Chapter 097. Paraneoplastic Neurologic Syndromes (Part 7)

Encephalitis and Encephalomyelitis: TreatmentMost types of paraneoplastic encephalitis and encephalomyelitis respond poorly to treatment. Stabilization of symptoms or partial neurologic improvement may occasionally occur, particularly if there is a satisfactory response of the tumor to treatment. The roles of plasma exchange, IVIg, and immunosuppression have not been established. Approximately 30% of patients with anti-Ma2-associated encephalitis respond to treatment of the tumor (usually a germ-cell neoplasm of the testis) and immunotherapy. Two other syndromes that are responsive to treatment of the tumor and immunotherapy are the encephalitis that associates with antibodies to the NR1/NR2 subunits of NMDA receptors in patients...
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Chapter 097. Paraneoplastic Neurologic Syndromes (Part 7) Chapter 097. Paraneoplastic Neurologic Syndromes (Part 7) Encephalitis and Encephalomyelitis: Treatment Most types of paraneoplastic encephalitis and encephalomyelitis respondpoorly to treatment. Stabilization of symptoms or partial neurologic improvementmay occasionally occur, particularly if there is a satisfactory response of the tumorto treatment. The roles of plasma exchange, IVIg, and immunosuppression havenot been established. Approximately 30% of patients with anti-Ma2-associatedencephalitis respond to treatment of the tumor (usually a germ-cell neoplasm ofthe testis) and immunotherapy. Two other syndromes that are responsive totreatment of the tumor and immunotherapy are the encephalitis that associateswith antibodies to the NR1/NR2 subunits of NMDA receptors in patients withteratoma of the ovary, and the encephalitis that associates with VGKC antibodiesin some patients with thymoma or SCLC. Paraneoplastic Cerebellar Degeneration This disorder is often preceded by a prodrome that may include dizziness,oscillopsia, blurry or double vision, nausea, and vomiting. A few days or weekslater, dysarthria, gait and limb ataxia, and variable dysphagia can appear. Theexamination usually shows downbeating nystagmus and, rarely, opsoclonus.Brainstem dysfunction, upgoing toes, or a mild neuropathy may occur, but moreoften the symptoms and signs are restricted to the cerebellum. Early in the course,MRI studies are usually normal; later, the MRI typically reveals cerebellaratrophy. The disorder results from extensive degeneration of Purkinje cells, withvariable involvement of other cerebellar cortical neurons, deep cerebellar nuclei,and spinocerebellar tracts. The tumors more frequently involved are SCLC, cancerof the breast and ovary, and Hodgkins lymphoma. Anti-Yo antibodies in patients with breast and gynecologic cancers andanti-Tr antibodies in patients with Hodgkins lymphoma are the two paraneoplasticantibodies typically associated with prominent or pure cerebellar degeneration.Antibodies to P/Q-type VGCC occur in some patients with SCLC and cerebellardysfunction; only some of these patients develop LEMS. Of note, a variabledegree of cerebellar dysfunction can be associated with virtually any type ofantibody-related PND of the CNS (Table 97-2). Cerebellar Degeneration: Treatment A number of single case reports have described neurologic improvementafter tumor removal, plasma exchange, IVIg, cyclophosphamide, rituximab, orglucocorticoids. However, large series of patients with antibody-positiveparaneoplastic cerebellar degeneration show that this disorder rarely improveswith any treatment. Paraneoplastic Opsoclonus-Myoclonus Syndrome Opsoclonus is a disorder of eye movement characterized by involuntary,chaotic saccades that occur in all directions of gaze; it is frequently associatedwith myoclonus and ataxia. Opsoclonus-myoclonus may be cancer-related oridiopathic. When the cause is paraneoplastic, the tumors involved are usuallycancer of the lung and breast in adults and neuroblastoma in children. Thepathologic substrate of opsoclonus-myoclonus is unclear. Most SCLC patients donot have detectable antineuronal antibodies. A small subset of patients with ataxia,opsoclonus, and other eye movement disorders develop anti-Ri antibodies; in rareinstances muscle rigidity, autonomic dysfunction, and dementia also occur. Thetumor most frequently involved in anti-Ri-associated syndromes is breast cancer. If the tumor is not successfully treated, the paraneoplastic opsoclonus-myoclonus syndrome in adults often progresses to encephalopathy, coma, anddeath. In addition to treating the tumor, symptoms may respond to immunotherapy(glucocorticoids, plasma exchange, and/or IVIg). At least 50% of children with opsoclonus-myoclonus have an underlyingneuroblastoma. Hypotonia, ataxia, behavioral changes, and irritability are frequentaccompanying symptoms. Many patients harbor antibodies to neuronal cell surfaceantigens of unknown identity. Neurologic symptoms often improve with treatmentof the tumor (including chemotherapy) and with glucocorticoids,adrenocorticotropic hormone (ACTH), plasma exchange, IVIg, and rituximab.Many patients are left with psychomotor retardation and behavioral and sleepproblems. Paraneoplastic Syndromes of the Spinal Cord The number of reports of paraneoplastic spinal cord syndromes, such assubacute motor neuronopathy and acute necrotizing myelopathy, has decreased inrecent years. This may represent a true decrease in incidence, due to improved andprompt oncologic interventions, or may be because of the identif ...