Table 3 Clinical features of NPDPSC E200K-129V (trans M) cases*
| Â | 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 | 9Â months | 8Â months | 7Â 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 4Â 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 4Â months, | ||
MMSE 19/30 (missing points on orientation and recall) at 4Â months | |||
MOCA 10/30 at 4Â months | |||
MMSE 27/30 at 5Â 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 4Â months | Right temporal slowing at 4Â months |
Brain MRI | Read normal at 2Â months. | Reported as only periventricular white matter changes at 2Â month. | Reported as high T2 signal in the cerebellar gray matter and vermis, cerebellar atrophy at 3Â months. |
At 3Â months, reported as symmetrical T2 and DWI hyperintensity in the caudate, putamen, and pulvinar | Restricted diffusion in the caudate at 4Â months | At 4Â 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 14746Â pg/mL | 14-3-3 4.5Â ng/mL | ||
glucose 65 (45–75) |  | (nl < 1.5 ng/mL, Mayo clinic) | |
Positive 14-3-3 | Â | CSF paraneoplastic panel: negative (Mayo clinic) | |
tau 20360Â pg/mL | |||
Other labs | Serum paraneoplastic panel negative | Â | 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 |