Other Neuroimmunologic Syndromes: an Overlap Between Primary and Paraneoplastic Processes

The astute neurologist confronted with an unusual, seemingly idiopathic clinical disorder, always needs to be vigilant, asking whether a difficult diagnostic problem could also have a neuroimmunologic basis and eventual potential clinical responsiveness to an immunosuppressive therapy. The recently defined condition associated with exposure to pig brain is an example of an occupational, environmentally induced, previously unrecognized neuroimmunologic disorder. This disorder affected 21 workers in two meat processing plants. Each patient had exposure to aerosolized brain tissue at the time of hog slaughter. This rapidly developing disorder led to a subacute neurologic syndrome most often characterized by a painful, sensory predominant, polyradiculoneuropathy developing within just a 4-week period. Less commonly, central nervous system involvement developed, producing a meningoencephalitis or transverse myelitis syndrome.

Nerve conduction studies localized abnormalities to the most proximal and distal nerve segments. Quantitative sensory and autonomic testing demonstrated large and small sensory fiber involvement as well as autonomic dysfunction affecting sweat fibers. Magnetic resonance imaging confirmed prominent nerve root and dorsal root ganglia abnormalities. Nerve biopsies revealed mild demyelination, axonal degeneration and perivascular inflammation. Cerebrospinal fluid (CSF) protein was elevated in most patients; in contrast, there was no significant CSF pleocytosis except for those individuals presenting with central nervous system involvement.

Distinctive neural-reactive immunoglobulin G (IgG) occurred in the serum in all and in the CSF in a high majority. In addition, voltage-gated potassium channel (VGKC) IgG was identified in 79% and myelin basic protein-specific IgG in 75%. When the probable occupational exposure facilitating the neuroimmunologic mechanism was identified, the method of brain harvesting was discontinued, and this disorder no longer occurs. However, this experience serves as an important bellwether for the astute neurologist considering other mysterious ailments.

Sometimes patients may have underlying idiopathic systemic disorders wherein a sudden and overwhelming potentially life-threatening neurologic deterioration develops without any obvious inciting mechanism. One needs to consider the potential that neuroimmunologic factors are playing an important role. Sometimes empiric treatment with methylprednisolone, intravenous immunoglobulin (IVIG), and/or plasmapheresis (PPx) in these settings, even when no specific antibodies are identified, can occasionally prove to be lifesaving.

An example of this occurred with a colleague who had scleromyxedema, an unusual chronic dermatologic condition. Over a 72-hour period, he developed severe skeletal muscular pain involving his extremities and truncal musculature, including his abdomen, where there was initial concern about a surgical emergency. While this was under investigation, sudden respiratory and cardiovascular distress occurred, followed by an acute encephalopathy with confusion leading to coma. Intense therapy with high-dose corticosteroids and antibiotics was unsuccessful; he became moribund with decerebrate posturing. The emergent introduction of plasmapheresis therapy led to a remarkable improvement; eventually he returned to medical practice.

We were not certain what led to the acute crisis in this patient; however, response to immunotherapy clearly implicated an autoimmune mechanism. One needs to always consider such a possibility with seemingly indeterminate acute neurologic disorders; sometimes a trial of immunosuppressive therapy can be lifesaving even when there is no previous “evidence-based” experience.

Paraneoplastic autoimmune disorders are discussed in the subsequent four plates. Some syndromes initially recognized as having a paraneoplastic context sometimes do not always occur with an underlying cancer. The Lambert-Eaton myasthenic syndrome (LEMS) is an excellent example; although historically associated with small cell lung cancer, it is now recognized to occur not only in young adults who never subsequently develop a cancer, but even in children as young as 8 years. The inciting immunologic mechanism for these LEMS variants has yet to be elucidated. Nevertheless, these are eminently treatable patients. Therefore their recognition is of paramount importance.

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