Paraneoplastic Diseases of the Central Nervous System.

Jonathan Galli,John Greenlee

doi:10.12688/f1000research.21309.1

Abstract

Paraneoplastic neurological syndromes are nonmetastatic complications of malignancy secondary to immune-mediated neuronal dysfunction or death. Pathogenesis may occur from cell surface binding of antineuronal antibodies leading to dysfunction of the target protein, or from antibodies binding against intracellular antigens which ultimately leads to cell death. There are several classical neurological paraneoplastic phenotypes including subacute cerebellar degeneration, limbic encephalitis, encephalomyelitis, and dorsal sensory neuropathy. The patient’s clinical presentations may be suggestive to the treating clinician as to the specific underlying paraneoplastic antibody. Specific antibodies often correlate with the specific underlying tumor type, and malignancy screening is essential in all patients with paraneoplastic neurological disease. Prompt initiation of immunotherapy is essential in the treatment of patients with paraneoplastic neurological disease, often more effective in cell surface antibodies in comparison to intracellular antibodies, as is removal of the underlying tumor.

Highlights

Paraneoplastic neurological syndromes are non-metastatic complications of systemic malignancy, in which clinical syndromes are the result of immune-mediated neuronal dysfunction or death
cerebrospinal fluid (CSF) evaluation is essential in these patients
Normal CSF does not exclude the possibility of paraneoplastic neurological injury[91]

Summary

Introduction

Paraneoplastic neurological syndromes are non-metastatic complications of systemic malignancy, in which clinical syndromes are the result of immune-mediated neuronal dysfunction or death. Similar to syndromes associated with antibodies against neuronal membranes, intravenous methylprednisolone is often used as initial treatment, with consideration of concomitant treatment with IVIG in more severe cases Plasmapheresis is a reasonable strategy to consider, the paraneoplastic antibody may not be removed from the CNS and patients often do not respond to treatment[13]. Both cyclophosphamide and rituximab have been used with some benefit in paraneoplastic disorders, neither treatment has demonstrated consistent response or decreasing titers of antibody[13,60,105,106]. Prompt treatment of the underlying malignancy is important in the overall patient outcome

PubMed Abstract

13. Greenlee JE

21. Dalmau J

52. Vernino S

73. Blaes F

89. Gwathmey KG