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Background Continuous spike and wave of sleep with encephalopathy (CSWS) is a rare and severe developmental electroclinical epileptic encephalopathy characterized by seizures, abundant sleep activated interictal epileptiform discharges, and cognitive regression or deceleration of expected cognitive growth. The cause of the cognitive symptoms is unknown, and efforts to link epileptiform activity to cognitive function have been unrevealing. Converging lines of evidence implicate thalamocortical circuits in these disorders. Sleep spindles are generated and propagated by the same thalamocortical circuits that can generate spikes and, in healthy sleep, support memory consolidation. As such, sleep spindle deficits may provide a physiologically relevant mechanistic biomarker for cognitive dysfunction in epileptic encephalopathies. Case presentation We describe the longitudinal course of a child with CSWS with initial cognitive regression followed by dramatic cognitive improvement after treatment. Using validated automated detection algorithms, we analyzed electroencephalograms for epileptiform discharges and sleep spindles alongside contemporaneous neuropsychological evaluations over the course of the patient’s disease. We found that sleep spindles increased dramatically with high-dose diazepam treatment, corresponding with marked improvements in cognitive performance. We also found that the sleep spindle rate was anticorrelated to spike rate, consistent with a competitively shared underlying thalamocortical circuitry. Conclusions Epileptic encephalopathies are challenging electroclinical syndromes characterized by combined seizures and a deceleration or regression in cognitive skills over childhood. This report identifies thalamocortical circuit dysfunction in a case of epileptic encephalopathy and motivates future investigations of sleep spindles as a biomarker of cognitive function and a potential therapeutic target in this challenging disease.

Seven children with advanced nasopharyngeal carcinoma younger than 20 years of age diagnosed between 1975 and 1986 (inclusive) were treated with a uniform adjuvant chemotherapy regimen, which consisted of vincristine (1.5 mg/m2; day 1), doxorubicin (45 mg/m2; day 1), 5-fluorouracil (8 mg/kg; days 1 through 5), and cyclophosphamide (7 mg/kg; days 1 through 5). This combination chemotherapy was given for 12 to 24 months after completion of radiation therapy. The radiation doses to the primary sites ranged from 6000 cGy to a maximum of 6800 cGy. The radiation doses for neck prophylaxis ranged from 4500 cGy to a total of 5000 cGy. Involved sites were irradiated to at least an additional boost of 1000 cGy. One patient had an external dose 6000 cGy to the primary site boosted with brachytherapy of 3000 cGy at the surface of an ovoid. After chemotherapy myelosuppression occurred in all patients and was tolerable. All seven patients are surviving, six disease-free, for 22 months to 12 years (median, 4 years). This study suggests that the combination of radiation therapy and chemotherapy as used here has acceptable toxicity and is effective and further suggests that children with nasopharyngeal carcinoma, even in its advanced stage at diagnosis, may be curable.