Chapter 097. Paraneoplastic Neurologic Syndromes (Part 8)

Paraneoplastic myelitis may present with upper or lower motor neuron symptoms, segmental myoclonus, and rigidity. This syndrome can appear as the presenting manifestation of encephalomyelitis and may be associated with SCLC and serum anti-Hu, anti-CV2/CRMP5, or anti-amphiphysin antibodies. Paraneoplastic myelopathy can also produce several syndromescharacterized by prominent muscle stiffness and rigidity. The spectrum ranges from focal symptoms in one or several extremities (stiff-limb syndrome or stiffperson syndrome) to a disorder that also affects the brainstem (known as encephalomyelitis with rigidity) and likely has a different pathogenesis.Paraneoplastic Stiff-Person SyndromeThis disorder is characterized by progressive muscle rigidity, stiffness, and painful spasms...
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Chapter 097. Paraneoplastic Neurologic Syndromes (Part 8) Chapter 097. Paraneoplastic Neurologic Syndromes (Part 8) Paraneoplastic myelitis may present with upper or lower motor neuronsymptoms, segmental myoclonus, and rigidity. This syndrome can appear as thepresenting manifestation of encephalomyelitis and may be associated with SCLCand serum anti-Hu, anti-CV2/CRMP5, or anti-amphiphysin antibodies. Paraneoplastic myelopathy can also produce several syndromescharacterized by prominent muscle stiffness and rigidity. The spectrum rangesfrom focal symptoms in one or several extremities (stiff-limb syndrome or stiff-person syndrome) to a disorder that also affects the brainstem (known asencephalomyelitis with rigidity) and likely has a different pathogenesis. Paraneoplastic Stiff-Person Syndrome This disorder is characterized by progressive muscle rigidity, stiffness, andpainful spasms triggered by auditory, sensory, or emotional stimuli. Rigiditymainly involves the lower trunk and legs, but it can affect the upper extremitiesand neck. Symptoms improve with sleep and general anesthetics.Electrophysiologic studies demonstrate continuous motor unit activity. Antibodiesassociated with the stiff-person syndrome target proteins [glutamic aciddecarboxylase (GAD), amphiphysin] involved in the function of inhibitorysynapses utilizing γ-aminobutyric acid (GABA) or glycine as neurotransmitters.Paraneoplastic stiff-person syndrome and amphiphysin antibodies are often relatedto breast cancer. By contrast, antibodies to GAD may occur in some cancerpatients but are much more frequently present in the nonparaneoplastic disorder. Stiff-Person Syndrome: Treatment Optimal treatment of stiff-person syndrome requires therapy of theunderlying tumor, glucocorticoids, and symptomatic use of drugs that enhanceGABA-ergic transmission (diazepam, baclofen, sodium valproate, tiagabine,vigabatrin). A benefit of IVIg has been demonstrated for the nonparaneoplasticdisorder but remains to be established for the paraneoplastic syndrome. Paraneoplastic Sensory Neuronopathy or Dorsal Root Ganglionopathy This syndrome is characterized by sensory deficits that may be symmetricor asymmetric, painful dysesthesias, radicular pain, and decreased or absentreflexes. All modalities of sensation and any part of the body including face andtrunk can be involved. Specialized sensations such as taste and hearing can also beaffected. Electrophysiologic studies show decreased or absent sensory nervepotentials with normal or near-normal motor conduction velocities. Symptomsresult from an inflammatory, likely immune-mediated, process that targets thedorsal root ganglia, causing neuronal loss, proliferation of satellite cells, andsecondary degeneration of the posterior columns of the spinal cord. The dorsalnerve roots, and less frequently the anterior nerve roots and peripheral nerves, mayalso be involved. Sensory Neuropathy: Treatment This disorder often precedes or is associated with encephalomyelitis andautonomic dysfunction and has the same immunologic and oncologic associations,e.g., anti-Hu antibodies and SCLC. As with anti-Hu-associated encephalomyelitis,the therapeutic approach focuses on prompt treatment of the tumor.Glucocorticoids occasionally produce clinical stabilization or improvement. Thebenefit of IVIg and plasma exchange is not proved. Paraneoplastic Peripheral Neuropathies These disorders may develop any time during the course of the neoplasticdisease. Neuropathies occurring at late stages of cancer or lymphoma usuallycause mild to moderate sensorimotor deficits due to axonal degeneration ofunclear etiology. These neuropathies are often masked by concurrent neurotoxicityfrom chemotherapy and other cancer therapies. In contrast, the neuropathies thatdevelop in the early stages of cancer often show a rapid progression, sometimeswith a relapsing and remitting course, and evidence of inflammatory infiltrates andaxonal loss or demyelination in biopsy studies. If demyelinating featurespredominate (Chap. 379), IVIg or glucocorticoids may improve symptoms.Occasionally anti-CV2/CRMP5 antibodies are present; detection of anti-Husuggests concurrent dorsal root ganglionitis. Guillain-Barré syndrome and brachial plexitis have occasionally beenreported in patients with lymphoma, but there is no clear evidence of aparaneoplastic association. Malignant monoclonal gammopathies include: (1) multiple myeloma andsclerotic myeloma associated with IgG or IgA monoclonal proteins; and (2)Waldenströms macroglobulinemia, B cell lymphoma, and chronic B celllymphocytic leukemia associated with IgM monoclonal ...