Samih Badarny

Mutations in the glucocerebrosidase gene and Parkinson disease: Phenotype–genotype correlation

Mutations in the glucocerebrosidase (GBA) gene have been recently identified as contributory to Parkinson disease (PD) in Ashkenazi Jews. In the present study, the clinical characteristics of Ashkenazi patients with PD with GBA mutations (n = 40) were compared to those of Ashkenazi patients with PD without any known GBA mutation (n = 108). The overall clinical manifestations and age at disease onset did not differ in patients with GBA mutations compared to patients without mutations.

Neuropsychological profile of DYT1 dystonia

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.

Tight junction proteins expression and modulation in immune cells and multiple sclerosis

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.

Distinguishing idiopathic Parkinson's disease from other parkinsonian syndromes by breath test

INTRODUCTION Diagnosis of different parkinsonian syndromes is linked with high misdiagnosis rates and various confounding factors. This is particularly problematic in its early stages. With this in mind, the current pilot study aimed to distinguish between Idiopathic Parkinsons Disease (iPD), other Parkinsonian syndromes (non-iPD) and healthy subjects, by a breath test that analyzes the exhaled volatile organic compounds using a highly sensitive nanoarray. METHODS Breath samples of 44 iPD, 16 non-iPD patients and 37 healthy controls were collected. The samples were passed over a nanoarray and the resulting electrical signals were analyzed with discriminant factor analysis as well as by a K-fold cross-validation method, to test the accuracy of the model. RESULTS Comparison of non-iPD with iPD states yielded 88% sensitivity, 88% accuracy, and 88% Receiver Operating Characteristic area under the curve in the training set samples with known identity. The validation set of this comparison scored 81% sensitivity and accuracy and 92% negative predictive value. Comparison between atypical parkinsonism states and healthy subjects scored 94% sensitivity and 85% accuracy in the training set samples with known identity. The validation set of this comparison scored 81% sensitivity and 78% accuracy. The obtained results were not affected by l-Dopa or MAO-B inhibitor treatment. CONCLUSIONS Exhaled breath analysis with nanoarray is a promising approach for a non-invasive, inexpensive, and portable technique for differentiation between different Parkinsonian states. A larger cohort is required in order to establish the clinical usefulness of the method.

Virtual Reality Feedback Cues for Improvement of Gait in Patients with Parkinson's Disease

Background Our aim was to study the effects of visual feedback cues, responding dynamically to patients self-motion and provided through a portable see-through virtual reality apparatus, on the walking abilities of patients with Parkinsons 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 Parkinsons disease using virtual reality visual feedback cues. Residual effects suggest the examination of this approach in a comprehensive therapy program.

Closed-loop auditory feedback for the improvement of gait in patients with Parkinson's disease

OBJECTIVE To study the effects of closed-loop auditory feedback cues, corresponding to patient self-motion, on the walking abilities of patients with Parkinsons 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 Parkinsons 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.

Mild cognitive impairment, dementia, and affective disorders in essential tremor: a prospective study.

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.

The impact of corticosteroid treatment on hemoglobin A1C levels among patients with type-2 diabetes with chronic obstructive pulmonary disease exacerbation

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/Fischers exact tests were used to compare between the parameters of the two groups. Wilcoxons 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.

Simultaneous bilateral knee injection of methylprednisolone acetate and the hypothalamic-pituitary adrenal axis: a single-blind case-control study.

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.

Effect of ropinirole on visuo-motor test in newly diagnosed Parkinson's disease patients

Objectives –  The aim of this study was to assess the sensitivity of the visuo‐motor test (VMT) compared with the Unified Parkinsons Disease Rating Scale (UPDRS) in newly diagnosed Parkinsons disease (PD) patients.