Focal paraneoplastic limbic encephalitis presenting as orgasmic epilepsy.

PURPOSE: To report orgasmic epilepsy as a manifestation of paraneoplastic limbic encephalitis in a patient with small cell lung cancer. CASE REPORT: A 57 years-old woman presented with 2 month history of daily spells that consisted of a sudden pleasure provoking feeling described 'like an orgasm' lasting for 30 s to 1 min. She was a heavy smoker and had noted recent weight loss. Bronchial biopsy, following the finding of a right lung mass, confirmed the diagnosis of small cell lung cancer (SCLC). Spells subsided after starting carbamazepine. The lung cancer was treated with chemotherapy and chest radiation therapy resulting in a complete radiologic response. RESULTS: Brain magnetic resonance imaging (MRI) revealed left temporal lobe area of increased signal on T2 and FLAIR sequence. T1-weighted images after contrast administration demonstrated a circumscribed area of enhancement in the left anterior medial temporal lobe. Electroencephalogram (EEG) showed focal left mid-temporal sharp waves and intermittent slowing. Anti-Hu antibodies were detected in her serum supporting a diagnosis of paraneoplastic limbic encephalitis as the cause of her orgasmic epilepsy. The patient has been followed for 2 years after treatment without tumor recurrence or neurological deterioration. CONCLUSION: Orgasmic epilepsy is another mode of presentation of paraneoplastic limbic encephalitis leading to the diagnosis of an occult SCLC. EEG and MRI findings suggest that in this case the seizures originated from the left hemisphere. It is possible that early recognition and treatment of the SCLC will improve the prognosis of this neurologic entity.

Paraneoplastic syndromes of the nervous system.

Paraneoplastic syndromes affecting the nervous system are unique among immune-mediated disorders in that the trigger of the immune response is known: tumor expression of proteins normally restricted to neurons (or other immunoprivileged sites, such as testis) but ectopically expressed in some cancers results in an immunological response characterized by high titers of antibodies targeting the "onconeuronal" antigen. A T-cell response is also elicited in some paraneoplastic syndromes and may be the cause of neuronal destruction. In some instances genes that code for the antigens recognized by the autoantibodies have been identified, cloned and sequenced. Some of the proteins so identified are RNA binding proteins but their specific function has not been identified. In some individuals with cancer but no paraneoplastic syndrome, low titers of antibody can be identified in the serum. Low titers of antibody are associated with a better prognosis of the cancer. Experimental animals immunized against a paraneoplastic antigen are partially protected against tumors that express that antigen.

Autoantibodies from patients with idiopathic ataxia bind to M-phase phosphoprotein-1 (MPP1).

In an attempt to identify unique disease-related autoantibodies, the serum from an ataxia and sensory neuropathy patient was used as a probe to isolate a 2.5-kd cDNA from a HeLa expression library. The nucleotide sequence was 99% identical to MPP1, a cell-cycle-related nuclear protein phosphorylated during mitosis. Expression of the cDNA in an in vitro translation system yielded a recombinant protein that migrated in SDS-PAGE at approximately 97 kd. This protein was immunoprecipitated by the prototype human serum, by an immune guinea pig anti-MPP1 serum, but not by normal human serum or preimmune guinea pig serum. Western blot analysis of HeLa cell proteins showed that the prototype human serum and immune guinea pig antiserum recognized an approximately 225-kd protein, suggesting that the isolated clone contained a partial cDNA. By indirect immunofluorescence, the affinity-purified antibody and a guinea pig antiserum reacted with nuclei of interphase HEp-2 cells and the cytoplasm of certain neuronal cells. Sera from 10 of 25 unselected patients with ataxia, 1 of 30 patients with peripheral neuropathy, 1 of 50 multiple sclerosis patients, 0 of 20 amyotrophic lateral sclerosis, 0 of 10 children with postviral ataxia, 0 of 10 systemic lupus erythematosus patients, 0 of 3 patients with hereditary cerebellar ataxia, 0 of 8 with ataxia telangiectasia, and 0 of 30 age- and gender-matched controls immunoprecipitated the recombinant MPP1 protein. None of the patients with anti-MPP1 antibodies had evidence of malignancy. This is the first report of MPP1 as a target autoantigen in patients with idiopathic ataxia.

Paraneoplastic syndromes.

The fact that a small cancer hidden in the chest, abdomen, or pelvis could destroy or damage portions of the nervous system, such as cerebellar Purkinje cells or cholinergic synapses, has intrigued neurologists since paraneoplastic syndromes were first described. In 1965, when little was known about their pathogenesis, a full issue of the journal Brain and an international symposium were devoted to paraneoplastic disorders. In this decade, the discovery of several paraneoplastic antibodies that react with both the nervous system and the causal cancer has rekindled interest in these syndromes (Table). Several other factors make these rare syndromes of clinical and scientific interest. A recent review by Dalmau and Posner contains a more comprehensive bibliography of paraneoplastic syndromes.

Neuro-ophthalmologic manifestations of a paraneoplastic syndrome and testicular carcinoma.

The authors report two patients with testicular cancer who exhibited supranuclear gaze disorders as a manifestation of a paraneoplastic brainstem encephalomyelitis. In the first patient, neuro-ophthalmic dysfunction was accompanied by a prominent limbic encephalitis whereas in the second patient, an unusual, mixed pendular and jerk nystagmus was manifested. Neuroimaging revealed an enhancing hypothalamic mass in the first patient and was negative in the second. Blood from both patients contained an antibody previously reported in a patient with limbic encephalitis and testicular cancer.

Neurologic complications of ovarian carcinoma.

BACKGROUND: Neurologic complications of ovarian carcinoma are uncommon and to the authors' knowledge the full spectrum has not been delineated previously. METHODS: The authors reviewed the findings of 121 neurologic consultations on 83 ovarian carcinoma patients between 1993 and 1996; this represents 4% of all ovarian carcinoma patients seen at the study institution in this time period. RESULTS: The most common reasons for consultation were altered mental status, pain, weakness, numbness, headache, and seizure. Twenty-seven consultations diagnosed metastatic disease, 14 diagnosed cerebrovascular disease, and 4 diagnosed paraneoplastic syndromes; however, iatrogenic complications (n=38) comprised the majority of diagnoses. Greater than 50% of patients improved neurologically after diagnosis and treatment. CONCLUSIONS: Neurologic disease accompanying ovarian carcinoma may be more common and more diverse than recognized previously. Definitive neurologic diagnosis and treatment benefits the majority of patients.

Paraneoplastic syndromes affecting the nervous system.

Paraneoplastic syndromes can affect virtually any portion of the nervous system. Most paraneoplastic syndromes are believed to be caused by an autoimmune reaction to an "onconeural" antigen shared by the cancer and the nervous system. The immune reaction may retard growth of the cancer, but it also damages the nervous system. Specific autoantibodies found in some individual paraneoplastic syndromes are usually associated with specific tumors. Neurological disorders, clinically and pathologically identical to paraneoplastic syndromes, may occur in some patients without cancer, but paraneoplastic antibodies are not found in these patients. The diagnosis of a paraneoplastic syndrome is based on its increased incidence in patients with cancer, the occasional response of the neurological syndrome to treatment of the underlying cancer, or the presence of specific autoantibodies. Some paraneoplastic syndromes respond to treatment of the underlying cancer or to immunosuppression but, for most syndromes, no effective treatment exists.

Paraneoplastic syndromes affecting the central nervous system.

Paraneoplastic syndromes affecting the nervous system are rare neurologic syndromes caused by cancer but not ascribable to metastases. Any portion of the nervous system may be involved in a paraneoplastic syndrome. The pathogenesis of these disorders appears to be an immune reaction against antigens shared by the cancer and the nervous system. Some disorders, such as the Lambert-Eaton myasthenic syndrome, are effectively treated by removal of autoantibodies directed against the presynaptic cholinergic synapse. In other disorders, such as paraneoplastic cerebellar degeneration or paraneoplastic sensory neuronopathy, neither removal of the autoantibody nor treatment of the cancer is effective.

Autoimmune paraneoplastic cerebellar degeneration in ovarian carcinoma patients treated with plasmapheresis and immunoglobulin. A case report.

BACKGROUND: Paraneoplastic cerebellar degeneration (PCD) is a remote effect of cancer most frequently associated with carcinoma of the ovary or lung. In many patients, antibodies to Purkinje cells are found. Progressive, incapacitating cerebellar dysfunction occurs in most cases, and no treatment has produced even a transient response in any significant proportion of patients. METHODS: A woman age 81 years with recurrent ovarian carcinoma and PCD, confirmed clinically, radiologically, and serologically, was treated with 5 exchanges of 1 plasma volume each, followed by intravenous immunoglobulin at a dose of 1g/Kg-1 body weight daily for 2 days. RESULTS: Several weeks after the treatment, the patient had significant improvement of her dizziness, tremor, and dysmetria. She refused maintenance therapy and began to deteriorate neurologically 3 months after the treatment. CONCLUSIONS: Although this is only a single case report, the authors believe that the dire prognosis of PCD and the lack of effective therapy warrant a trial of this combined treatment early in the course of the disease. Confirmatory evidence of the efficacy of such an approach would be welcomed.