Question 181#

Which one of the following is least associated with Miller-Fisher syndrome?

A. Anti-GQ1b antibodies

Correct Answer D: Postural hypotension due to autonomic involvement is not a feature of Miller Fisher syndrome, but may be seen in Guillain-Barre syndrome.

Guillain-Barre syndrome:

Guillain-Barre syndrome describes an immune mediated demyelination of the peripheral nervous system often triggered by an infection (classically Campylobacter jejuni).

Pathogenesis: 

• Cross reaction of antibodies with gangliosides in the peripheral nervous system
• Correlation between anti-ganglioside antibody (e.g. anti-GM1) and clinical features has been demonstrated
• Anti-GM1 antibodies in 25% of patients

Miller Fisher syndrome:

• Variant of Guillain-Barre syndrome
• Associated with ophthalmoplegia, areflexia and ataxia. The eye muscles are typically affected first
• Usually presents as a descending paralysis rather than ascending as seen in other forms of Guillain- Barre syndrome
• Anti-GQ1b antibodies are present in 90% of cases

Question 182#

A 67-year-old man who has a history of type 2 diabetes mellitus and benign prostatic hypertrophy presents with burning pain in his feet. This has been present for the past few months and is getting gradually worse. He has tried taking duloxetine but unfortunately has received no benefit. Clinical examination is unremarkable other than diminished sensation to fine touch on both soles.

What is the most suitable initial management?

A. Carbamazepine

Correct Answer C: Amitriptyline would normally be first choice but given his history of benign prostatic hyperplasia it is better to avoid amitriptyline due to the risk of urinary retention.

Diabetic neuropathy:

NICE updated it's guidance on the management of diabetic neuropathy in 2010:

• First-line: oral duloxetine. Oral amitriptyline if duloxetine is contraindicated
• Second-line treatment: if first-line treatment was with duloxetine, switch to amitriptyline or pregabalin, or combine with pregabalin. If first-line treatment was with amitriptyline, switch to or combine with pregabalin
• Other options: pain management clinic, tramadol (not other strong opioids), topical lidocaine for localized pain if patients unable to take oral medication

Gastroparesis: 

• Symptoms include erratic blood glucose control, bloating and vomiting
• Management options include metoclopramide, domperidone or erythromycin (prokinetic agents)

Question 183#

A 49-year-old man is prescribed procyclidine for Parkinson's disease.

What is the mechanism of action?

A. Antimuscarinic

Correct Answer A: 

Parkinson's disease: management:

Currently accepted practice in the management of patients with Parkinson's disease (PD) is to delay treatment until the onset of disabling symptoms and then to introduce a dopamine receptor agonist. If the patient is elderly, levodopa is sometimes used as an initial treatment.

Dopamine receptor agonists:

• e.g. Bromocriptine, ropinirole, cabergoline, apomorphine
• Ergot-derived dopamine receptor agonists (bromocriptine, cabergoline, pergolide*) have been associated with pulmonary, retroperitoneal and cardiac fibrosis. The Committee on Safety of Medicines advice that an echocardiogram, ESR, creatinine and chest x-ray should be obtained prior to treatment and patients should be closely monitored
• Patients should be warned about the potential for dopamine receptor agonists to cause impulse control disorders and excessive daytime somnolence
• Nasal congestion and postural hypotension are also seen in some patients

Levodopa: 

• Usually combined with a decarboxylase inhibitor (e.g. Carbidopa or benserazide) to prevent peripheral metabolism of levodopa to dopamine
• Reduced effectiveness with time (usually by 2 years)
• Unwanted effects: dyskinesia (involuntary writhing movements), 'on-off' effect, dry mouth, anorexia, palpitations, postural hypotension, psychosis
• No use in neuroleptic induced parkinsonism

MAO-B (Monoamine Oxidase-B) inhibitors:

• e.g. Selegiline
• Inhibits the breakdown of dopamine secreted by the dopaminergic neurons

Amantadine: 

• Mechanism is not fully understood, probably increases dopamine release and inhibits its uptake at dopaminergic synapses

COMT (Catechol-O-Methyl Transferase) inhibitors:

• e.g. Entacapone
• COMT is an enzyme involved in the breakdown of dopamine, and hence may be used as an adjunct to levodopa therapy
• Used in established PD

Antimuscarinics: 

• Block cholinergic receptors
• Now used more to treat drug-induced parkinsonism rather than idiopathic Parkinson's disease
• Help tremor and rigidity
• e.g. Procyclidine, benzotropine, trihexyphenidyl (benzhexol) 

*Pergolide was withdrawn from the US market in March 2007 due to concern regarding increased incidence of valvular dysfunction.

Question 184#

Which one of the following features is least typically of motor neuron disease?

A. Fasciculation

Correct Answer D: Ataxia is not a feature of motor neuron disease.

Motor neuron disease: features:

Motor neuron disease is a neurological condition of unknown cause which can present with both upper and lower motor neuron signs. It rarely presents before 40 years and various patterns of disease are recognized including amyotrophic lateral sclerosis, progressive muscular atrophy and bulbar palsy.

There are a number of clues which point towards a diagnosis of motor neuron disease:

• Fasciculation
• Absence of sensory signs/symptoms*
• Lower motor neuron signs in arms and upper motor neuron signs in legs
• Wasting of the small hand muscles/tibialis anterior is common

Other features: 

• Doesn't affect external ocular muscles
• No cerebellar signs
• Abdominal reflexes are usually preserved and sphincter dysfunction if present is a late feature

The diagnosis of motor neuron disease is clinical, but nerve conduction studies will show normal motor conduction and can help exclude a neuropathy. Electromyography shows a reduced number of action potentials with an increased amplitude. MRI is usually performed to exclude the differential diagnosis of cervical cord compression and myelopathy.

*Vague sensory symptoms may occur early in the disease (e.g. limb pain) but 'never' sensory signs.

Question 185#

A 35-year-old man presents with progressive weakness of his hands. On examination you notice wasting of the small muscles of the hand. A diagnosis of syringomyelia is suspected.

Which one of the following features would most support this diagnosis? 

A. Hyper-reflexia in the upper limbs

Correct Answer C: Syringomyelia - spinothalamic sensory loss (pain and temperature).

Syringomyelia:
Overview:

• Development of cavity (syrinx) within the spinal cord
• If extends into medulla then termed syringobulbia
• Strongly associated with the Arnold-Chiari malformation

Features: 

• Maybe asymmetrical initially
• Slowly progressives, possibly over years
• Motor: wasting and weakness of arms
• Sensory: spinothalamic sensory loss (pain and temperature)
• Loss of reflexes, bilateral upgoing plantars
• Also seen: Horner's syndrome