Hyperkinetic movement disorders in congenital disorders of glycosylation.

BACKGROUND AND PURPOSE: Congenital disorders of glycosylation (CDG) represent an increasing number of rare inherited metabolic diseases associated with abnormal glycan metabolism and disease onset in infancy or early childhood. Most CDG are multisystemic diseases mainly affecting the central nervous system. The aim of the current study was to investigate hyperkinetic movement disorders in patients affected by CDG and to characterize phenomenology based on CDG subtypes. METHODS: Subjects were identified from a cohort of patients with CDG who were referred to the University Hospital of Catania, Italy. Patients were evaluated by neurologists with expertise in movement disorders and videotaped using a standardized protocol. RESULTS: A variety of hyperkinetic movement disorders was detected in eight unrelated CDG patients. Involuntary movements were generally observed early in childhood, maintaining a clinical stability over time. Distribution ranged from a generalized, especially in younger subjects, to a segmental/multifocal involvement. In patients with phosphomannomutase 2 CDG, the principal movement disorders included dystonia and choreo-athetosis. In patients affected by other CDG types, the movement disorders ranged from pure generalized chorea to mixed movement disorders including dystonia and complex stereotypies. CONCLUSIONS: Hyperkinetic movement disorder is a key clinical feature in patients with CDG. CDG should be considered in the differential diagnosis of childhood-onset dyskinesia, especially when associated with ataxia, developmental delay, intellectual disability, autism or seizure disorder.

Association between non-communicable disease multimorbidity and health care utilization in a middle-income country: population-based study.

OBJECTIVE: The objective was to analyze possible inequalities by gender in the utilization of health services (general practitioner [GP] and hospital), among people with non-communicable diseases (NCDs) in the Republic of Serbia, with special reference to multimorbidity. In addition, we examined the prevalence patterns of NCDs by sociodemographic characteristics of the population. STUDY DESIGN: This study is a population-based, cross-sectional survey. METHODS: A secondary analysis from the 2013 Serbian National Health Survey included 13,765 adults aged ≥20 years. Multivariable logistic and linear regression analyses were performed to assess the association between NCDs and health care utilization. RESULTS: Multimorbidity was present in 30.2% of the total sample. An increased number of NCDs was associated with a higher utilization of both primary (odds ratio [OR] for having any GP visit is 3.17 in males and 3.14 in females; unstandardized coefficient [B] for number of GP visits is 0.33 for both gender) and secondary health care services (OR for having any hospitalization is 2.45 in males and 1.97 in females; B for number of overnight stays in hospital is 1.62 in males and 0.97 in females) in Serbia. CONCLUSIONS: Our study provided strong evidence that an increased number of NCDs was significantly associated with a higher utilization of health care services in Serbia. There is a need for wise, decisive, and integrated care interventions for effective management of NCDs and their risk factors. Further research is necessary with special emphasis on the role of the health system in satisfying needs of such patients.

Past, present, and future of Parkinson's disease: A special essay on the 200th Anniversary of the Shaking Palsy.

This article reviews and summarizes 200 years of Parkinson's disease. It comprises a relevant history of Dr. James Parkinson's himself and what he described accurately and what he missed from today's perspective. Parkinson's disease today is understood as a multietiological condition with uncertain etiopathogenesis. Many advances have occurred regarding pathophysiology and symptomatic treatments, but critically important issues are still pending resolution. Among the latter, the need to modify disease progression is undoubtedly a priority. In sum, this multiple-author article, prepared to commemorate the bicentenary of the shaking palsy, provides a historical state-of-the-art account of what has been achieved, the current situation, and how to progress toward resolving Parkinson's disease. © 2017 International Parkinson and Movement Disorder Society.

Globus pallidus internus neuronal activity: a comparative study of linear and non-linear features in patients with dystonia or Parkinson's disease.

Movement disorders such as Parkinson's disease (PD) and dystonia are associated with alterations of basal ganglia motor circuits and abnormal neuronal activity in the output nucleus, the globus pallidus internus (GPi). This study aims to compare the electrophysiological hallmarks for PD and dystonia in the linear and non-linear time stamp domains in patients who underwent microelectrode recordings during functional stereotactic surgery for deep brain stimulation (DBS) or pallidotomy. We analyzed single-unit neuronal activity in the posteroventral lateral region of the GPi in awake patients prior to pallidotomy or the implantation of DBS electrodes in 29 patients with PD (N = 83 neurons) and 13 patients with dystonia (N = 41 neurons) under comparable conditions. The discharge rate and the instantaneous frequency of the GPi in dystonia patients were significantly lower than in PD patients (P < 0.001), while the total number of bursts, the percentage of spikes in bursts and the mean duration of bursts were higher (P < 0.001). Further, non-linear analysis revealed higher irregularity or entropy in the data streams of GPi neurons of PD patients compared to the dystonia patients group (P < 0.001). This study indicates that both linear and non-linear features of neuronal activity in the human GPi differ between PD and dystonia. Our results may serve as the basis for future studies on linear and non-linear analysis of neuronal firing patterns in various movement disorders.

Quality of life in patients with alopecia areata: a hospital-based cross-sectional study.

BACKGROUND: Previous studies suggest that alopecia areata (AA) may significantly affect patient quality of life (QoL). There are no studies that assess QoL in Serbian AA patients. OBJECTIVES: This study aims to assess the impact of AA on patients' QoL in comparison to patients affected by other skin diseases and to determine the impact of sociodemographic and clinical characteristics of AA patients on QoL. METHODS: A hospital-based cross-sectional study of 60 patients with AA was conducted at the Clinic of Dermatovenereology, Clinical Center of Serbia, Belgrade between April 2012 and June 2013. The severity of hair loss was assessed using the Severity of Alopecia Tool (SALT). Patients' self-assessment of QoL was measured by three self-administered questionnaires: The Short Form-36 Health Survey (SF-36), Dermatology Life Quality Index (DLQI) and The Skindex-29. RESULTS: Sixty AA patients (16 males and 44 females) with mean age of 37.35 ± 14.26 years completed the questionnaires. We confirmed that QoL of our AA patients was impaired. Compared with patients suffering from psoriasis, atopic dermatitis and onychomycosis AA patients presented significantly better QoL. Severity of disease (SALT) correlated only with personal relationship - dimension of DLQI (ρ = 0.29, P < 0.05) and social functioning - dimension of Skindex (ρ = 0.26, P < 0.05). No correlation was observed between severity of the disease and SF-36 subscales. AA patients with depression had significantly worse QoL in daily activities, leisure, work or school and personal relationships - DLQI dimensions, and emotions and social functioning - Skindex subscales. CONCLUSION: Our study demonstrates that AA influences QoL, but to a lesser degree than observed for psoriasis, atopic dermatitis and onychomycosis.

The EIF4G1 gene and Parkinson's disease.

Variants in the EIF4G1 gene have been recently identified to be responsible for autosomal dominant PD (PARK18), but its role in the PD-related neurodegeneration is unclear. Several EIF4G1 mutation/variants were found to be associated with PD, and functional studies have suggested that these variants may impair the ability of cells to rapidly and dynamically respond to stress, thus probably participating in the development of PD, and these indicated that EIF4G1 variants may play an important role in pathogenicity of PD, although the frequency is low. Further studies involving large sample size of patients with PD from diverse populations, as well as studies of EIF4G1 expression and in scaffold function, are warranted.

Bolivian kindred with combined spinocerebellar ataxia types 2 and 10.

BACKGROUND: Spinocerebellar ataxias (SCA) are a group of rare hereditary neurodegenerative disorders. Rare cases of two SCA mutations in the same individual have been reported in the literature, however, family descriptions are lacking. AIMS: To characterize a family with combined SCA2 and SCA10 mutations. MATERIALS & METHODS: Analysis of the clinical features and genetic findings of a Bolivian family expressing both SCA2 and SCA10 mutations. RESULTS: The index case and his mother had both SCA2 and SCA10 mutations with a combined clinical phenotype of both disorders, including slow saccades (SCA2) and seizures (SCA10). The uncle of the index case had only an SCA10 mutation. DISCUSSION: Although the presence of two SCA mutations in the same individuals may be coincidental, the low probability of having both mutations suggests that these mutations might be particularly prevalent in Bolivian population. CONCLUSION: This is the first description of a family with two SCA mutations with affected subjects having a combined SCA2 and SCA10 phenotype.

Biliary Enterocytozoon bieneusi infection in a dog under immunomodulatory therapy.

An 8-year-old female spayed Labrador retriever was presented for the evaluation of severe weight loss 10 weeks after starting an immunomodulatory treatment, including prednisolone and cyclosporine, for meningoencephalitis of unknown origin. Plasma biochemistry analysis showed mild to moderate increases in liver enzyme activities and a moderate decrease in urea concentration. Abdominal ultrasound revealed mild hepatomegaly and a large gall bladder with unremarkable wall and content. Cholecystocentesis was performed and bile was examined both cytologically and by molecular methods, which revealed the presence of Enterocytozoon bieneusi. Treatment was initiated with albendazole but was discontinued due to the development of severe neutropenia. The medical management was subsequently changed to fenbendazole and the dog made a complete recovery. This report describes the first case of clinical manifestation and successful treatment of biliary E. bieneusi infection in a dog.

Changes in cognitive-emotional and physiological symptoms of depression following STN-DBS for the treatment of Parkinson's disease.

BACKGROUND AND PURPOSE: Subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to have beneficial effects on the motor features of Parkinson's disease (PD), but its impact on non-motor symptoms, most notably mood, has not been fully explored. METHODS: In the first study to independently compare the emotional-cognitive and somatic/physiological symptoms of depression, we examined mood differences in 17 bilateral STN-DBS and 22 matched non-surgical PD patients at baseline and 6 months. RESULTS: The STN-DBS group reported higher levels of depression at baseline with significant endorsement of physical symptomatology. Postoperatively, no significant between-group differences in physical symptoms of depression were found. In contrast, a significant group by time interaction for cognitive-emotional symptoms of depression was found, with the STN-DBS group reporting an increase in psychological symptoms of distress. The STN-DBS group also reported an increase in anxiety following surgery. The suicide rate of 5% found in our study is consistent with other postoperative studies in PD. The impact of changes in levodopa and psychotropic medication are also explored. CONCLUSIONS: Preliminary results suggest that the motor improvement often observed in patients with PD following bilateral STN-DBS may be partially offset by an increase in affective-cognitive symptoms of depression.

Alternating verbal fluency performance following bilateral subthalamic nucleus deep brain stimulation for Parkinson's disease.

BACKGROUND AND PURPOSE: Despite common occurrences of verbal fluency declines following bilateral subthalamic nucleus deep brain stimulation (STN-DBS) for the treatment of Parkinson's disease (PD), alternating fluency measures using cued and uncued paradigms have not been evaluated. METHODS: Twenty-three STN-DBS patients were compared with 20 non-surgical PD patients on a comprehensive neuropsychological assessment, including cued and uncued intradimensional (phonemic/phonemic and semantic/semantic) and extradimensional (phonemic/semantic) alternating fluency measures at baseline and 6-month follow-up. RESULTS: STN-DBS patients demonstrated a greater decline on the cued phonemic/phonemic fluency and the uncued phonemic/semantic fluency tasks compared to the PD patients. For STN-DBS patients, verbal learning and information processing speed accounted for a significant proportion of the variance in declines in alternating phonemic/phonemic and phonemic/semantic fluency scores, respectively, whilst only naming was related to uncued phonemic/semantic performance for the PD patients. Both groups were aided by cueing for the extradimensional task at baseline and follow-up, and the PD patients were also aided by cueing for the phonemic/phonemic task on follow-up. CONCLUSIONS: These findings suggest that changes in alternating fluency are not related to disease progression alone as STN-DBS patients demonstrated greater declines over time than the PD patients, and this change was related to declines in information processing speed.

LINGO1 variants in essential tremor and Parkinson's disease.

The leucine-rich repeat and Ig domain containing 1 gene (LINGO1), recently considered to be conferred increased risk of essential tremor (ET), has been also implicated in Parkinson disease (PD). As the two common movement disorders have overlapping clinical and pathological features, it has been postulated that the LINGO1 gene may play a role in the pathogenesis of the two diseases. Here, we review published reports of the LINGO1 variants in ET and PD in an attempt to better understand the molecular and pathogenic relationship of LINGO1 to the two disorders.

Revisiting the relationship between essential tremor and Parkinson's disease.

BACKGROUND: The relationship between essential tremor and Parkinson's disease has been a subject of reviews and debates for long time, but there is now growing evidence that the two common movement disorders are pathogenically related, at least in some patient populations. METHODS: PubMed as well as authors' own files were searched for relevant keywords regarding overlap between the disorders in clinical features as well as on epidemiologic, genetic, imaging, and pathological studies. RESULTS: New findings in each of these categories are critically reviewed and placed in the context of previously published data. DISCUSSION: Although we believe that there is compelling evidence for the notion that some patients with "pure" ET evolve into PD, the biologic nature of the association is not well understood. Furthermore, it is not clear what factors predict which ET patients later develop PD and whether patients with PD are more likely to develop ET. Further epidemiologic, clinical, genetic, imaging, and pathological studies are needed to better understand this mixed, ET-PD phenotype.

Gender differences in smoking experience and cessation: do wealth and education matter equally for women and men in Serbia?

BACKGROUND: Although nowadays smoking is less popular, one-third of adults in Serbia still smoke regularly. The aim of this study was to analyze associations of smoking experience and quitting with gender and socio-economic status. METHODS: Cross-sectional, population-based nationally representative household survey (Health Survey, 2006). Age- and multivariate-adjusted logistic regression analyses were used to analyze predictors of smoking experience and cessation. RESULTS: Of 12 365 interviewed, 51.1% used to smoke: current smokers accounted for 36.8% and former smokers for 14.3%. Higher educated women were more prone to smoking [secondary school: odds ratio (OR), 1.75; 95% confidence interval (CI), 1.52-2.01; university degree: OR, 1.53; 95% CI, 1.26-1.86], whereas for men the opposite was observed (university degree: OR, 0.72; 95% CI, 0.60-0.86). Education also was 'pro-quitting' factor (university degree: OR, 1.46; 95% CI, 1.07-1.99 for women; university degree: OR, 1.61; 95% CI, 1.23-1.80 for men). To quit smoking, wealth status was gradually more important for women, while just the richest men were more likely to quit smoking (OR, 1.45; 95% CI, 1.09-1.93). CONCLUSION: The poorest women in Serbia and the least educated men are those least likely to quit smoking, which indicates that ability to quit is predicted by socio-economic status.

A randomised, double-blind, placebo-controlled study of topiramate in the treatment of Tourette syndrome.

OBJECTIVE: To investigate the effects of topiramate on Tourette syndrome (TS). BACKGROUND: Dopamine-receptor-blocking drugs have been traditionally used to control tics in patients with TS, but these neuroleptics are associated with potentially limiting side effects. METHODS: This is a randomised, double-blind, placebo-controlled, parallel group study. To be included in the study, subjects required a DSM-IV diagnosis of TS, were 7-65 years of age, had moderate to severe symptoms (Yale Global Tic Severity Scale (YGTSS) > or =19), were markedly impaired as determined by the Clinical Global Impression (CGI) scale severity score of > or =4 and were taking no more than one drug each for tics or TS comorbidities. RESULTS: There were 29 patients (26 males), mean age 16.5 (SD 9.89) years, randomised, and 20 (69%) completed the double-blind phase of the study. The primary endpoint was Total Tic Score, which improved by 14.29 (10.47) points from baseline to visit 5 (day 70) with topiramate (mean dose 118 mg) compared with a 5.00 (9.88) point change in the placebo group (p = 0.0259). There were statistically significant improvements also in the other components of the YGTSS as well as improvements in various secondary measures, including the CGI and premonitory urge CGI. No differences were observed in the frequency of adverse events between the two treatment groups. CONCLUSION: This double-blind, placebo-controlled trial provides evidence that topiramate may have utility in the treatment of moderately severe TS.

Clinical efficacy and tolerability of Xeomin in the treatment of blepharospasm.

BACKGROUND AND PURPOSE: Blepharospasm is classified as a focal dystonia, and botulinum toxin type A (BoNT/A) has been shown to be a highly effective and well-tolerated symptomatic treatment. Xeomin, the latest addition to BoNT/A preparations, is a purified, freeze-dried BoNT/A that is free from complexing proteins. METHODS AND RESULTS: In a double-blind, parallel-group, multicentre study, 300 patients with blepharospasm received either Xeomin or Botox 15-80 U (J Neural Transm 2006; 113: 303). Both treatments produced statistically significant improvements from baseline in the Jankovic Rating Scale at week 3 (primary efficacy variable; Xeomin: -2.90; Botox: -2.67; P < 0.0001 from baseline for both), with the difference between treatments (-0.23) indicating that Xeomin was clinically non-inferior to Botox. No significant differences were found between Xeomin and Botox for all secondary variables. There were no clinically relevant differences between Xeomin and Botox in safety parameters, with 40 of 148 patients (27.0%) treated with Xeomin reporting adverse events versus 45 of 155 patients (29.0%) treated with Botox. The most common adverse event was ptosis (6.1% Xeomin and 4.5% Botox). CONCLUSION: Clinical evidence to date suggests that Xeomin is an effective treatment for blepharospasm that does not differ from Botox in terms of its potency, duration of effect or adverse reaction profile.

Examination of the MSX1 gene in patients with Parkinson's disease.

BACKGROUND: Several genetic variants in transcription factor genes have been reported to be associated with Parkinson's disease (PD). The muscle segment homeobox drosophila homolog of 1 gene (MSX1) is a major upstream regulator of the dopaminergic neuronal subtype specification. AIMS OF THE STUDY: To determine whether genetic variation in the coding region of the MSX1 gene plays a role in the etiology of PD. METHODS: We searched for genetic variations in the coding region of the MSX1 gene in 202 patients with PD and 200 normal controls by PCR-single-strand conformation polymorphism (PCR-SSCP) and sequencing. RESULTS: No mutation in the MSX1 gene was identified in our cohort. CONCLUSIONS: Mutations in the coding region of the MSX1 gene play little or no role in the development of PD.

McLeod syndrome: Five new pedigrees with novel mutations.

OBJECTIVE: To present five new McLeod Syndrome (MLS) pedigrees with novel XK gene mutations, review the literature of this disorder, and discuss the typical and atypical clinical features noted with these new mutations. METHODS: This is a multi-center retrospective review of five MLS cases with novel gene mutations. Genotypic and phenotypic information has been obtained from each center. RESULTS: Five novel mutations are reported in this Case series. New clinical findings include prolonged asymptomatic elevated creatine kinase (CK) levels, vocal tics, presence of obstructive sleep apnea (OSA), and one patient of Vietnamese ethnicity. CONCLUSIONS: We expand on the clinical and genetic spectrum of MLS demonstrating the clinical variability of MLS.

Parkinson's disease: clinical features and diagnosis.

OBJECTIVE: Parkinson's disease (PD) is a progressive neurological disorder characterised by a large number of motor and non-motor features that can impact on function to a variable degree. This review describes the clinical characteristics of PD with emphasis on those features that differentiate the disease from other parkinsonian disorders. METHODS: A MedLine search was performed to identify studies that assess the clinical characteristics of PD. Search terms included "Parkinson's disease", "diagnosis" and "signs and symptoms". RESULTS: Because there is no definitive test for the diagnosis of PD, the disease must be diagnosed based on clinical criteria. Rest tremor, bradykinesia, rigidity and loss of postural reflexes are generally considered the cardinal signs of PD. The presence and specific presentation of these features are used to differentiate PD from related parkinsonian disorders. Other clinical features include secondary motor symptoms (eg, hypomimia, dysarthria, dysphagia, sialorrhoea, micrographia, shuffling gait, festination, freezing, dystonia, glabellar reflexes), non-motor symptoms (eg, autonomic dysfunction, cognitive/neurobehavioral abnormalities, sleep disorders and sensory abnormalities such as anosmia, paresthesias and pain). Absence of rest tremor, early occurrence of gait difficulty, postural instability, dementia, hallucinations, and the presence of dysautonomia, ophthalmoparesis, ataxia and other atypical features, coupled with poor or no response to levodopa, suggest diagnoses other than PD. CONCLUSIONS: A thorough understanding of the broad spectrum of clinical manifestations of PD is essential to the proper diagnosis of the disease. Genetic mutations or variants, neuroimaging abnormalities and other tests are potential biomarkers that may improve diagnosis and allow the identification of persons at risk.

Cognitive declines following bilateral subthalamic nucleus deep brain stimulation for the treatment of Parkinson's disease.

BACKGROUND: We investigated the cognitive and psychiatric outcome 6 months after bilateral subthalamic nucleus deep brain stimulation (DBS) for the treatment of Parkinson's disease (PD) using a disease control group. METHODS: 23 patients who underwent DBS were compared with 28 medically treated patients with PD at baseline and at 6 months for neuropsychological measures. In addition to the group outcomes, we report reliable change indices (RCI) and a dementia caseness analysis. RESULTS: Patients who underwent DBS demonstrated a significant decline in verbal memory compared with the control group (p<0.003), and trends for decline on oral information processing, including verbal fluency, timed transcription and word naming. Patients who underwent DBS demonstrated declines in attention, set shifting and semantic fluency but these changes were similar to the rate of decline in the PD group. RCI indicated that patients who underwent DBS demonstrated clinically significant declines in verbal fluency (p<0.01) and inhibition of a dominant response (p<0.003), with trends for declines in set shifting (p<0.02) and verbal long term recall (p<0.08), indicative of frontostriatal dysfunction. Patients who underwent DBS did not demonstrate significant changes in depression, anxiety or psychological distress scores. The caseness analysis revealed that one of the patients who underwent DBS (4%) converted to dementia over 6 months compared with none of the PD controls. CONCLUSIONS: Our findings demonstrated that patients who underwent DBS experienced declines in verbal recall and trends for declines in oral information processing 6 months following surgery, even when good motor outcome was achieved. Potential candidates should be counselled about the risk of mild frontostriatal cognitive declines following DBS to weigh the risks and benefits of surgery.

Mozart's movements and behaviour: a case of Tourette's syndrome?

In this review, we intend to explore the often asked question: "Did Mozart have Tourette's syndrome?" Although there are numerous reports attributing Mozart's peculiar personality and behaviour to a spectrum of neurobehavioural disorders such as Tourette's syndrome, autistic disorder, Asperger's syndrome, attention deficit hyperactivity disorder, obsessive-compulsive disorder and paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection, the evidence for any of these disorders is lacking. Whether Mozart's behaviour was nothing more than a reflection of his unique personality or a more complex neurological disorder, aggravated later in life by enormous demands by his father and society, his behaviour has been the subject of many biographies. It will also remain unknown to what extent his accomplishments and failures were shaped by his childhood experiences, pressured lifestyle, and his innate genius and extraordinary talent. Lessons from his life may have important implications for other gifted individuals and savants whose special attributes may lead them to succeed or, on the other hand, suppress their emotional growth and make them more vulnerable to stress and failure.