Colin P. O'Leary

Acute oropharyngeal palsy is associated with antibodies to GQ1b and GT1a gangliosides.

Three patients with acute oropharyngeal palsy had high titre anti-GQ1b and anti-GT1a IgG antibodies. No patients had ophthalmoplegia or ptosis. In all patients limb ataxia or areflexia were present without notable limb weakness. These patients describe an oropharyngeal variant of Guillain-Barré syndrome in terms of anti-GQ1b antibody reactivity and show that high titre anti-GQ1b antibodies, serologically indistinguishable from those found in Miller Fisher syndrome, can occur in a clinical setting without ophthalmoplegia. The anti-GQ1b and anti-GT1a antibody assays may be helpful tests when considering the differential diagnosis of acute oropharyngeal palsy.

Lipid arrays identify myelin-derived lipids and lipid complexes as prominent targets for oligoclonal band antibodies in multiple sclerosis.

The presence of oligoclonal bands of IgG (OCB) in cerebrospinal fluid (CSF) is used to establish a diagnosis of multiple sclerosis (MS), but their specificity has remained an enigma since its first description over forty years ago. We now report that the use of lipid arrays identifies heteromeric complexes of myelin derived lipids as a prominent target for this intrathecal B cell response.

Autoimmune ataxic neuropathies (sensory ganglionopathies)

Autoimmune ataxic neuropathies are a subset of the sensory ataxic neuropathies which are characterized by ataxia as the dominant presenting feature. The major known causes of autoimmune ataxic neuropathies include sensory variants of the Guillain-Barré syndrome, including Miller-Fisher syndrome, subsets of immunoglobulin M paraproteinaemic neuropathy, paraneoplastic neuropathy and the neuropathy associated with Sjögrens syndrome. Identified antigens as targets for autoantibodies include gangliosides, myelin associated glycoprotein, Hu antigen and extractable nuclear antigens. Some recent studies support the pathogenic role of anti-GD1b ganglioside antibody in autoimmune ataxic neuropathies. The major site of pathology in autoimmune ataxic neuropathies is the dorsal root ganglion, but dorsal roots and peripheral nerve myelin and axons may also be affected.

Mechanisms of Action of Anti-GM1 and Anti-GQ1b Ganglioside Antibodies in Guillain-Barré Syndrome

Anti-GM1 and anti-GQ1b ganglioside antibodies are found in association with acute and chronic peripheral neuropathies, including Guillain-Barré syndrome. They are believed to arise as a result of molecular mimicry with immunogenic microbial polysaccharides. Although anti-ganglioside antibodies are suspected to play a causal role in neuropathy pathogenesis, the details of this have yet to be proven. The approach in this laboratory to solving this issue has been to generate anti-GM1 and anti-GQ1b monoclonal antibodies from peripheral blood lymphocytes of affected patients and to study their immunolocalization in peripheral nerve and their electrophysiologic effects in animal models in which peripheral nerve sites are exposed to anti-ganglioside antibodies. These data show that anti-ganglioside antibody-reactive epitopes are widely distributed in peripheral nerve and can cause electrophysiologic abnormalities in a variety of model systems; thus, these data support the view that anti-ganglioside antibody-reactive epitopes may directly contribute to neuropathy pathogenesis.

Muscle hypertrophy in multifocal motor neuropathy is associated with continuous motor unit activity

Multifocal motor neuropathy (MMN) is typically associated with distal upper limb weakness and wasting. However, proximal muscle bulk, particularly of biceps brachii, may be well preserved even in the presence of severe proximal weakness. Here we report 3 patients with MMN who had true muscle hypertrophy of severely weakened biceps muscles and positive motor symptoms including cramp and fasciculations in these muscles. Electromyographic studies demonstrated markedly impaired recruitment in the affected muscles and continuous motor unit activity comprising multiple fasciculation potentials at a frequency of up to 30 per minute. We propose that this continuous motor unit activity may have contributed to the hypertrophy in these muscles.

The role of antiglycolipid antibodies in peripheral neuropathies.

The role of antiglycolipid antibodies in peripheral neuropathy continues to be defined in terms of clinical-serological associations and innovative experimental work establishing the role of these antibodies in pathogenesis. The present review focuses on the major developments in this field over the past 12 months.

Mechanisms of action of anti-GM 1 and anti-GQ 1b ganglioside antibodies in Guillain-Barré syndrome

Anti-GM1 and anti-GQ1b ganglioside antibodies are found in association with acute and chronic peripheral neuropathies, including Guillain-Barré syndrome. They are believed to arise as a result of molecular mimicry with immunogenic microbial polysaccharides. Although anti-ganglioside antibodies are suspected to play a causal role in neuropathy pathogenesis, the details of this have yet to be proven. The approach in this laboratory to solving this issue has been to generate anti-GM1 and anti-GQ1b monoclonal antibodies from peripheral blood lymphocytes of affected patients and to study their immunolocalization in peripheral nerve and their electrophysiologic effects in animal models in which peripheral nerve sites are exposed to anti-ganglioside antibodies. These data show that anti-ganglioside antibody-reactive epitopes are widely distributed in peripheral nerve and can cause electrophysiologic abnormalities in a variety of model systems; thus, these data support the view that anti-ganglioside antibody-reactive epitopes may directly contribute to neuropathy pathogenesis.

PRIMARY CNS LYMPHOMA MASQUERADING AS TUMEFACTIVE DEMYELINATION

A 47 year old female presented with sub–acute cognitive decline and personality change, without any significant focal neurology. An MRI scan showed extensive white matter signal change and oedema with a few enhancing focal lesions and minimal mass effect. The radiological differential diagnosis consisted of primary CNS tumour/Lymphoma, Demyelination and CNS vasculitis. Oligoclonal bands were only detected in CSF, but numerous other investigations turned out to be unhelpful. An image guided, burr–hole brain biopsy of the most prominent and enhancing left frontal lesion, showed non–specific reactive changes, which proved to be non–diagnostic. Patient declined a repeat biopsy. Subsequently she was treated with high dose pulsed steroids and showed a marked clinical improvement. Initial follow up imaging showed some radiological improvement and she remained clinically stable over the ensuing months. Serial imaging there after, continued to show a chaotic background, with regression of earlier lesions and appearance of new lesions. There was also a changing enhancement pattern of some of the existing lesions. During this period she only had a single episode of right leg weakness, gait ataxia and intermittent visual impairment. This too responded well to a course of high dose steroids. An aggressive, multifocal, tumefactive demyelinating process was thought to be the most likely diagnosis at this stage. She was then commenced on Natalizumab, nearly a year after her first presentation. After two doses of Natalizumab, she presented acutely with left sided focal motor seizures and a left hemiparesis. Neuroimaging at this stage showed clear radiological deterioration. A repeat brain biopsy was again declined by the patient. Following a further dose of Natalizumab and continuing clinical and radiological progression, an open brain biopsy was finally carried out. This showed a high grade B–cell Non Hodgkin Lymphoma. She has since been commenced on intrathecal Methotrexate and also underwent whole brain radiotherapy. This is an example of a Primary CNS lymphoma behaving initially as an aggressive tumefactive demyelination, both clinically and radiologically. It also illustrates the difficulties of getting a definitive diagnosis, despite appropriate investigations, which in this case included multiple brain imaging and a brain biopsy.

Mechanisms of Action of Anti‐GM1and Anti‐GQ1bGanglioside Antibodies in Guillain‐Barré Syndrome

Anti-GM1 and anti-GQ1b ganglioside antibodies are found in association with acute and chronic peripheral neuropathies, including Guillain-Barré syndrome. They are believed to arise as a result of molecular mimicry with immunogenic microbial polysaccharides. Although anti-ganglioside antibodies are suspected to play a causal role in neuropathy pathogenesis, the details of this have yet to be proven. The approach in this laboratory to solving this issue has been to generate anti-GM1 and anti-GQ1b monoclonal antibodies from peripheral blood lymphocytes of affected patients and to study their immunolocalization in peripheral nerve and their electrophysiologic effects in animal models in which peripheral nerve sites are exposed to anti-ganglioside antibodies. These data show that anti-ganglioside antibody-reactive epitopes are widely distributed in peripheral nerve and can cause electrophysiologic abnormalities in a variety of model systems; thus, these data support the view that anti-ganglioside antibody-reactive epitopes may directly contribute to neuropathy pathogenesis.