Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinson's disease study.

Estimates of the spectrum and frequency of pathogenic variants in Parkinson's disease (PD) in different populations are currently limited and biased. Furthermore, although therapeutic modification of several genetic targets has reached the clinical trial stage, a major obstacle in conducting these trials is that PD patients are largely unaware of their genetic status and, therefore, cannot be recruited. Expanding the number of investigated PD-related genes and including genes related to disorders with overlapping clinical features in large, well-phenotyped PD patient groups is a prerequisite for capturing the full variant spectrum underlying PD and for stratifying and prioritizing patients for gene-targeted clinical trials. The Rostock Parkinson's disease (ROPAD) study is an observational clinical study aiming to determine the frequency and spectrum of genetic variants contributing to PD in a large international cohort. We investigated variants in 50 genes with either an established relevance for PD or possible phenotypic overlap in a group of 12 580 PD patients from 16 countries [62.3% male; 92.0% White; 27.0% positive family history (FH+), median age at onset (AAO) 59 years] using a next-generation sequencing panel. Altogether, in 1864 (14.8%) ROPAD participants (58.1% male; 91.0% White, 35.5% FH+, median AAO 55 years), a PD-relevant genetic test (PDGT) was positive based on GBA1 risk variants (10.4%) or pathogenic/likely pathogenic variants in LRRK2 (2.9%), PRKN (0.9%), SNCA (0.2%) or PINK1 (0.1%) or a combination of two genetic findings in two genes (∼0.2%). Of note, the adjusted positive PDGT fraction, i.e. the fraction of positive PDGTs per country weighted by the fraction of the population of the world that they represent, was 14.5%. Positive PDGTs were identified in 19.9% of patients with an AAO ≤ 50 years, in 19.5% of patients with FH+ and in 26.9% with an AAO ≤ 50 years and FH+. In comparison to the idiopathic PD group (6846 patients with benign variants), the positive PDGT group had a significantly lower AAO (4 years, P = 9 × 10-34). The probability of a positive PDGT decreased by 3% with every additional AAO year (P = 1 × 10-35). Female patients were 22% more likely to have a positive PDGT (P = 3 × 10-4), and for individuals with FH+ this likelihood was 55% higher (P = 1 × 10-14). About 0.8% of the ROPAD participants had positive genetic testing findings in parkinsonism-, dystonia/dyskinesia- or dementia-related genes. In the emerging era of gene-targeted PD clinical trials, our finding that ∼15% of patients harbour potentially actionable genetic variants offers an important prospect to affected individuals and their families and underlines the need for genetic testing in PD patients. Thus, the insights from the ROPAD study allow for data-driven, differential genetic counselling across the spectrum of different AAOs and family histories and promote a possible policy change in the application of genetic testing as a routine part of patient evaluation and care in PD.

Comparative analysis of freezing of gait in distinct Parkinsonism types by diffusion tensor imaging method and cognitive profiles.

Freezing of gait (FOG) is an episodic gait pattern that is common in advanced Parkinson's disease (PD) and other atypical parkinsonism syndromes. Recently, disturbances in the pedunculopontine nucleus (PPN) and its connections have been suggested to play a critical role in the development of FOG. In this study, we aimed to demonstrate possible disturbances in PPN and its connections by performing the diffusion tensor imaging (DTI) technique. We included 18 patients of PD with FOG [PD-FOG], 13 patients of PD without FOG [PD-nFOG] and 12 healthy subjects as well as a group of patients with progressive supranuclear palsy (PSP), an atypical parkinsonism syndrome which is very often complicated with FOG [6 PSP-FOG, 5 PSP-nFOG]. To determine the specific cognitive parameters that can be related to FOG, deliberate neurophysiological evaluations of all the individuals were performed. The comparative analyses and correlation analyses were performed to reveal the neurophysiological and DTI correlates of FOG in either group. We have found disturbances in values reflecting microstructural integrity of the bilateral superior frontal gyrus (SFG), bilateral fastigial nucleus (FN), left pre-supplementary motor area (SMA) in the PD-FOG group relative to the PD-nFOG group. The analysis of the PSP group also demonstrated disturbance in left pre-SMA values in the PSP-FOG group likewise, while negative correlations were determined between right STN, left PPN values and FOG scores. In neurophysiological assessments, lower performances for visuospatial functions were demonstrated in FOG ( +) individuals for either patient group. The disturbances in the visuospatial abilities may be a critical step for the occurrence of FOG. Together with the results of DTI analyses, it might be suggested that impairment in the connectivity of disturbed frontal areas with disordered basal ganglia, maybe the key factor for the occurrence of FOG in the PD group, whereas left PPN which is a nondopaminergic nucleus may play a more prominent role in the process of FOG in PSP. Moreover, our results support the relationship between right STN, and FOG as mentioned before, as well as introduce the importance of FN as a new structure that may be involved in FOG pathogenesis.

Sleep disorders and polysomnography findings in patients with autoimmune encephalitis.

BACKGROUND: Sleep disorders in patients with autoimmune encephalitis (AE) are increasingly reported. Early recognition and treatment have significant importance regarding the potential of sleep disorders' effect on morbidity and even mortality. There are a limited number of studies related to polysomnography (PSG) in these patients. Here, we report the clinical and PSG data of patients with AE and sleep disorders, with a particular interest in sleep-related breathing disorders (SRBD). METHODS: Seventeen patients with diagnosed AE and acute or subacute onset sleep complaints who underwent video-electroencephalography-PSG recordings in our tertiary center were investigated. RESULTS: The mean age was 50, with eight females and nine males. The detected antibodies were against leucine-rich glioma-inactivated 1(LGI-1) in 6, anti-contactin-associated protein-2(CASPR2) in 3, voltage-gated potassium channel complex antigens(VGKC) in 1, anti-glycine in 1, dipeptidyl-peptidase-like protein-6(DPPX) in 1, anti-Hu in 1, and anti-amphiphysin in 1. All commercially available and known autoimmune encephalitis-related antibodies were negative in 3 of the patients. Final diagnosis after PSG was circadian rhythm sleep disorder (n = 3), periodic limb movement disorder (n = 3), insomnia (n = 5), central apnea with or without Cheyne-Stokes breathing (CSB) (n = 4), obstructive sleep apnea (OSA) (n = 4), non-rapid eye movement (NREM) and REM parasomnia (n = 8), faciobrachial dystonic seizures (n = 2), and subclinical seizures (n = 1). Sleep microstructure was disrupted in 9, REM periods without atonia occurred in 4, and brief sleep fragments consisting of theta activity interspersed with faster rhythms existed in 7 patients. Nearly half of our patients (47%) had SRBD, and the mean apnea-hypopnea index (AHI) was 14. CONCLUSIONS: Sleep disorders are frequent and essential components of AEs. Systematic clinical questionnaires and routine PSG assessments would significantly impact the correct diagnosis and proper treatment of SRBD and the overall prognosis of AE.

Targeted resequencing reveals high-level mosaicism for a novel frameshift variant in WDR45 associated with beta-propeller protein-associated neurodegeneration.

OBJECTIVES: Beta-propeller protein-associated neurodegeneration (BPAN) is a rare X-linked dominant neurodegenerative disease, which is characterized by iron accumulation in the basal ganglia. BPAN is associated with pathogenic variation in WDR45, which has been reported almost exclusively in females most probably due to male lethality in the hemizygous state. METHODS: Whole exome sequencing (WES) and targeted deep sequencing were performed for a male with a clinical diagnosis of BPAN at the age of 37. RESULTS: The novel frameshift variant in WDR45 detected by WES was further analyzed with targeted resequencing to detect a mosaic variant with a level of 85.5% in the blood sample of the proband. DISCUSSION: Although the main role of WDR45 remains elusive, recent studies show that WDR45 may contribute to neurodegeneration through defects in autophagy, iron storage and ferritin metabolism, mitochondria organization, and endoplasmic reticulum homeostasis. The extend of spatiotemporal haploinsufficiency of WDR45 frameshifting variants caused by mosaicism in males may lead to variable clinical severity, which may be hard to elaborate clinically. Promising genetic analysis strategies using targeted deep sequencing may help determine the clinical outcome of somatic mosaicism in neurological disorders including BPAN. Additionally, we suggest that deep sequencing should be conducted in cerebrospinal fluid samples to provide more reliable results in terms of reflecting the mosaicism level in the brain for future studies.

Intercountry comparisons of advanced Parkinson's disease symptoms and management: Analysis from the OBSERVE-PD observational study.

OBJECTIVES: In the absence of widely accepted criteria, determining when a patient with Parkinson's disease (PD) may benefit from more advanced treatments such as device-aided therapy (DAT) so far remains a matter of physician judgment. This analysis investigates how classification of PD varies across countries relative to measures of disease severity. MATERIALS AND METHODS: The OBSERVational, cross-sEctional PD (OBSERVE-PD) study included consecutive patients with PD at centers that offer DATs in 18 countries. In this subgroup analysis, we explore intercountry differences in identification of advanced versus non-advanced PD based on physician's clinical judgment, symptoms assessed using Delphi consensus criteria, use of DAT, motor and non-motor symptoms, and caregiver support. Demographic and clinical characteristics were obtained through review of medical records. RESULTS: Overall, 1342 of 2615 patients (51.3%) were assessed by physicians as having advanced PD. The proportion of patients in different countries identified as having advanced PD (24.4-82.2%) varied. In 15 of 18 countries, a greater proportion of patients with advanced PD, according to select Delphi criteria, were identified by physicians as having advanced PD than with non-advanced PD. There was a wide variability across countries in the proportion of patients with no dyskinesia, disabling dyskinesia, dyskinesia pain, and non-motor symptoms who were identified by physicians as having advanced versus non-advanced PD. CONCLUSIONS: The proportion of patients identified with advanced PD symptoms varies widely across countries, despite differences on the patients' profiles, indicating a need for objective diagnostic criteria to help identify patients who may benefit from DAT.

Post-COVID-19 longitudinally extensive transverse myelitis: is it a new entity?

INTRODUCTION: To the best of our knowledge, here we present two post-COVID19 longitudinally extensive transverse myelitis (LETM) with atypical presentations CASE PRESENTATIONS: A 44-year-old male who did not have any previous medical condition and a 73-year-old male foreigner who did not have any disease other than type 2 diabetes mellitus were admitted to our neurology clinic in the same period with similar clinical presentations of transverse myelitis. Upon admission, paraplegia and urinary-fecal incontinence were observed in their neurological examination. Neurological complaints had started within approximately 3-4 weeks following the resolution of the COVID-19 infection. Thoracic lower segment LETM was observed on spinal magnetic resonance imaging (MRI) in one of the patients, and long segment myelitis extending from the lower thoracic segment to the conus medullaris was observed in the other one. No significant diagnostic positivity was present in their diagnostic evaluation. In both cases, we assume a post-infectious etiology in terms of secondary immunogenic overreaction following COVID-19. CONCLUSION: Our patients improved with multiple treatments such as methylprednisolone, intravenous immunoglobulin, and plasmapheresis. Whether post-infectious myelitis behaves differently from other viral infections after COVID-19 is currently unclear. Long lag times appear to be a post-infectious neurological complication resulting from the host response to the virus.

Multicenter study of levodopa carbidopa intestinal gel in Parkinson's disease: the Turkish experience

Background/aim: Our purpose was to determine the efficacy of levodopa carbidopa intestinal gel (LCIG) in a series of Turkish patients with Parkinson's disease (PD). Materials and methods: We had telephone calls with 54 patients from 11 neurology centers who were on LCIG treatment, and 44 patients or their caregivers were included in an eight-item survey between September 2015 and June 2016. The reliability and validity of the survey were evaluated with intraclass correlation coefficients for every question separately. Results: Average age of the patients were 63.48 and the duration of PD was 12.79 years. Average LCIG treatment period was 15.63 months. Percentages of the patients who reported they were 'better' after LCIG treatment were as follows: 80% for time spent off, 55% for dyskinesia, 65% for tremor, 85% for gait disorder, 50% for pain, 50% for sleep disorders, 42.5% for depression, 32.5% for incontinence, and 70% for activities of daily living. Cronbach's alpha was 0.795 and the intraclass correlation coefficient was reliable for the items. Conclusion: As detected by a survey performed by telephone calls with good interrater reliability, patients with PD improve with LCIG treatment in many aspects of the disease.

Characterizing advanced Parkinson's disease: OBSERVE-PD observational study results of 2615 patients.

BACKGROUND: There are currently no standard diagnostic criteria for characterizing advanced Parkinson's disease (APD) in clinical practice, a critical component in determining ongoing clinical care and therapeutic strategies, including transitioning to device-aided treatment. The goal of this analysis was to determine the proportion of APD vs. non-advanced PD (non-APD) patients attending specialist PD clinics and to demonstrate the clinical burden of APD. METHODS: OBSERVE-PD, a cross-sectional, international, observational study, was conducted with 2615 PD patients at 128 movement disorder centers in 18 countries. Motor and non-motor symptoms, activities of daily living, and quality-of-life end points were assessed. The correlation between physician's global assessment of advanced PD and the advanced PD criteria from a consensus of an international group of experts (Delphi criteria for APD) were evaluated. RESULTS: According to physician's judgment, 51% of patients were considered to have APD. There was a moderate correlation between physician's judgment and Delphi criteria for APD (K = 0.430; 95% CI 0.406-0.473). Activities of daily living, motor symptom severity, dyskinesia duration/disability, "Off" time duration, non-motor symptoms, and quality-of-life scores were worse among APD vs. non-APD patients (p < 0.0001 for all). APD patients (assessed by physicians) had higher disease burden by motor and non-motor symptoms compared with non-APD patients and a negative impact on activities of daily living and quality of life. CONCLUSIONS: These findings aid in identifying standard APD classification parameters for use in practicing physicians. Improvements in identification of APD patients may be particularly relevant for optimizing treatment strategies including transitioning to device-aided treatment.

Modulation of Cerebellar-Cortical Connections in Multiple System Atrophy Type C by Cerebellar Repetitive Transcranial Magnetic Stimulation.

OBJECTIVE: This study aims at modulating the altered cerebellar-cortical interactions in patients with multiple system atrophy-cerebellar subtype (MSA-C) by using cerebellar repetitive transcranial magnetic stimulation (rTMS). We hypothesized that cerebellar modulation by low-frequency rTMS can resolve the abnormal cortical excitability in multiple system atrophy cerebellar subtype. MATERIALS AND METHODS: We studied detailed effects of rTMS of the cerebellum on reaction time (RT) and short-latency afferent inhibition (SAI) response in MSA-C group, Alzheimer Disease (AD) group, and a control group of healthy individuals. The RT and SAI responses were measured before and after 1 Hz cerebellar rTMS in all groups. The study was conducted in the neurophysiology laboratory in Hacettepe University Hospital. RESULTS: Our results indicated that motor cortex disinhibition was predominant in patients with AD and MSA-C. In AD and control groups, there were no changes in SAI after rTMS. However, after application of rTMS over the cerebellum in MSA-C patients, the pathological disinhibition and RT results showed an improvement compared to their previous results. CONCLUSION: Our study highlights that cerebellar rTMS impairs abnormal cerebellar-cortical inhibitory connections in case of MSA-C.

Sensorimotor integration training in Parkinson`s disease.

OBJECTIVE: To determine the effects of sensorimotor integration training on postural control in Parkinson`s disease. METHODS: This prospective, randomized controlled trial was conducted at Hacettepe University (Ankara, Turkey). The study was carried out from August 2012 until March 2015 and included 24 Parkinson`s patients with stage 2-3 according to the Modified Hoehn&Yahr Rating Scale. The patients were divided into 2 groups (control and study). The control group received conventional physiotherapy; the study group received sensorimotor integration training combined with conventional physiotherapy, 2 times per week for 6 weeks. We assessed the patients with clinical balance tests and computerized dynamic posturography. Assessments were performed at baseline, 7- and 12-weeks follow-up. RESULTS: Computerized dynamic posturography posturography values (5th and 6th positions, composite balance, and vestibular system scores) were higher in the study group than in the control group. The improvements were maintained at the 12-week follow up except 6th positions scores (p<0.05). CONCLUSION: Sensorimotor integration training combined with conventional physiotherapy approach ameliorated postural control by improving vestibular system in patients with Parkinson`s disease by improving sensory processes.

Mitochondrial serine protease HTRA2 p.G399S in a kindred with essential tremor and Parkinson disease.

Essential tremor is one of the most frequent movement disorders of humans and can be associated with substantial disability. Some but not all persons with essential tremor develop signs of Parkinson disease, and the relationship between the conditions has not been clear. In a six-generation consanguineous Turkish kindred with both essential tremor and Parkinson disease, we carried out whole exome sequencing and pedigree analysis, identifying HTRA2 p.G399S as the allele likely responsible for both conditions. Essential tremor was present in persons either heterozygous or homozygous for this allele. Homozygosity was associated with earlier age at onset of tremor (P < 0.0001), more severe postural tremor (P < 0.0001), and more severe kinetic tremor (P = 0.0019). Homozygotes, but not heterozygotes, developed Parkinson signs in the middle age. Among population controls from the same Anatolian region as the family, frequency of HTRA2 p.G399S was 0.0027, slightly lower than other populations. HTRA2 encodes a mitochondrial serine protease. Loss of function of HtrA2 was previously shown to lead to parkinsonian features in motor neuron degeneration (mnd2) mice. HTRA2 p.G399S was previously shown to lead to mitochondrial dysfunction, altered mitochondrial morphology, and decreased protease activity, but epidemiologic studies of an association between HTRA2 and Parkinson disease yielded conflicting results. Our results suggest that in some families, HTRA2 p.G399S is responsible for hereditary essential tremor and that homozygotes for this allele develop Parkinson disease. This hypothesis has implications for understanding the pathogenesis of essential tremor and its relationship to Parkinson disease.

Progressive neurodegenerative syndrome in a patient with X-linked agammaglobulinemia receiving intravenous immunoglobulin therapy.

A progressive encephalopathy of unknown etiology has been described in patients with primary immunodeficiency disorders. In this report, we characterize the clinical features of this progressive neurodegenerative dementing disorder in a young man with Bruton agammaglobulinemia, through neuropsychological tests and a video sequence. The clinical course of the encephalopathy seems rather uniform: Cognition, especially frontal lobe function, is affected in the early stages, and some patients develop movement disorders. The syndrome causes severe cognitive and physical disability, and can eventually be fatal. The autoimmunity results from dysregulated immune responses, but the underlying mechanism has not yet been fully explained.

PSMF1 variants cause a phenotypic spectrum from early-onset Parkinson's disease to perinatal lethality by disrupting mitochondrial pathways.

Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson's disease (PD) and neurodegeneration. This approach ultimately catalyzes the identification of potential biomarkers and therapeutic targets. Here, we identify PSMF1 as a new gene implicated in PD and childhood neurodegeneration. We find that biallelic PSMF1 missense and loss-of-function variants co-segregate with phenotypes from early-onset PD and parkinsonism to perinatal lethality with neurological manifestations across 15 unrelated pedigrees with 22 affected subjects, showing clear genotype-phenotype correlation. PSMF1 encodes the proteasome regulator PSMF1/PI31, a highly conserved, ubiquitously expressed partner of the 20S proteasome and neurodegeneration-associated F-box-O 7 and valosin-containing proteins. We demonstrate that PSMF1 variants impair mitochondrial membrane potential, dynamics and mitophagy in patient-derived fibroblasts. Additionally, we develop models of psmf1 knockdown Drosophila and Psmf1 conditional knockout mouse exhibiting age-dependent motor impairment, with diffuse gliosis in mice. These findings unequivocally link defective PSMF1 to early-onset PD and neurodegeneration and suggest mitochondrial dysfunction as a mechanistic contributor.

Acute effects of lumbosacral mobilization on balance and functional activities in idiopathic Parkinson's disease:A randomised controlled trial.

BACKGROUND: Decreased axial rotation, impaired coordination between axial segments and axial tone contribute to gait, balance and postural disorders in Parkinson's Disease. AIMS: The aim of our study was to examine the acute effects of lumbosacral mobilization on balance and functional activities in patients with idiopathic Parkinson's Disease. METHODS: This study was a randomized controlled clinical trial conducted at Hacettepe University. The study included 28 patients with Parkinson's Disease who were between stage 2-3 according to the Modified Hoehn&Yahr Staging Scale. Participants were randomised to the study group, including 10 minutes of lumbosacral mobilization, or the control group, including no intervention. The Unified Parkinson's Disease Rating Scale (UPDRS), Modified Parkinson's Activity Scale (MPAS), Dynamic Gait Index (DGI), and static posturography test (Modified Clinical Test of Sensory Interaction and Balance - mCTSIB) were all examined twice. RESULTS: The UPDRS, MPAS, DGI values and the composite score with the soft ground eyes open condition in the mCTSIB were improved in the study group (p < 0.05). DGI and MPAS values reached the level of significance between the groups (p < 0.05). CONCLUSION: This study is the first to examine the effect of lumbosacral mobilization on balance and functional activities in patients with Parkinson's disease. Lumbosacral mobilization is an effective method in PwPD. Lumbosacral mobilization may be an alternative way for these patients to improve their balance and functional activities.

Effects of freezing of gait on balance in patients with Parkinson's disease.

OBJECTIVES: The aim of the study was to evaluate the effects of freezing of gait (FOG) on static and dynamic balance. METHODS: Twenty patients with Parkinson's disease with and without FOG [PD+FOG (68,6±6,39 years) and PD-FOG group (70,6±4,57 years)] and 10 healthy individuals (68,4±4,92 years) with similar demographic characteristics were included in the study. Balance was compared between the three groups. Balance was evaluated with clinical tests Limits of stability (LoS) and body sway were measured using the E-LINK FP3 Force Plate and the Korebalance Balance Evaluation System, which measure the balance in static and dynamic conditions. Center of pressure (COP) change and average sway velocity were evaluated with the Zebris RehaWalk system. RESULTS: Total and subscale scores of the Unified Parkinson's Disease Rating Scale were significantly higher in the PD+FOG group (p<0.05). The balance test results for both groups were similar (p>0.05). The PD+FOG group performed worse on the computerized static balance tests, the COP analysis, and the dynamic balance total score than the other two groups (p<0.05). The PD+FOG group had significantly greater sustained weight deviation than the healthy controls (p<0.05). Patients with Parkinson's disease had a lower LoS in the posterior direction than healthy controls (p<0.05). DISCUSSION: FOG affects the dynamic balance more negatively than the static balance. In addition, FOG reduces LoS in the posterior direction and increases body sway in the anterior-posterior direction, which can lead to falls.

Do cervical stabilization exercises change the effects of conventional exercises in patients with Parkinson's disease?

OBJECTIVES: The aim of this study was to examine whether cervical stabilization exercises (CSEs) change the effects of conventional exercises (CEs) in patients with PD. METHODS: Twenty-five patients with PD were randomized into two groups. While the experimental group (EG) received CSEs in addition to CEs, the control group (CG) received only CEs. Both programs lasted 8 weeks. Eighteen participants were able to complete the study. The outcomes were the changes in posture, cervical joint position sense (JPS), balance assessment, 10-m walking tests (10MWT), and the Timed Up & Go (TUG) test. RESULTS: At the end of the study, significant improvement was observed in both groups in terms of trunk rotation angle and pelvic asymmetry, the time parameter of TUG, and the 10MWT (p < 0.05). In the EG, greater improvement was detected in the Berg Balance Scale, static posturography, postural alignment, JPS, and the cadence parameter of TUG (p < 0.05). DISCUSSION: CEs and CSEs could improve walking speed and posture in patients with PD, but if CSEs are added to CEs, greater improvements could be achieved in JPS and postural control.(Clinical Trials ID: NCT03854747).

Short latency afferent inhibition in Parkinson's disease patients with dementia.

BACKGROUND: Cortical cholinergic deficiency occurs in Parkinson's disease (PD) and is more severe in PD dementia (PDD). Short-latency afferent inhibition (SAI) can be used as an in vivo test for the evaluation of the cholinergic circuit in the cerebral motor cortex. METHODS: SAI and neuropsychological profile were studied in nondemented PD, PDD, Alzheimer's disease (AD) patients, and age-matched controls. RESULTS: SAI was significantly impaired in AD cases (94.7 ± 6.2 versus 55.5 ± 4.0; P < 0.0001). In PD patients, it was not different from controls (61.4 ± 5.8 versus 55.5 ± 4.0; P = 0.412). PDD cases demonstrated a significant impairment in SAI (91.4 ± 5.2 versus 55.5 ± 4.0; P < 0.0001). A high correlation was found between SAI and Mini-Mental State Examination (r = -0.68; P < 0.0001). CONCLUSIONS: These findings add further evidence that differential cholinergic deficiency occurs in PD and PDD. SAI can be a neurophysiological correlate of PDD.

The effect of electrical stimulation in combination with Bobath techniques in the prevention of shoulder subluxation in acute stroke patients.

OBJECTIVE: To examine the efficiency of electrical stimulation in combination with Bobath techniques in the prevention of inferior and anterior shoulder subluxation in acute stroke patients. DESIGN: A prospective randomized controlled trial. SETTING: Intensive care unit and inpatient clinics of neurology in a university hospital. SUBJECTS: Forty-eight patients with acute stroke, divided equally into control and study groups. INTERVENTION: Subjects in both groups were treated in accordance with the Bobath concept during the early hospitalization period. In addition to Bobath techniques, electrical stimulation was also applied to the supraspinatus muscle, mid and posterior portions of the deltoid muscle of patients in the study group. MAIN MEASURES: Two radiological methods were used to measure the horizontal, vertical and total asymmetry and vertical distance values of the shoulder joint. Motor functions of the arm were evaluated with the Motor Assessment Scale. RESULTS: The hospitalization period was 12.62 ± 2.24 days for the control group and 11.66 ± 1.88 days for the study group. Shoulder subluxation occurred in 9 (37.5%) subjects in the control group, whereas it was not observed in the study group. All shoulder joint displacement values were higher in the control group than in the study group (horizontal asymmetry P = 0.0001, vertical asymmetry P = 0.0001, total asymmetry P = 0.0001, vertical range P = 0.002). CONCLUSION: Application of electrical stimulation combined with the Bobath approach proved to be efficient in preventing inferior and anterior shoulder subluxation in the acute stages of stroke.

Prevalence of cerebrotendinous xanthomatosis in cases with idiopathic bilateral juvenile cataract in ophthalmology clinics in Turkey.

PURPOSE: To determine the prevalence of cerebrotendinous xanthomatosis (CTX) in patients with idiopathic bilateral juvenile cataract in Turkey. METHODS: In this multicenter, epidemiologic observational study, patients with idiopathic bilateral juvenile cataract (aged ≥1 year at study entry) were identified from the records of 31 ophthalmology clinics. The Mignarri suspicion index determined in all potential CTX patients; blood samples were collected, and genetic testing for CYP27A1 gene mutation was performed. Cholestanol levels of the patients were measured, and those with a level of ≥3.75 µg/mL (threshold value) underwent genetic testing for mutations in the CYP27A1 gene. RESULTS: CTX was diagnosed in 7 of 452 patients (1.55%) with bilateral juvenile cataract. There was no significant difference between patients with a Mignarri score of <100 (n = 8) and those with a score of ≥100 (n = 19) with respect to cholestanol levels and genetic test results. Genetic testing was undertaken in 27 patients based on elevated cholestanol levels. Of these 27, 7 (26%) had CYP27A1 gene mutations. Of these 7 patients with genetically confirmed CTX, 5 (71%) were in the group with higher Mignarri score (≥100). CONCLUSIONS: CTX is a treatable condition, and early detection is crucial for avoiding irreversible neurological manifestations. Screening using the Mignarri suspicion index and cholestanol blood levels can be helpful in identifying suspected cases of CTX.