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Sporadic Fatal Insomnia in a Young Woman: A Diagnostic Challenge: Case Report

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Case Reports

Sporadic Fatal Insomnia in a Young Woman: A Diagnostic Challenge: Case Report

Karen M Moody et al. BMC Neurol.

Abstract

Background: Sporadic fatal insomnia (sFI) and fatal familial insomnia (FFI) are rare human prion diseases.

Case presentation: We report a case of a 33-year-old female who died of a prion disease for whom the diagnosis of sFI or FFI was not considered clinically. Following death of this patient, an interview with a close family member indicated the patient's illness included a major change in her sleep pattern, corroborating the reported autopsy diagnosis of sFI. Genetic tests identified no prion protein (PrP) gene mutation, but neuropathological examination and molecular study showed protease-resistant PrP (PrPres) in several brain regions and severe atrophy of the anterior-ventral and medial-dorsal thalamic nuclei similar to that described in FFI.

Conclusions: In patients with suspected prion disease, a characteristic change in sleep pattern can be an important clinical clue for identifying sFI or FFI; polysomnography (PSG), genetic analysis, and nuclear imaging may aid in diagnosis.

Figures

Figure 1
Figure 1
Histology and immunohistochemistry. A: Severe neuronal loss and astrogliosis of the mediodorsal thalamic nucleus in the present case. Neurons are indicated by arrows, reactive astrocytes by circles. B: For comparison, the same thalamic nucleus is shown in an age-matched subject without prion disease; neurons are indicated by arrows. C: Immunohistochemistry for glial fibrillary acidic protein (GFAP) reveals reactive astrocytic gliosis in the mediodorsal thalamic nucleus of the present case but not in a control subject of the same age without prion disease (D). E: Prominent astrogliosis in the frontal cortex. The inset (lower left corner) depicts three reactive astrocytes at higher magnification. F: Fine spongiform degeneration of the parietal cortex. G: Intense punctate or "synaptic" PrP immunostaining and sparse clusters of small granules in the cerebral cortex (parahippocampal gyrus; 3F4 antibody).
Figure 2
Figure 2
Hematoxylin-eosin staining of the mediodorsal thalamic nucleus. As seen in the present case, the hematoxylin-eosin staining of the mediodorsal thalamic nucleus also shows severe neuronal loss in a fatal familial insomnia (FFI) control case. The arrow indicates a thalamic neuron.
Figure 3
Figure 3
Western blot analysis. A: The unglycosylated fraction of PrPres shows a gel mobility of approximately 19 kDa matching PrPres type 2 in each brain region examined. S1 (μl): volume of brain supernatant (see Methods) loaded into the gel; T1: PrPres type 1 (20 kDa) from a case of sCJD with genotype 129MM used as control. B: Western blot showing PrPres from the thalamic nuclei indicated after probing with the 1:4,000 concentration of 3F4 compared to 1:40,000 in A. Fc: frontal cortex; Pc: parietal cortex; Tc: temporal cortex; Oc: occipital cortex; Hi: hippocampus; Ec: entorhinal cortex; Cn: caudate nucleus; Av: anterior ventral thalamic nucleus; Dm: mediodorsal thalamic nucleus; Plv: thalamic pulvinar; Ce: cerebellum.

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