Table 2.

Clinical and Histopathological Findings in Kindreds with the Codon-178 PrP Mutation.

Kindred*	No. of Patients	Age at Onset (yr)	Duration of Disease (mo)	Clinical Signs	EEG†	Histopathology
		mean (range)
ST; Hungarian–Romanian ancestry23,24	4‡	41 (38–45)	15 (10–20)	Presenting with memory deficit, “nervousness,” confusion, and disorientation, then tremors or myoclonus, ataxia, hyperreflexia, speech difficulties, mutism, vegetative disturbances	−	Widespread spongiosis of cerebral cortex especially hippocampus, and basal ganglia; occasional mild spongiosis and gliosis, but no neuronal loss in the anterior ventral and mediodorsal thalamus; no changes in cerebellum and olives
OS; Finnish ancestry20–22	6§	50 (46–53)	21 (11–36)	Presenting with memory deficit, then ataxia, disorientation, speech difficulties progressing to mutism, tremors or myoclonus, and hyperreflexia	−	Spongiosis of cerebral cortex, as in kindred ST; moderate spongiosis, neuronal loss, and gliosis in thalamus; no changes in cerebellum and olives
AB; French ancestry25	2¶	47 (46–48)	≈ 12 (10–14?)	Presenting with memory deficit and tremor, then ataxia, speech impairment, myoclonus, hyperreflexia, and global deterioration of mental functions	−	Cerebral cortical spongiosis
Present study; Italian ancestry3	7∥	49 (35–61)	13 (7–25)	Subject IV-21 (onset at 52 yr): presenting with insomnia and vegetative disturbances, then enacted dreams, confusion, dysarthria, mutism, myoclonus, hyperreflexia, spasticity and incontinence (duration of 9 mo)	−	Severe atrophy of anterior ventral and mediodorsal thalamic nuclei; various degrees of gliosis of other thalamic nuclei and cerebral cortex; torpedo formation in cerebellum; various degrees of atrophy of olives; mild cerebral cortical spongiosis in Subject V-58 only
				Subject IV-37 (onset at 61 yr): presenting with insomnia and vegetative disturbances, then enacted dreams, dysarthria, ataxia, myoclonus, and rigidity (duration of 18 mo)	−
				Subject V-58 (onset at 35 yr): presenting with ataxia, then dysarthria, insomnia, vegetative disturbances, mutism, enacted dreams, confusion, myoclonus, and generalized myoclonic seizures (duration of 25 mo)	+

^*The first three kindreds are identified according to the nomenclature of Masters et al.²⁰

^†A plus sign indicates the presence of periodic spike activity on electroencephalography (EEG), and a minus sign its absence.

^‡Subjects II, III-l (autopsy), III-7 (autopsy and biopsy), and III-8 (autopsy).

^§Subjects IV-11, V-8 (biopsy), V-12 (autopsy), V-15, V-18 (biopsy), and V-30.

^¶Subjects III-2 and I1I-3 (biopsy).

^∥Subjects IV-20 (autopsy), IV-21 (clinical examination and autopsy), IV-34 (autopsy), IV-37 (clinical examination and autopsy), IV-75 (autopsy), IV-92 (autopsy), and V-58 (clinical examination and autopsies).