Sporadic Fatal Insomnia in an Adolescent

Abstract

The occurrence of sporadic prion disease among adolescents is extremely rare. A prion disease was confirmed in an adolescent with disease onset at 13 years of age. Genetic, neuropathologic, and biochemical analyses of the patient’s autopsy brain tissue were consistent with sporadic fatal insomnia, a type of sporadic prion disease. There was no evidence of an environmental source of infection, and this patient represents the youngest documented case of sporadic prion disease. Although rare, a prion disease diagnosis should not be discounted in adolescents exhibiting neurologic signs. Brain tissue testing is necessary for disease confirmation and is particularly beneficial in cases with an unusual clinical presentation.

Sporadic Fatal Insomnia in Europe: Phenotypic Features and Diagnostic Challenges

“…Although this discrepancy may also be attributed to the relative low sensitivity of the tests performed, or perhaps to interlaboratory variability, taken together, our findings indicate that the clinical phenotype in patients with sFI better match that of the FFI MV heterozygotes at PRNP codon 129, which notoriously manifest less prominent sleep and autonomic disturbances than the MM homozygotes. 12,14,21,22 This difference is consistent with the evidence from FFI brains that the amount of prion protein deposition in the cortex and the degree of cortical pathology strongly depend on disease duration. 35 EEG, brain MRI, and CSF 14-3-3 were all unrevealing in our cohort.…”

“…Age at onset (mean = 43 years) in the present series was even younger than previously reported in sFI cases (mean = 46 years) or in FFI patients carrying MM at codon 129 (mean = 51 years) and significantly younger than in typical sCJD patients (mean = 67 years). [6][7][8][9][11][12][13][14][15][16][17][18][19][20][21][22][23][44][45][46] The result confirms that sFI is a disease of young or middle-aged adults rather than of the elderly, which is intriguing because this is difficult to reconcile with the current leading hypothesis of a "stochastic" origin of sporadic prion disease increasing with age. 20 Furthermore, the comparable or even earlier onset of sFI cases in comparison to FFI subjects indicates that age at onset in FFI, and possibly other genetic prion diseases, mainly depends on the specific prion strain (ie, M2T) rather than on the presence of the PRNP mutation, as commonly believed.…”

“…[6][7][8][9][11][12][13][14][15][16][17][18][19][20][21][22][23][44][45][46] Notably, one of the patients reported here had one of the longest clinical courses reported to date in sporadic human prion disease (Patient 11, 96 months). [6][7][8][9][11][12][13][14][15][16][17][18][19][20][21][22][23][44][45][46] Notably, one of the patients reported here had one of the longest clinical courses reported to date in sporadic human prion disease (Patient 11, 96 months).…”

“…The disease duration (mean = 30 months) in our series largely overlapped with that previously reported in sFI (mean = 26 months) and was, therefore, significantly longer than that of FFI carrying MM at codon 129 (about 10 months). [6][7][8][9][11][12][13][14][15][16][17][18][19][20][21][22][23][44][45][46] Notably, one of the patients reported here had one of the longest clinical courses reported to date in sporadic human prion disease (Patient 11, 96 months). 44 Regarding clinical manifestations, a significant and novel finding was the presence of psychiatric symptoms and a cognitive impairment, involving mainly memory, spatial and temporal orientation, language, executive functions, and attention in all patients during the early or middle disease stages, which is more consistent with CJD than FFI.…”

“…10 Whereas the recognized patients with FFI are numerous and belong to >50 families worldwide, only about 30 cases of CJD MM2T and a few cases with mixed MM2T and MM2C features (MM2T+C) have been recorded to date. 6,8,9,[11][12][13][14][15][16][17][18][19][20][21][22][23] Moreover, whereas the first description of FFI dates back to 1986 and its recognition as a genetic prion disease to 1992, the characterization of sFI as a distinct sporadic prion disease subtype was only achieved in 1999. 6,8 It is noteworthy, however, that a few cases previously reported under the terms thalamic dementia, thalamic degeneration, or thalamic form of CJD, either sporadic or familial, likely belonged to the same disease entity.…”