Sensory disturbances in Creutzfeldt-Jakob disease.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disease characterized by rapidly progressive dementia, motor impairments, and psychiatric symptoms. Sensory disturbances were occasionally reported as well. The study aims to describe the sensory symptoms of the disease. METHODS: The CJD Israeli National Database was screened for patients who presented sensory symptoms throughout the disease course. Symptoms, characteristics, and distribution were reviewed and the demographic and clinical data (sex, etiologies of the disease, age of onset, disease duration, neurological exam finding, tau protein level, EEG and MRI findings) were compared with the demographics and clinical data of CJD without sensory symptoms. Then, the patients with sensory symptoms were divided into patients with symptom distribution consistent with peripheral nervous system (PNS) involvement and central nervous system (CNS) involvement. The demographics and clinical data of the 2 groups were compared. RESULTS: Eighty-four CJD patients with sensory symptoms and 645 CJD patients without sensory symptoms were included in the study. Sensory symptoms were more common in genetic E200K CJD patients (14.6% vs. 5.6% respectively, p = 0.0005) (chi-squared test). Numbness and neuropathic pain were the most common symptoms and distribution of symptoms of "stocking gloves" with decreased deep tendon reflexes suggesting peripheral neuropathy in 44% of the patients. In these patients, the classical EEG findings of Periodic Sharp Wave Complexes were less often found (58% vs. 22%, p = 0.02) (chi-squared test). CONCLUSIONS: Sensory symptoms are more common in E200K patients and often follow peripheral neuropathy distribution that suggests PNS involvement.

The epidemiological and clinical characteristics of patients with young-onset genetic Creutzfeldt-Jakob disease.

OBJECTIVES: The onset of Creutzfeldt-Jakob disease (CJD) is usually around the age of 60, but younger patients have been described as well. Our study characterizes the demographic and clinical features of young-onset CJD patients. METHODS: The CJD Israeli National Database was reviewed, and the patients were divided into groups of young (<40-year-old) (Y|) and older disease onset (>40-year-old) (O). Each group was further divided into sporadic (sCJD) and genetic (gCJD) patients. Clinical and demographic parameters were compared between the groups. RESULTS: The study included 731 patients (Y- 18 patients, O- 713 patients). MRI showed classical features more often in the older population (O-76.9%, Y-36%, p = 0.006). Rapidly progressive dementia as a presenting feature was more common in the older group (O = 58%, Y = 27.7%, p = 0.019) whereas cerebellar onset (gait instability, dysarthria) was more common in the younger group (O = 6.7%, Y = 27.7%, p = 0.036)). Among gCJD patients, rapidly progressive dementia was commonly seen in older patients (O = 54%, Y = 21% p = 0.008) whereas cerebellar symptoms were seen in young patients (O = 7%, Y = 30% p = 0.01) Typical MRI findings were seen in 37% of young people compared to 87% of older patients (p = 0.002). No significant differences were between young and older patients in the sCJD group. CONCLUSION: Young-onset gCJD patients have unique disease features including less typical brain MRI changes, a lower prevalence of dementia, and a higher prevalence of cerebellar signs at disease onset.

The consequences of switching from Gilenya® to generics for fingolimod.

BACKGROUND: On May 2017, two generic drugs for fingolimod were introduced into the market in Israel, and most MS patients treated with Gilenya® (Novartis) were switched to fingolimod (Teva), or to Finolim (Rafa). In this study we analyzed the consequences of switching to generic fingolimod in a single MS center. METHODS: Study population included relapsing MS patients who were treated with Gilenya® for at least two year before May 2017, switched to generic fingolimod and remained on treatment for at least 2 years thereafter. Data before and after the switch were compared. RESULTS: Twenty-seven patients fulfilled the inclusion criteria (F = 20, RRMS=20, SPMS=7, average age 49±11.4 years, average disease duration=16.6 ± 7.6 years). Seventeen patients had to be switched back to the original Gilenya® due to intolerable new or worsening clinical adverse events (n = 9), clinical relapse (n = 1), clinical relapse with adverse events (n = 3), elevation of liver enzymes > X3 ULN (n = 3) and elevation of amylase (n = 1). Expanded Disability Status Scale (EDSS) score increased in 4 patients during the year before the switch, and in 12 patients during the year of treatment with generic fingolimod (p = 0.036). CONCLUSION: The tolerability, retention rate and probably efficacy of generic fingolimod seems to be lower than the original Gilenya®.

Intraoperative Deterioration of Neurophysiological Potentials of the Spinal Tracts in Cervical Spine Surgery: Correlation With Patient-Related and Procedure-Related Variables.

PURPOSE: To identify characteristics associated with higher incidence of intraoperative deterioration of neurophysiological potentials related to spinal tracts in cervical spine surgeries. METHODS: Electrophysiological raw data and neurophysiological case reports of 1,611 patients from multiple medical centers, who underwent cervical spine surgery for decompression and/or fusion, were retrospectively reviewed. Patient-related and procedure-related variables were identified and analyzed for correlation with intraoperative neurophysiological event of the spinal tracts. The neurophysiological events were analyzed for identification of collective characteristics. RESULTS: The study cohort presented consistent dominancy of male over female patients (67% vs. 33%). Intraoperative deterioration of spinal tract-derived potentials was noted in 10.5% of the total cases, which was not correlated with gender, age, or indication of the surgery. Higher incidence of neurophysiological events was noted in patients with impaired baseline of motor evoked potentials from the thenar muscle ( P = 0.01) or somatosensory evoked potentials of the posterior tibial nerve ( P = 0.0002). Procedures of circumferential approach or procedures that involved ≥3 spinal levels demonstrated higher incidence of neurophysiological events as well ( P = 0.0003 and 0.001, respectively). CONCLUSIONS: Patients with deteriorated neurophysiological baseline and procedures of extensive intervention are at higher risk of intraoperative neurophysiological event in cervical spine surgery. Inclusion of intraoperative neurophysiological monitoring should be encouraged in complicated cases of cervical spine surgeries.

Genetic Creutzfeldt-Jakob disease in Turkish Jews-demographic and clinical features.

BACKGROUND: The largest cluster of genetic Creutzfeldt- Jakob Disease (CJD) exists in Libyan Jews carrying the E200K mutation in the PRNP gene. However, there is another cluster of genetic CJD with E200K mutation in families of Turkish-Jewish origin. AIMS: In this retrospective study, we aim to describe the demographic and clinical features of this population of patients. MATERIAL AND METHODS: The Israeli National CJD database was searched for demographic, clinical, imaging, and laboratory data of genetic CJD patients of Libyan and Turkish ancestry with the E200K mutation. The data of Libyan and Turkish patients were compared with notice similar or different demographic or clinical courses. RESULTS: Four hundred and twenty-three patients with CJD of Libyan (L) ancestry and 27 patients with CJD of Turkish (T) ancestry were identified. There were no significant differences in demographic and clinical data between the two populations (age of onset: T = 62 ± 8.8, L = 60 ± 9.7; age of death: T = 63 ± 8.6, L = 61 ± 9.7; and disease duration: T = 7.8 ± 8.4 months, L = 9.6 ± 13.6 months). Rapidly progressive dementia was the most common presentation in both groups, followed by pure cerebellar onset. The levels of tau protein in CSF did not differ between groups (T = 1290 ± 397.6 pg/ml, L = 1276 ± 594.2 pg/ml). MRI and EEG showed classical CJD features in most patients in both groups. DISCUSSION: The E200K mutation is the most common mutation among gCJD patients and was reported in different ethnical populations, suggesting several independent haplotypes of the mutation. The Turkish-Jew cluster, first described in this study, shares similar demographic and clinical features with the bigger cluster of Libyan-Jews CJD patients. CONCLUSION: E200K gCJD patients of Turkish ancestry share similar demographic and clinical features to patients of Libyan descent, suggesting a common origin of both populations.

Epidemiological and clinical characteristics of patients with late-onset Creutzfeldt-Jakob disease.

BACKGROUND: Creutzfeldt-Jacob disease (CJD) is a fatal neuro-degenerative disease, characterized by rapid and intense deterioration, mainly cognitive, leading to death. The typical onset of the disease is around the age of 67. PURPOSE: To characterize the demographic and clinical features of the population of CJD patients with late-onset disease. METHODS: In this retrospective study, the Israeli national database of prion diseases was screened for CJD patients with disease age of onset > 80 years between 1960 and 2016. Patient's demographic and clinical data were collected including sex, type of disease (sporadic/ genetic), clinical presentation, lab results including tau protein level, imaging, and EEG characteristics. Then, the clinical and demographic data of patients with late onset (> 80 years) (L) and patients with usual age of onset (< 80 years) (U) were compared. RESULTS: The study included 728 patients, 23 patients (3.3%) with late-onset disease (82.2.4±4 years, range 80-88) and 705 with usual disease onset (61.31 ± 9.47 years, range 34-80). Sporadic CJD was more common in the late-onset group (18/23 patients (78.2%) (L) vs. 256/705 patients (36.3%) (U)) (p = 0.0001, chi-square test). Classical EEG finding of periodic sharp wave activity were seen more often in the late-onset patients (55% (L) vs. 32.5% (U)) (p = 0.05, chi-square test). The rest of the demographic and clinical features were similar in both groups. CONCLUSION: Late- and usual-onset diseases are similar in most of demographic and clinical features suggesting a common disease type with normal distribution of age of onset.

Spatial distribution of abnormal EEG activity in Creutzfeldt-Jakob disease.

OBJECTIVES: Electroencephalogram (EEG) pattern in Creutzfeldt-Jakob disease (CJD) is characterized by diffuse abnormal activity, although lateralization to one hemisphere has been described in the first stages of the disease. This study aimed to determine whether abnormal EEG activity predominantly occurs in anterior versus posterior brain regions. METHODS: As part of a prospective study, the demographics, clinical features and MRI findings of genetic E200K CJD patients were collected. EEG was performed and the recordings reviewed for the typical periodic sharp wave complex (PSWC) and non-specific slow activity. Data were analyzed using the qEEG tool, and the activity in anterior and posterior regions of the brain compared. RESULTS: Eleven genetic E200K CJD patients were included in the study (67% women). The average age was 59.1 ±â€¯8.4 SD years and the average disease duration was 2.4 ±â€¯2.1 months. EEG showed the classic PSWC pattern in 5/11 (45%) of the patients, and slow activity was seen in 9/11 (82%). EEG was normal in 2 patients. PSWC activity was diffuse in 2/5 patients and unilateral in 3/5 patients; slow activity was diffuse in 9 patients. Quantitative analysis of PSWC and slow activity showed no significant difference between anterior and posterior distribution. CONCLUSION: The abnormal EEG activity in CJD is diffuse with no clear spatial predominance in anterior or posterior brain regions.

Association between cervical disc disease and lesions of multiple sclerosis.

BACKGROUND: Cervical discopathy and demyelinating lesions often co-exist in patients with multiple sclerosis (MS). Our study examines the possible association between these two pathologies. METHODS: Medical records and cervical magnetic resonance imaging scans of MS patients with cervical discopathy who were seen at our MS clinic during 2018 were retrospectively reviewed. The severity of the disc disease was classified as grade I (no compression), grade II (compression of the dural sac) and grade III (cord compression). The spinal cord in each scan was divided into six segments corresponding to the intervertebral space of the spine (C1-C6). Each segment was defined as containing demyelinating lesion and disc pathology (group 1), demyelinating lesion without disc pathology (group 2), disc pathology without demyelinating lesion (group 3) and no demyelinating lesion or disc pathology (group 4). Fisher's exact test was used to test the association between demyelinating lesions and disc pathology. RESULTS: Thirty-four MS patients with cervical discopathy were included in the study (26 females; average age 42.9 ± 13.7 years; average disease duration 8.4 ± 5.4 years). A total of 204 spinal cord segments were evaluated. Twenty-four segments were classified as group 1, 27 segments as group 2, 52 segments as group 3 and 101 segments as group 4. There was no association between demyelinating lesions and the grade of disc disease (p = 0.1 for grade I, p = 0.3 for grade II and p = 1 for grade III disc disease). CONCLUSION: Our study did not find any association between cervical disc disease and demyelinating spinal cord lesion.

Familial Creutzfeldt-Jakob disease homozygous to the E200K mutation: clinical characteristics and disease course.

OBJECTIVE: To characterize the demographic, clinical features and disease course of familial Creutzfeldt-Jakob disease (fCJD) patients homozygous to the E200K mutation. METHODS: The Israeli National CJD Database was screened for patients homozygous to the E200K mutation. Patients' demographic data, clinical presentation and neurological findings, tau protein levels in the cerebrospinal fluid (CSF) and EEG, were assessed. RESULTS: Ten homozygous E200K patients were identified (80% males). Average age of onset was 47.5 ± 6.1 years (range 40-56) and the average age of death was 49.3 ± 7. 7 years (range 42-63) with average disease duration of 27.7 ± 9.7 months (range 2-97). Initial clinical presentation included behavioral change in 4/10 patients, cognitive decline in 3/10 patients and focal neurological deficits in 2/10 patients. Throughout the disease course, the clinical signs in descending order of prevalence included cerebellar (70%), brainstem (60%), extrapyramidal (50%), pyramidal (50%), frontal lobe signs (30%), and disturbances of ocular motility (30%) Compared to the 228 heterozygous E200K fCJD patients, the 10 homozygous patients were significantly younger at disease onset (47.5 vs 59.7 years, p < 0.001), had a longer disease duration (27.7 vs 8.5 months, p < 0.001) and presented more frequently with behavioral changes as initial manifestation (4/10 vs. 34/228, p = 0.05). CONCLUSIONS: Homozygous E200K fCJD patients are characterized by a relatively younger age of onset and longer disease duration. Behavioral changes as a presenting symptom were more common in homozygous patients and cerebellar dysfunction was the most common neurological manifestation throughout the disease course.

Intraoperative monitoring of corticospinal tracts in anterior cervical decompression and fusion surgery: Excitability differentials of lower extremity muscles.

OBJECTIVE: This study examines and compares excitability characteristics of tibialis anterior (TA) and abductor hallucis (AH) transcranial motor evoked potentials (tcMEP) during anterior cervical decompression and fusion (ACDF) surgery. METHODS: Electrophysiological and clinical data of 89 patients who underwent ACDF procedure were retrospectively reviewed. TcMEP data of TA and AH muscles from 178 limbs were analyzed for availability, robustness and stability during the procedure. RESULTS: TA tcMEP was available at 83% whereas AH tcMEP was available at 99% of the monitored lower limbs at preposition baseline. Availability of both TA and AH tcMEP was demonstrated in 147/178 limbs. The baseline amplitude of AH tcMEP was significantly greater than that of TA tcMEP recorded from the same limb (744.6 ±â€¯54.0 and 326.9 ±â€¯33.3 µV, respectively). Simultaneous deterioration of TA and AH tcMEP data was demonstrated in 10/147 limbs. Deterioration of either TA or AH tcMEP data accompanied by unchanged tcMEP data from the other lower limb muscle was noted in 32/147 compared to 1/147 limbs, respectively. The deteriorated TA and AH tcMEP data returned to baseline before closing at incidence of 17% compared to 46%, respectively. No new lower extremity (LE) neurological deficit was presented postoperatively in any patient. CONCLUSIONS: AH tcMEP is a more reliable candidate than TA tcMEP for intraoperative LE monitoring in ACDF procedure. SIGNIFICANCE: The excitability differentials in LE tcMEP in ACDF is a variable that need to be considered while interpreting intraoperative neurophysiological data.

The association of quantitative EEG and MRI in Creutzfeldt-Jakob Disease.

INTRODUCTION: Previous studies showed concordance between the typical Periodic Sharp Wave Complex (PSWC) activity in EEG of Creutzfeldt-Jakob Disease (CJD) patients and the MRI findings, while the concordance with slow activity in EEG is less established. The aim of this study was to better characterize the association between MRI findings and EEG changes using quantitative EEG (qEEG) analysis. METHODS: The demographics, clinical features, and the MRI findings of 12 familial E200K patients with CJD were gathered. EEG test was done and reviewed for the typical PSWC and for the non-specific slow activity. A possible association between the MRI findings and the EEG activity was examined. Then, EEG was analyzed using qEEG tool, and the association between the qEEG finding and the MRI was examined. RESULTS: Twelve patients were included in the study (67% women). Cortical MRI lesions finding were seen in 6/12 (50%) of the patients, and deep gray mater lesions were seen in 8/12 patients (67%). EEG showed the classic PSWC in 6/12 (50%) of the patients where slow activity was seen in 10/12 (83%). Slow activity and cortical MRI findings were associated in only 2/6 (33%) where deep gray matter findings and the slow activity had concordance of 4/8 (50%). qEEG analysis improved this concordance between slow activity and cortical findings to 3/6 (50%) and with the deep gray matter findings to 5/8 (63%). CONCLUSIONS: Quantitative EEG analysis modesty but not significantly, improves the association of EEG slow activity in familial E200K CJD patients with MRI findings.

Effect of Intra- and Extraoperative Factors on the Efficacy of Intraoperative Neuromonitoring During Cervical Spine Surgery.

INTRODUCTION: The purpose of the present study was to examine the effect of various extra- and intraoperative factors on the ability of neuromonitoring to predict neurological complications. METHODS: We reviewed the data from 592 patients who had undergone cervical spine surgery with neuromonitoring at Assuta Medical Center from 2006 to 2013. We compared the somatosensory evoked potentials, transcranial electric motor evoked potentials, and electromyographic signals collected throughout surgery with the patient surgical outcome measures, demographic data, pre-existing pathological features found on neurological examination, and radiographic findings. Descriptive and inferential analyses were used to estimate the relative explanatory power contributed by these factors. RESULTS: We included 468 patients in the present study. Neuromonitoring changes occurred in 100 patients, and the appropriate clinical intervention was undertaken in all 100, with recovery of the signals in 69. A transient neuromonitoring change was not associated with a poor outcome (only 8 of 69 patients). However, a permanent neuromonitoring change was associated with a new neurological deficit (13 of 31 patients) Changes occurring during positioning or decompression were associated with better clinical outcomes than were changes occurring during the rest of the procedure. Extraoperative factors were not associated with an increased risk of neuromonitoring changes during surgery or poorer surgical outcomes. CONCLUSIONS: Permanent neuromonitoring changes predicted for new neurological deficits. However, transient changes were not associated with a new deficit. Neuromonitoring changes occurring during positioning and decompression had better clinical outcomes compared with those occurring during the rest of the procedure.

Disease duration in E200K familial Creutzfeldt-Jakob disease is correlated with clinical, radiological, and laboratory variables.

Previous studies have suggested that disease duration in Creutzfeldt-Jakob disease (CJD) may be related to the radiological findings or cerebrospinal fluid (CSF) tau levels; however, it is not yet established whether clinical, radiological, and laboratory findings at diagnosis can predict survival or have a prognostic value. The aim of this study was to examine whether the disease duration is correlated with clinical, radiological, and laboratory variables. The study population consisted of consecutive familial CJD (fCJD) patients that were assessed within 1 week from the diagnosis including the CJD neurological scale (CJD-NS), Minimental Status Examination, Frontal Assessment Battery, NIH Stroke Scale, and the expanded disability status scale. In addition, a single MRI study was done and measurements of the extent of the cortical and subcortical involvement were performed. CSF was examined as part of the workout, and tau levels were determined. Sixty-nine fCJD patients were included in the study (43 males, mean age 59.3 ± 8.4, range 44-79 years). The mean disease duration was 7.3 ± 6.9 months (median 5.6 months, range 2-20 months). A significant correlation was found between the disease duration and the CJD-NS, the disease burden as reflected by the degree of cortical involvement by DWI, and the CSF tau levels. The findings of the current study reveal that several findings at disease onset including the disease severity, the cortical changes, and the tau levels are each individually correlated with disease duration and can be used by the clinician as a tool to predict the disease course and prognosis.

A retrospective analysis of the development of seizure frequency in patients with seizures during a period of military conflict.

PURPOSE: A period of military conflict is characterized by high level of stress. In this study, we examined the seizure frequency in a civilian population of patients with seizures during a period of military conflict. METHODS: This retrospective study investigated seizure frequency in patients with seizures seen at the epilepsy clinic of Barzilai Medical Center during the summer of 2014 when the military operation "Protective Edge" between Israel and Gaza took place. Data collected included age, gender, type of seizures, diagnosis, medications, geographic area of living, medical history, imaging, EEG findings and seizure frequency before, during and after the period of conflict. The study was approved by the local Institutional Review Board. RESULTS: Sixty-three (35 men, 55%) patients were included in the study. No significant change in seizure frequency was seen in most patients Mean frequency of seizures was one/3 months during the military operation, not significantly different from seizure frequency before and after the period of conflict. Demographic data, disease duration, findings on MRI or EEG, drug therapy or distance from the Gaza Strip were not associated with change in seizure frequency. However, an increased seizure frequency during the period of military conflict was found in patients with Psychogenic Non-Epileptic Seizures (PNES) compared with patients with epileptic seizures (p = 0.04, Fisher's exact test). CONCLUSION: Our study did not show any significant change in seizure frequency during a period of military conflict in most of patients with epilepsy. However, the frequency of spells increased in patients with PNES during this period.

Mycosis fungoides - A cutaneous lymphoproliferative disorder in a patient treated with fingolimod for multiple sclerosis.

Fingolimod was the first oral disease-modifying drug approved for the treatment of relapsing-remitting multiple sclerosis (MS). It has previously been associated with rare cases of lymphoma. Here we describe the first case of mycosis fungoides - a cutaneous lymphoproliferative disorder, in an MS patient treated with fingolimod. who developed histologically confirmed mycosis fungoides 3 years after starting fingolimod. The drug was withdrawn and the patient was treated with radiotherapy and surgical excision with remission. This report points to a possible association between fingolimod and skin lymphoproliferative disorder and emphasizes the need for periodic skin examination.

Spinal intradural extramedullary tumors: the value of intraoperative neurophysiologic monitoring on surgical outcome.

Nerve sheath tumors and meningiomas account for most intradural extramedullary (IDEM) tumors. These tumors are benign and amenable to complete surgical resection. In recent years, these surgeries are performed with intraoperative neurophysiologic monitoring (IONM) in order to minimize neurological injury, but the evidence for the statistical efficacy of this utility is lacking. This paper evaluates IONM benefits in IDEM tumor resection. Data of patients treated surgically for spinal intradural tumors from 1998 to 2003 was previously collected and analyzed. We retrospectively evaluated patients' charts operated in the years 2011 to 2013. Patients' medical files were reviewed including radiological examinations and electrophysiological reports. The data was collected and evaluated. Forty-one cases of meningioma or nerve sheath tumor resection surgery were performed in the study period. The surgical results were compared to 70 cases of historical controls. Demographic data was similar in these two groups. Sensitivity, specificity, and positive and negative predicted values of IONM were 75, 100, 100, and 97%, respectively. New neurological deficit rate was evident in 10 and 14% for the study and control groups, respectively (not significant). While IONM predicts neurological deficits with high accuracy level, this study does not suggest that there is a significant global benefit of IONM in these cases. As reported by others, in this series, the rate of new neurological deficits in non-monitored cases is similar to the monitored cases series; hence, IONM role in preventing new neurological deficits has yet to be proven.

Efficacy of Head Repositioning in Restoration of Electrophysiological Signals During Cervical Spine Procedures.

PURPOSE: To evaluate the frequency of loss of neurophysiological potentials during head positioning, the usefulness of head repositioning to restore the potentials, and the effect on neurological outcome. METHODS: We retrospectively reviewed consecutive cervical spine surgeries performed at the Israel Spine Center, Assuta Medical Center, during 2006 to 2013. Surgeries performed with neuromonitoring (transcranial-electric motor evoked potentials, somatosensory evoked potentials, electromyographic recordings) were included. Demographic data, medical history, findings at neurological examination and imaging, electrophysiological data recorded during surgery, and neurological outcomes were collected and analyzed. RESULTS: Three hundred eighty-one patients met inclusion criteria. Loss of potentials detected in nine patients during patient positioning and repositioning was undertaken with the aim of restoring electrophysiological signals. In 5/9 patients, repositioning resulted in immediate reappearance of potentials; in 1/5, potentials were affected again during decompression. In 4/9, repositioning did not immediately restore electrophysiological signals; in », potentials reappeared later during the decompression and in ¾, potentials had not recovered till the conclusion of surgery. There were new neurological deficits in 2/9, including one patient with loss of potential that was not restored with repositioning and the one in whom potential was restored but lost again during decompression. CONCLUSIONS: Intraoperative neuro monitoring is an efficient tool to alert the surgical team to potential neurological damage. Head reposition often restores the electrophysiological signals with possible prevention of impending sequelae.

CSF tau correlates with the degree of cortical involvement in E200K familial Creutzfeldt-Jakob disease.

Cerebrospinal fluid (CSF) tau was found to correlate with disease severity and cognitive status in E200K familial Creutzfeldt-Jakob disease (fCJD) patients. The objective of the present study was to test whether tau levels in the CSF also correlate with the disease burden as reflected by the degree of cortical involvement in DWI MRI. Forty-four consecutive E200K fCJD patients (25 males, mean age 58.6±7.5, range 48-75 years) were recruited to the study and had a CSF tau examination as well as measurements of the extent of the cortical involvement in the DWI axial MRI. Correlation was tested using Pearson test. A significant correlation (r=0.617 p<0.0001) was found between CSF tau levels and the extent of cortical involvement. This correlation between tau levels and the disease burden reinforce the notion that tau can be used as a biomarker reflecting the extent of disease in patients with E200K fCJD.

Clinical radiological correlation in E200K familial Creutzfeldt-Jakob disease.

The use of diffusion MRI improved the accuracy of diagnosis in Creutzfeldt-Jakob disease (CJD) and expanded our knowledge of the changes occurring in the brain during the disease. The aim of this study was to test whether in patients with E200K familial CJD (fCJD) the clinical severity correlates with the disease burden as reflected by the extent of cortical involvement in DWI MRI. Consecutive fCJD patients were examined by a neurologist who performed several tests including the CJD neurological scale (CJD-NS), MiniMental status examination (MMSE), Frontal Assessment Battery (FAB), NIH Stroke Scale (NIHSS), and the expanded disability status scale (EDSS). A simultaneously acquired MRI was analyzed by measuring the extent of cortical involvement in the DWI axial sequence. Correlations were tested for using Pearson test. Fifty-two fCJD patients (35 males, mean age 59.4 ± 5.7 years) were recruited to the study. Significant negative correlation was found between the extent of cortical involvement and the cognitive performance of the patients as reflected by their MMSE and FAB scores. In addition, a significant positive correlation was found between the MRI and the clinical disease severity scales CJD-NS and EDSS. The correlation between clinical scales of severity and cognitive dysfunction and the disease burden confirms the reliability of the CJD-NS scale. Further studies are warranted to examine whether MRI may serve not only for diagnosis but also as a biomarker for follow-up of disease progression and the efficacy of potential treatments.

Familial Creutzfeldt-Jakob disease with the E200K mutation: longitudinal neuroimaging from asymptomatic to symptomatic CJD.

Familial Creutzfeldt-Jakob disease (fCJD) in Jews of Libyan ancestry is caused by an E200K mutation in the PRNP gene. While carriers are born with this mutation, they usually remain asymptomatic until middle age. Early detection of conversion is crucial for understanding and eventually for the treatment of the disease. The aim of this study was to report longitudinal MRI data in E200K individuals who eventually converted from healthy mutation carriers to clinically symptomatic CJD. As a part of a prospective study, asymptomatic E200K mutation carriers were scanned annually until their conversion to symptomatic disease. Standardized diffusion and anatomical MR sequences were performed before and after clinical conversion in the subjects and those were compared to 15 non-carrier siblings ("healthy controls"). Blinded radiological readings and region of interest analyses were performed. Radiological readings of individual cases failed to detect characteristic changes in the scans taken before the conversion. Region of interest analysis of diffusion changes in pre-symptomatic stage was inconclusive; however, ADC reduction was found in early and late stages of the disease. Computerized volumetric analysis revealed monotonic volume reductions in thalamus, putamen and caudate following conversion, and the lateral ventricles showed dilatation of up to 62 % after clinical conversion. Although the clinical manifestations at disease onset are variable, the diffusion abnormalities and/or volume changes in the thalamus and basal ganglia during conversion may indicate early involvement of the thalamostriatal neuronal circuit.