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Dementia is often associated but is relatively mild There are characteristic spongiform changes, as in SSE Brain tissue from patients with this disease, when inoculated into chimpanzees, has produced a spongiform encephalopathy (Masters et al) Molecular genetic studies of affected members demonstrate a mutation of the prion protein gene This syndrome should be considered as a small familial subset of SSE, of slowly progressive type Fatal Familial Insomnia This is another very rare familial disease; it is characterized by intractable insomnia, sympathetic overactivity, and dementia, leading to death in 7 to 15 months (see also page 340) The pathologic changes, consisting of neuronal loss and gliosis, are found mainly in the medial thalamic nuclei Studies of a few families have shown a mutation of the prion protein gene, and brain material was found to contain a protease-resistant form of the gene Transmission of the disease by inoculation of infected brain material has not been accomplished (Medori et al) Kuru This disease, which occurs exclusively among the Fore linguistic group of natives of the New Guinea highlands, was the rst slow infection due to a nonconventional transmissible agent to be documented in human beings Clinically the disease takes the form of an afebrile, progressive cerebellar ataxia, with abnormalities of extraocular movements, weakness progressing to immobility, incontinence in the late stages, and death within 3 to 6 months of onset In some ways it is similar to the ataxic (Brownell-Oppenheimer) variant of Creutzfeldt-Jakob disease The remarkable epidemiologic and pathologic similarities between kuru and scrapie were pointed out by Hadlow (1959), who suggested that it might be possible to transmit kuru to subhuman primates This was accomplished in 1966 by Gajdusek and coworkers; inoculation of chimpanzees with brain material from affected humans produced a kuru-like syndrome in chimpanzees after a latency of 18 to 36 months Since then the disease has been transmitted from one chimpanzee to another and to other primates by using both neural and nonneural tissues The pioneering work in this eld led to the awarding of a Nobel Prize Histologically there is a nonin ammatory loss of neurons and spongiform change throughout the brain, but predominantly in the cerebellar cortex, with astroglial proliferation and PAS-positive stellate plaques of amyloid-like material ( kuru plaques ) The transmissible agent has not been visualized, however Kuru has gradually disappeared, apparently because of the cessation of ritual cannibalism by which the disease had been transmitted In this ritual, infected brain tissue was ingested and rubbed over the body of the victim s kin (women and young children of either sex), permitting absorption of the infective agent through conjunctivae, mucous membranes, and abrasions in the skin.

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ADAMS H, MILLER D: Herpes simplex encephalitis: A clinical and pathological analysis of twenty-two cases Postgrad Med J 49:393, 1973 AICARDI J, GOUTHIERES F, ARSENIO-NUNES HL, LEBON P: Acute measles encephalitis in children with immunosuppression Pediatrics 55:232, 1977 ANDERSON NE, WILLOUGHBY EW: Chronic meningitis without predisposing illness A review of 83 cases Q J Med 63:283, 1987 ANDERSON NE, WILLOUGHBY EW, SYNEK BK: Leptomeningeal and brain biopsy in chronic meningitis Aust N Z J Med 26:703, 1995 ANLAR B, SAATCI I, KOSE, et al: MRI nding in subacture sclerosing panencephalitis Neurology 47:1278, 1996 ASNIS DS, CONETTA R, TEIXEIRA AA, et al: The West Nile virus outbreak of 1999 in New York: The Flushing Hospital experience Clin Infect Dis 30:413, 2000

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ASTROM KE, MANCALL EL, RICHARDSON EPJr: Progressive multifocal leukoencephalopathy Brain 81:93, 1958 AURELIUS E, JOHANSSON B, SKOLDENBERG B, et al: Rapid diagnosis of herpes simplex encephalitis by nested polymerase chain reaction assay of cerebrospinal uid Lancet 337:189, 1991 BARNETT GH, ROPPER AH, ROMEO J: Intracranial pressure and outcome in adult encephalitis J Neurosurg 68:585, 1988 BEGHI E, NICOLOSI A, KURLAND LT, et al: Encephalitis and aseptic meningitis, Olmstead County, Minnesota, 1950 1981: Epidemiology Ann Neurol 16:283, 1984 BELL JE: The neuropathology of adult HIV infection Rev Neurol 154:816, 1998 BODIAN D: Histopathologic basis of clinical ndings in poliomyelitis Am J Med 6:563, 1949 BROWN P: Guidelines for high risk autopsy cases: Special precautions for Creutzfeldt-Jakob disease, in Autopsy Performance and Reporting North eld, IL, College of American Pathologists, 1990, chap 12, pp 67 74 BROWN P, CATHALA F, CASTAIGNE P, et al: Creutzfeldt-Jakob disease: Clinical analysis of a consecutive series of 230 neuropathologically veri ed cases Ann Neurol 20:597, 1986 BROWNELL B, OPPENHEIMER DR: An ataxic form of subacute presenile polioencephalopathy (Creutzfeldt-Jakob disease) J Neurol Neurosurg Psychiatry 20:350, 1965 CATHALA F, BROWN P, CHATELAIN J, et al: Maladie de Creutzfeldt-Jacob en France: Interet des formes familiales Presse Med 15:379, 1986 CHARLESTON AJ, ANDERSON NE, WILLOUGHBY EW: Idiopathic steroid responsive chronic lymphocytic meningitis: Clinical features and long term outcome in 17 patients Aust N Z J Med 28:784, 1998 CHESEBRO B: BSE and prions: Uncertainties about the agent Science 279: 42, 1998 CHUMAKOV M, VOROSHILOVA M, SHINDAROV L, et al: Enterovirus 71 isolated from cases of epidemic poliomyelitis-like disease in Bulgaria Arch Virol 60:329, 1979 COHEN BA, ROWLEY AH, LONG CM: Herpes simplex type 2 in a patient with Mollaret s meningitis: Demonstration by polymerase chain reaction Ann Neurol 35:112, 1994 CONNOLLY AM, DODSON WE, PRENSKY AL, RUST RS: Cause and outcome of acute cerebellar ataxia Ann Neurol 35:673, 1994 CORNBLATH DR, MCARTHUR JC, KENNEDY PGE, et al: In ammatory demyelinating peripheral neuropathies associated with human T-cell lymphotropic virus type III infection Ann Neurol 21:32, 1987 DAVIS LE, JOHNSON RT: An explanation for the localization of herpes simplex encephalitis Ann Neurol 5:2, 1979 DAWSON JR: Cellular inclusions in cerebral lesions of epidemic encephalitis Arch Neurol Psychiatry 31:685, 1934 DENNY-BROWN D, ADAMS RD, FITZGERALD PJ: Pathologic features of herpes zoster: A note on geniculate herpes Arch Neurol Psychiatry 51:216, 1944 DERESIEWICZ RL, THALER SJ, HSU L, et al: Clinical and neuroradiologic manifestations of eastern equine encephalitis N Engl J Med 336:1867, 1997 DEVINSKY O, CHO E-S, PETITO CK, PRICE RW: Herpes zoster myelitis Brain 114:1181, 1991 DONAT JF, RHODES KH, GROOVER RV, et al: Etiology and outcome in 42 children with acute nonbacterial encephalitis Mayo Clin Proc 55: 156, 1980 DRACHMAN DA, ADAMS RD: Herpes simplex and acute inclusion-body encephalitis Arch Neurol 7:45, 1962 DUELAND AN, DEVLIN M, MARTIN JR, et al: Fatal varicella-zoster virus meningoradiculitis without skin involvement Ann Neurol 29:569, 1991 EIDELBERG D, SOTREL A, VOGEL H, et al: Progressive polyradiculopathy in acquired immune de ciency syndrome Neurology 36:912, 1986 ENDERS JF, WELLER TH, ROBBINS FC: Cultivation of Lansing strain of poliomyelitis virus in cultures of various human embryonic tissues Science 109:85, 1949.

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