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To identify characteristics associated with higher incidence of intraoperative deterioration of neurophysiological potentials related to spinal tracts in cervical spine surgeries.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.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).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.

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.

To characterize the demographic, clinical features and disease course of familial Creutzfeldt–Jakob disease (fCJD) patients homozygous to the E200K mutation. 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. 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

BACKGROUND AND PURPOSE Previous studies have reported conflicting results regarding possible anticipation in familial E200K Creutzfeldt-Jakob disease (fCJD). Our objective was to use a large database to assess the age of disease onset (AODO) in CJD. METHODS The study population included 477 CJD patients [266 with fCJD, 145 with sporadic CJD (sCJD) and 66 patients of Libyan origin but negative family history] from the Israeli registry of CJD conducted since 1954. In all patients, AODO in relatives and family trees was documented. Comparison of AODO was done using a paired t test and regression using Pearson correlation for birth and year of onset. RESULTS The initial analysis in 52/73 families in which more than one generation was affected revealed an AODO of 63.30 ± 9.44 in the first generation compared to 56.96 ± 8.99 in the second generation (P

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.

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.

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 ± 8.4 SD years and the average disease duration was 2.4 ± 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.

Highlights • Lower extremity (LE) muscles demonstrate intraoperative excitability differences. • Abductor hallucis is a suitable LE muscle for monitoring the corticospinal tract (CST). • CST monitoring with two LE muscles includes advantages but also practical limitations., 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 ± 54.0 and 326.9 ± 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.

To characterize the demographic, clinical features and disease course of familial Creutzfeldt-Jakob disease (fCJD) patients homozygous to the E200K mutation.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.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).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.

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.

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.

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.

Background and propose Familial Creutzfeldt−Jakob disease (fCJD) in Jews of Libyan ancestry is caused by an E200K mutation in the PRNP gene. The typical presenting symptoms include cognitive decline, behavioral changes and gait disturbances; however, some patients may have an unusual presentation such as a stroke-like presentation, alien hand syndrome or visual disturbances. The aim of this paper is to describe uncommon presentations in our series of consecutive patients with E200K fCJD. Methods The study group included consecutive fCJD patients followed up as part of a longitudinal prospective study ongoing since 2003 or hospitalized since 2005. The clinical diagnosis of probable CJD was based on accepted diagnostic criteria and supported by typical magnetic resonance imaging, electroencephalographic findings, elevated cerebrospinal fluid tau protein levels and by genetic testing for the E200K mutation. Disease symptoms and signs were retrieved from the medical files. Results The study population included 77 patients (42 men) with a mean age of disease onset of 60.6 ± 7.2 years. The most prevalent presenting symptoms were cognitive decline followed by gait impairment and behavioral changes. However, six patients had an unusual presentation including auditory agnosia, monoparesis, stroke-like presentation, facial nerve palsy, pseudobulbar syndrome and alien hand syndrome. Conclusions Our case series illustrates the wide phenotypic variability of the clinical presentation of patients with fCJD and widens the clinical spectrum of the disease. A high level of clinical suspicion may prove useful in obtaining early diagnosis and therefore avoiding costly and inefficient diagnostic and therapeutic strategies.

Tetanus is a disease caused by a neurotoxin produced by the Gram-positive bacillus (C. tetani), found in the soil and human and animal feces. C. tetani is a mobile, spore-forming obligate anaerobe. Under anaerobic conditions as in necrotic and infected tissue, the tetanus bacillus secretes two toxins: tetanospasmin and tetanolysin. Tetanospasmin leads to the clinical syndrome of tetanus comprised of a triad of rigidity, muscle spasms and, if severe, autonomic dysfunction. We describe a case of a 31-year-old patient who presented with painful stiffness especially of the trunk, intermittent diffuse muscle spasms, difficulty swallowing and opening his mouth. After clinical workup a diagnosis of tetanus was made. The patient was treated with active vaccination by tetanus toxoid (TDaP), and passive vaccination (Tetanus Immune Globulin -TIG), antibiotics, pain relief agents and muscle relaxants and his symptoms resolved gradually. He was discharged from the hospital in a good condition 14 day after his admission.

The largest cluster of E200K familial Creutzfeldt-Jakob disease (fCJD) which occurs is in Jews of Libyan origin in Israel. Insomnia is a very common early complaint in those patients and may even be the presenting symptom. The aim of this study was to assess and characterize sleep pathology in E200K fCJD patients. To do so, sleep studies of 10 consecutive fCJD patients were compared with those of 39 age and gender-matched controls. All patients presented pathological sleep characterized by fragmentation of sleep, loss of sleep spindles and reduced REM sleep amount. Respiration was characterized by irregular rhythm, periodic breathing, apneas and hypopneas, either central or obstructive. EMG recordings revealed repeated movements in sleep, with loss of REM atonia. Comparing to controls, a significant decrease of total sleep time, sleep efficacy and slow-wave sleep as well as a significant increase in the number of awakenings, apnea-hypopnea index and mixed and central apneas were evident in CJD patients. Comparison of two sequential sleep studies in one patient revealed a 40 % reduction of the total sleep time, a 40 % reduction in sleep efficacy and a 40-fold increase of the number of arousals in the second study. A significant correlation was found between the disease severity, as reflected by the CJD Neurological Scale and Periodic leg movement index. These definite and characteristic sleep pathologies in patients with fCJD associated with the E200K mutation may serve as a new diagnostic tool in the disease.

Layered transition metal di-chalcogenide (TMD) materials exhibit a unique combination of structural anisotropy combined with rich chemistry that confers controllability over physical properties such as bandgap and magnetism. Most research in this area is focused on single layers that are technologically challenging to produce, especially when trying to dope and alloy the host lattice. In this work, we use MoS2 flakes as a model system for the production of deliberately oriented films for practical applications in which anisotropic materials are required. The proposed production method combines ball milling with exfoliation in solution of MoS2 flakes, followed by their arrangement on a large centimeter-scale substrate by a simple and non-expensive procedure. The results show that the level of orientation achieved using the proposed system is as good as that of materials that were pressed and subjected to thermal treatment. The ball milling and exfoliation processes maintain the original crystalline structure of the MoS2 flakes, and the XRD results show that additional crystallographic phases were not produced. Lattice parameters are preserved, which verifies that other species such as water molecules did not intercalate into the MoS2 molecules. The proposed method of producing oriented films is universal, and as such, it is useful both for pure materials and for mixtures of compounds, the latter of which can be used to produce films with specifically tailored physical properties.

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.

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.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.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 ¼, 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.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.

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 p0.0001) 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.

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.

Animal studies and clinical observations suggest that epilepsy is associated with inflammation. Translocator protein (TSPO) (18 kDa), a marker of inflammation, is increased in vitro in surgical samples from patients with temporal lobe epilepsy. TSPO can be measured in the living human brain with PET and the novel radioligand 11C-PBR28. In this study, we sought to determine whether in vivo expression of TSPO is increased ipsilateral to the seizure focus in patients with temporal lobe epilepsy. Methods: Sixteen patients with unilateral temporal lobe epilepsy and 30 healthy subjects were studied with 11 CPBR28 PET and MRI. Uptake of radioactivity after injection of 11 C-PBR28 was measured from regions of interest drawn bilaterally onto MR images. Brain uptake from ipsilateral and contralateral hemispheres was compared using a paired-samples t test. Results: We found that brain uptake was higher ipsilateral to the seizure focus in the hippocampus, parahippocampal gyrus, amygdala, fusiform gyrus, and choroid plexus but not in other brain regions. This asymmetry was more pronounced in patients with hippocampal sclerosis than in those without. Conclusion: We found increased uptake of radioactivity after injection of 11C-PBR28 ipsilateral to the seizure focus in patients with temporal lobe epilepsy, suggesting increased expression of TSPO. Studies in larger samples are required to confirm this finding and determine the clinical utility of imaging TSPO in temporal lobe epilepsy.

Objectives To develop a scale sensitive for the neurological manifestations of Creutzfeldt-Jakob disease (CJD).

Background: Calcium concentrations in serum are maintained within an exquisitely narrow range. Our aim was to examine the association between serum calcium and albumin-adjusted calcium (calciumadj) levels and stroke outcome in a cohort of unselected patients with acute stroke. Methods: Consecutive patients hospitalized due to acute stroke (ischemic or intracerebral hemorrhage) throughout a large medical center were systematically assessed and followed for 1 year. Baseline total calcium and calciumadj levels were collapsed into groups of low (10 mg/dl) levels and linear and quadratic relations with outcome were examined. Result: Among 784 patients (mean age 70.7 ± 12.5 years, 42.5% females), the mean ± SD total calcium level was 9.3 ± 0.6 mg/dl. For total calcium, the adjusted hazard ratio (HR) for all-cause death over 1 year was 1.83 [95% confidence interval (CI) 1.22–2.75] among patients with low versus normal levels. For calciumadj, the adjusted HR for all-cause death among women was over 3-fold higher among patients with high calciumadj levels versus those with normal levels (3.31; 95% CI 1.70–6.46), while no such associations were observed among men. In models developed to estimate the linear and quadratic relations, each unit increment in total calcium squared was associated with an increased adjusted HR of all-cause death over 1 year (p = 0.02) confirming nonlinear associations, and each unit increment in calciumadj squared was associated with an increased adjusted HR of all-cause death over 1 year among women (p < 0.001) but not among men (p = 0.70). Conclusions: Serum calcium concentrations are a marker of mortality in acute stroke patients, but the associations are not linear, increasing at both extremes of calcium levels. Our findings suggest that long-term survival is optimal in a distinct range of serum calcium levels.

Background: The largest cluster of familial Creutzfeldt–Jakob disease (fCJD) exists in Jews of Libyan origin. Familial Mediterranean fever (FMF) is an inflammatory disease also common in this population. Objectives: We hypothesized that FMF, as a pro-inflammatory condition, may affect the course of CJD. Methods: Three hundred and seventy-two consecutive patients diagnosed clinically and genetically as CJD were included in the study. Two hundred and thirty-six had fCJD, and 136 had sporadic disease (sCJD). Review of the patient’s records revealed three patients with FMF–CJD co-morbidity. In addition, 50 DNA samples of patients with CJD were genotyped as homozygote, heterozygote, and non-carriers of the FMF mutation. The demographic and clinical variables of the groups were compared. Results: The three patients with FMF had an earlier age of onset and significantly shorter disease duration than the patients without FMF. Heterozygote carriers did not differ in disease onset and duration from patients without FMF. Conclusions: The shorter disease duration of CJD patients with FMF may indicate the importance of pro-inflammatory factors in the disease.

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.

While myoclonus and ataxia are considered common in patients with familial Creutzfeld-Jakob disease (fCJD), other movement disorders are less prevalent.To systemically evaluate the frequency of extrapyramidal signs and movement disorders in patients with fCJD.A detailed neurological examination, with special emphasis on movement disorders and extrapyramidal signs, was conducted in 43 consecutive symptomatic CJD patients (26 males and 17 females; mean age 58.7 +/- 8.9 yrs, range 43-77 years) carrying the E200K mutation in the PRNPgene.Limb or gait ataxia was noted in 38 patients (88%) (37 patients, 86%, had ataxia at presentation). Myoclonus was evident in 25/43 patients (58%) (21 patients, 49%, at presentation). In 95% of the patients (41/43) (37/43, 86% at presentation) at least one extrapyramidal sign throughout the disease course was noted, the most prevalent being rigidity (28/43, 65% of the patients; and 22/43, 51% at presentation), followed by the glabellar sign (24/43, 56% of the patients; and 22/43, 51% at presentation), bradykinesia (19/43, 44%; and 15/43, 35% at presentation), dystonia (15/43, 35%; 12/43, 28% at presentation) and tremor (13/43, 30%; 12/43, 28% at presentation).In this unique population of fCJD patients, myoclonus was less prevalent than previously reported while other extrapyramidal signs were common and occurred at a relatively early stage of the disease. The high prevalence of movement disorders can be added to other phenomena characteristic of this familial disorder among Libyan lews. Whether this is attributable to the E200K mutation itself or to some other mechanism has still to be elucidated.

Blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI), an important research and clinical tool, depends on relatively greater transient increases in (regional cerebral blood flow) rCBF than cerebral metabolic rate for oxygen during neural activity. We investigated whether reduced resting rCBF in patients with temporal lobe epilepsy affects BOLD signal during fMRI language mapping.We used [(15)O] water positron emission tomography (PET) to measure rCBF, and 3 Tesla echo planar imaging (EPI) BOLD fMRI with an auditory description decision task in 33 patients with temporal lobe epilepsy (16 men; mean age 33.6 ± standard deviation [SD] 10.6 years; epilepsy onset 14.8 ± 10.6 years; mean duration 18.8 ± 13.2 years; 23 left focus, 10 right focus). Anatomic regions drawn on structural MRI, based on the Wake Forest Pick Atlas, included Wernicke's area (WA), inferior frontal gyrus (IFG), middle frontal gyrus (MFG), and hippocampus (HC). Laterality indices (LIs), and asymmetry indices (AIs), were calculated on coregistered fMRI and PET.Twelve patients had mesial temporal sclerosis (seven on the left), two patients had a tumor or malformation of cortical development (both left), one patient a right temporal cyst, and 18 patients had normal MRI (14 left). Decreasing relative left WA CBF correlated with decreased left IFG voxel activation and decreasing left IFG LI. However, CBF WA AI was not related to left WA voxel activation itself or WA LI. There was a weak positive correlation between absolute CBF and fMRI activation in left IFG, right IFG, and left WA. Patients with normal and abnormal MRI did not differ in fMRI activation or rCBF AIs.Reduced WA rCBF is associated with reduced fMRI activation in IFG but not WA itself, suggesting distributed network effects, but not impairment of underlying BOLD response. Hypoperfusion in TLE does not affect fMRI clinical value.

Memory deficits and depression are common in patients with temporal lobe epilepsy (TLE). Previous positron emission tomography (PET) studies have shown reduced mesial temporal 5HT1A-receptor binding in these patients. We examined the relationships among verbal memory performance, depression, and 5HT1A-receptor binding measured with 18F-trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl-N-(2-pyridyl) cyclohexane carboxamide (18FCWAY) PET in a cross-sectional study.We studied 40 patients (24 male; mean age 34.5 ± 10.7 years) with TLE. Seizure diagnosis and focus localization were based on ictal video-electroencephalography (EEG) recording. Patients had neuropsychological testing with Wechsler Adult Intelligence Score III (WAIS III) and Wechsler Memory Score III (WMS III) on stable antiepileptic drug (AED) regimens at least 24 h since the last seizure. Beck Depression Inventory (BDI) scores were obtained. We performed interictal PET with 18FCWAY, a fluorinated derivative of WAY 100635, a highly specific 5HT1A ligand, and structural magnetic resonance imaging (MRI) scans to estimate partial volume and plasma free fraction corrected 18FCWAY volume of distribution (V/f1).Hippocampal V/f1 was significantly lower in area ipsilateral than contralateral to the epileptic focus (73.7 ± 27.3 vs. 95.4 ± 28.4; p0.001). We found a significant relation between both left hippocampal 18FCWAY V/f1 (r = 0.41; p0.02) and left hippocampal volume (r = 0.36; p0.03) and delayed auditory memory score. On multiple regression, there was a significant effect of the interaction of left hippocampal 18FCWAY V/f1 and left hippocampal volume on delayed auditory memory, but not of either alone. High collinearity was present. In an analysis of variance including the side of the seizure focus, the effect of left hippocampal 18FCWAY V/f1 but not focus laterality retained significance. Mean BDI was 8.3 ± 7.0. There was a significant inverse relation between BDI and 18FCWAY V/f1 ipsilateral to the patient's epileptic focus (r = 0.38 p0.02). There was no difference between patients with a right or left temporal focus. There was no relation between BDI and immediate or delayed auditory memory.Our study suggests that reduced left hippocampal 5HT1A-receptor binding may play a role in memory impairment in patients with TLE.

Pruritus, a common feature of animal prion diseases such as scrapie, is rarely reported in humans with Creutzfeldt–Jakob disease (CJD), and its anatomical background is not well defined. The present study was undertaken to carry out a methodical prospective search for the prevalence of pruritus in CJD patients and investigate its anatomical substrate by MRI. The study group included consecutive familial and sporadic CJD patients carrying the E200K PRNP mutation followed up in a longitudinal prospective study between the years 2005 and 2008. Pruritus was prospectively screened for and diffusion-weighted imaging (DWI) was used to correlate brain diffusion abnormalities with pruritus in CJD patients. Pruritus was present in 6/31 (19.35%) patients with familial disease (fCJD) and in none of the patients with sporadic disease (sCJD). Pruritus was a presenting symptom in one patient and evolved during the course of the disease in the other five patients. The pruritus was generalized in three patients, regional in two and localized in one patient. It was transient in one patient and continued throughout the disease in five patients. DWI showed that pruritus was significantly associated with reduced diffusion in the several areas known to be affected by CJD, but most significantly in the midbrain periaqueductal grey matter. Pruritus is relatively common in patients with familial CJD carrying the E200K mutation. Our findings point to a central origin that involves damage to the inhibitory gating mechanism for itch in the periaqueductal grey matter.

Chronic fatigue syndrome (CFS) is characterized by severe disabling fatigue lasting for more than 6 months associated with physical and mental disturbances such as headache, arthralgia, myalgia, memory impairment, sore throat and tender lymph nodes. The exact pathogenesis is still unknown. Several models were proposed to explain its etiology including chronic infection, endocrine dysfunction, autonomic imbalance, depression, decreased immunity states and an aberrant reaction to infection. No convincing evidence was found to support any of the suggested pathogenic mechanisms. The current concept is that CFS pathogenesis is a multi factorial condition in which an infective agent cause an aberrant immune response characterized by a shift to Th-2 dominant response. When the response fails to be switched-off, a chronic immune activation occurs and clinically expressed as the symptomatology of CFS. Vaccinations are used in order to stimulate the immune system to induce a persistent immunity against the favorable antigens. Several syndromes that contain chronic fatigue as one of their symptoms, such as "Gulf war syndrome" and macrophagic myofasciitis were related to vaccinations. Can vaccinations induce the aberrant immune response of CFS? Little is known about this issue. There are some reports on CFS occurring after vaccination, but few prospective and retrospective studies failed to find such an association. A working group of the Canadian Laboratory Center for Disease Control (LCDC) that was founded in order to examine the suspected association between CFS and vaccinations concluded that there is no evidence that relates CFS to vaccination. Further studies are requested to examine this issue since it is very conceivable that if infection can lead to CFS, vaccination may also lead to it in the same immune-mediated pathogenesis.