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.

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.

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.

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.

Treatment options for chorea.

INTRODUCTION: Chorea is defined as jerk-like movements that move randomly from one body part to another. It is due to a variety of disorders and although current symptomatic therapy is quite effective there are few etiology- or pathogenesis-targeted therapies. The aim of this review is to summarize our own experience and published evidence in the treatment of chorea. Areas covered: After evaluating current guidelines and clinical practices for chorea of all etiologies, PubMed was searched for the most recent clinical trials and reviews using the term 'chorea' cross referenced with specific drug names. Expert commentary: Inhibitors of presynaptic vesicular monoamine transporter type 2 (VMAT2) that cause striatal dopamine depletion, such as tetrabenazine, deutetrabenazine, and valbenazine, are considered the treatment of choice in patients with chorea. Some clinicians also use dopamine receptor blockers (e.g. antipsychotics) and other drugs, including anti-epileptics and anti-glutamatargics. 'Dopamine stabilizers' such as pridopidine and other experimental drugs are currently being investigated in the treatment of chorea. Deep brain stimulation is usually reserved for patients with disabling chorea despite optimal medical therapy.

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.

Psychogenic (functional) parkinsonism.

Psychogenic parkinsonism (PP), although often quite disabling, is one of the least commonly reported subtypes of psychogenic movement disorders. There are certain features that help distinguish PP from idiopathic Parkinson's disease, such as abrupt onset, early disability, bilateral shaking and slowness, nondecremental slowness when performing repetitive movements, voluntary resistance against passive movement without cogwheel rigidity, distractibility, "give-way" weakness, stuttering speech, bizarre gait, and a variety of behavioral symptoms. While the diagnosis of PP is clinical, functional imaging evaluating the integrity of nigrostriatal pathways can help distinguish PP from other types of parkinsonism. PP can coexist in patients with organic parkinsonism, adding to the challenge of making a diagnosis of PP. Being cognizant of the clinical signs of psychogenic movement disorders, including PP, will lead to earlier diagnosis and hopefully improved outcomes.

Metabolic syndrome in patients with chronic obstructive pulmonary disease: frequency and relationship with systemic inflammation.

BACKGROUND: Metabolic syndrome (MetS) is frequent in patients with chronic obstructive pulmonary disease (COPD). Systemic inflammation plays an important role in both COPD and MetS. The aim of this study was to assess the frequency of MetS in COPD patients and to evaluate the status of systemic inflammation in COPD patients with MetS and those without MetS. METHODS: This cross-sectional study included 98 consecutive stable COPD patients. The MetS was defined using the criteria of the International Diabetes Federation. Components of MetS and markers of systemic inflammation: C-reactive protein (CRP), fibrinogen, and leukocyte count were measured. All patients underwent spirometry. The staging of COPD was made according to the Global initiative for chronic obstructive lung disease (GOLD) criteria. RESULTS: MetS was present in 37.8 % COPD patients. The frequencies of MetS in patients with GOLD stages I, II, III, and IV were 33.3 %, 48.8 %, 31.6 %, and 23.1 %, respectively. MetS frequencies were not significantly different between GOLD stages. The multivariate logistic regression analysis revealed leukocyte count and CRP level as significant independent predictors of the presence of Mets in COPD patients (OR =1.321, 95%CI: 1.007-1.628, p =0.009 and OR =1.184, 95%CI: 1.020-1.376, p =0.027 respectively). CONCLUSIONS: This study shows that MetS is frequent in patients with COPD. Systemic inflammatory markers are higher in COPD patients with MetS than in patients without MetS. These findings suggest that physicians should screen COPD patients for associated MetS and elevated circulatory inflammatory markers. Management of these disorders should reduce the risk of cardiovascular morbidity and mortality in these patients. Hippokratia 2016, 20(2):110-114.

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.

Discrimination and Romani health: a validation study of discrimination scales among Romani women in Macedonia and Serbia.

OBJECTIVES: Scales used to assess discrimination in public health research have rarely been validated outside of high income countries. Our objective was to validate the Experiences of Discrimination (EOD) scale and the Everyday Discrimination Scale (EDS) among 410 Romani women in Macedonia and Serbia. METHODS: Romani female interviewers conducted interviews in 2012-2013. We used a multiple indicator multiple cause approach to test a one-factor model for each scale and to assess differential item functioning (DIF) by age, wealth, country, and education. We also measured associations between the EOD and EDS with smoking in the past year and psychological distress. RESULTS: Three items of the EOD were conceptually irrelevant. Two items of the EDS were not conditionally independent. DIF was found by country for one item in each scale. After excluding these items, all scales exhibited good model fit and were associated with smoking (EOD beta = 0.40, 95% CI = 0.18, 0.63; EDS beta = 0.33, 95% CI = 0.12, 0.54) and psychological distress (EOD beta = 0.26, 95% CI = 0.15, 0.37; EDS beta = 0.26, 95% CI = 0.04, 0.47). CONCLUSIONS: Discrimination scales can be adapted for use among Romani women and are associated with both smoking and psychological distress.

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.

Continuous in-home monitoring of essential tremor.

BACKGROUND: Essential tremor (ET) is typically measured in the clinic with subjective tremor rating scales which require the presence of a clinician for scoring and are not appropriate for measuring severity throughout the day. Motion sensors can accurately rate tremor severity during a set of predefined tasks in a laboratory. METHODS: We evaluated the ability of motion sensors to quantify tremor during unconstrained activities at home. 20 ET subjects wore a wireless sensor continuously for up to 10 h daily on two days and completed hourly standardized tremor assessments involving pre-defined tasks. Mathematical models were used to predict tremor rating scores from the sensor data. RESULTS: At home tremor scores from hourly standardized assessments correlated with at home tremor scores estimated during unconstrained activities immediately following the standardized assessments. The hourly standardized assessments did not significantly fluctuate throughout the day, while fluctuations in the continuous assessments tended to follow changes in voluntary activity level. Both types of tremor ratings (standardized and continuous) showed high day-to-day test-retest reliability with intraclass correlation coefficients ranging from 0.67 to 0.90 for continuous ratings and 0.77 to 0.95 for standardized ratings. CONCLUSIONS: Results demonstrate the feasibility of continuous monitoring of tremor severity at home, which should provide clinicians with a measure of the temporal pattern of tremor in the context of daily life and serve as a useful tool for the evaluation of novel anti-tremor medications in clinical trials.

Mobility, mood and site of care impact health related quality of life in Parkinson's disease.

OBJECTIVE: Examine the correlates of Health Related Quality of Life (HRQL) in a large cohort of Parkinson's disease (PD) patients from National Parkinson Foundation (NPF) Centers of Excellence (COEs). BACKGROUND: Improving outcomes for PD will depend upon uncovering disease features impacting HRQL to identify targets for intervention and variables for risk-adjustment models. Differences in HRQL outcomes between COEs could uncover modifiable aspects of care delivery. METHODS: This cross-sectional study examined the relative contribution of demographic, social, clinical and treatment features potentially related to HRQL, as measured by the PDQ-39, in 4601 consecutive subjects from 18 COEs. Stepwise linear regression was utilized to identify correlates of HRQL. RESULTS: The variability in the PDQ-39 summary index score correlated with H&Y stage (R(2) = 22%), Timed up and Go (TUG) (17%), disease duration (11%), comorbidities (8%), cognitive status (8%), antidepressant use (6%) and center at which a patient received care (5%). Stepwise regression reordered the importance of the variables, with the H&Y first and TUG and the center becoming equal and the second most important variables determining the PDQ-39 total score. All independent variables together accounted for 44% of the variability in HRQL. CONCLUSIONS: We confirmed many but not all HRQL associations found in smaller studies. A novel observation was that the site of care was an important contributor to HRQL, suggesting that comparison of outcomes and processes among centers may identify best practices.

Trauma and suicidality in war affected communities.

PURPOSE: The aim was to assess whether experiences of war trauma remain directly associated with suicidality in war affected communities when other risk factors are considered. MATERIALS AND METHODS: In the main sample 3313 participants from former Yugoslavia who experienced war trauma were recruited using a random sampling in five Balkan countries. In the second sample 854 refugees from former Yugoslavia recruited through registers and networking in three Western European countries. Sociodemographic and data on trauma exposure, psychiatric diagnoses and level of suicidality were assessed. RESULTS: In the main sample 113 participants (3.4%) had high suicidality, which was associated with number of potentially traumatic war experiences (odds ratio 1.1) and war related imprisonment (odds ratio 3) once all measured risk factors were considered. These associations were confirmed in the refugee sample with a higher suicidality rate (10.2%). DISCUSSION AND CONCLUSIONS: Number of potentially traumatic war experiences, in particular imprisonment, may be considered as a relevant risk factor for suicidality in people affected by war.

Childhood stiff-person syndrome improved with rituximab.

INTRODUCTION: Stiff-person syndrome (SPS) is manifested by fluctuating rigidity of axial musculature with painful episodic spasms due to simultaneous co-contraction of agonist and antagonist muscles. We present a case report and video illustrating response to treatment with rituximab. MATERIALS AND METHODS: Case description and video are provided. A literature search for other reports of treatment with rituximab was performed. RESULTS: Nine cases in addition to our case were described. Substantial clinical benefit was reported in 7/9 (78%) cases. Four out of 9 (44%) cases displayed persistent anti-glutamic acid decarboxylase (GAD) antibody positivity. CONCLUSION: Rituximab is an important treatment strategy in SPS. The persistence of anti-GAD antibody positivity even with clinical remission remains to be elucidated.

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.

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.

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.