Statistical shape analysis of putamen in early-onset Parkinson's disease.

OBJECTIVE: To investigate the shape differences in the putamen of early-onset Parkinson's patients compared with healthy controls and to assess and to assess sub-regional brain abnormalities. METHODS: This study was conducted using the 3-T MRI scans of 23 early-onset Parkinson's patients and age and gender matched control subjects. Landmark coordinate data obtained and Procrustes analysis was used to compare mean shapes. The relationships between the centroid sizes of the left and right putamen, and the durations of disease examined using growth curve models. RESULTS: While there was a significant difference between the right putamen shape of control and patient groups, there was not found a significant difference in terms of left putamen. Sub-regional analyses showed that for the right putamen, the most prominent deformations were localized in the middle-posterior putamen and minimal deformations were seen in the anterior putamen. CONCLUSION: Although they were not as pronounced as those in the right putamen, the deformations in the left putamen mimic the deformations in the right putamen which are found mainly in the middle-posterior putamen and at a lesser extend in the anterior putamen.

Natural History, Phenotypic Spectrum, and Discriminative Features of Multisystemic RFC1 Disease.

OBJECTIVE: To delineate the full phenotypic spectrum, discriminative features, piloting longitudinal progression data, and sample size calculations of replication factor complex subunit 1 (RFC1) repeat expansions, recently identified as causing cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). METHODS: Multimodal RFC1 repeat screening (PCR, Southern blot, whole-exome/genome sequencing-based approaches) combined with cross-sectional and longitudinal deep phenotyping in (1) cross-European cohort A (70 families) with ≥2 features of CANVAS or ataxia with chronic cough (ACC) and (2) Turkish cohort B (105 families) with unselected late-onset ataxia. RESULTS: Prevalence of RFC1 disease was 67% in cohort A, 14% in unselected cohort B, 68% in clinical CANVAS, and 100% in ACC. RFC1 disease was also identified in Western and Eastern Asian individuals and even by whole-exome sequencing. Visual compensation, sensory symptoms, and cough were strong positive discriminative predictors (>90%) against RFC1-negative patients. The phenotype across 70 RFC1-positive patients was mostly multisystemic (69%), including dysautonomia (62%) and bradykinesia (28%) (overlap with cerebellar-type multiple system atrophy [MSA-C]), postural instability (49%), slow vertical saccades (17%), and chorea or dystonia (11%). Ataxia progression was ≈1.3 Scale for the Assessment and Rating of Ataxia points per year (32 cross-sectional, 17 longitudinal assessments, follow-up ≤9 years [mean 3.1 years]) but also included early falls, variable nonlinear phases of MSA-C-like progression (SARA points 2.5-5.5 per year), and premature death. Treatment trials require 330 (1-year trial) and 132 (2-year trial) patients in total to detect 50% reduced progression. CONCLUSIONS: RFC1 disease is frequent and occurs across continents, with CANVAS and ACC as highly diagnostic phenotypes yet as variable, overlapping clusters along a continuous multisystemic disease spectrum, including MSA-C-overlap. Our natural history data help to inform future RFC1 treatment trials. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that RFC1 repeat expansions are associated with CANVAS and ACC.

Contribution of functional dopamine D2 and D3 receptor variants to motor and non-motor symptoms of early onset Parkinson's disease.

In the present study, we focused on investigating the contribution of functional dopamine D2 and D3 receptor variants to motor and/or non-motor symptoms of early onset Parkinson's disease (EOPD). Three functional single nucleotide polymorphisms (SNPs), DRD3 rs6280, DRD2 rs2283265 and DRD2 rs1076560, were genotyped in 128 Turkish EOPD patients and then, statistical analysis was conducted for the potential impacts of SNPs on clinical parameters. All three SNPs were found to be statistically significant in terms of PD-related pain: DRD3 [rs6280; risk allele "T" for pain; p = 0.031; odds ratio (OR)=4.25], DRD2 [rs2283265; risk allele "A" for pain; p = 0.001; OR=8.47] and, DRD2 [rs1076560; risk allele "A" for pain; p = 0.022; OR=4.58]. Additionally, bilateral disease [p = 0.011; OR=5.10] and gender [risk group "female"; p = 0.003; OR=8.53] were also identified as significant univariate risk factors for PD-related pain. Based on logistic regression analysis conducted with the significant univariate risk factors, this the first report to clarify that a female patient with bilateral PD and DRD2 rs2283265 polymorphism has a significant risk for PD-related pain. Our findings might contribute to improve life quality by offering treatment options for pain in PD patients with these clinical and genetic features.

Evaluation of anxiety and depression scales and quality of LIFE in cervical dystonia patients on botulinum toxin therapy and their relatives.

OBJECTIVE: In this study, quality of life and psychiatric comorbid disorders were investigated in patients with cervical dystonia and their spouses and we also investigated the effect of botulinum toxin (BTX) treatment on these parameters. MATERIAL AND METHOD: Thirty patients with cervical dystonia (CD) on BTX treatment and their spouses (n = 30) were included. Beck Depression Scale (BDS), State-Trait Anxiety Inventory I and II (STAI-I, STAI-II), Hospital Anxiety Scale (HAS), Hospital Depression Scale (HDS) for psychiatric comorbid disease assessment, Toronto Western Spasmodic Torticollis Scale (TWSTRS) for disease activity assessment, and Craniocervical Dystonia Questionnaire (CDQ-24), Cervical Dystonia Impact Profile (CDIP-58), and Short Form 36 (SF-36) questionnaires for quality of life assessment were used. BDS, STAI-I and STAI-II, HAS, HDS, and SF-36 scales were also obtained from the spouses. The same tests were applied both before and 8 weeks after the BTX treatment. CONCLUSION: In our study, an increase in psychiatric comorbid disorders such as depression and anxiety was observed and the quality of life was adversely affected in all areas in patients. In the spouses of the patients, the rates of psychiatric comorbid disorders such as depression and anxiety were found to be increased when compared to healthy subjects while vitality, mental health, and general health perception were found to be negatively affected. Patients showed improvements in anxiety level, disease activity, and overall quality of life scales after BTX treatment.

Turkish Standardization of Movement Disorders Society Unified Parkinson's Disease Rating Scale and Unified Dyskinesia Rating Scale.

BACKGROUND: Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Unified Dyskinesia Rating Scale (UDysRS) were developed as standard tools to rate Parkinson's disease (PD) and drug-induced dyskinesias of PD. As these scales have become widely used, there is a need for translation to non-English languages. Here we present the standardization for the Turkish translations. METHODS: The scales were translated into Turkish and then back-translated to English. These back-translations were reviewed by the MDS team. After cognitive pretesting, movement disorder specialists from nine centers tested 352 patients for MDS-UPDRS, and 250 patients for UDysRS. Confirmatory factor analyses (CFAs) were used to determine if the factor structures for the reference standards could be confirmed in the Turkish data. The comparative fit indexes (CFIs) for the scales were required to be 0.90 or higher. Exploratory factor analyses (EFAs) were conducted to explore the underlying factor structure without the constraint of a pre-specified factor structure. RESULTS: For both scales, the CFIs were 0.94 or greater as compared to the reference standard factor structures. The factor structures were consistent with that of reference standards, although there were some differences in some areas as compared to the EFA of the reference standard dataset. This may be due to the inclusion of patients with different stages of PD and different cultural properties of raters and patients. CONCLUSIONS: These results demonstrate that the Turkish translations of MDS-UPDRS and UDysRS have adequate clinimetric properties. They are established as the official translations and can be reliably used in Turkish speaking populations.

Epigenetic approach to early-onset Parkinson's disease: low methylation status of SNCA and PARK2 promoter regions.

Background and aim The effect of epigenetic modifications in the genes related to Parkinson's disease (PD) is still unclear. In the present study, we investigated methylation status of SNCA and PARK2 genes in patients with early-onset Parkinson's disease (EOPD). Materials and methods The promoter region methylation status of SNCA and PARK2 genes was evaluated by methylation specific-PCR (MSP) in 91 patients with EOPD and 52 healthy individuals. Results The methylation of SNCA and PARK2 promoter regions were significantly lower in EOPD patients compared to the control group (P = 0.013 and P = 0.03, respectively). We also found that the methylation status of the SNCA might be associated with positive family history of PD (P = 0.042). Conclusion Although it should be supported by further analysis, based on the results of the present study, the methylation status of SNCA and PARK2 genes might contribute to EOPD pathogenesis.

Mutation analysis of the PARKIN, PINK1, DJ1, and SNCA genes in Turkish early-onset Parkinson's patients and genotype-phenotype correlations.

OBJECTIVE: Variations in PARK genes (PRKN, PINK1, DJ-1, and SNCA) cause early-onset Parkinson's disease (EOPD) in different populations. In the current study, we aimed to evaluate the frequencies of variations in PARK genes and the effects of these variations on the phenotypes of Turkish EOPD patients. METHODS: All coding regions and exon-intron boundaries of the PRKN, PINK1, DJ-1, and SNCA genes were screened by heteroduplex analysis followed by direct sequencing of the detected variants in 50 Turkish EOPD patients. These variants were evaluated using SIFT, PolyPhen, HSF, and LOVD web-based programs. RESULTS: The frequency of EOPD-associated variations in the PRKN gene was 34%. Among these variations, p.A82E in exon 3 and p.Q409X in exon 11 was determined to be pathogenic. We also defined previously unknown cryptic variations, including c.872-35 G>A and c.872-28T>G in exon 8 of PRKN and c.252+30 T>G and c.322+4 A>G in exons 4 and 5 of DJ1, respectively, that were associated with EOPD. Although no significant association was observed between the PARK gene mutations and clinical features (P>0.05), the alterations were related to the clinical symptoms in each patient. CONCLUSION: An increasing number of studies report that PRKN, PINK1, DJ1 and SNCA mutations are associated with early-onset Parkinson's disease; however, a limited number of studies have been conducted in Turkey. Additionally, our study is the first to evaluate the frequency of SNCA mutations in a Turkish population. The aim of this study was determine the frequency distributions of the PRKN, PINK1, DJ1, and SNCA gene mutations and to analyze the relationships between these genetic variations and the clinical phenotype of EOPD in Turkish patients.

Impaired cognitive performance and hippocampal atrophy in Parkinson disease.

BACKGROUND/AIM: Dementia is common in Parkinson disease (PD). Since magnetic resonance imaging has been used, hippocampal atrophy has been shown in PD patients with or without dementia. In this study we sought the correlation of cognitive decline with bilateral hippocampal volume in PD patients. MATERIALS AND METHODS: Thirty-three patients with diagnosis of idiopathic PD and 16 healthy subjects were included in this study. PD patients were divided into two groups as normal cognitive function and mild cognitive impairment (MCI). The Mini-Mental State Examination and detailed cognitive assessment tests were performed for all patients for cognitive analyses. Depression was excluded by the Geriatric Depression Scale. RESULTS: The mean onset age of disease was 55 years for PD patients without dementia and 59 for PD patients with MCI. According to the Hoehn-Yahr scales, 24% of patients had grade 1, 58% had grade 2, and 18% had grade 3 disease. Right and left hippocampal volumes decreased along with cognitive test scores in PD patients. Increased right hippocampal volume was correlated with forward number test in the MCI-PD group. CONCLUSION: These findings suggest that memory deficit is associated with hippocampal atrophy in PD patients.

Sporadic Creutzfeldt-Jacob Disease: An 8-Year Experience from a Single Center in Turkey.

INTRODUCTION: Our aim was to conduct a retrospective review to demonstrate the clinical, radiological, and electrophysiological features of patients with sporadic Creutzfeldt-Jacob disease (sCJD). METHOD: A total of 10 patients (5 female and 5 male, with a mean age of 45 years from a range of 40 to 67 years) out of 8.259 adult patients hospitalized from January 2000 to December 2008 were diagnosed with sCJD. RESULTS: Eight of the patients were diagnosed on the basis of clinical, radiological, electroencephalography (EEG), and cerebrospinal fluid (CSF) findings. Two other patients also had a pathological diagnosis. The most common signs and symptoms were behavioral disturbances, movement disorders, cognitive decline, myoclonus, psychosis, focal neurological deficit, and aphasia. Nine of the patients had periodic sharp wave discharges on EEG. Seven patients were positive for the 14.3.3 protein in the CSF. Five patients had pulvinar signs-a bilateral increased signal in the pulvinar thalami-on cranial magnetic resonance imaging. Eight patients were diagnosed with probable sCJD; two were diagnosed with definite sCJD. All of the patients died as a result of the disease within 24 months after the onset of symptoms. DISCUSSION: sCJD should be considered in the diagnosis of patients who present with rapidly progressive dementia. Clinical and radiological data appear to be sufficient for the diagnosis. However, detailed molecular examinations of the subtypes of the disease may be required for early diagnosis of cases given the wide spectra of CJD.

Structural and neurochemical evaluation of the brain and pons in patients with Wilson's disease.

PURPOSE: The aim of this study was to examine the structural-neurochemical abnormalities of the frontal white matter (FWM), deep gray matter nuclei, and pons in patients with Wilson's disease (WD) using proton magnetic resonance spectroscopy (MRS) and diffusion-weighted imaging (DWI). MATERIALS AND METHODS: Nine patients with WD and 14 age-matched controls were examined with MRS. N-Acetylaspartate (NAA), choline (Cho), and creatine (Cr) peaks were calculated. DWI scans from six WD patients and six controls were also obtained. The relative metabolite ratios and apparent diffusion coefficient (ADC) values of the WD patients were compared to those of the control subjects by using statistical measures. RESULTS: Measurements in the thalamus and pons showed significantly lower NAA/Cho and NAA/Cr ratios in the WD group than in the control group (P < 0.05). Thalamic and pontine Cho/Cr ratios in the patient group were significantly higher than those of the control group (P < 0.05). No statistically significant relation was found between the patient and control groups as a result of the MRS examinations of FWM and all ADC measurements (P > 0.05). CONCLUSION: MRS is a noninvasive, valuable modality for detecting structural-neurochemical changes of the brain stem and deep gray matter in patients with WD. The contribution of DWI in these patients is limited.

Primary gait ignition disorder: report of three cases.

Gait ignition failure (GIF) classifications all had major limitations. Few years ago, a new and simpler classification was proposed by Liston. The aim of this paper is to discuss three GIF patients with respect to this new classification. All three patients presented with hesitation to start walking and turning and their neurological examination revealed start and turn hesitation without any other abnormality. We classified our patients according to Liston's classification as ignition apraxia, which enabled us to approach the patients in a practical way. This classification helps to understand the underlying pathologies and combines clinical characteristics and pathophysiology. We reported our experience with pergolide in the treatment of patients suffering from primary GIF and underline the fact that more research is needed on the treatment of this condition.

The prevalence and clinical features of restless legs syndrome: a door to door population study in Orhangazi, Bursa in Turkey.

BACKGROUND: Restless leg syndrome (RLS) has negative effects on the quality of life of the patients. Epidemiological studies on RLS are limited. AIM: To determine the prevalence of RLS among people aged 40 years and above in Orhangazi district of Bursa, Turkey. MATERIALS AND METHODS: The study was carried out between 2004 and 2005. This population-based study was conducted in two phases. In the phase 1, residents conducted door-to-door interviews using a short questionnaire to determine the possible cases of RLS. In the phase 2, physicians ascertained the suspected cases of RLS. Diagnosis of RLS was made using the criteria proposed by the International Restless Legs Syndrome Study Group (IRLSSG) and also the rating scale for RLS. RESULTS: Out of 1, 256 subjects screened in phase 1, 1,124 (89.6%) were included in the study. Also, 161 cases with suspected symptoms of RLS were detected in phase 1, 49 of the suspected cases could not be evaluated in phase 2. A diagnosis of RLS was also made in 60 cases during phase 2. CONCLUSIONS: We defined the prevalence of RLS as 9.71% among 40 years of age and older population. The prevalence of RLS did not differ by age and was 2.6 times more in women. None of the patients were diagnosed as RLS sought medical care for the symptoms, possibly due to lack of knowledge of patients and physicians about RLS. Prevalence studies help to provide knowledge on morbidity, which is essential for diagnosis and early treatment.

Adult onset tics after peripheral injury.

We describe a case with adult onset motor tics after peripheral trauma. A 43-year-old man suffered a left shoulder dislocation during a motorcycle accident 21 years ago. Within 2 weeks after the injury, he noticed the gradual onset of involuntary jerking movements of his left shoulder, which was markedly exacerbated after second left shoulder injury 2 years later. The involuntary movements are phenomenologically identical to tics typically associated with Tourette syndrome (TS), but without the involvement of any other body part and without phonic tics or the typical TS co-morbidities, such as attention deficit or obsessive-compulsive disorder.

Hereditary chin tremor in Parkinson's disease.

Hereditary chin tremor (HCT) is characterized by rhythmical, involuntary movements of the chin muscles usually inherited in an autosomal dominant pattern. We describe a 74-year old man with familial, childhood-onset chin tremor, and a 3-year history of progressive hand tremor, gait difficulty, and other parkinsonian features. Since chin tremor often occurs in Parkinson's disease (PD), a coexistent HCT may not be recognized unless past and family history of tremor is carefully explored.

The first Susac's syndrome case in Turkey.

Susac's syndrome is a vasospastic disease resulting from bilateral microangiopathy of the brain, cochlea and retina. It is characterized by encephalopathy, bilateral sensorineural fluctuating hearing loss and visual loss. It is very uncommon and usually affects women during young adulthood. Since all three symptoms of the triad may not be present, the clinical diagnosis is difficult. Therefore, neuroimaging, particularly magnetic resonance imaging, has an important role in establishing the diagnosis. In this case report, we present a young woman who had all the symptoms of Susac's syndrome. This is the first Susac's syndrome case reported in Turkey.

Clinical characteristics of tension-type headache and migraine in adolescents: a student-based study.

BACKGROUND AND OBJECTIVES: Adolescent headaches, particularly migraine, might present with different features from adult headaches. The objectives of this study were to investigate the characteristics of tension-type headache and migraine, to find the sensitivity and specificity of the diagnostic criteria of the IHS classification according to age and gender. METHODS: A multistep, stratified, cluster sampling method was used for subject selection. The estimated sample size was 2387. The study was conducted in two phases: the questionnaire and the face to face interview phases. During the semistructured interview, a clinical diagnosis has been made and clinical characteristics have been recorded. RESULTS: All headaches fulfilled the criteria of duration. The most common feature of migraine was moderate to severe (92.4%), pulsating pain (79.2%). For ETTH, bilateral localization (91.3%) and mild to moderate pain intensity (90.6%) were the most common features. Younger adolescents showed mixed headache characteristics. Highest sensitivities for migraine were duration (100%), moderate to severe pain (92.4%), and pulsating quality of pain (79.2%). Vomiting, trigger factors food and alcohol had a high specificity for migraine. CONCLUSIONS: Our data strongly support continuum hypothesis. In early adolescence headaches might present with mixed headache characteristics. Age and gender have some influence on headache characteristics, particularly on migraine. The sensitivity and specificity of case definition criteria of ICHD-2 for adolescent migraine is moderate and need to be reconsidered.