High prevalence of self-reported non-motor symptoms and lack of correlation with motor severity in adult patients with idiopathic isolated dystonia.

BACKGROUND: Although abnormal movements and postures are the hallmark of dystonia, non-motor symptoms (NMS) are common and negatively affect quality of life. OBJECTIVES: The aim of this study was to screen dystonia patients for NMS and analyze their association with clinical parameters, including motor disability. METHODS: Adult patients with idiopathic isolated dystonia were interviewed and examined. Dystonia severity was evaluated with the Fahn-Marsden Dystonia Rating Scale and the presence of NMS was assessed using a list of 29 complaints. RESULTS: A hundred and two patients (63.7% female) were enrolled. Dystonia began after 20 years of age in 61.8% and was focal or segmental in 82.8% of patients. Only eight patients (7.8%) had no NMS and 59.8% reported more than five. The most prevalent NMS were pain (72.5%) and anxiety (63.7%), followed by difficulty recalling information (44.1%), sadness/anhedonia (41.2%), and difficulty falling asleep (38.2%). No correlation was found between the total number of NMS and dystonia severity (p = 0.18) or regular botulinum toxin use (p = 0.66). The majority of NMS domains correlated with each other. CONCLUSIONS: Our results confirm a high prevalence of NMS among dystonia patients, even in those with mild motor disability. The pathophysiology of NMS in dystonia remains to be completely understood.

The prevalence of PRKRA mutations in idiopathic dystonia.

INTRODUCTION: DYT-PRKRA (DYT16) is considered a rare cause of dystonia-parkinsonism. The significance of this gene as a cause of dystonia and its phenotypical characterization must be determined in larger cohorts. We aimed to investigate the role of PRKRA in patients with dystonia. METHODS: We sequenced PRKRA in 153 unrelated Brazilian patients with idiopathic dystonia. The frequency of novel missense variants was investigated in healthy Brazilian controls and in public databases. Homozygosity in the PRKRA region was assessed through polymorphic markers. RESULTS: PRKRA variants were identified in seven probands with isolated dystonia, including a novel c.C795A variant in compound heterozygosity with the previously described c.C665T variant. Heterozygosity in the gene region was observed in two probands who were homozygous for c.C665T, indicating that this mutation originated from independent events, suggesting a hotspot. CONCLUSION: PRKRA is not an unusual cause of idiopathic dystonia. In this cohort, it was responsible for 4.5% of the total of cases (4.9% of the isolated dystonia cases). The most common phenotype was early-onset isolated focal dystonia followed by generalization, parkinsonism was not observed. This is first report of PRKRA causing adulthood-onset dystonia. Screenings of large cohorts are recommended to investigate the role of this gene in isolated dystonia, as well as in dystonia-parkinsonism cases worldwide.

Screening of GNAL variants in Brazilian patients with isolated dystonia reveals a novel mutation with partial loss of function.

GNAL was identified as a cause of dystonia in patients from North America, Europe and Asia. In this study, we aimed to investigate the prevalence of GNAL variants in Brazilian patients with dystonia. Ninety-one patients with isolated idiopathic dystonia, negative for THAP1 and TOR1A mutations, were screened for GNAL variants by Sanger sequencing. Functional characterization of the Gαolf protein variant was performed using the bioluminescence resonance energy transfer assay. A novel heterozygous nonsynonymous variant (p. F133L) was identified in a patient with cervical and laryngeal dystonia since the third decade of life, with no family history. This variant was not identified in healthy Brazilian controls and was not described in 63,000 exomas of the ExAC database. The F133L mutant exhibited significantly elevated levels of basal BRET and severely diminished amplitude of response elicited by dopamine, that both indicate substantial functional impairment of Gαolf in transducing receptor signals, which could be involved in dystonia pathophysiology. GNAL mutations are not a common cause of dystonia in the Brazilian population and have a lower prevalence than THAP1 and TOR1A mutations. We present a novel variant that results in partial Gαolf loss of function.

Novel THAP1 variants in Brazilian patients with idiopathic isolated dystonia.

THAP1 mutations are associated with idiopathic isolated dystonia in different ethnicities, but the importance of this gene as a cause of dystonia in the Brazilian population has not been determined. The aim of this study was to investigate the prevalence of THAP1 variants in Brazilian patients with idiopathic dystonia and to describe their clinical characteristics including non-motor symptoms. One hundred and ten unrelated patients with non-TOR1A (DYT1) idiopathic isolated dystonia and family members were evaluated and screened for genetic variants. Variants with a potential pathological role were observed in 9.0% of families studied, of which four were novel. The variants were identified in approximately 12% of patients with the age of onset below 40 years. In most of the patients, the onset of the disease was before early adulthood. The upper limb was the most common site of the onset, and approximately half of the patients had dysphonia. Pain, anxiety, and sleep-onset insomnia were the most prevalent non-motor symptoms, and their prevalence was not different from that observed in THAP1-negative patients. Therefore, THAP1 variants are an important cause of dystonia among individuals with an early-onset disease and a positive family history. The phenotypical heterogeneity among patients carrying similar variants shows that other factors may be modulating the disease.

Cor pulmonale in a patient with Brown-Vialetto-Van Laere syndrome: a case report.

Brown-Vialetto-Van Laere syndrome (BVVLS) is a rare neurological disease characterized by sensorineural hearing loss and multiple cranial nerve palsies, usually involving the VIIth and IXth to XIIth cranial nerves. We describe the clinical and pathological features of a 33-year-old woman with BVVLS. The patient developed progressive exertional dyspnea, with clinical and laboratory findings of right-sided heart failure and pulmonary hypertension. She developed status epilepticus in the setting of cardiac deterioration and respiratory infection, and died of cardiogenic and septic shock. Autopsy disclosed bilateral neuronal loss and gliosis in the inferior colliculi, locus coeruleus and facial and vestibular nuclei. Cor pulmonale is a complication of hypoventilation-induced hypoxia and hypercapnia and had not yet been reported in BVVLS.

Risk factors for depression in truck drivers.

OBJECTIVE: Depression is a major public health problem. Work stress is associated with depression and workers whose jobs impose high levels of psychological demands, such as truck drivers, may be at increased risk. The aim of this study was to investigate the prevalence and correlates of depression in truck drivers. METHOD: This was a cross-sectional study of 300 male truck drivers. Presence and severity of depression were assessed by the Mini International Neuropsychiatric Interview followed by the Beck Depression Inventory Short Form. Relevant demographic, clinical and occupational data were collected using a purpose-built questionnaire. RESULTS: The prevalence of depression among truck drivers was 13.6%. Multivariate analysis showed that being 45 years or older had a protective effect (OR=0.19; P=0.02), whereas low educational level (OR=3.03; P=0.01), use of stimulants (OR=5.03; P<0.01) and wage-earning (OR=2.84; P=0.01), as opposed to self-employment, increased the risk for depression. CONCLUSIONS: Truck drivers are at increased risk for depression when compared to the general population. Efforts to increase awareness of this problem and to limit the use of stimulants, as well as measures to improve job satisfaction, particularly among the wage-earning drivers, may have a positive impact on mental health in these workers.

Risk factors for pulmonary complications after emergency abdominal surgery.

OBJECTIVE: Pulmonary complications are common after abdominal surgery. Although a variety of risk factors have been described for these complications, studies so far have focused on elective interventions. The aim of this study was to determine the incidence and predictors of pulmonary complications following emergency abdominal surgery. METHODS: This was a prospective cohort study. Pre and intra-operative data were collected through interview and chart review and their association with the occurrence of postoperative pulmonary complications (PPC) were analyzed. RESULTS: Two hundred and sixty-six consecutive adult patients were included and seventy-five (28.2%) developed PPC. Age >50 years (adjusted OR=3.86; P<0.001), body mass index (BMI) <21 kg/m(2) or 30 kg/m(2) (adjusted OR=2.43; P=0.007) and upper or upper/lower abdominal incision (adjusted OR=2.57; P=0.027) were independently associated with PPC. Patients submitted to multiple procedures tended to be at a higher risk for PPC (adjusted OR=1.73; P=0.079). The development of PPC was associated with prolonged hospital stay (P<0.001) and increased death rate (P<0.001). CONCLUSIONS: Pulmonary complications are frequent among patients undergoing abdominal emergency surgery and lead to increased length of hospital stay and death rate. Older age, abnormal BMI, upper or upper/lower abdominal incision and multiple procedures are predictors of PPC in this setting.

Amantadine reduces the duration of levodopa-induced dyskinesia: a randomized, double-blind, placebo-controlled study.

We evaluated the effects of amantadine on levodopa-induced dyskinesia (LID) in eighteen consecutive Parkinson's disease (PD) patients in a randomized, double-blind, placebo-controlled study. The primary outcomes were the Clinical Dyskinesia Rating Scale (CDRS) and the Unified Parkinson's Disease Rating Scale (UPDRS) part IVa score changes. The secondary outcomes were the UPDRS II and III score changes. Amantadine did not change the CDRS score for hyperkinesia or dystonia, but decreased the duration of LID and its influence on daily activities (p=0.04) and the UPDRS II score (p=0.01) more than placebo. These findings show that amantadine reduces the duration of LID and improves motor disability in PD.

Swallowing abnormalities and dyskinesia in Parkinson's disease.

Gastrointestinal abnormalities in Parkinson's disease (PD) have been known for almost two centuries, but many aspects concerning their pathophysiology have not been completely clarified. The aim of this study was to characterize the oropharyngeal dynamics in PD patients with and without levodopa-induced dyskinesia. Fifteen dyskinetic, 12 nondyskinetic patients, and a control group were included. Patients were asked about dysphagia and evaluated with the Unified Parkinson's Disease Rating Scale Parts II and III and the Hoehn and Yahr scale. Deglutition was assessed using modified barium swallow with videofluoroscopy. Nondyskinetic patients, but not the dyskinetic ones, showed less oropharyngeal swallowing efficiency (OPSE) for liquid food than controls (Dunnett, P = 0.02). Dyskinetic patients tended to have a greater OPSE than nondyskinetic (Dunnett, P = 0.06). Patients who were using a higher dose of levodopa had a greater OPSE and a trend toward a smaller oral transit time (Pearson's correlation, P = 0.01 and 0.08, respectively). Neither the report of dysphagia nor any of the PD severity parameters correlated to the videofluoroscopic variables. In the current study, dyskinetic patients performed better in swallowing function, which could be explained on the basis of a greater levodopa dose. Our results suggest a role for levodopa in the oral phase of deglutition and confirm that dysphagia is not a good predictor of deglutition alterations in PD.

Snoring and excessive daytime sleepiness in Parkinson's disease.

Recent recognition of daytime sleepiness in Parkinson's disease (PD) has prompted a search for its causes. Sleepy patients may be more susceptible to sleep attacks after the use of dopamine agonists and the recognition of sleep disturbances in PD may influence important therapeutic decisions. To identify clinical factors influencing excessive daytime sleepiness (EDS) and sleep complaints in PD, we studied 86 consecutive patients with clinical diagnosis of PD using a sleep questionnaire, the Epworth Sleepiness Scale, the Unified Parkinson's Disease Rating Scale and the Montgomery and Asberg Depression Rating Scale. Patients with cognitive dysfunction were not included in the study. We found that 49 patients (53.3%) had insomnia, 45 (49.9%) restless legs syndrome (RLS), 51 (55.4%) vivid dreams, 61 (71.8%) snoring and 29 (31.5%) had EDS. RLS was more frequent in patients with longer duration of illness. Snoring was the most important risk factor associated with EDS (OR=3.64, 95% CI=1.11-11.9, P=0.03) and a marginal association between motor dysfunction and EDS was observed (OR=1.06, 95% CI=1.00-1.12, P=0.05).