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Background: Patients with cervical dystonia (CD) typically require regular injections of botulinum toxin to maintain symptomatic control. We aimed to document long-term patient satisfaction with CD symptom control in a large cohort of patients treated in routine practice. Methods: This was a prospective, international, observational study (NCT01753349) following the course of adult CD treated with botulinum neurotoxin type A (BoNT-A) over 3 years. A comprehensive clinical assessment status was performed at each injection visit and subjects reported satisfaction in two ways: satisfaction with symptom control at peak effect and at the end of treatment cycle. Results: Subject satisfaction remained relatively stable from the first to the last injection visit. At 3 years, 89.9% of subjects reported satisfaction with symptom control at peak effect and 55.6% reported satisfaction with symptom control at end of treatment cycle. By contrast, objective ratings of CD severity showed an overall reduction over 3 years. Mean ± SD Toronto Western Spasmodic Rating Scale (TWSTRS) Total scores (clinician assessed at end of treatment cycle) decreased from 31.59 ± 13.04 at baseline to 24.49 ± 12.43 at 3 years (mean ± SD reduction from baseline of − 6.97 ± 11.56 points). Tsui scale scores also showed gradual improvement; the percent of subjects with a tremor component score of 4 reduced from 12.4% at baseline to 8.1% at 3 years. Conclusions: Despite objective clinical improvements over 3 years, subject satisfaction with symptom control remained relatively constant, indicating that factors other than symptom control also play a role in patient satisfaction. [ABSTRACT FROM AUTHOR]

The article How satisfied are cervical dystonia patients after 3 years of botulinum toxin type A treatment? [ABSTRACT FROM AUTHOR]

Background: Hematologic malignancies (HMs) are well-known underlying comorbidities of pyoderma gangrenosum (PG). However, studies quantifying the likelihood of PG after HMs are yet to be performed., Objective: To investigate the bidirectional association between PG and several HMs, namely acute leukemia, chronic leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, and multiple myeloma., Methods: A population-based retrospective cohort study was conducted to study the risk of HMs in patients with PG ( n = 302) as compared to age-, sex-and ethnicity-matched control subjects ( n = 1,799). A case-control design was used to estimate the likelihood of PG in individuals with a preexisting history of HMs. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were estimated by Cox regression and logistic regression, respectively., Results: The prevalence of preexisting HM was higher in patients with PG than in controls (6.7% vs. 0.9%, respectively). The likelihood of having PG was significantly greater among patients with a history of HM (adjusted OR, 7.88; 95% CI, 3.85-16.15; p < 0.001), particularly during the first year following the diagnosis. This association was significant for acute leukemia, chronic leukemia, non-Hodgkin lymphoma, and multiple myeloma but not for Hodgkin lymphoma. The incidence rate of HM was 3.3 (95% CI, 1.2-7.4) and 1.6 (95% CI, 0.9-2.6)/1,000 person-years among patients with PG and controls, respectively. Relative to controls, patients with PG were not more likely to develop subsequent HM (adjusted HR, 2.22; 95%CI, 0.77-6.45; p = 0.142). Compared to other patients with PG, those with HM-associated PG experienced an increased all-cause mortality rate (adjusted HR, 2.19; 95%CI, 1.09-4.40; p = 0.028)., Conclusion: HM, particularly acute leukemia and multiple myeloma, are associated with an elevated likelihood of provoking PG., Competing Interests: AC served as an advisor, investigator, or speaker for Abbvie, BI, Dexcel Pharma, Janssen, Novartis, Perrigo, Pfizer, and Rafa. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kridin, Ankary-Khaner, Kridin, Cohen and Badarny.)

Objective: Our knowledge about the association between vitiligo and Parkinson's disease (PD) is sparse. We sought to investigate the bidirectional epidemiological association between vitiligo and PD., Methods: A population-based study was conducted using Clalit Health Services (CHS) database (2002-2019) using both a cohort study and a case-control study design. Adjusted hazard ratio (HR) and odds ratio (OR) were calculated by multivariate Cox and logistic regressions, respectively., Results: Overall, 20,851 vitiligo patients and 102,475 controls were included. The incidence of new-onset PD was 2.9 (95% CI, 2.1-4.1) and 4.3 (95% CI, 3.8-4.9) cases per 10,000 person-years among patients with vitiligo and controls, respectively. Patients with vitiligo had a significantly decreased risk of developing new-onset PD [adjusted HR, 0.62; 95% confidence interval (CI), 0.43-0.89, p = 0.009]. On the other hand, the likelihood of having vitiligo after a preexisting diagnosis of PD was not statistically different (adjusted OR, 0.80; 95% CI, 0.61-1.06; p = 0.117). Relative to the remaining patients with vitiligo, those with vitiligo and comorbid PD experienced an elevated risk of all-cause mortality (adjusted HR, 2.63; 95% CI, 1.82-3.80; p < 0.001) and higher prevalence of cardiometabolic comorbidities., Conclusion: Vitiligo is associated with a lower risk of developing PD. The presence of comorbid PD predisposes patients with vitiligo to elevated mortality and cardiometabolic outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kridin, Ofir, Weinstein and Badarny.)

The Galilee region of Israel boasts a rich ethnic diversity within its Arab population, encompassing distinct Muslim, Christian, Druze, and Bedouin communities. This preliminary exploratory study uniquely examined potential ethnic and gender differences in ischemic stroke characteristics across these Arab subgroups, which are seldom investigated separately in Israel and are typically studied as a homogeneous "Arab" sector, despite significant variations in their ethnicity, culture, customs, and genetics. The current study aimed to comparatively evaluate stroke characteristics, including recurrence rates, severity, and subtypes, within and across these distinct ethnic groups and between genders. When examining the differences in stroke characteristics between ethnic groups, notable findings emerged. The Bedouin population exhibited significantly higher rates of recurrent strokes than Muslims (M = 0.55, SD = 0.85 vs. M = 0.25, SD = 0.56; p < 0.05). Large vessel strokes were significantly more prevalent among Christians (30%) than Druze (9.9%; p < 0.05). Regarding gender differences within each ethnic group, several disparities were observed. Druze women were six times more likely to experience moderate to severe strokes than their male counterparts ( p < 0.05). Interestingly, Druze women also exhibited a higher representation of cardio-embolic stroke (19.8%) compared with Druze men (4.6%; p < 0.001). These findings on the heterogeneity in stroke characteristics across Arab ethnic subgroups and by gender underscore the need to reconsider the approach that views all ethnic groups comprising the Arab sector in Israel as a homogeneous population; instead, they should be investigated as distinct communities with unique stroke profiles, requiring tailored culturally aware community-based prevention programs and personalized therapeutic models. The identified patterns may guide future research to develop refined, individualized, and preventive treatment approaches targeting the distinct risk factors, healthcare contexts, and prevention needs of these diverse Arab populations.

Sarcoidosis is a chronic granulomatous disease of unknown cause characterized by the presence of non-caseating granulomas. The disease can affect any organ including the nervous system. Neurosarcoidosis occurs in about 5% patients with sarcoidosis. The clinical presentation of neurosarcoidosis is varied, and it can involve the brain, spinal cord and peripheral nervous system, separately or in different combinations. The diagnosis of neurosarcoidosis is challenging, as biopsies from the nervous system are not readily available. Anti-TNFα agents are becoming one of the cornerstone treatments for neurosarcoidosis. In this case-based review, we discuss two cases of neurosarcoidosis with different clinical presentations. The first patient presented with confusion, while the second presented with walking difficulty and neurogenic bladder. Both patients were treated with methylprednisolone pulse therapy with rapid, but non-complete, improvement. Therefore, infliximab was initiated in both cases with subsequent improvement in the clinical manifestations and imaging findings, emphasizing the effectiveness and safety of infliximab in cases of severe neurosarcoidosis. In conclusion, the goal of neurosarcoidosis management is to prevent organ system damage and minimize the toxic cumulative adverse effects of glucocorticoid use. In this case-based review we discuss the various presentations, the diagnosis and the treatment of neurosarcoidosis.

Background and purpose: This study aimed to investigate the differences in intracerebral hemorrhage (ICH) between Jews and Arabs residing in northern Israel, focusing on risk factors, hemorrhage volume, and functional outcome. Methods: A retrospective analysis was conducted utilizing a population-based registry to investigate intracerebral hemorrhage (ICH) characteristics, risk factors, and outcomes. The registry consisted of inpatients diagnosed with hemorrhagic stroke. Due to the wide variation in data on ICH characteristics and the limited availability of population-based data on predictors of ICH survival and functional outcomes, we collected retrospective data on all adult patients admitted to the Galilee Medical Center with a diagnosis of ICH. Data were obtained from the registry covering the period from 2013 to 2019. Ethnic differences and risk factors associated with intracranial hemorrhage (ICH) were examined within a diverse population of 241 patients, comprising 52.70% Jews ( n = 127) and 47.30% Arabs ( n = 114). Results: The results of this study revealed significant differences in age, obesity rates, and intracerebral hemorrhage (ICH) location between the two ethnic groups. Hypertension emerged as the most prevalent condition among ICH patients in both ethnic groups (76.70%), followed primarily by anticoagulant use (63.60%), dyslipidemia (60.70%), diabetes (44.60%), obesity (30.60%), smoking (24.60%), and a history of cardiovascular disease (21.80%). Furthermore, 20.90% of the patients had a history of previous cerebrovascular accidents (CVA). Arab patients with ICH were generally younger (62.90 ± 16.00 years) and exhibited higher rates of obesity (38.70%) compared to Jewish patients with ICH (70.17 ± 15.24 years, 23% obesity; p = 0.001, p = 0.013, respectively). Hemorrhage volume was identified as a crucial determinant of patient outcomes, with larger volumes associated with poorer Modified Rankin Scale (mRS) scores at discharge and higher mortality rates. Interestingly, patients without hypertension had higher hemorrhage volumes compared to those with hypertension. The extent of hemorrhage into the ventricles did not significantly correlate with mRS at discharge in our dataset. Conclusions: This study highlights significant differences in the characteristics and outcomes of intracranial hemorrhage (ICH) between Jews and Arabs in northern Israel. The findings reveal variations in age, obesity rates, and ICH location between the two groups. While hypertension was the most prevalent risk factor for both populations, other risk factors differed. Notably, hemorrhage volume emerged as a crucial prognostic factor, aligning with previously published data. These findings underscore the necessity for tailored approaches that consider ethnic-specific factors in the risk assessment, prevention, and management of ICH. Further research is warranted to elucidate the underlying mechanisms and develop interventions aimed at improving outcomes and enhancing healthcare practices in ICH management.

Stroke is a leading cause of death worldwide. Multiple factors influence the severity of stroke. Normal functional and biological differences seen between the hemispheres may also be related to stroke severity. In the present study, we examined the differences in the severity of stroke as a function of stroke side, and whether patients' vagal nerve activity moderated such differences. We included 87 patients with an ischemic stroke, whose medical records were retrospectively examined for background information (age, gender), stroke side and severity by NIHSS, length of stay in hospital, inflammation such as C-reactive protein, and vagal nerve activity. The vagal activity was indexed by patients' heart-rate variability (HRV), fluctuations in the intervals between normal heartbeats, derived from patients' ECG. Results revealed that patients with left-side stroke had significantly worse NIHSS scores (10.6) than those with right-sided stroke (7.6, p < 0.05). However, when dividing the sample into those with low versus high HRV (at the median), only when HRV was low, did patients with left-side stroke have a worse NIHSS score (10.9) compared to those with right-sided stroke (6.5, p < 0.05). In contrast, no differences in stroke severity were seen between left stroke (10.2) and right stoke (8.7, p > 0.05), when HRV was high. These results tended to remain the same when statistically controlling for age effects, which was related to NIHSS, but not to the stroke side. These findings suggest that patients with left-sided stroke may have more severe strokes than those with right-sided ones, but that adequate vagal nerve activity may protect against such differences. Possible mechanisms and suggestions for future directions are provided.

Competing Interests: Competing interests: None declared.

Parkinson's disease (PD) is taking a staggering toll on healthcare systems worldwide, with the bulk of the expenditures invested in the late stages of the disease. Considering the rising life expectancy and the increasing prevalence of PD across the globe, a clear understanding of the early signs and treatment options available for advanced PD (APD), will facilitate tailoring management programs and support services. This task is complicated by the lack of both global consensus in defining APD and standardized care guidelines. This perspective prepared by a panel of movement disorder specialists, proposes to extend and optimize currently accepted PD coding to better reflect the diverse disease manifestations, with emphasis on non-motor features. The panel seeks to promote timely diagnosis by adjustment of evaluation tools for use by community neurologists and suggests modification of eligibility criteria for advanced therapy. Moreover, it advocates multidisciplinary assessments of APD patients to drive personalized, patient-centered and holistic management. Overall, earlier and more targeted intervention is expected to markedly improve patient quality of life., Competing Interests: Author TG was member of the advisory board on Advanced Parkinson’s disease 23.07.2020 supported by Abbvie, consultant and/or scientific advisor/lecturer for Neuroderm, AbbVie, Cytora, Allergan, Teva, and Medison, and received research support from Parkinson’s Foundation and Israel Innovation Authority. Author SH-B had received funding for research from Abbvie and speaker honoraria from Abbvie, Medison, and Allergan, consultancy fees from Neuroderm, Abbvie, and Takeda and Teva, and advisory fees from Teva and Abbvie. Author MK was consultant and lecturer for Teva, Medison, and Abbvie. Author ZN participated in advisory boards, received speaker fees from Abbvie and Teva, and had received educational travel bursaries from Abbvie and Teva. Author YZ participated in advisory boards, received speaker fees from Abbvie, Medison, and Teva, and had received educational travel bursaries from Abbvie and Teva. Author GY was consultant for Abbvie and Takeda. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gurevich, Arkadir, Badarny, Benizri, Cohen, Djaldetti, Hassin-Baer, Kestenbaum, Nitsan, Zlotnik and Yahalom.)

Purpose: Diabetes mellitus (DM) represents one of the most frequent comorbidities in patients with acromegaly. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) represent an important class for diabetes management. However, limited data is reported regarding the use of this class in patients with acromegaly and diabetes., Methods: Reporting data regarding patients with acromegaly and diabetes under treatment with SGLT2i., Results: 29 acromegalic patients with diabetes were identified. Treatment with SGLT-2i was documented in nine patients, out of them 5 females and 4 males with a mean age (SD) of 61 ± 12 yr. The mean (SD) duration of treatment with SGLT2i was 27.5 ± 7.3 months. Mean HbA1c before and after SGLT-2i initiation was 8.1 ± 1.1 and 7.0 ± 0.9% respectively. Mean IGF-1 level (SD) before SGLT-2i initiation was 177 ± 68 ng/mL and the mean GH level (SD) was 0.7 ± 0.5 µg/L. All nine patients are still under treatment with SGLT2i and none of them had reported any adverse reaction related to SGLT2i., Conclusions: The present article provides us for the first time with new data regarding the use of SGLT2i among acromegalic patients with diabetes.

Abstract: Botulinum toxin A is considered an effective treatment for involuntary facial movements. We examined whether treatment efficacy maintained or changed over time with two products, Botox and Dysport, in patients with hemifacial spasm, facial synkinesis and benign essential blepharospasm.We retrospectively investigated 87 consecutive patients (51 women, 36 men) who had undergone treatment for ≥6 years. Long-term effects, as well as side effects of Botox or Dysport local injections were evaluated. The first three treatments were considered the titration period and not taken into account when testing for dose changes.Mean treatment duration was 10 years (range 6-11, SD 1.0), 2441 treatments were administered, 1162 with Botox and 1279 with Dysport, the two brands were interchanged as needed. Good to full improvement was seen in 90% of patients both with both brands. Injection doses and treatment responses were consistent during the study with both drugs. No major side effects were reported, and relatively few minor adverse events were reported, with clear reduction from the titration period (6.1%), to the remainder of the study (3.9%).Botulinum toxin (BTX-A) is a satisfactory long-term treatment without need for dose increase over. Both Botox and Dysport were effective when used interchangeably., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

We present a 75-year-old man who was admitted to our hospital due to 4 months of general deterioration, gait disturbance and cognition impairment which appeared very close to the start of levetiracetam (LEV) as a new antiepileptic drug. Brain CT shows central and less peripheral atrophy of brain, and diagnosis of normal pressure hydrocephalus was raised; however, removal of 30 cc of cerebrospinal fluid (CSF) by lumbar puncture in order to amend walking did not lead to gait improvement. After excluding metabolic, vascular, infection, inflammatory and other reasons explaining his status. Thinking that may be any correlation between LEV added in the last months and his clinical condition, we stopped LEV. Several days after that, there is marked improvement in his general sensation, alertness and cognitive status and there is marked improvement in walking balance to the point of being able to walk without the use of walker or cane or help from other person. Certain cognitive impairment and gait difficulties are not known as side effects of LEV treatment., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Early diagnosis of Parkinson's disease (PD) is important because it affects the choice of therapy and is subject to a relatively high degree of error. In addition, early detection of PD can potentially enable the start of neuroprotective therapy before extensive loss of dopaminergic neurons of the substantia nigra occurs. However, until now, studies for early detection of PD using volatile biomarkers sampled only treated and medicated patients. Therefore, there is a great need to evaluate untreated patients for establishing a real world screening and diagnostic technology. Here we describe for the first time a clinical trial to distinguish between de novo PD and control subjects using an electronic system for detection of volatile molecules in exhaled breath (sensor array). We further determine for the first time the association to other common tests for PD diagnostics as smell, ultrasound, and nonmotor symptoms. The test group consisted of 29 PD patients after initial diagnosis by an experienced neurologist, compared with 19 control subjects of similar age. The sensitivity, specificity, and accuracy values of the sensor array to detect PD from controls were 79%, 84%, and 81% respectively, in comparison with midbrain ultrasonography (93%, 90%, 92%) and smell detection (62%, 89%, 73%). The results confirm previous data showing the potential of sensor arrays to detect PD.

Early-onset Parkinson's disease (EOPD) is less common than the typical adult-onset PD and may be associated with a genetic etiology. Mutations in several genes are known to cause autosomal recessive (AR) PD. This study aimed to detect the etiology of EOPD in consanguineous families or families living in a specific small geographic region in Israel. Six families with EOPD affecting more than a single individual were recruited. Homozygous mapping analysis using a single-nucleotide polymorphism-based array was performed in all families, followed by Sanger sequencing of related genes based on the mapping results. In addition, all families underwent PARK2 sequencing and testing for large deletions and duplications in PD-associated genes. Different truncating mutations were detected in the PARK2 gene among affected individuals of three families: c.996C>A (p.Cys332X) and c.101delA in either homozygous or compound heterozygous fashion. Exon 4 deletion was detected in a heterozygous manner in a late-onset PD and in homozygous state in early-onset disease in the same family. No disease-causing mutations were detected in any other tested genes. In total, mutations in the PARK2 gene were detected in four of the six tested families with a history of EOPD. These results further demonstrate the role of PARK2 in AR PD. We recommend genetic analysis for the PARK2 gene when AR PD is suspected.

We report on an artificially intelligent nanoarray based on molecularly modified gold nanoparticles and a random network of single-walled carbon nanotubes for noninvasive diagnosis and classification of a number of diseases from exhaled breath. The performance of this artificially intelligent nanoarray was clinically assessed on breath samples collected from 1404 subjects having one of 17 different disease conditions included in the study or having no evidence of any disease (healthy controls). Blind experiments showed that 86% accuracy could be achieved with the artificially intelligent nanoarray, allowing both detection and discrimination between the different disease conditions examined. Analysis of the artificially intelligent nanoarray also showed that each disease has its own unique breathprint, and that the presence of one disease would not screen out others. Cluster analysis showed a reasonable classification power of diseases from the same categories. The effect of confounding clinical and environmental factors on the performance of the nanoarray did not significantly alter the obtained results. The diagnosis and classification power of the nanoarray was also validated by an independent analytical technique, i.e., gas chromatography linked with mass spectrometry. This analysis found that 13 exhaled chemical species, called volatile organic compounds, are associated with certain diseases, and the composition of this assembly of volatile organic compounds differs from one disease to another. Overall, these findings could contribute to one of the most important criteria for successful health intervention in the modern era, viz. easy-to-use, inexpensive (affordable), and miniaturized tools that could also be used for personalized screening, diagnosis, and follow-up of a number of diseases, which can clearly be extended by further development., Competing Interests: The authors declare no competing financial interest.

Objective: To study the effects of closed-loop auditory feedback cues, corresponding to patient self-motion, on the walking abilities of patients with Parkinson's disease, in comparison to the effects of open-loop (metronome-like) auditory cues., Methods: Sixteen patients on their regular medication schedule participated. A device which translates patient steps into a clicking cue sounded by earphones provides auditory feedback for gait pattern correction. Walking speed and stride length are measured. Device-on performance is compared to device-off performance and to baseline performance, and short-term residual performance following 15 min rest is compared to baseline performance., Results: Device-on performance was found to represent, on average, 10.72%±19.53% improvement in walking speed and 6.77%±6.57% improvement in stride length with respect to device-off performance, and an average improvement of 12.37%±18.37% in walking speed and 4.30%±3.64% in stride length with respect to baseline performance, with 87.5% and 81.25% of the patients improving their walking speed and stride length, respectively. Average short-term residual performance showed 9.09%±6.34% improvement in walking speed and 6.52%±4.36% improvement in stride length, compared to baseline performance, with 85.71% of the patients improving in both walking speed and stride length., Conclusions: Closed-loop auditory feedback improves walking speed and stride length in patients with Parkinson's disease. Improvement in walking speed is more pronounced than improvement in stride length. Yet, in contrast to previously studied open-loop auditory cues, training with closed-loop auditory feedback results in non-negligible on-line improvement in stride length. Moreover, in contrast to previously reported results of open-loop auditory cuing, training with closed-loop auditory feedback has residual effects, which suggest the examination of this approach in a comprehensive therapy program., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Corticosteroid-induced hyperglycemia is a known adverse effect. There are no studies on the impact of corticosteroid treatment on hemoglobin A1c (HbA1c) levels in type-2 diabetes patients with chronic obstructive pulmonary disease (COPD) exacerbation., Methods: HbA1c levels were evaluated in type-2 diabetes patients with COPD exacerbation on admission to the hospital (group-1) and 3-months later. Demographic, clinical, laboratory variables and total steroid dose were documented. Age- and sex-matched group of type-2 diabetes patients with COPD who were admitted for other reasons (group-2), were asked to participate as a control group. Mann-Whitney and Chi square/Fischer's exact tests were used to compare between the parameters of the two groups. Wilcoxon's signed rank test was used to compare between HbA1c levels at baseline and 3 months later. Multi-variate linear regression analysis was used to find predictors for a change in HbA1c levels in group-1 patients., Results: 23 and 21 patients in groups 1 and 2 respectively, completed the study. There were 39 male (∼89%) patients. Mean age of the patients was 66.2 ± 8.2 years. In both groups, anti-diabetic management was augmented. There was no significant change in the HbA1c levels in group-1 (p = 0.416), however there was a significant decrease in HbA1c levels in group-2 (p = 0.032). Total dose of steroids was a predictor for an increase in HbA1c levels in group-1 patients (p = 0.026)., Conclusions: Type-2 diabetes patients who were treated with steroids for COPD exacerbation had no significant change in HbA1c levels. Total dose of steroids was a predictor for an increase in HbA1c levels., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Backgrounds: Ramadan fast is a religious custom in Islam. Increased serum uric acid level during this month had been reported in past studies of nongout patients., Objectives: The objective of this study was to assess the impact of Ramadan fast on patients with gout., Methods: All Moslem patients with gout from the registry of Nazareth Hospital, who intended to fast during Ramadan, were asked to participate in our study (group 1). Data regarding age, gender, income, education, duration of gout, meds, adherence to low-purine diet, and gouty attacks were documented. Age- and gender matched Moslem patients from the same registry, but who did not intend to fast during Ramadan, were asked to participate as a control group (group 2). Just prior to and at the end of Ramadan, blood for uric acid, creatinine, and urea levels were obtained as well as body mass index, from all the patients. During Ramadan, patients were monitored for gouty arthritis or renal calculi attacks, as well as low-purine diet and medicine adherence., Results: Twenty-one and 22 patients from groups 1 and 2, respectively, completed the study. Mean serum uric acid, urea, creatinine, and body mass index levels at the end of Ramadan fasts in group 1 patients were 8.11 mg/dL, 26.38 mmol/L, 0.87 mg/dL, and 31.0 kg/m, respectively, as compared with 7.92 mg/dL (P = 0.707), 24.54 mmol/L (P = 0.769), 0.84 mg/dL (P = 0.180), and 30.5 kg/m (P = 0.907) respectively, obtained just prior to the fast. No significant change in any parameter was seen also in group 2 patients. There also was no significant change between the 2 groups in arthritis or renal calculi attacks and also in medication and low-purine diet adherence, during Ramadan., Conclusions: There was no risk for a significant increase in gouty arthritic/renal calculi attacks or serum uric acid in patients with gout during Ramadan fast.

Background: It is now reported that non-motor features, cognitive and affective problems, are becoming a major factor in essential tremor (ET). The aim of this study was to investigate the prevalence of cognitive and affective dysfunction in ET and to prospectively follow-up changes in the subjects., Methods: Fifty-two persons over the age of 50 years were recruited from the Movement Disorder Clinic. The subjects underwent baseline neurological, cognitive, and mood assessments and repeat assessment 2 years later., Results: The mean age was 68 years, with an average age of ET onset of 55.8 years and with a mean disease duration of 11.7 years. At initial cognitive assessment using various instruments and the Clinical Dementia Rating Scale, 69.2% had mild cognitive impairment (MCI). There were disturbances in phonemic fluency, verbal memory, concentration, and semantic fluency; 25% suffered from anxiety and 17.6% from depression. During the 2 years there was an annual 8.4% conversion rate to dementia, with all convertors initially suffering from MCI. Another 25% converted from no initial cognitive impairment to MCI within 2 years. At follow-up the same percentage was still suffering from anxiety., Discussion: The study confirms our hypothesis that ET patients suffer from MCI and anxiety. Though a control group was not used, the conversion rates for patients without ET and with/without MCI are known. The uniqueness of this study is that at follow-up, those with ET and MCI had a similar conversion rate to dementia to those suffering from MCI only. Additionally, persons with ET and no initial cognitive impairment were found to be at greater risk for developing MCI than the normal population. Clinicians must increase their awareness of cognitive impairment and anxiety in persons with ET and begin immediate treatment when indicated.

Background: Our aim was to study the effects of visual feedback cues, responding dynamically to patient's self-motion and provided through a portable see-through virtual reality apparatus, on the walking abilities of patients with Parkinson's disease., Methods: Twenty patients participated. On-line and residual effects on walking speed and stride length were measured., Results: Attaching the visual feedback device to the patient with the display turned off showed a negligible effect of about 2%. With the display turned on, 56% of the patients improved either their walking speed, or their stride length, or both, by over 20%. After device removal, and waiting for 15 minutes, the patients were instructed to walk again: 68% of the patients showed over 20% improvement in either walking speed or stride length or both. One week after participating in the first test, 36% of the patients showed over 20% improvement in baseline performance with respect to the previous test. Some of the patients reported that they still walked on the tiles in their minds., Discussion: Improvements in walking abilities were measured in patients with Parkinson's disease using virtual reality visual feedback cues. Residual effects suggest the examination of this approach in a comprehensive therapy program.

Objective: The objective of this study was to evaluate the effect of simultaneous bilateral intra-articular injection (IAI) of methylprednisolone acetate (MPA) on the hypothalamic-pituitary-adrenal axis in patients with knee osteoarthritis., Methods: Nonselected patients with symptomatic bilateral knee osteoarthritis had simultaneous IAI of 80 mg MPA at each knee (group 1). Just before the injection and on weeks 1, 2, 4, 6, and 8 after it, patients had 1 µg adrenocorticotropin hormone stimulation test. Age- and sex-matched patients had simultaneous IAI of 60 mg of hyaluronic acid in each knee (group 2) and the same protocol of adrenocorticotropin hormone stimulation tests. Demographic, clinical, and laboratory parameters were documented in all the patients. Secondary adrenal insufficiency (SAI) was defined as poststimulation serum cortisol levels of less than 18 µg/dL., Results: Twenty patients were enrolled in each group. There were 15 women and 5 men in each group. Mean age of the patients in group 1 was 60.3 (SD, 7.6) years. Twelve patients (60%) from group 1 had evidence of SAI versus 3 patients in group 2 (P = 0.003). In all the patients who had SAI in group 1, it was observed in week 1 with decreasing frequency of SAI at the subsequent time points. Yet, 2 patients (10%) from group 1 had evidence of SAI 8 weeks after the IAI. Secondary adrenal insufficiency did not significantly correlate with any demographic, clinical, or laboratory parameter., Conclusions: Secondary adrenal insufficiency was very common following simultaneous bilateral IAI of 80 mg of MPA. Although it was transient, SAI could still be observed nearly 2 months after the IAI, in 10% of the patients.

The tight junction proteins (TJPs) are major determinants of endothelial cells comprising physiological vascular barriers such as the blood-brain barrier, but little is known about their expression and role in immune cells. In this study we assessed TJP expression in human leukocyte subsets, their induction by immune activation and modulation associated with autoimmune disease states and therapies. A consistent expression of TJP complexes was detected in peripheral blood leukocytes (PBLs), predominantly in B and T lymphocytes and monocytes, whereas the in vitro application of various immune cell activators led to an increase of claudin 1 levels, yet not of claudin 5. Claudins 1 and 5 levels were elevated in PBLs of multiple sclerosis (MS) patients in relapse, relative to patients in remission, healthy controls and patients with other neurological disorders. Interestingly, claudin 1 protein levels were elevated also in PBLs of patients with type 1 diabetes (T1D). Following glucocorticoid treatment of MS patients in relapse, RNA levels of JAM3 and CLDN5 and claudin 5 protein levels in PBLs decreased. Furthermore, a correlation between CLDN5 pre-treatment levels and clinical response phenotype to interferon-β therapy was detected. Our findings indicate that higher levels of leukocyte claudins are associated with immune activation and specifically, increased levels of claudin 5 are associated with MS disease activity. This study highlights a potential role of leukocyte TJPs in physiological states, and autoimmunity and suggests they should be further evaluated as biomarkers for aberrant immune activity and response to therapy in immune-mediated diseases such as MS., (© 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.)

Background: Essential tremor (ET) and Parkinson's disease (PD) are probably the most common movement disorders. As ethnic differences have been reported in ET, we designed the present study to evaluate the prevalence of ET and that of Parkinson's disease (PD) in the Druze villages of northern Israel., Methods: A two-phase, door-to-door survey was undertaken. Residents aged ≥51 years who agreed to participate and answered "yes" to tremor or PD-related screening questions and 3% of subjects who screened negative were evaluated. Diagnostic criteria for ET were similar to those used in Sicilian and Spanish studies. PD was diagnosed according to Gelb's criteria., Results: The target population consisted of 9,086, the study cohort of 3,980 residents. Tremor was observed in 36 subjects. In 27, the tremor fully met the criteria for ET. The prevalence of ET (age ≥65) was 1.49% (95% CI 0.91-2.07%). PD was diagnosed in 23 subjects. The prevalence of PD (age ≥65) was 1.13 (95% CI 0.62-1.64%). Leucine-rich repeat protein kinase 2 (G2019S mutation) was evaluated in subjects diagnosed with tremor PD and those screened for assessment of the validity of the questionnaire. None carried the mutation., Discussion: The prevalence of ET in the Druze population is low and similar to the prevalence of PD.

Background: Local corticosteroid injection (LCI) for the treatment of carpal tunnel syndrome (CTS), using the classic method, is usually associated with improvement in different electrophysiologic parameters of the median nerve. However, there is no correlation between the clinical response and these electrophysiologic parameters., Objectives: To evaluate the effect of our novel approach of LCI for the treatment of CTS on repeated electrophysiologic studies of the median nerve., Methods: Patients with symptomatic CTS with duration of symptoms of less than 1 year were offered an LCI of 12 mg methylprednisolone acetate using a novel approach and asked to repeat the electrophysiologic study one month later. Pearson correlation test was used to correlate between the difference of similar electrophysiologic parameters and duration of favorable clinical response and also between the differences among themselves., Results: Thirteen patients completed the study and 25 hands were injected. Improvement in median distal sensory and motor latency was noted in 61% and 75% of the hands respectively. There was no correlation between duration of clinical response and the differences of either the distal latency (sensory or motor) or the amplitude. There was also no correlation between the differences of motor median distal latency and sensory median distal latency., Conclusions: LCI at the carpal tunnel using our approach is also associated with favorable electrophysiologic results similar to what has been reported using the classic approach.

Background: Long-term therapy with botulinum toxin is sometimes associated with therapy failure following repeated injections of the neurotoxin, presumably due to specific antibody production. Primary therapy failure with botulinum toxin is less common and poorly understood., Objectives: To examine the effectiveness of the botulinum neurotoxin Dysport in patients with blepharospasm and hemifacial spasm after primary or secondary failure with Botox treatments., Methods: In this case series study, eight patients with blepharospasm and hemifacial spasm who experienced primary or secondary therapy failure with Botox were treated with Dysport. In order to render an equivalent Dysport dose, a conversion ratio of 1:3 to 1:4 Botox/Dysport was used., Results: Two patients, one with blepharospasm and the other with hemifacial spasm, who showed primary therapeutic failure with Botox showed good response to Dysport treatments. One patient with tardive blepharospasm did not respond to either drug. Two patients with blepharospasm and three patients with hemifacial spasm who experienced Botox secondary therapy failure responded well to Dysport treatments., Conclusions: Botox and Dysport are both serotype A botulinum toxins but carry different characteristics of biological activity. These differences possibly account for the favorable therapeutic response to Dysport in patients with hemifacial spasm or blepharospasm following failure with Botox treatments.

The common belief that primary dystonia is a purely motor disorder has recently been challenged. We examined separately the cognitive profiles of symptomatic (SYM) and nonsymptomatic (N-SYM) groups of carriers of DYT1 mutation using a comprehensive neuropsychological test battery. Self-report inventories of anxiety, depression, and pain levels were also administered, as well as manual motor dexterity assessment. Each group was matched with healthy controls by age, sex, mother tongue, and education. No significant differences between the SYM group to its control group were found on cognitive tests evaluating verbal and nonverbal abstract abilities, attention, information processing speed, and spatial organization. However, the SYM group showed increased verbal memory retroactive interference. Interestingly, the patients also showed higher semantic fluency performance. No significant differences between the N-SYM group to controls were found. It was concluded that symptomatic DYT1 mutation carriers do not suffer the distinctive cognitive decline that is seen in other primary degenerative extrapyramidal disorders., (Copyright 2006 Movement Disorder Society.)

The objective of the study was to compare the favorable response rate, time duration, and pain level of local corticosteroid injection using a novel approach for the treatment of carpal tunnel syndrome vs a classic approach. Patients with symptomatic carpal tunnel syndrome of less than 1-year duration were randomized for local corticosteroid injection using either the classic approach or a novel approach. In our approach (novel), we used a 29 gauge x 1/2-in. needle and a 1-ml insulin syringe containing 12 mg of methylprednisolone mixed with 0.15 ml of lidocaine 2%, and the site of the injection was 2-3 cm distal to the middle of wrist crease. In the classic approach, we used a 25 gauge x 3-cm needle and a 2-ml syringe injecting 35 mg of methylprednisolone mixed with 0.5 ml of lidocaine 2%, 3-4 cm proximal to the wrist crease and just ulnar to the tendon of the flexor carpi radialis muscle. Response rate was evaluated 1, 3, 6, and 12 weeks after the injection, and also the duration of time of the procedure and the level of pain using the visual analogue scale were compared between the two groups. Forty-two patients signed the consent form, and all of them completed the study [21 patients in the classic approach group (group 1) and 21 patients in the novel approach group (group 2)]. The favorable response rates were 100, 81, 71, and 57% in group 1 and 100, 71, 67, and 57% in group 2 after 1, 3, 6, and 12 weeks, respectively. There was no significant difference in the favorable response rate between the two groups (p=0.468, 95% CI=-12-31%, after 3 weeks). The average duration of time of the procedure in group 1 was 26.71+/-32.83 s compared to 8.48+/-1.123 s (p=0.021) in group 2. The average grade of pain expressed by the patients in group 1 was 4.38+/-1.523 compared to 3.62+/-1.071 in group 2 (p=0.065). In conclusion, local corticosteroid injection using the novel approach for the treatment of carpal tunnel syndrome is helpful, and the favorable response rates are comparable to those using the classic approach after 1, 3, 6, and 12 weeks. The novel approach is much less time consuming and is not more painful.

Hemifacial Spasm (HFS) is considered a peripheral disease of the facial nerve caused by vascular compression at the nerve root in the pontocerebellar angle. We aimed to study the natural course of HFS and especially, to examine the relationships with psychological status or physical activities, in order to assess the possible role of the facial nucleus in the pathogenesis. Ninety-five consecutive patients with HFS, 52 men and 43 women, with a mean age of 62 + 12.7 years and a mean disease duration of 7.5 + 6.5 years, were personally interviewed by 2 of the authors (SB and HK). A detailed questionnaire was completed with direct and indirect questions regarding the relationship between the severity of the spasms and emotional status or physical activity. We found strong association between emotional stress and tiredness and aggravation of the spasms in 85% and 54% of the patients, respectively. Talking increased the spasm severity in 58% of the patients and eating or drinking aggravated the spasm in 28% of the patients. Physical activity, head position, the season of the year or the time during the day had no effect on the clinical status. Botulinum toxin was injected to 78 patients with an overall subjective rate of improvement of > 70% in 74% of the patients (23% graded their rates of improvement as > 90%). In conclusion, HFS is a movement disorder of the facial nerve which is highly influenced by emotional status to support an involvement of the facial nucleus in the pathogenesis. Botulinum toxin is a very effective long term treatment for this disorder.

Levodopa ethylester (LDEE), a highly soluble prodrug of levodopa, may overcome the impaired absorption of regular levodopa, due mainly to a combination of levodopa's poor solubility and delayed gastric emptying. We conducted a double-blind, levodopa-controlled, multicenter study of oral LDEE solution compared with standard levodopa-carbidopa (LD-CD) tablets. Sixty-two patients with Parkinson's disease who had "delayed on" and "no-on" subtypes of response fluctuations were randomly assigned for treatment with LDEE-CD or LD-CD 250/25 mg for 4 weeks (phase A). Only the first morning and first post-lunch dose of LD were replaced. This was followed by a 2-week extension with a supplementation of carbidopa (25 mg) to each replaced dose (phase B). Patients filled home diaries 2 weeks before and during the trial period in which times of turning on and off for the two doses were reported. In phase A, mean latency to turning on was reduced by 21% (morning dose) and 17% (post-lunch dose) in the LDEE-CD group. Percentage of no-on episodes after the post-lunch dose was decreased by 21% in the LDEE-CD group but increased by 36% in the LD-CD group (P < 0.01). In phase B, LDEE-CD decreased latencies to on after the morning and post-lunch doses and no-on episodes after the post-lunch dose. The beneficial effects of LDEE were supported by the pharmacokinetic data. Results indicate that LDEE solution is beneficial in ameliorating delayed on and no-on response fluctuations. This effect of LDEE is due to more rapid levodopa absorption., (Copyright 2002 Movement Disorder Society.)

Essential tremor (ET) is the most prevalent extrapyramidal disorder, yet its diagnosis is still controversial. This article introduces new findings that pertain to this diagnostic problem. Twenty-three patients with ET were studied. Patients with parkinsonism, cerebellar signs, severe head injury, or those under neuroleptic medication were excluded. Twenty-five normal subjects served as control subjects. Visuomotor tests involving tracking and tracing along three different paths with both the right and left hands, were used. Performance was assessed by measuring test duration, directional error, the proportion of the cumulative test time during which directional error exceeded half the maximal possible level (PT50%), the mean distance from the model path, the velocity of the hand movement, and the number of tracking interruptions. In 15 of 23 patients performance was the same as in the control subjects. These patients were defined as having a "simple condition" of ET (ETs). Considerable visuomotor impairment was found in eight patients who were regarded as having a "complex condition" of ET (ETc). Patients with ETc had significantly lower tracking speed, more tracking interruptions, longer test duration, greater directional error, greater PT50%, and greater distance from path than patients with ETs or control subjects. Most patients with ET appear to have normal visuomotor capabilities (ETs) but some display significant visuomotor disturbances (ETc). Considering the presence of similar impairments in patients with early Parkinson's disease and the increased prevalence of parkinsonism in patients with ET, it is possible that preclinical parkinsonism exists in patients with ETc. Further follow up of patients with ETc is necessary to verify this possibility.

Facial synkinesis is an involuntary activation of muscles innervated by the zygomatic or mandibular branch of the facial nerve in conjunction with voluntary activation of the other branch. It appears frequently after recovery from peripheral facial nerve paralysis. We report 10 patients with facial synkinesis following Bell's palsy with a mean duration of synkinesis of 7 +/- 4 years before treatment with periorbital injections of Botulinum toxin type A. 9 had marked subjective and objective improvement starting a few days after injection and lasting 4-9 months. The results suggest a useful treatment option for post-Bell's palsy facial synkinesis with Botulinum toxin type A.