Variants of Guillain-Barre Syndrome

Several variants of GBS are recognized. These disorders share similar patterns of evolution, recovery, symptom overlap, and probable immune-mediated pathogenesis.

  1. The Miller-Fisher syndrome is a common variant of GBS and is observed in about 5% of all GBS cases. The syndrome consists of ataxia, ophthalmoplegia, and areflexia. Ataxia primarily is noted during gait and in the trunk with lesser involvement of the limbs. Motor strength characteristically is spared. The usual course is one of gradual and complete recovery over weeks to months. A close association exists between antiganglioside antibodies and the Fisher variant. Anti-GQ1b antibodies, triggered by certain C jejuni strains, have a relatively high specificity and sensitivity for the disease. Dense concentrations of GQ1b ganglioside are found in the oculomotor, trochlear, and abducens nerves, which may explain the relationship between anti-GQ1b antibodies and ophthalmoplegia.
  2. The acute motor axonal neuropathy (AMAN) variant is associated closely with enteric C jejuni infections and high titers of antibodies to gangliosides (GM1, GD1a, and GD1b). Patients with AMAN have pure motor symptoms and appear clinically very similar to patients with the demyelinating form of GBS with ascending symmetric paralysis. AMAN is distinguished by electrodiagnostic study results that are consistent with a pure motor axonopathy. Biopsies show Wallerian-like degeneration without significant lymphocytic inflammation. Many cases have been reported in rural areas of China, especially in children and young adults during the summer months. Pure axonal cases may occur more frequently in other parts of the world outside Europe and North America. AMAN cases also may be different from cases of axonal GBS described in the West. Prognosis is often quite favourable and recovery is rapid.
  3. The axonal form of GBS, also referred to as acute motor-sensory axonal neuropathy (AMSAN), often presents with rapid and severe paralysis with delayed and poorer recovery compared to the electrophysiologically similar AMAN cases. Like AMAN, axonal GBS also is associated with preceding C jejuni diarrhea. Pathologic findings show severe axonal degeneration of motor and sensory nerve fibres with little demyelination.
  4. A pure sensory variant of GBS has been described in the medical literature, typified by rapid onset of sensory loss and areflexia in a symmetric and widespread pattern. Lumbar puncture studies show albuminocytologic dissociation in the cerebral spinal fluid (CSF) and electromyography (EMG) results show characteristic signs of a demyelinating process in the peripheral nerves. Prognosis is generally good, but immunotherapies, such as plasma exchange and intravenous immunoglobulins (IVIG), can be tried in patients with severe disease or slow recovery.
  5. Acute pandysautonomia without significant motor or sensory involvement is a rare presentation of GBS. Dysfunction of the sympathetic and parasympathetic systems results in severe postural hypotension, bowel and bladder retention, anhidrosis, decreased salivation and lacrimation, and pupillary abnormalities.
  6. The pharyngeal-cervical-brachial variant is distinguished by isolated facial, oropharyngeal, cervical, and upper limb weakness without lower limb involvement. Other unusual clinical variants with restricted patterns of weakness are observed only in rare cases.
  7. MUTIFOCIAL MOTOR NEUROPY (MMN) MMN is a curious chronic demyelinating neuropathy that differs from CIDP in two important respects. First , the demyelination is restricted to motor axons – those that control the muscles. Therefore, MMN patients have weakness but no numbness, tingling or pain. Second, the demyelination is very patchy, affecting nerves in a seemingly random pattern and affecting only very short segment of the nerves. Therefore, the weakness only affects a few muscles. Like CIDP, this demyelination is thought to be immune mediated. The most obvious effect of this motor nerve demyelination is weakness, although the initial symptoms, at least in retrospect, may be muscle cramps or muscle twitching (called fasciculations). Most patients also develop muscle atrophy (wasting). The symptoms develop very slowly and usually progress over many years. Patients often do not seek medical advice until they have had the disease for 10 years or more. They may be completely unaware of muscle weakness in some areas and seek medical advice only when important functions, such as hand function, are affected. One of my patients had virtually complete paralysis of the biceps muscle and had subconsciously developed trick movements to bend his elbow, and he remained completely unaware of that weakness until the hand became weak and he could no longer manipulate his nail clippers. Another curious feature is that the weakness is most often worse in the arms and hands, whereas most neuropathies including CIDP, mainly affect the legs. The development of weakness, muscle atrophy, and fasciculations led to several patients with MMN being diagnosed with amyotrophic lateral sclerosis (Lou Gehrig’s disease). Distinguishing MMN for Lou Gehrig’s is critically important since MMN is a benign disease and is treatable, whilst Lou Gehrig’s disease is always fatal and has no treatment. Peripheral nerves in patients (with Lou Gehrig’s) may be endangered enough to feel on clinical examination or enlargement can be seen with magnetic resonance imaging (MRI scan). On rare occasions, the enlargement may be so striking that it is thought to be a tumour. One of my patients developed a large swelling above the clavicle (collar bone) that was thought to be a tumour. The “tumour” was removed and found to be a hugely enlarged nerve. Similar nerve enlargement can be seen in CIDP but it is much less common.