch for complications, including hyponatraemia (SIADH), hydrocephalus (obstruction of cerebral aqueduct by blood) and vasospasm causing ischaemic deficits.

NB. If the scan is negative and the history highly suggestive of a subarachnoid haemorrhage, a lumbar puncture is necessary.

• A lumbar puncture is performed to look for blood-stained CSF and xanthochromia (bilirubin discoloration of CSF due to cell lysis). Xanthochromia may be detected from ~12 hours to 3 weeks after SAH. Visible inspection of a centrifuged sample is often sufficient to detect xanthochromia, but laboratory spectrophotometry is more sensitive.

Remember

If a close family member has also had a subarachnoid haemorrhage then the rest of the family should be screened by MR angiography.

Conditions that can mimic subarachnoid haemorrhage include sudden onset of meningitis or viral meningism, migraine, spontaneous subdural haemorrhage and post-coital headache. The last of these is a headache of very sudden onset but is a benign self-limiting condition, perhaps a variant of migraine. With the availability of MR angiography, patients are now often scanned to exclude aneurysms. Finally, low-pressure headache may be of sudden onset. This is a poorly understood condition where headache may occur suddenly on standing and generally settles when lying down. There is meningeal enhancement on MRI and a low CSF pressure. The condition is again self-limiting. At least some cases relate to CSF leaks, sometimes from lumbar puncture (post-lumbar puncture headache), occasionally from Valsalva manoeuvres.

Progress.

In this patient, a posterior communicating aneurysm was found and she was treated with an intravascular coil insertion. She made a good recovery.

Further reading

van Gijn J, Kerr RS, Rinkel GJ. Subarachnoid haemorrhage. Lancet. 2007;369:306–318.

Case history (2)

A 35-year-old man complains of continuous headache day and night. He used to have a different headache, which was episodic. This previous headache was unilateral, throbbing and would last a few hours; it was also associated with photophobia, visual scotomata and nausea. The new headache has no such features. He has to take about eight paracetamol tablets a day to control the pain.

What is this new headache due to?

Migraine headache, which was also the cause of this man’s original headache. The headache sometimes becomes transformed into a more chronic headache punctuated by migraine-like exacerbations. Often the patient is given regular analgesia, which has a well-known effect of actually perpetuating headache.

What action should you take?

A brain scan is not often necessary in a clearly chronic headache with no signs, although the patient often expects one. It is more necessary to take a proper history and institute the correct management.

Management

Progress.

This patient was reassured that he did not have malignant or serious disease.

Chronic analgesia abuse should be stopped and he was advised to reduce this gradually over a month. He was told to expect that his headaches would be worse over this period.

Case history (3)

A 40-year-old man comes to A&E with severe headache, which then settles on arrival. This has happened before and he has always been discharged immediately. On taking a history, it transpires that he gets an excruciating headache that comes on gradually at about the same time every day. The headache is unilateral, pounding, involves the side of the face and is associated with a watering eye and nose. He jumps up and down in agitation with the pain. The symptoms generally only last about an hour.

What is the cause of this headache?

This description is typical for cluster headache. Each cluster may last a few weeks, with several months of relief in between.

Cluster headache

Cluster headache is distinct from migraine and consists of recurrent bouts of excruciating unilateral pain that typically wake the patient. Attacks cluster around one eye. Cluster headache affects adults, mainly males aged 30–40 years. Alcohol and glyceryl trinitrate can provoke attacks. Severe pain can last for several hours and is associated with vomiting. One cheek and nostril become congested. Transient ispilateral Horner’s syndrome is common. One bout of cluster attacks, with pain every few nights, usually lasts 1 to 2 months. Despite excruciating pain there are no sequelae. Bouts recur at intervals over several years but tend to disappear after the age of 55.

Progress.

In this patient, treatment with analgesics and prophylactic migraine drugs did not help. However, his attacks were attenuated with subcutaneous sumatriptan. Oxygen inhalation also helped on occasions. A short course of oral prednisolone reduced the frequency of attacks.

Case history (4)

A 30-year-old woman has a long history of short but severe headaches on one side of the face, lasting only a few minutes but occurring several times a day. There is considerable flushing and rhinorrhoea on the same side during each attack. There is no trigger to the attacks.

What is the cause of this headache?

The patient has paroxysmal hemicrania; the attacks are longer in duration than in trigeminal neuralgia but shorter than in cluster headaches or migraine. There is generally some associated autonomic disturbance, as seen here. There is a specific and often extremely rewarding response to indometacin, as occurred in this woman.

Some causes of acute, episodic and chronic headache are given in Box 15.3.

Movement disorders

• Akinetic-rigid syndromes, i.e. slowed movement with increased tone.

• Dyskinesias – added, uncontrollable movements.

Both may co-exist.

Case history (1)

A 22-year-old woman develops an acute gastrointestinal illness with abdominal pain, vomiting and diarrhoea. After 2 days she becomes generally stiff and has prolonged episodes of painful spasm of the axial muscles with opisthotonic posturing. Her eyes periodically roll upwards involuntarily (oculogyric crises). She had been given metoclopramide for her vomiting.

Diagnosis.

Oculogyric crises from metoclopramide.

Acute dystonic reactions can occur in sensitive individuals after relatively modest doses of drugs with central anti-dopaminergic action, such as neuroleptics or certain anti-emetics, e.g. metoclopramide. Neuroleptic malignant syndrome can also occur.

Treatment of oculogyric crisis involves the identification and stoppage of the responsible agent. These acute dystonias respond generally to intravenous centrally acting anti-muscarinics, e.g. procyclidine 5–10 mg.

Anti-emetics, e.g. domperidone, ondansetron or granesetron do not produce dystonia.

Hyperkinetic movement disorder

Progress.

This woman was given IV procyclidine 5 mg IV. Her dystonia settled within 24 hours.

Case history (2)

A 40-year-old man has a 1-year history of involuntary facial movements and a shuffling gait. There is a past history of schizophrenia, for which he was given haloperidol. On examination he has intermittent involuntary protrusion of his tongue, grimacing and blepharospasm. He has some writhing movements of his left arm and repetitive rubbing of the soles of his feet on the floor when sitting. Voluntary arm movements are slow. He walks slowly with a shuffling gait and stooped posture.

Diagnosis.

Tardive dyskinesia. This develops in patients previously, as well as currently, on anti-psychotic medication. The movement disorder may be a complex mixture of hyperkinetic restlessness (akathisia), dystonia and choreoathetosis, and hypokinetic bradykinesia. They are late and difficult to reverse. The effects of anti-dopaminergics are thought to be due to long-term dysregulation of dopaminergic pathways. Sometimes, in the short term, increases in anti-psychotic drug doses actually temporarily improve the hyperkinetic aspects (direct anti-dopaminergic action), but this is likely to lead to worsened long-term problems. The drugs that are good for avoiding acute extrapyramidal side effects are also good for minimising long-term side effects.

Progress.

In this patient the haloperidol was gradually reduced and stopped. His symptoms improved. He has been told of the risk of recurrence on further anti-psychotic therapy.

Guillain–Barré syndrome

This is an acute sensori-motor polyneuropathy which often follows a gastrointestinal, e.g. Campylobacter, cytomegalovirus, or a respiratory infection.

Case history

A 34-year-old woman is brought to A&E by her relatives; she has a 1-week history of difficulty walking. She had had mild gastroenteritis due to Campylobacer jejuni about 5 weeks before but had recovered from this. Her relatives thought she was ‘putting it on’ but became a bit concerned when they found that she was unable to climb the stairs to her flat.

On examination she looked well and was orientated; but she was extremely anxious because she thought she was becoming paralysed. She had a symmetrical weakness in her limbs, which was worse proximally. Reflexes were absent and she had normal plantar responses. There was a mild sensory deficit of a glove and stocking distribution

What is the diagnosis?

This could be the Guillain–Barré syndrome. Do not leave this patient unattended because the progression can be fast and her respiratory muscles can be affected within a few hours.

Investigations

What should you do?

Admit her. Once on the ward, perform a lumbar puncture. In this patient, the CSF protein is raised. She gets progressively weaker and is having difficulty breathing,

Prognosis

80% of patients make a full recovery, as occurred in this patient.

Spinal cord compression

This produces radicular pain at the level of the cord lesion, with a spastic tetraparesis or paraparesis below the level; sensory loss below the cord level is also present.

Case history

A 56-year-old man is admitted with a 2-week history of weakness in his legs. He has no other complaints but admits that he is a heavy smoker.

On examination there is weakness of both legs, which is more marked distally; the left leg is more severely affected. Knee and ankle jerks are slightly brisk and he has a bilateral extensor plantar response. There are no sensory signs. He has no neurological deficit in his arms.

NB. This is a medical emergency.

This patient has a mild paraparesis and a cord lesion must be exluded.

Investigations

• Routine bloods show a Hb of 100 g/L with an ESR of 100 mm/h.

• CXR was normal, making carcinoma with secondaries unlikely despite him being a heavy smoker.

• Thoracic and lumbar spinal X-rays showed an osteolytic lesion at T10.

The preliminary tests have taken 3 days and the patient is now incontinent of urine and his leg weakness is worse. Urgent neurological referral is required.

MRI scan shows a lesion at T10. Urgent decompression is performed by a neurosurgeon but the patient still requires a urinary catheter.