Hanna Rosenmann

Hadassah Medical Center, Yerushalayim, Jerusalem District, Israel

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Publications (54)237.46 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Journal of Neurology 12/2014; · 3.58 Impact Factor
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    ABSTRACT: 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.
    Journal of Neurology 12/2014; · 3.58 Impact Factor
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    ABSTRACT: Background Although seizures (other than myoclonus) are frequently reported in Creutzfeldt-Jakob disease (CJD), their frequency, clinical manifestations, and effect on the disease course is unknown.Objectives To characterize the frequency of seizures in E200K familial and sporadic CJD, to describe its semiology, EEG and MRI findings.Methods In this retrospective study, we reviewed all patients with CJD who were seen in the Sheba Medical Center between the years 2003–2012 and underwent clinical evaluation, genetic testing, EEG and MRI studies. The diagnosis of seizures was carried out based on documentation of episodes consistent with seizures or episode of unresponsiveness correlated with ictal activity in EEG.ResultsSixty-four probable patients with CJD were included in the study, 57 (89%) with E200K familial (fCJD) and 7 (11%) with sporadic (sCJD). Seizures occurred in 8 patients: 3 of 7 (43%) in patients with sCJD compared to 5/57 (9%) in patients with E200K fCJD (P = 0.04, chi-square test). Two of E200K fCJD patients with seizures had other non-prion etiologies for seizures (brain metastasis, known history of temporal lobe epilepsy which started 44 years before the diagnosis of CJD). Seizures occurred late in the course of the disease with an average of 12 days between the onset of seizures and death.Conclusion Seizures in E200K fCJD were infrequent and occurred late in the disease course. This difference suggests that E200K fCJD represents a separate subtype of the disease with distinct clinical characteristics.
    Acta Neurologica Scandinavica 10/2014; · 2.47 Impact Factor
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    Neurobiology of Aging 03/2014; 35(3):719. · 6.17 Impact Factor
  • Hanna Rosenmann, Zeev Meiner
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    ABSTRACT: Frontotemporal dementia (FTD) is the second most common cause of young onset dementia after Alzheimer's disease. FTD presents with progressive changes in behavior, personality and language deficits and it is a clinically, pathologically and genetically heterogeneous disorder. Histopathological heterogeneity includes various intraneuronal inclusions, mostly positive for tau or ubiquitin, with TDP-43 positive, and more rarely FUS positive. About 30-50% of FTD patients are familial with an autosomal dominant pattern of inheritance. Mutations in a number of genes are associated with FTD, most commonly in MAPT or GRN genes, and in the C90RF72, and more rarely in VCP, TARDBP or FUS. Recently, a new pathological classification of FTD was developed according to the precipitate proteins denoted frontotemporal lobe degeneration (FTLD) including FTLD-Tau, FTLD-TDP43, FTLD-FUS, FTLD-UBS and more. There is a correlation between the clinical type and pathological findings and this correlation is important for understanding the mechanism as well as the intervention. Unfortunately, there is no effective treatment for FTD but we hope that recent developments will make advances towards finding effective therapy.
    Harefuah 11/2013; 152(11):661-6, 687.
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    Experimental Neurology 09/2013; 247:8. · 4.65 Impact Factor
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    ABSTRACT: The recent studies of others and of us showing robust efficacy of anti-tangle immunotherapy, directed against phosphorylated (phos)-tau protein, may pave the way to clinical trials of phos-tau immunotherapy in Alzheimer's-disease and other tauopathies. At this stage addressing the safety of the phos-tau-immunotherapy is highly needed, particularly since we have previously shown the neurotoxic potential of tau-immunotherapy, specifically of full-length unphosphorylated-tau vaccine under a CNS-proinflammatory milieu [induced by emulsification in complete-Freund's-adjuvant (CFA) and pertussis-toxin (PT)] in young wild-type (WT)-mice. The aim of our current study was to address safety aspects of the phos-tau-immunotherapy in both neurofibrillary-tangle (NFT)-mice as well as in WT-mice, under challenging conditions of repeated immunizations with phos-tau peptides under a CNS-proinflammatory milieu. NFT- and WT-mice were repeatedly immunized (7 injections in adult-, 4 in aged-mice) with phos-tau peptides emulsified in CFA-PT. A paralytic disease was evident in the phos-tau-immunized adult NFT-mice, developing progressively to 26.7% with the number of injections. Interestingly, the WT-mice were even more prone to develop neuroinflammation following phos-tau immunization, affecting 75% of the immunized mice. Aged mice were less prone to neuroinflammatory manifestations. Anti-phos-tau antibodies, detected in the serum of immunized mice, partially correlated with the neuroinflammation in WT-mice. This points that repeated phos-tau immunizations in the frame of a proinflammatory milieu may be encephalitogenic to tangle-mice, and more robustly to WT-mice, indicating that -under certain conditions- the safety of phos-tau immunotherapy is questionable.
    Experimental Neurology 07/2013; · 4.65 Impact Factor
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    ABSTRACT: The cerebrospinal fluid (CSF) biomarkers amyloid beta 1-42, total tau, and phosphorylated tau are used increasingly for Alzheimer's disease (AD) research and patient management. However, there are large variations in biomarker measurements among and within laboratories. Data from the first nine rounds of the Alzheimer's Association quality control program was used to define the extent and sources of analytical variability. In each round, three CSF samples prepared at the Clinical Neurochemistry Laboratory (Mölndal, Sweden) were analyzed by single-analyte enzyme-linked immunosorbent assay (ELISA), a multiplexing xMAP assay, or an immunoassay with electrochemoluminescence detection. A total of 84 laboratories participated. Coefficients of variation (CVs) between laboratories were around 20% to 30%; within-run CVs, less than 5% to 10%; and longitudinal within-laboratory CVs, 5% to 19%. Interestingly, longitudinal within-laboratory CV differed between biomarkers at individual laboratories, suggesting that a component of it was assay dependent. Variability between kit lots and between laboratories both had a major influence on amyloid beta 1-42 measurements, but for total tau and phosphorylated tau, between-kit lot effects were much less than between-laboratory effects. Despite the measurement variability, the between-laboratory consistency in classification of samples (using prehoc-derived cutoffs for AD) was high (>90% in 15 of 18 samples for ELISA and in 12 of 18 samples for xMAP). The overall variability remains too high to allow assignment of universal biomarker cutoff values for a specific intended use. Each laboratory must ensure longitudinal stability in its measurements and use internally qualified cutoff levels. Further standardization of laboratory procedures and improvement of kit performance will likely increase the usefulness of CSF AD biomarkers for researchers and clinicians.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 05/2013; 9(3):251–261. · 14.48 Impact Factor
  • H Rosenmann
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    ABSTRACT: The drawbacks of amyloid immunotherapy, including the development of encephalitis, the lack of clinical improvement and of any effect on neurofibrillary tangles (NFTs), coupled with the central role of NFTs in dementia, may point that clearance of amyloid pathology is not sufficient for improving the dementia symptoms in Alzheimer's disease (AD) patients. This further supported the concept that immunotherapy targeting the NFT proteinous aggregates may be preferential. Yet, the encephalitogenicity of full-length tau protein under a proinflammatory CNS milieu, reported by us in immunized mice, demands to carefully and selectively target pathological tau, while not the normal functional tau, and assuring both efficacy (anti-NFT effect) as well as safety (free of encephalitis) of a potential vaccine. Accumulating evidence from animal studies shows that tau-immunotherapy, targeting selectively pathological tau, particularly the phosphorylated-tau isoforms, reduces the tau-pathology and improves the symptoms of dementia. These findings are based on studies from different research groups, including our laboratory, conducted in different animal models and using various immunization protocols. There is also evidence that the decrease in NFTs is antibody-mediated involving the endosomal/lysosomal pathway. No adverse effects were reported by the research groups, including also our study in which mice were immunized with a single injection of phosphorylated-tau peptide under a CNS proinflammatory milieu. In this review, I discuss the studies reported in this field, focusing on different approaches, different immunization protocols and mechanistic aspects, with a focus on the promising efficacy of the tau-immunotherapy, while addressing the safety issues already in the preclinical stage, before progressing to clinical trials.
    Current Alzheimer research 03/2013; · 4.97 Impact Factor
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    ABSTRACT: Adult polyglucosan body disease (APBD) is an autosomal recessive leukodystrophy characterized by neurogenic bladder, progressive spastic gait, and peripheral neuropathy. Polyglucosan bodies accumulate in the central and peripheral nervous systems and are often associated with glycogen branching enzyme (GBE) deficiency. To improve clinical diagnosis and enable future evaluation of therapeutic strategies, we conducted a multinational study of the natural history and imaging features of APBD. We gathered clinical, biochemical, and molecular findings in 50 APBD patients with GBE deficiency from Israel, the United States, France, and the Netherlands. Brain and spine magnetic resonance images were reviewed in 44 patients. The most common clinical findings were neurogenic bladder (100%), spastic paraplegia with vibration loss (90%), and axonal neuropathy (90%). The median age was 51 years for the onset of neurogenic bladder symptoms, 63 years for wheelchair dependence, and 70 years for death. As the disease progressed, mild cognitive decline may have affected up to half of the patients. Neuroimaging showed hyperintense white matter abnormalities on T2 and fluid attenuated inversion recovery sequences predominantly in the periventricular regions, the posterior limb of the internal capsule, the external capsule, and the pyramidal tracts and medial lemniscus of the pons and medulla. Atrophy of the medulla and spine was universal. p.Y329S was the most common GBE1 mutation, present as a single heterozygous (28%) or homozygous (48%) mutation. APBD with GBE deficiency, with occasional exceptions, is a clinically homogenous disorder that should be suspected in patients with adult onset leukodystrophy or spastic paraplegia with early onset of urinary symptoms and spinal atrophy. ANN NEUROL 2012;72:433-441.
    Annals of Neurology 09/2012; 72(3):433-41. · 11.19 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE:Human prion diseases are known to cause gray matter degeneration in specific cerebral structures, but evidence for white matter involvement is scarce. We used DTI to test the hypothesis that white matter integrity is disrupted in human CJD during the early stages of the disease.MATERIALS AND METHODS:Twenty-one patients with the E200K variant of CJD and 19 controls participated in DTI studies conducted on a 1.5T MR imaging scanner. The data were quantitatively analyzed and mapped with a voxelwise TBSS method.RESULTS:We found significant reductions of FA in patients with CJD in distinct and functionally relevant white matter pathways, including the corticospinal tract, internal capsule, external capsule, fornix, and posterior thalamic radiation. Moreover, these FA deficits increased with disease duration, and were mainly determined by increase of radial diffusivity, suggesting elevated permeability of axonal membranes.CONCLUSIONS:The findings suggest that some of the symptoms of CJD may be caused by a functional dysconnection syndrome, and that the leukoencephalopathy is progressive and detectable fairly early in the course of the disease.
    American Journal of Neuroradiology 05/2012; · 3.17 Impact Factor
  • Zeev Meiner, Hanna Rosenmann
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    ABSTRACT: Alzheimer's disease is the leading cause of dementia in advanced age with a prevalence of above 40% among persons 80 years or older. In recent years, new studies have made some important discoveries regarding the pathogenesis of the diseases and potential therapeutic measures. These developments have led to the announcement of new guidelines for the diagnosis of the disease published by the National Institute on Aging and the ALzheimer's Association. These guidelines expand the definition of ALzheimer's disease to include 2 new phases of the disease: pre-symptomatic and mildly symptomatic but pre-dementia. For the first time, the guidelines also incorporated the usage of biological markers to assist in the diagnosis of the disease, although they are still only in the research agenda. These biomarkers include atrophy of the medial temporal lobe by MRI, reduction of glucose metabolism in specific brain areas by PET-FDG and presence of beta-amyloid staining in the brain by PET-amyloid scan. In addition, there are also cerebrospinal fluid ICSF) biomarkers characteristic of Alzheimer's disease, which consist of low levels of Abeta42 and elevated levels of total and phosphorylated TAU. These biomarkers may be used to diagnose the disease in the early pre-symptomatic phase, to differentiate Alzheimer's disease from other causes of dementia and may be helpful in the follow-up of newly developed specific treatments.
    Harefuah 05/2012; 151(5):289-93, 318.
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    ABSTRACT: While myoclonus and ataxia are considered common in patients with familial Creutzfeld-Jakob disease (fCJD), other movement disorders are less prevalent. Objectives: 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.
    The Israel Medical Association journal: IMAJ 03/2012; 14(3):162-5. · 0.98 Impact Factor
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    Hanna Rosenmann, David Blum, Rakez Kayed, Lars M Ittner
    International journal of Alzheimer's disease. 01/2012; 2012:707482.
  • Hanna Rosenmann
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    ABSTRACT: Reliable biomarkers for Alzheimer's disease (AD) are highly needed in the clinic. As a fluid surrounding the brain and reflecting the major neuropathological features characteristic to the AD brain, the cerebrospinal fluid (CSF) provides the natural source for AD biomarkers. The expected use of an ideal AD biomarker is for the following purposes: (1) diagnosis, (2) prediction, (3) monitoring of disease progression, and (4) drug discovery. Review of the literature revealed that CSF analysis, specifically amyloid-beta (Aβ42, total (T)-tau, and phosphorylated (P)-tau, are reliable markers for AD diagnosis, even at very early stages, particularly vs. healthy controls, while more limited evidence for distinguishing from other dementias. As for prediction, abnormal CSF markers are predictors of cognitive decline in healthy subjects, converting from MCI to development of AD, and of the rate of cognitive decline in mild AD. Regarding monitoring disease progression, the use of CSF biomarkers does not seem very promising since a comparison of the marker levels between baseline and following years of follow-up revealed a remarkable stability of biomarker levels in CSF. As for the use in drug discovery, it is estimated that using CSF markers for the selection of subjects for clinical trials may reduce robustly sample size and trial costs. Yet, since no effective drug is currently available, the contribution of CSF AD biomarkers in drug discovery cannot be currently fully assessed. Nevertheless, testing CSF for evidence of CNS inflammation may help safety monitoring in AD clinical trials. Factors affecting CSF biomarker levels that should be taken into account are assay variability as well as effects of age, gender, apoE and other genetic variations, education, and time of day. Much effort has been and is still being dedicated into developing and validating CSF AD biomarkers by many centers in the world. Identifying additional CSF components, reflecting not only the lesions characteristic to AD (plaques and tangles) but also more functional and structural brain parameters, may provide a wider profile of the changes taking place in AD brains, and be further used as reliable CSF biomarkers for AD monitoring.
    Journal of Molecular Neuroscience 11/2011; 47(1):1-14. · 2.89 Impact Factor
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    ABSTRACT: Epidemiological studies show that stimulating activities reduce the risk of dementia. In animal models of Alzheimer disease, there have been conflicting results of the effects of environmental enrichment (EE) on disease-related amyloid pathology. Here, we tested the direct effect of EE, independently of amyloid pathology, on brain neurofibrillary tangles (NFTs), which best correlate with dementia. We exposed transgenic mice (E257K/P301S-Tau-Tg driven by the natural tau promoter) to moderate nonstrained EE or regular environment. Concomitant with neurogenesis, we detected a decrease in NFT burden and a decrease in the activation of microglia in EE versus regular-environment mice. There was also a trend toward improvement in cognitive tasks in the EE mice. Increased immunoreactivity of brain-derived neurotrophic factor, which is involved in the regulation of tau phosphorylation, was detected in the EE mice, suggesting its possible involvement in the beneficial effects on NFTs and other parameters in the EE mice. These results suggest that NFTs may be directly responsive to environmental stimulating activities and that even nonstrained activities may mitigate tauopathies independent of the involvement of amyloid.
    Journal of Neuropathology and Experimental Neurology 07/2011; 70(7):610-21. · 4.35 Impact Factor
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    ABSTRACT: Padma® 28 is a multicompound herbal preparation based on the camphor formulas from traditional Tibetan medicine (TTM). It contains a variety of different secondary plant substances, which include terpenes and polyphenols such as flavonoids and tannins. As a rich source of antioxidant polyphenols, this herbal Padma 28 preparation seems to be a promising candidate for the treatment of degenerative diseases such as Alzheimer's disease (AD), a condition involving oxidative stress. Moreover, polyphenols have also been shown to mitigate AD neuropathology. The study investigated the protective effect of Padma 28 and of certain polyphenols on the neurotoxicity of PC12 cells induced by the neurotoxins: amyloid-beta (Aβ), glutamate, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 3-nitropropionate (3-NP), known to be involved in AD, Parkinson's disease (PD), amyotrophic-lateral-sclerosis (ALS) and Huntington's disease (HD), respectively. The decrease in cell viability induced by each of the toxins was significantly attenuated by Padma 28 treatment. Also, a decrease in the oxidative capacity of PC12 cells treated with Padma 28 was noted, indicating that the decrease in cell viability induced by the toxins might have been the result of an oxidative stress which could be attenuated by Padma 28 acting as a potent antioxidant. Padma 28, which is available in Europe and USA, seems to be a promising candidate for the treatment of CNS diseases.
    Phytotherapy Research 03/2011; 25(5):740-3. · 2.40 Impact Factor
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    ABSTRACT: One of the largest clusters of genetic Creutzfeldt-Jakob disease (gCJD) is found among Jews of Libyan origin in Israel and is linked to the E200K mutation in PRNP (gCJDE200K). The aim of this study was to compare the levels of cerebrospinal fluid (CSF) biomarkers, Tau and 14-3-3 proteins, between gCJDE200K patients, sporadic CJD (sCJD) patients and non-CJD controls in Israel between the years 1996-2006. The levels of Tau and 14-3-3 proteins in CSF were measured by ELISA and immunoblotting, respectively. CSF Tau levels were similar in gCJDE200K and sCJD, both were significantly higher than in controls [1,107 ± 470 pg/ml [33/46 (72%)] of the cases >1,000 pg/ml, 1,280 ± 580 pg/ml [25/30 (83.3%)], and 354 ± 338 pg/ml [17/243 (6.9%)], respectively, p < 0.001]. 14-3-3 was detected in CSF of 41/53 (77%) of each gCJDE200K and sCJD patients tested, but only in 70/417 (16.8%) of controls (p < 0.001). An inverse correlation was found between disease duration and Tau levels in both gCJDE200K and sCJD (r = -0.464 and r = -0.284). No difference was found in Tau or 14-3-3 between the various codon 129 genotypes. We conclude that CSF biomarkers, Tau and 14-3-3, may be used in the diagnosis in both patients' populations, presenting a similar sensitivity yet Tau assay having higher specificity.
    Journal of Neurology 02/2011; 258(2):255-62. · 3.58 Impact Factor
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    ABSTRACT: To develop a scale sensitive for the neurological manifestations of Creutzfeldt-Jakob disease (CJD). A 26-item CJD neurological status scale (CJD-NS) was created based on characteristic disease manifestations. Each sign was assigned to one of eight neurological systems to calculate a total scale score (TSS) and a system involvement score (SIS). The scale was administered to 37 CJD patients, 101 healthy first-degree relatives of the patients and 14 elderly patients with Parkinson's disease (PD). The mean TSS (±SD) was significantly higher in patients with CJD (13.19 ± 5.63) compared with normal controls (0.41 ± 0.78) and PD patients (9.71 ± 3.05). The mean SIS was also significantly different between the CJD (5.19 ± 1.22) and PD (2.78 ± 1.18 P ≤ 0.01) groups reflecting the disseminated nature of neurological involvement in CJD. Using a cutoff of TSS > 4 yielded a sensitivity of 97% for CJD, and specificity of 100% against healthy controls. All individual items showed excellent specificity against healthy subjects, but sensitivity was highly variable. Repeat assessments of CJD patients over 3-9 months revealed a time-dependent increase in both the TSS and the SIS reflecting the scale's ability to track disease progression. The CJD-NS scale is sensitive to neurological signs and their progression in CJD patients.
    Acta Neurologica Scandinavica 02/2011; 124(6):368-74. · 2.47 Impact Factor
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    ABSTRACT: 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.
    Journal of Neurology 01/2011; 258(1):89-95. · 3.58 Impact Factor

Publication Stats

701 Citations
237.46 Total Impact Points

Institutions

  • 1997–2014
    • Hadassah Medical Center
      • • Department of Neurology
      • • Department of Physical Medicine and Rehabilitation
      Yerushalayim, Jerusalem District, Israel
  • 1996–2013
    • Hebrew University of Jerusalem
      • • Department of Neurobiology
      • • Faculty of Dental Medicine
      • • Hadassah Medical School
      Jerusalem, Jerusalem District, Israel
  • 2006
    • AHEPA University Hospital
      Saloníki, Central Macedonia, Greece