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Table 3 Clinical features of NPDPSC E200K-129V (trans M) cases*

From: Genetic CJD with a novel E200G mutation in the prion protein gene and comparison with E200K mutation cases

  Patient C Patient E Patient F
Age/gender 37 yo/male 57 yo/female 67 yo/female
Age of onset 37 yo 57 yo 67 yo
Duration of illness 9 months 8 months 7 months
First symptom Gait difficulty Gait difficulty and nonspecific dizzy feeling Veering to the left and worsening gait
Other symptoms and cognitive tests Speech difficulty; dysarthria Blurry and double vision at 2–3 months Weak voice,
Hands tremor,
MOCA 19/30 at 4 months Curled hands, clumsy hands Unable to write,
Short term memory decline at 2–3 months
Cognition deterioration MMSE 25/30 (no recall, no copy of design) at 4 months,
MMSE 19/30 (missing points on orientation and recall) at 4 months
MOCA 10/30 at 4 months
MMSE 27/30 at 5 months (remote recall 0/3)
Myoclonus and other abnormal neurological findings Myoclonus + in arms Myoclonus - vertical gaze palsy+ Myoclonus - postural tremor+, bradykinesia +
EEG N/A Intermixed bursts of delta and theta activity at 4 months Right temporal slowing at 4 months
Brain MRI Read normal at 2 months. Reported as only periventricular white matter changes at 2 month. Reported as high T2 signal in the cerebellar gray matter and vermis, cerebellar atrophy at 3 months.
At 3 months, reported as symmetrical T2 and DWI hyperintensity in the caudate, putamen, and pulvinar Restricted diffusion in the caudate at 4 months At 4 months, restricted diffusion in the caudate bilaterally, subtle restriction in the thalamic pulvinar area, left greater than right, and questionable high cortical intensity in the mesial frontal and parietal high convexities on DWI but no corresponding ADC findings, increased signal in the entire cerebellum on DWI
Other imaging Unremarkable C, T, and L spine MRIs Disc bulging on C-spine MRI Normal pelvic US and breast MRI
CSF profile Clear, colorless, WBC 0, protein 61(15–60), Positive 14-3-3 Clear, colorless, WBC 0, protein 46 (12–60), glucose 84 (40–70)
tau 14746 pg/mL 14-3-3 4.5 ng/mL
glucose 65 (45–75)   (nl < 1.5 ng/mL, Mayo clinic)
Positive 14-3-3   CSF paraneoplastic panel: negative (Mayo clinic)
tau 20360 pg/mL
Other labs Serum paraneoplastic panel negative   Serum paraneoplastic panel negative
PrPSc type 2 2 2
Family history for CJD Unknown Positive for progressive movement problems and dementia: 2 family members + for genetic testing for prion disease Father died of CJD at age 69 within 6 months
Histological and immunohistochemical findings 1.Vacuolation and reactive astrocytosis Similar to patient C but with less intense PrPSc immunostaining and no plaque-like PrP Sc formations.; Global cerebellar atrophy Similar to patient C but with less intense PrP Sc immunostaining and no plaque-like PrP Sc formations.; Focal cerebellar atrophy
1) Intense in the cerebral neocortex, basal ganglia, hippocampus, and cerebellum
2) Mild to moderate vacuolation in the thalamus
3) Vacuolation more severe in the basal ganglia than the cerebral cortex and thalamus
2. PrP Sc deposits
1) Diffuse and plaque like deposits in the cerebral cortex
2) Presence of intraneuronal PrPSc deposit
3) Moderate PrPSc deposits in the hippocampus and entorhinal cortex
4) Severe diffuse PrPSc deposits in the cerebellar molecular and granular layers, occasional small PrPSc aggregates in the cerebellar granular layer; Marked global atrophy of the cerebellum
5) Linear and curvilinear PrPSc deposits in the midbrain and cerebellar dentate nucleus
  1. * There were six E200K-129 V NPDPSC cases (A-F). No clinical information was available for Cases A and B. Case D, an 85 yo woman with dementia and known family history of E200K presenting with confusion but no other known clinical history, was not included in the table due to limited clinical information. Her MRI reportedly showed atrophy, chronic, microvascular ischemic change. Pathology revealed senile plaques of Alzheimer’s disease and mild vacuolation throughout the neocortex. Vacuolation was mild in the hippocampus, moderate in the entorhinal cortex and putamen. The cerebellum showed vacuolation without atrophy and also had focal PrPSc deposit with a perpendicular orientation to the cerebellar pial surface. Immunostaining was similar to that of Patient C but no plaque-like PrP formations were observed overall. PrPSc was type 2; N/A = not available.