Neurological Paraneoplastic Syndromes - immunologically mediated* complications (“remote” effects) of systemic cancer affecting nervous system.
*i.e. do not reflect effects of direct invasion / metastatic disease, metabolic / nutritional disorders, infection, stroke, or complications of therapy
antibodies (in serum and CSF) recognize antigens shared by neurons and tumor cells (i.e. antibodies also confer some degree of antitumor effect).
occur in 1-3% of cancer patients.
in 2/3 cases, neurological syndrome precedes diagnosis of cancer (months ÷ years).
most common cancers - lung (usually oat cell*), breast, ovary.
*small cell carcinoma of lung (Kulchitsky basal neuroendocrine cells in bronchial epithelium arise from neural crest cells)
clinical manifestations differ even in seemingly homogeneous antibody-positive syndrome - some patients have encephalitis, some have sensory neuropathy or autonomic neuropathy, some are asymptomatic, and some have more than one syndrome.
some tumor types are associated with multiple types of autoantibodies.
some patients have easily controlled neoplasms but die of neurologic disorder!
I. Brain & Cranial Nerves (Subacute) cerebellar degeneration
Limbic encephalitis and other dementias and brain stem encephalitis as part of encephalitis, encephalomyelitis
II. Spinal Cord and Dorsal Root Ganglia Necrotizing myelopathy; myelitis, as part of encephalomyelitis
Subacute motor neuronopathy
Motor neuron disease (ALS)
III. Peripheral Nerves Subacute or chronic sensorimotor peripheral neuropathy
Mononeuritis multiplex and microvasculitis of peripheral nerve
Peripheral neuropathy with islet-cell tumors
Peripheral neuropathy associated with paraproteinemia
IV. Neuromuscular Junction & Muscle Lambert-Eaton syndrome
Acute necrotizing myopathy
Stiff-person (Moersch-Woltman) syndrome
International expert group classification (2004):
A. Definite paraneoplastic syndromes:
classical syndromes (i.e. encephalomyelitis, limbic encephalitis, subacute cerebellar degeneration, opsoclonus/myoclonus, subacute sensory neuronopathy, chronic gastrointestinal pseudo-obstruction, LEMS, dermatomyositis) + cancer that develops within 5 years of diagnosis of neurological disorder, regardless of presence of paraneoplastic antibodies.
nonclassical syndrome that objectively improves or resolves after cancer treatment, provided that syndrome is not susceptible to spontaneous remission.
nonclassical syndrome with paraneoplastic antibodies (well characterized or not) and cancer that develops within 5 years of diagnosis of neurological disorder.
neurological syndrome (classical or not) with well-characterized paraneoplastic antibodies (i.e. anti-Hu, anti-Yo, anti-Ri, anti-amphiphysin, anti-CV2, anti-Ma2)
B. Possible paraneoplastic syndromes:
classical syndrome without paraneoplastic antibodies and no cancer but at high risk to have underlying tumor (e.g. smoking history).
neurological syndrome (classical or not) without cancer but with partially characterized paraneoplastic antibodies.
nonclassical neurological syndrome, no paraneoplastic antibodies, and cancer that presents within 2 years of neurological syndrome.
- of exclusion (unless characteristic autoantibodies are found in serum or CSF).