Insomnia associated with thalamic involvement in E200K Creutzfeldt-Jakob disease.

BACKGROUND: Insomnia with predominant thalamic involvement and minor cortical and cerebellar pathologic changes is not characteristic of familial Creutzfeldt-Jakob disease (CJD) but is a hallmark of fatal familial insomnia. OBJECTIVE: To report a 53-year-old woman with intractable insomnia as her initial symptom of disease. METHODS: The authors characterized clinical, pathologic, and molecular features of the disease using EEG, polysomnography, neurohistology, Western blotting, protein sequencing, and prion protein (PrP) gene (PRNP) analysis. RESULTS: The patient developed dysgraphia, dysarthria, bulimia, myoclonus, memory loss, visual hallucinations, and opisthotonos, as well as pyramidal, extrapyramidal, and cerebellar signs. Polysomnographic studies showed an absence of stages 3 and 4, and REM. She died 8 months after onset. On neuropathologic examination, there was major thalamic involvement characterized by neuronal loss, spongiform changes, and prominent gliosis. The inferior olivary nuclei exhibited chromatolysis, neuronal loss, and gliosis. Spongiform changes were mild in the neocortex and not evident in the cerebellum. PrP immunopositivity was present in these areas as well as in the thalamus. PRNP analysis showed the haplotype E200K-129M. Western blot analysis showed the presence of proteinase K (PK)-resistant PrP (PrP(sc)) with the nonglycosylated isoform of approximately 21 kd, corresponding in size to that of type 1 PrP(sc). N-terminal protein sequencing demonstrated PK cleavage sites at glycine (G) 82 and G78, as previously reported in CJD with the E200K-129 M haplotype. CONCLUSIONS: Insomnia may be a prominent early symptom in cases of CJD linked to the E200K-129M haplotype in which the thalamus is severely affected.

Craniocerebral involvement in lymphoma.

Nine-hundred-eighty-nine patients with lymphoma were studied. Fifty-three cases (5.3%) had lymphomatous craniocerebral infiltration. The principal factors of risk for this complication were: advanced stage of the lymphoma (III or IV), diffuse histiocytic, diffuse poorly differentiated lymphocytic, or mixed cellularity lymphoma histological type, bone marrow involvement, and previous systemic chemotherapy. Thirty-two per cent of the cases of meningeal lymphomatous infiltration were asymptomatic and represented autopsy findings. CT-scan was an useful test to detect brain focal parenchymatous infiltration, as opposed to meningeal infiltration. Mean survival time in patients with lymphomatous meningeal infiltration was 4.3 months, following the combined use of systemic chemotherapy, radiation therapy and intrathecal methotrexate. Two cases had primary cerebral lymphoma, although without associated immunodeficiency. Twenty patients (2%) had intracranial hemorrhage, in clear relationship with platelet alterations. Fifteen patients (1.5%) had CNS infection, caused by common bacteria or opportunistic agents. In 7 cases, the diagnosis was made at autopsy. Thirty-six autopsies were performed. In 8 cases (22%), pathologic findings such as, demyelination, microcalcifications, coagulative necrosis, or gliosis, suggested complications from treatment.

Peripheral nervous system and spinal cord involvement in lymphoma.

Nine-hundred-eighty-nine patients with diagnosis of lymphoma were studied. Forty-six cases (4.6%) had compressions of the spinal cord or roots. Forty-two patients (4.2%) had Herpes zoster virus infections, which in 6 cases were of disseminated type. The major predisposing factors for infection were: advanced stage of lymphoma, previous systemic chemotherapy and splenectomy. Toxic polyneuropathy secondary to chemotherapy was found in 39 patients (3.9%). In 14 cases, the polyneuropathic symptoms were the main complaint (Group 1), while in the remaining 25 cases the diagnosis was made during neurological consultations because of unrelated symptoms (Group 2). Both groups did not have significant differences in the total dose of chemotherapy received. The electrophysiological studies showed an axonal neuropathy in both groups. The discontinuation of chemotherapy was found to be a limiting factor in the appearance of neuropathic symptoms. Other less frequent forms of involvement were: compression of peripheral nerves or nerve plexi from lymphadenopathies (3 cases), radiation myelopathy (1 case), and Guillain-Barré Syndrome associated with Hodgkin's Lymphoma (1 case).