27th June 2023

Demyelinating diseases of the peripheral nervous system

Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) describes a collection of acute immune-mediated polyneuropathies usually triggered by a recent upper respiratory infection or gastroenteritis (especially in association with infection by Campylobacter jejuni). Vaccination within the previous 4 weeks also appears to be a common trigger. Typical clinical features include a symmetrical muscle weakness which gradually appears over the course of days to short weeks. On examination, flaccid weakness of the upper and lower limbs is easily identified, starting in the lower limbs and following a distal-to-proximal progression. Absent or greatly reduced deep tendon reflexes are also a frequent finding. Cranial nerve involvement, such as facial nerve palsies, oropharyngeal weakness and ophthalmoplegia, can also be seen. Autonomic symptoms such as arrhythmias, hypotension and respiratory muscle weakness are common complications which may require review by the critical care team and warrant close monitoring, such as regular forced vital capacity testing. The diagnosis of GBS is usually made clinically, however, it can be assisted by using nerve conduction studies or a lumbar puncture, which reveals high protein levels within the cerebrospinal fluid.

The most common form of the disease, acute inflammatory demyelinating polyneuropathy (AIDP), is associated with clinical and electrophysiological evidence of peripheral demyelination and lymphocytic infiltration of the sural nerve in biopsies. In these cases, a focal inflammatory response affecting the myelin sheath or myelin-producing Schwann cells causes the development of areas of demyelination along the peripheral nerves. This phenomenon leads to a slowing of the propagation of saltatory electrical signalling, which manifests as muscle weakness when a threshold is reached. Axonal loss is a phenomenon that can be observed in most forms of GBS but can also be a predominant feature in certain variants. The Miller-Fisher variant of GBS is characterised by the clinical triad of ataxia, ophthalmoplegia and areflexia, in association with the presence of antibodies against GQ1b.

Pharmacological treatment of GBS includes intravenous immunoglobulins for five days to patients within four weeks of symptom onset, or plasma exchange therapy as an alternative. Regular assessment of respiratory muscle function with forced vital capacity is important to identify early involvement of the respiratory muscles; respiratory deterioration often warrants admission to intensive care for consideration of intubation and ventilation.

Chronic inflammatory demyelinating polyneuropathy

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a subset of rare, immune-mediated polyradiculoneuropathies. Although multiple forms exist, CIDP typically presents with a slowly progressive symmetrical motor neuropathy affecting both proximal and distal peripheral nerves. Sensory impairment may also be identified, although usually less severe than the limb weakness. Examination findings include areflexia with signs of lower motor neuron disease and patchy sensory loss. High protein levels are found on cerebrospinal fluid analysis. Nerve conduction studies are key to diagnosis and will reveal multiple partial conduction blocks and prolonged distal motor latency, suggestive of demyelination. The presence of ‘onion bulb formations’ of axons are a pathognomonic finding frequently seen in biopsy results. CIDP can be treated with intravenous immunoglobulins or plasma exchange, although intravenous high-dose steroids are an alternative.

Charcot-Marie-Tooth disease

Charcot-Marie-Tooth disease (CMT) is a spectrum of primary hereditary disorders causing both motor and sensory neuropathies which are slowly progressive. CMT are typically inherited in an autosomal dominant manner, although recessive and X-linked forms have been identified as well. There are a wide number of mutations known to cause CMT.

The most common form of CMT is CMT1a, which is associated with a duplication of the PMP22 gene leading to cumulative damage to the myelin sheath of the peripheral nerve axons. Patients with CMT1 will often present as teenagers or young adults with distal weakness and paraesthesia, causing frequent falls and ankle sprains. On examination, a gradual loss of proprioception and vibration can be identified. Over time, the atrophy will often lead to foot deformities such as pes cavus and hammer toes. Sleep apnoea is also commonly seen in these patients.

Patients with CMT2 commonly present in the second or third decade of life with distal symptoms such as reduced sensation and muscle weakness with atrophy. This form of the condition is typically associated with direct damage to the axons. Mutations to the MFN2 gene are associated with CMT2a, which is the most common cause of CMT2.

Electromyography with subsequent genetic testing is key to establishing a reliable diagnosis for most patients. Management remains supportive, with daily physiotherapy exercises and orthotics playing a central role in reducing the severity of deformities. Disability is known to increase with age, although symptom severity, age of onset and rate of progression vary considerably. Patients with CMT are also considered to be at higher risk from iatrogenic neurotoxicity, therefore, the disease is listed as a contra-indication to several drugs such as amiodarone, vincristine and tacrolimus.