Impulse control disorders in Parkinson's disease: a retrospective analysis of 1824 patients in a 12-year period.

OBJECTIVE: This study aims to clinically evaluate the impulse control disorders (ICDs) encountered in treating Parkinson's disease. METHOD: This is a retrospective analysis between 2010 and 2022. We retrieved the medical records of all patients diagnosed with idiopathic Parkinson's disease. The demographic and clinical findings were recorded. ICDs constituted a specific item in the examination, and each one (compulsive shopping, compulsive eating, pathological gambling, hypersexuality, punding, dopamine dysregulation syndrome, and hobbyism) was noted separately. RESULTS: In the study period, we identified 1824 patients (56.2% men, n = 1025). The mean age was 70.5 ± 11.9 years. In the cohort, 128 (7%) patients with Parkinson's disease had one or more ICDs. The ICDs were compulsive shopping, punding/hobbyism, compulsive eating, hypersexuality, pathological gambling, and dopamine dysregulation syndrome. When we compared patients with and without ICDs, patients with ICDs were younger (p ≤ 0.001), and the men/women ratio was higher in this group with ICDs. Although the mean daily pramipexole dose was higher in patients with ICDs, mean daily long-acting pramipexole dose was only 1.4 ± 0.92 mg/day. CONCLUSION: The significant findings in this study were (i) the lower frequency of ICDs (7%); (ii) the common occurrence of compulsive shopping, punding/hobbyism, and compulsive eating; and (iii) the development of ICDs under relatively lower doses of pramipexole. We suggest that ICDs in Parkinson's disease should be associated with a personal trait with dopamine agonists, and potential electrophysiological or genetic markers of this trait warrant further analysis to avoid treatment in these patients.

Ataxia in a Movement Disorders Outpatient Clinic: a Single-Center Experience in Turkey.

The etiology may not be determined in patients with ataxia despite detailed evaluations. The aim of this study was to investigate the clinical and laboratory characteristics of a large cohort of patients with adult-onset ataxia of different etiologies, particularly, undetermined etiologies despite extensive clinical, genetic, laboratory, electrophysiological, and imaging investigations. The medical records of all patients diagnosed with ataxia of subacute-chronic onset between January 2011 and March 2021 were reviewed retrospectively. The records of patients with symptom onset after 16 years of age were included in the study. In all patients, clinical and demographic findings were noted. Etiologies were classified as acquired, hereditary, degenerative (multiple system atrophy-cerebellar, MSA-C), functional, and undetermined. During the study period, we determined 74 patients with ataxia and 59 (35 males) patients met the study criteria. The age range was 22-87 years. The etiologies were hereditary (n = 19), acquired (n = 14), MSA-C (n = 9), functional (n = 2), and undetermined (n = 15). The patients with hereditary etiologies and undetermined causes were significantly younger at admission and at symptom onset (p = 0.001 and p = 0.000). There was a significant delay until diagnosis in patients with hereditary etiologies compared to other etiologies. In acquired etiologies, axial findings (71.4%) were more prominent whereas extremity and axial findings were more common in patients with hereditary etiologies (83.3%, p = 0.030). There were systemic and radiological indicators such as hearing loss, juvenile cataract, or dentate hyperintensity in certain disorders. Hereditary etiologies are as common as acquired or degenerative etiologies in adults. However, they have an earlier onset and delayed diagnosis. Therefore, we should recognize the extracerebellar neurological, systemic, and neuroimaging findings.

The effect of kinesiophobia on physical activity, balance, and fear of falling in patients with Parkinson's disease.

PURPOSE: Kinesiophobia is defined as the fear of movement and activity resulting from a feeling of vulnerability to painful injury or re-injury. This study aimed to determine the effect of kinesiophobia on physical activity, balance, and fear of falling in patients with Parkinson's disease. METHODS: The study, which was designed as a cross-sectional type, was conducted with 86 patients with Parkinson's disease (age 61.25 SD [9.72] years old) by face-to-face interviews with the patients. The Tampa Scale of Kinesiophobia, International Physical Activity Questionnaire-Short Form, Berg Balance Scale, Falls Efficacy Scale, Visual Analog Scale - Fear of Falling, Unified Parkinson's Disease Rating Scale - motor score, and the Hoehn and Yahr scale were used to evaluate the patients. RESULTS: Patients with Parkinson's disease who had high levels of kinesiophobia had lower levels of physical activity, worse balance, and higher disease severity and fear of falling. A correlation was found between the Tampa Scale score and physical activity, balance, fear of falling, falls efficacy, and disease motor score (p < .001; r = -0.38, -0.54, 0.67, 0.57, and 0.37, respectively). According to multiple linear regression analysis, kinesiophobia explained the dependent variables to varying degrees ranging from 13% to 44% (p < .001). CONCLUSIONS: Patients with Parkinson's disease may have kinesiophobia. Rehabilitation programs to support functional capacity for these patients should be developed considering the presence of kinesiophobia.

Hand Pronation-Supination Movement as a Proxy for Remotely Monitoring Gait and Posture Stability in Parkinson's Disease.

The Unified Parkinson's Disease Rating Scale (UPDRS) is a subjective Parkinson's Disease (PD) physician scoring/monitoring system. To date, there is no single upper limb wearable/non-contact system that can be used objectively to assess all UPDRS-III motor system subgroups (i.e., tremor (T), rigidity (R), bradykinesia (B), gait and posture (GP), and bulbar anomalies (BA)). We evaluated the use of a non-contact hand motion tracking system for potential extraction of GP information using forearm pronation-supination (P/S) motion parameters (speed, acceleration, and frequency). Twenty-four patients with idiopathic PD participated, and their UPDRS data were recorded bilaterally by physicians. Pearson's correlation, regression analyses, and Monte Carlo validation was conducted for all combinations of UPDRS subgroups versus motion parameters. In the 262,125 regression models that were trained and tested, the models within 1% of the lowest error showed that the frequency of P/S contributes to approximately one third of all models; while speed and acceleration also contribute significantly to the prediction of GP from the left-hand motion of right handed patients. In short, the P/S better indicated GP when performed with the non-dominant hand. There was also a significant negative correlation (with medium to large effect size, range: 0.3-0.58) between the P/S speed and the single BA score for both forearms and combined UPDRS score for the dominant hand. This study highlights the potential use of wearable or non-contact systems for forearm P/S to remotely monitor and predict the GP information in PD.

Genetic variants of vitamin D metabolism-related DHCR7/NADSYN1 locus and CYP2R1 gene are associated with clinical features of Parkinson's disease.

PURPOSE/AIM OF THE STUDY: Parkinson's disease (PD) is the second most common neurodegenerative disorder. Vitamin D deficiency is suggested to be related to PD. A genome-wide association study indicated that genes involved in vitamin D metabolism affect vitamin D levels. Among these genes, single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) and vitamin D binding protein (VDBP/GC) genes have also been demonstrated to be associated with PD risk. Our aim was to investigate the relevance of SNPs within the 7-dehydrocholesterol reductase/nicotinamide adenine dinucleotide synthetase 1 (DHCR7/NADSYN1) locus and vitamin D 25-hydroxylase (CYP2R1) gene, which encode important enzymes that play a role in the vitamin D synthesis pathway, with PD and its clinical features. MATERIALS AND METHODS: Genotypes of 382 PD patients and 240 cognitively healthy individuals were evaluated by a LightSNiP assay for a total of 10 SNPs within the DHCR7/NADSYN1 locus and CYP2R1 gene. RESULTS: There were no significant differences in the allele and genotype distributions of any of the SNPs between any patient groups and healthy subjects. However, our results indicated that all of the SNPs within the DHCR7/NADSYN1 locus and CYP2R1 gene, except rs1993116, were associated with clinical motor features of PD including initial predominant symptom, freezing of gait (FoG) and falls as well as disease stage and duration of the disease. CONCLUSIONS: In conclusion, genetic variants of the DHCR7/NADSYN1 locus and the CYP2R1 gene might be related to the inefficient utilization of vitamin D independent from vitamin D levels, and it might result in differences in the clinical features of PD patients.

Walking training augments the effects of expiratory muscle training in Parkinson's disease.

OBJECTIVES: To investigate the effects of walking training combined with respiratory muscle training (RMT) on pulmonary function, respiratory muscle strength, and functional exercise capacity in patients with Parkinson's disease. MATERIALS & METHODS: Thirty patients with Parkinson's disease were included in the study. Patients were randomly divided into two groups: the walking and RMT group (W + RMT, n = 15) and the RMT (n = 15) group. Spirometry, respiratory muscle strength, and a 6-min walking test were measured before and after the eighth week of the study. RMT was performed using inspiratory and expiratory threshold loading methods. Walking training intensity was adjusted according to the 6-min walking test. Patients performed 15 min of inspiratory muscle training and 15 min of expiratory muscle training in both groups, and 15 min of walking training in the W + RMT group in addition to RMT, twice per day, 5 days/week, for a total of 8 weeks at home. Training intensity was adjusted once per week for the groups at the hospital. RESULTS: Respiratory muscle strength and 6-min walking distance were significantly increased (p = .001), and UPDRS-III scores were significantly improved (W + RMT: p = .008 and RMT: p = .01) in the two groups. The increase in maximal expiratory pressure was significantly higher in the W + RMT group than in the RMT group (p = .007). CONCLUSION: Walking training increases the effect of expiratory muscle training in patients with Parkinson's disease.

The Complex Genetic Landscape of Hereditary Ataxias in Turkey and Implications in Clinical Practice.

BACKGROUND: The genetic and epidemiological features of hereditary ataxias have been reported in several populations; however, Turkey is still unexplored. Due to high consanguinity, recessive ataxias are more common in Turkey than in Western European populations. OBJECTIVE: To identify the prevalence and genetic structure of hereditary ataxias in the Turkish population. METHODS: Our cohort consisted of 1296 index cases and 324 affected family members. Polymerase chain reaction followed by Sanger sequencing or fragment analysis were performed to screen for the trinucleotide repeat expansions in families with a dominant inheritance pattern, as well as in sporadic cases. The expansion in the frataxin (FXN) gene was tested in all autosomal recessive cases and in sporadic cases with a compatible phenotype. Whole-exome sequencing was applied to 251 probands, selected based on the family history, age of onset, and phenotype. RESULTS: Mutations in known ataxia genes were identified in 30% of 1296 probands. Friedreich's ataxia was found to be the most common recessive ataxia in Turkey, followed by autosomal recessive spastic ataxia of Charlevoix-Saguenay. Spinocerebellar ataxia types 2 and 1 were the most common dominant ataxias. Whole-exome sequencing was performed in 251 probands with an approximate diagnostic yield of 50%. Forty-eight novel variants were found in a plethora of genes, suggesting a high heterogeneity. Variants of unknown significance were discussed in light of clinical data. CONCLUSION: With the large sample size recruited across the country, we consider that our results provide an accurate picture of the frequency of hereditary ataxias in Turkey. © 2021 International Parkinson and Movement Disorder Society.

Low Levels of LRRK2 Gene Expression are Associated with LRRK2 SNPs and Contribute to Parkinson's Disease Progression.

Parkinson's disease (PD) is a chronic neurodegenerative disease that has relatively slow progression with motor symptoms. Leucine-rich repeat kinase 2 (LRRK2) gene mutations and polymorphisms are suggested to be associated with PD. In this study, we aimed to investigate the association between single-nucleotide polymorphisms (SNPs) of the LRRK2 gene, namely, rs11176013, rs10878371, rs11835105, and PD. Genotypes of 132 PD cases and 133 healthy individuals were determined by qRT-PCR. Haplotype analysis was performed. Additionally, LRRK2 mRNA expression levels were determined in 83 PD cases and 55 healthy subjects. The relationship between LRRK2 mRNA levels, the target SNPs, and clinical data was also investigated. Our results indicated that the "GG" genotype and "G" allele of rs11176013 and the "CC" genotype and "C" allele of rs10878371 were more frequent in cases. The "GCG" haplotype was significantly more frequent in cases. LRRK2 mRNA expression levels in patients were significantly lower than those in healthy individuals. The patients with the "CC" genotype for rs10878371 and the "GG" genotype for rs11176013 had decreased LRRK2 mRNA levels. We found that the rs11176013 "GG" genotype and the rs10878371 "CC" genotype were less frequently seen in cases with akinetic rigid or combined akinetic rigid and tremor-dominant initial symptoms. Consequently, our results demonstrate that the rs11176013 and rs10878371 polymorphisms are associated with PD in a Turkish cohort, and moreover, these results suggest that these polymorphisms may affect the expression of the LRRK2 gene and disease progression and thus play a role in the pathogenesis of PD.

Estimation of Parkinson's disease severity using speech features and extreme gradient boosting.

In recent years, there is an increasing interest in building e-health systems. The systems built to deliver the health services with the use of internet and communication technologies aim to reduce the costs arising from outpatient visits of patients. Some of the related recent studies propose machine learning-based telediagnosis and telemonitoring systems for Parkinson's disease (PD). Motivated from the studies showing the potential of speech disorders in PD telemonitoring systems, in this study, we aim to estimate the severity of PD from voice recordings of the patients using motor Unified Parkinson's Disease Rating Scale (UPDRS) as the evaluation metric. For this purpose, we apply various speech processing algorithms to the voice signals of the patients and then use these features as input to a two-stage estimation model. The first step is to apply a wrapper-based feature selection algorithm, called Boruta, and select the most informative speech features. The second step is to feed the selected set of features to a decision tree-based boosting algorithm, extreme gradient boosting, which has been recently applied successfully in many machine learning tasks due to its generalization ability and speed. The feature selection analysis showed that the vibration pattern of the vocal fold is an important indicator of PD severity. Besides, we also investigate the effectiveness of using age and years passed since diagnosis as covariates together with speech features. The lowest mean absolute error with 3.87 was obtained by combining these covariates and speech features with prediction level fusion. Graphical Abstract Framework for the proposed UPDRS estimation model.

Altered Transcriptional Profile of Mitochondrial DNA-Encoded OXPHOS Subunits, Mitochondria Quality Control Genes, and Intracellular ATP Levels in Blood Samples of Patients with Parkinson's Disease.

Mitochondrial dysfunctions are significant contributors to neurodegeneration. One result or a cause of mitochondrial dysfunction might be the disruption of mtDNA transcription. Limited data indicated an altered expression of mtDNA encoded transcripts in Alzheimer's disease (AD) or Parkinson's disease (PD). The number of mitochondria is high in cells with a high energy demand, such as muscle or nerve cells. AD or PD involves increased risk of cardiomyopathy, suggesting that mitochondrial dysfunction might be systemic. If it is systemic, we should observe it in different cell types. Given that, we wanted to investigate any disruption in the regulation of mtDNA encoded gene expression in addition to PINK1, PARKIN, and ATP levels in peripheral blood samples of PD cases who are affected by a neurodegenerative disorder that is very well known by its mitochondrial aspects. Our results showed for the first time that: 1) age of onset > 50 PD sporadic (PDS) cases: mtDNA transcription and quality control genes were affected; 2) age of onset <50 PDS cases: only mtDNA transcription was affected; and 3) PD cases with familial background: only quality control genes were affected. mtDNA copy number was not a confounder. Intracellular ATP levels of PD case subgroups were significantly higher than those of healthy subjects. We suggest that a systemic dysregulation of transcription of mtDNA or mitochondrial quality control genes might result in the development of a sporadic form of the disease. Additionally, ATP elevation might be an independent compensatory and response mechanism. Hyperactive cells in AD and PD require further investigation.

Myoclonus in the elderly: A retrospective analysis of clinical and electrophysiological characteristics of patients referred to an electrophysiology laboratory.

BACKGROUND AND OBJECTIVE: Late-onset myoclonus in the elderly is mainly related to dementia or systemic disease. In this report, we aimed to investigate the clinical and electrophysiological features of patients with late-onset myoclonus. PATIENTS AND METHOD: We retrospectively assessed the medical records of patients who were referred to our electromyography laboratory. From these records, we included all patients who had myoclonus which started after the age of 60 years and in whom it was confirmed by polymyography. Demographic, clinical and electrophysiological findings were retrieved from the medical records. RESULTS: There were 63 patients with myoclonus. Types of myoclonus were spinal segmental (n = 2), cortical (n = 25) and probable cortico-subcortical involving upper extremities (n = 36). The latter two types displayed reflex sensitivity. Four patients (one with multifocal cortical myoclonus and others with probable cortico-subcortical myoclonus) were diagnosed with probable CJD. Other diagnoses were Parkinsons's disease, Parkinson-plus or dementia syndromes, vascular parkinsonism, polyneuropathy, Celiac disease and post-hypoxic encephalopathy. Eleven patients did not have a specific diagnosis. CONCLUSIONS: Myoclonus in our cohort was mostly associated with parkinsonism. Cortical myoclonus is not rare in the elderly age group. Myoclonus in polyneuropathy is irregular, tremor-like with electrophysiological characteristics similar to the cortical subtype.

Electrophysiological Investigations in Orthostatic Myoclonus: Preliminary Findings.

We report the clinical and electrophysiological findings in seven patients with orthostatic myoclonus (OM) associated with gait initiation failure and falls. OM is one of the causes of unsteadiness of stance and gait, and it may develop as a symptom of neurodegenerative disorders. Both positive myoclonic bursts and negative myoclonus may be seen in electrophysiological recordings, and electrophysiological analysis suggests a subcortical origin for OM.

Rapid Alleviation of Parkinson's Disease Symptoms via Electrostimulation of Intrinsic Auricular Muscle Zones.

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) and the pedunculopontine nucleus (PPN) significantly improve cardinal motor symptoms and postural instability and gait difficulty, respectively, in Parkinson's disease (PD). Objective and Hypothesis: Intrinsic auricular muscle zones (IAMZs) allow the potential to simultaneously stimulate the C2 spinal nerve, the trigeminal nerve, the facial nerve, and sympathetic and parasympathetic nerves in addition to providing muscle feedback and control areas including the STN, the PPN and mesencephalic locomotor regions. Our aim was to observe the clinical responses to IAMZ stimulation in PD patients. Method: Unilateral stimulation of an IAMZ, which includes muscle fibers for proprioception, the facial nerve, and C2, trigeminal and autonomic nerve fibers, at 130 Hz was performed in a placebo- and sham-controlled, double-blinded, within design, two-armed study of 24 PD patients. Results: The results of the first arm (10 patients) of the present study demonstrated a substantial improvement in Unified Parkinson's Disease Ratings Scale (UPDRS) motor scores due to 10 min of IAMZ electrostimulation (p = 0.0003, power: 0.99) compared to the placebo control (p = 0.130). A moderate to large clinical difference in the improvement in UPDRS motor scores was observed in the IAMZ electrostimulation group. The results of the second arm (14 patients) demonstrated significant improvements with dry needling (p = 0.011) and electrostimulation of the IAMZ (p < 0.001) but not with sham electrostimulation (p = 0.748). In addition, there was a significantly greater improvement in UPDRS motor scores in the IAMZ electrostimulation group compared to the IAMZ dry needling group (p < 0.001) and the sham electrostimulation (p < 0.001) groups. The improvement in UPDRS motor scores of the IAMZ electrostimulation group (ΔUPDRS = 5.29) reached moderate to high clinical significance, which was not the case for the dry needling group (ΔUPDRS = 1.54). In addition, both arms of the study demonstrated bilateral improvements in motor symptoms in response to unilateral IAMZ electrostimulation. Conclusion: The present study is the first demonstration of a potential role of IAMZ electrical stimulation in improving the clinical motor symptoms of PD patients in the short term.

GC and VDR SNPs and Vitamin D Levels in Parkinson's Disease: The Relevance to Clinical Features.

Vitamin D deficiency is suggested to be associated with Parkinson's disease (PD). Our aim was to investigate the serum 25-hydroxyvitamin D3 (25OHD) levels of PD patients in Turkish cohort, to investigate any association of vitamin D binding protein (GC) genotypes with PD due to the significant role of GC in vitamin D transport, to determine whether vitamin D receptor (VDR) haplotype that we previously demonstrated to be a risk haplotype for AD is also a common haplotype for PD and to investigate any relevant consequence of serum 25OHD levels, GC or VDR genotypes on clinical features of PD. Three hundred eighty-two PD patients and 242 healthy subjects were included in this study. The serum 25OHD levels were investigated by CLIA, and GC and VDR SNPs were evaluated with LightSnip. Our results indicated a strong relationship between low serum 25OHD levels and PD (p < 0.001). rs7041 of GC and ApaI of VDR were associated with the PD risk (p < 0.05). Minor allele carriers for BsmI of VDR gene in both PD patients and healthy subjects had significantly higher levels of serum 25OHD (p < 0.05). The homozygous major allele carriers for rs2282679, rs3755967 and rs2298850 of GC gene in PD patients with slower progression had significantly higher levels of serum 25OHD (p  < 0.05). Minor allele carriers for FokI of VDR gene were more frequent in patients with advanced-stage PD (p < 0.05). Consequently, this is the first study demonstrating GC gene as a risk factor for PD. The relationship between PD's clinical features and low 25OHD or risk genotypes might have effects on PD independently.

An updated comprehensive systematic review of Cladophialophora bantiana and analysis of epidemiology, clinical characteristics, and outcome of cerebral cases.

Cladophialophora bantiana is a phaeoid fungus that only rarely has been isolated from sources other than the human brain. It has a particular tropism for the central nervous system (CNS). We have integrated and updated large-scale data related to several aspects of C. Bantiana and reviewed all the available reports on its cerebral infections, focusing on their geographical distribution, infection routes, immune status of infected individuals, type and location of infections, clinical manifestations and treatment and outcome, briefly looking over the spectrum of other disease entities associated with C. bantiana, that is, extra-cerebral and animal infections and on the environmental sources of this fungus. Among the agents of phaeohyphomycosis, a term used to describe an infection caused by a dark pigmented fungus, C. bantiana has some significant specific features. A total of 120 case reports were identified with a significantly higher percentage of healthy subjects than immune-debilitated patients (58.3% vs. 41.7%). Infections due to C. bantiana occur worldwide. The main clinical manifestations are brain abscess (97.5%), coinfection of brain tissue and meninges (14.2%) and meningitis alone (2.5%). Among immunocompetent patients, cerebral infection occurred in the absence of pulmonary lesions. The mortality rate is 65.0% regardless of the patient's immune status. The therapeutic options used include surgery or antifungals alone, and the combination of both, in most cases the fatal outcome being rapid after admission. Since the fungus is a true pathogen, laboratory workers should be made aware that BioSafety Level-3 precautions might be necessary.

A case of central nervous system infection due to Cladophialophora bantiana / Un caso de infección del sistema nervioso central por Cladophialophora bantiana

Background. Cladophialophora bantiana is a melanised mold with a pronounced tropism for the central nervous system, almost exclusively causing human brain abscesses. Case report. We describe a case of cerebral infection by this fungus in an otherwise healthy 28-year-old coal-miner. Environmental occurrence, route of entry, and incubation period of this fungus are unknown, but our case is informative in that the first symptoms occurred about eight weeks after known traumatic inoculation. Lesions were compatible with tuberculous granulomas, and the patient initially received antitubercular treatment. Melanised fungal cells were seen in a brain biopsy and abscess materials. Therapy was switched from empirical antitubercular treatment to amphotericin B (0.5mg/kg/d), but was changed to voriconazole 200mg/d, i.v. on the basis of antifungal susceptibility test results. The patient responded clinically, and gradually improved. The isolate was identified by sequencing of the Internal Transcribed Spacer domain of rDNA. Conclusions. Given the non-specific clinical manifestations of C. bantiana cerebral abscesses, clinicians and laboratory workers should suspect infections caused by C. bantiana, particularly in immunocompromised patients with a trauma history (AU)

Antecedentes. Cladophialophora bantiana es un hongo pigmentado con un marcado tropismo por el sistema nervioso central que produce abscesos cerebrales en el hombre prácticamente de forma exclusiva. Caso clínico. Describimos un caso de infección cerebral por dicho hongo en un paciente, por otra parte sano, de 28 años de edad y minero del carbón. El hábitat natural, así como la puerta de entrada y el período de incubación de las infecciones por este hongo, son desconocidos, pero el presente caso demuestra que los primeros síntomas se produjeron aproximadamente ocho semanas después de su inoculación traumática. Las lesiones fueron compatibles con granulomas tuberculosos, por lo que el paciente recibió inicialmente tratamiento antituberculoso. Se observaron células fúngicas melanizadas en una biopsia cerebral, por lo que el tratamiento fue sustituido por anfotericina B (0,5mg/kg/d) y fue de nuevo cambiado por voriconazol intravenoso (200mg/d) con base en los resultados de la prueba de sensibilidad antifúngica. El paciente respondió clínicamente y mejoró de forma gradual. El hongo aislado fue identificado por secuenciación de los espaciadores transcribibles internos del ADN ribosómico. Conclusiones. Teniendo en cuenta las manifestaciones clínicas no específicas de los abscesos cerebrales por C. bantiana, los clínicos y el personal de laboratorio deberían considerar la posibilidad de la existencia de infecciones por este patógeno neurotrópico especialmente en pacientes inmunocomprometidos con antecedentes de trauma (AU)

A case of central nervous system infection due to Cladophialophora bantiana.

BACKGROUND: Cladophialophora bantiana is a melanised mold with a pronounced tropism for the central nervous system, almost exclusively causing human brain abscesses. CASE REPORT: We describe a case of cerebral infection by this fungus in an otherwise healthy 28-year-old coal-miner. Environmental occurrence, route of entry, and incubation period of this fungus are unknown, but our case is informative in that the first symptoms occurred about eight weeks after known traumatic inoculation. Lesions were compatible with tuberculous granulomas, and the patient initially received antitubercular treatment. Melanised fungal cells were seen in a brain biopsy and abscess materials. Therapy was switched from empirical antitubercular treatment to amphotericin B (0.5mg/kg/d), but was changed to voriconazole 200mg/d, i.v. on the basis of antifungal susceptibility test results. The patient responded clinically, and gradually improved. The isolate was identified by sequencing of the Internal Transcribed Spacer domain of rDNA. CONCLUSIONS: Given the non-specific clinical manifestations of C. bantiana cerebral abscesses, clinicians and laboratory workers should suspect infections caused by C. bantiana, particularly in immunocompromised patients with a trauma history.

FBXO7 mutations in Parkinson's disease and multiple system atrophy.

Mutations in the F-box only protein 7 (FBXO7) gene, located on chromosome 22q12-q13, have recently been identified as having distinct clinical features in patients with hereditary Parkinson's disease (PD). Pathologically, α-synuclein-positive inclusions have been identified using anti-FBXO7 antibody staining techniques. In the present study, we screened entire exons of FBXO7 from 271 patients (231 PD and 40 multiple system atrophy [MSA]), of which 221 samples were of Japanese origin. The PD patients (n = 231) comprised 31 autosomal dominant, 82 autosomal recessive, and 118 sporadic forms. The 40 cases of MSA consisted of 8 autosomal dominant, 2 autosomal recessive, and 30 sporadic forms. We detected a Turkish patient with autosomal recessive inheritance, harboring a homozygous truncating mutation, Arg498Stop (p.R498X), in the FBXO7 gene. Consequently, we evaluated her and assessed the correlation between her clinical manifestations and genotypic analysis, although the FBXO7 p.R498X gene has lower frequency than others. Her age at onset was 17 years, and she clinically manifested with progressive parkinsonism and cognitive decline. In contrast, no pathogenic mutations in FBXO7 among PD and MSA patients of Japanese or other ethnicities were observed. Based on recent literature, we reviewed and compared the clinical findings and population differences between documented FBXO7 cases.