Mechanisms of drug action in Parkinson's disease. (1) Decarboxylase inhibitors (carbidopa and benserazide) decrease side-effects by

reducing peripheral conversion of levodopa to dopamine by aromatic amino acid decarboxylase (AAAD).

2) (2) Active transport of levodopa into the brain may be inhibited by competition from dietary amino acids after a high-protein meal.

3) (3) In the nigrostriatal neurons, levodopa is converted into dopamine.4) (4) Amantadine enhances the release of dopamine at the nerve terminal.5) (5) Dopamine agonists act directly on striatal receptors.6) (6) The monoamine oxidase type B (MAO-B) inhibitor selegiline increases the

availability of neuronal dopamine by reducing its metabolism outside the neuron.

7) (7) The catechol-O-methyl-transferase (COMT) inhibitor entacapone prolongs the availability of dopamine by inhibiting the metabolism of dopamine and levodopa outside the neuron

Hemifacial spasm This usually presents after middle age with intermittenttwitching around one eye, spreading ipsilaterally toother facial muscles. The spasms are exacerbated bytalking, eating and stress. Hemifacial spasm is usuallyidiopathic (similarly to trigeminal neuralgia, it has beensuggested that it is due to an aberrant arterial loop irritatingthe 7th nerve just outside the pons), but may besymptomatic and secondary to structural lesions or MS.Drug treatment is not effective but injections of botulinumtoxin into affected muscles help, although theseusually have to be repeated every 3 months or so. Inrefractory cases, microvascular decompression may beconsidered.

Guillain–Barré syndromeGuillain–Barré syndrome (GBS) is a heterogeneous group of immune-mediated conditions with an incidenceIthe most common variant is an acute inflammatorydemyelinating polyneuropathy (AIDP).

Axonalvariants, either motor (acute motor axonal neuropathy, AMAN) or sensorimotor (acute motor and sensoryaxonal neuropathy, AMSAN), (often associated with Campylobacter jejuni).

The hallmark is an acute paralysis evolving over days or weeks with loss of tendon reflexes. About two-thirds ofthose with AIDP have a prior history of infection, and autoimmune response triggered by the precedinginfection causes demyelination. A number of GBS variantshave been described, associated with specific

anti-ganglioside antibodies; the best-recognised isMiller Fisher syndrome, which involves anti-GQ1bantibodies

Clinical features Distal paraesthesia and limb pains (often severe) precede a rapidly ascending muscle weakness, from lower to upper limbs, more marked proximally than distally. Facial and bulbar weakness commonly develops, and respiratory weakness requiring ventilatory support occurs in 20% of cases.

most patients, weakness progresses for 1-3 weeks, but rapid deterioration to respiratory failure can develop within hours. On examination there is diffuse weakness with widespread loss of reflexes.

An unusual axonal variant described by Miller Fisher comprises the triad of ophthalmoplegia, ataxia and areflexia. Overall, 80% of patients recover completely within 3-6 months, 4% die, Adverse prognostic features include older age, rapid deterioration to ventilation and evidence of axonal loss on EMG.

Investigations The CSF protein is elevated at some stage of the illness but may be normal in the first 10 days. There is usually no rise in CSF cell number (a lymphocytosis of > 50 × 106 cells/L suggests an alternative diagnosis).

Electrophysiological studies are often normal in the early stages but show typical changes after a week or so, with conduction block and multifocal motor slowing, sometimes most evident proximally as delayed F-waves

Investigation to identify an underlying cause, such as cytomegalovirus, mycoplasma or Campylobacter, requires a chest X-ray, stool culture and

appropriate immunological blood tests. Antibodies to the ganglioside GQ1b are found in the Miller Fisher variant. Acute porphyria ( should be excluded by urinary porphyrin estimation, and serum lead should be measured if there are only motor signs.

Management

During the phase of deterioration, regular monitoring of respiratory function (vital capacity and arterial blood gases) is required, as respiratory failure may develop with little warning and require ventilatory support. Ventilation may be needed if the vital capacity falls below 1 L, but intubation is more often required because of bulbar incompetence leading to aspiration. General management to protect the airway and prevent pressure sores and venous thrombosis is essential. Corticosteroid therapy has been shown by RCT to be ineffective. However, plasma exchange and intravenous immunoglobulin therapy shorten the duration of ventilation and improve prognosis, provided treatment is started within 14 days of the onset of symptoms