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Paraneoplastic Neurologic Disease and Lymphoma
Abstract & Commentary
By John Caronna, MD, Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Caronna reports no financial relationships relevant to this field of study.
Synopsis: Non-Hodgkin B-cell lymphomas are more likely to be associated with peripheral nerve disorders, and Hodgkin's disease with central nervous system syndromes.
Source: Briani C, Vitaliani R, Grisold W, et al. Spectrum of paraneoplastic disease associated with lymphoma. Neurology 2011;76:705-710.
The authors report the clinical and immunologic characteristics of 53 patients with lymphoma and definite or possible paraneoplastic neurologic disease (PND) collected from the database of the Paraneoplastic Neurological Syndromes EURO-Network. Hodgkin lymphoma (HL) was diagnosed in 24 patients and non-Hodgkin lymphoma (NHL) in 29. Nineteen (79%) HL patients had PND affecting the central nervous system (CNS) and 5 patients (21%) had peripheral nervous system (PNS) PND. In the NHL group, 12 patients (41%) had CNS PND and 17 (59%) had PNS involvement. (See Table.)
Paraneoplastic cerebellar degeneration (PCD) was present in 21 patients, and there was a higher prevalence in the HL group (16). PNS and motor neuron involvement were more common in the NHL group. Anti-neuronal antibodies were more frequently detected in patients with PCD: anti-Tr antibodies in 12 patients and anti-GAD in 1 patient. No anti-neuronal antibodies were identified in patients with motor neuron disease or PNS involvement and treatment of the underlying lymphoma was not always followed by recovery of neurologic function. Therefore, motor neuron disease and peripheral neuropathic syndromes are only "possible" paraneoplastic diseases by current diagnostic guidelines.1 The authors concluded that the low prevalence of Guillain-Barré syndrome in the EURO-Net database suggests that any association with lymphoma is coincidental.
The tumors commonly associated with PND of the CNS express neuroendocrine proteins (e.g., small-cell lung cancer and neuroblastoma), affect organs with immunoregulatory properties (e.g., thymoma), or contain neural tissue (e.g., teratomas). In contrast, tumors that derive from cells that produce immunoglobulins (e.g., plasma-cell dyscrasias and B-cell lymphomas) are more commonly associated with PND of the PNS than other tumor types.2
In patients with small-cell lung cancer paraneoplastic sensory neuronopathy, in association with anti Hu antibodies, and sensorimotor axonal neuropathy with anti-CV2 (anti-CRMP5) antibodies have been described. Chronic inflammatory demyelinating neuropathy, multifocal motor neuropathy with conduction block, vasculitic neuropathies, and motor neuron disease, all have been reported as possible paraneoplastic disorders but without detection of anti-neuronal antibodies.3
The present report provides no new immunologic information concerning lymphoma-associated PND. Anti-Tr antibodies previously have been associated with PCD in HL and anti-CV2 (anti-CRMP5) antibodies have been associated with encephalomyelitis, sensory neuropathy, and cerebellar ataxia, as well as chorea, uveitis, and optic neuritis.2 Ma2 antibodies previously have been associated with cerebellar and brainstem dysfunction especially in young men with testicular germ-cell tumors.2 The authors did not find immunologic evidence that motor neuron disease is a paraneoplastic disease. Nevertheless, the current series provide useful clinical information on the spectrum of PND in patients with lymphoma.
1. Graus F, Delattre JY, Antoine JC, et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 2004;75:1135-1140.
2. Dalmau J, Rosenfeld MR. Paraneoplastic syndromes of the CNS. Lancet Neurol 2008;7:327-340.
3. Rudnicki SA, Dalmau J. Paraneoplastic syndromes of the peripheral nerves. Curr Opin Neurol 2005;18: 598-603.