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Adult onset idiopathic dystonia (AOID) is the third most common movement disorder in adults. Co-existing depressive symptoms and disorders represent major contributors of disability and quality of life in these patients, but their prevalence remains unclear. We investigated the point prevalence of supra-clinical threshold depressive symptoms/depressive disorders in AOID in a systematic review with qualitative synthesis and meta-analysis. Our search identified 60 articles suitable for qualitative synthesis and 54 for meta-analysis. The overall pooled prevalence of either supra-clinical threshold depressive symptoms or depressive disorders was 31.5 % for cervical dystonia, 29.2 % for cranial dystonia, and 33.6 % for clinical samples with mixed forms of AOID. Major depressive disorder was more prevalent than dysthymia in cervical dystonia, whereas dysthymia was more prevalent in cranial dystonia. In cervical dystonia, the prevalence of supra-clinical threshold depressive symptoms screened by rating scales was higher than that of depressive disorders diagnosed with structured interviews. Prevalence studies using rating scales yielded higher heterogeneity. More research is warranted to standardize screening methodology and characterization of mood disorders in AOID.

Cellular and molecular mechanisms involving immune-competent cells can modulate normal brain development, influencing the genesis, refinement, and maintenance of neural circuits. There is increasing evidence in support of the contribution of an early immune priming to the abnormal trajectories of maturation of cortico-subcortical circuits associated with the generation of tics. During postnatal life, the hyperreactivity of systemic immune pathways and neuroinflammation may contribute to natural fluctuations of the behavioral features manifesting in Tourette syndrome and related disorders. Moreover, abnormalities in the parallel development of neural and immune systems, as well as in stress responses, are reflected in the higher risk of autoimmune and allergic illnesses in people with these neurodevelopmental disorders. There is still limited knowledge regarding the efficacy of direct and indirect immune-modulatory interventions in the treatment of these disorders. There are also limitations in knowledge of the key molecular pathways associated with gut dysbiosis that can influence neuroimmune interactions in these disorders. This chapter provides an up-to-date summary of the existing knowledge around these themes, highlighting existing gaps that need to be addressed by future research in order to develop breakthrough, disease-modifying, immunological, hormonal, and microbiota-based therapeutic interventions.

Several associations between patients with infections, particularly group A streptococcal (GAS) infections, and subsequent tics and obsessive–compulsive symptoms have been established in population-based studies, suggesting at least a nonspecific role of infections in a subgroup of patients with tics. Expanding the clinical entity of pediatric autoimmune neuropsychiatric disorders associated with streptococcus, a broader spectrum named pediatric acute-onset neuropsychiatric syndromes (PANS) has been proposed, which encompasses phenotypes dominated by obsessive–compulsive symptoms or eating behavior abnormalities and includes tics as accompanying features. PANS are defined by the temporal course but are not limited to post-infectious etiologies. In chronic tic disorders, GAS infections do not seem to be a major determinant of tic exacerbations, although a potential interactive effect with psychosocial stress cannot be excluded. The role of other pathogens in influencing course and onset of tic disorders remains uncertain. The complex interaction of patient-specific attributes (neurochemical and immune vulnerability genes leading to maladaptive neuropsychiatric or immune function) with environmental attributes (psychosocial stress, injuries, substance exposures, and pathogen-specific properties) creates an interesting and ongoing research challenge.

BACKGROUND AND PURPOSE Clinically relevant anxiety and anxiety disorders are commonly associated with adult-onset isolated dystonia, contributing substantially to quality-of-life impairment in patients with this movement disorder. However, the prevalence of anxiety symptoms and disorders in adult-onset isolated dystonia remains unclear. We aimed to conduct a systematic review and meta-analysis of the prevalence of anxiety symptoms/disorders in adult-onset isolated dystonia. METHODS Studies reporting the prevalence of anxiety disorders determined through diagnostic interviews or from clinically relevant anxiety symptoms detected with rating scales were identified in three databases (MEDLINE, EMBASE and PsycINFO). The gray literature was also examined to detect studies not captured through the search strategy. RESULTS The search strategy yielded 6535 citations; 34 studies met the inclusion criteria. The overall prevalence of clinically relevant anxiety symptoms and anxiety disorders for cervical dystonia was 40% (95% confidence interval [CI] 20% to 60%); for studies examining cranial dystonia it was 25% (95% CI 21% to 30%); for studies exploring mixed populations of adult-onset isolated dystonia it was 33.3% (95% CI 22% to 43%), 26% (95% CI 12% to 40%) for laryngeal dystonia, and 32% (95% CI 21% to 43%) for upper limb dystonia. Social phobia was the most prevalent anxiety disorder across the different forms of adult-onset isolated dystonia. Between-study statistical heterogeneity was high for most prevalence estimates. CONCLUSIONS Clinically relevant anxiety and anxiety disorders are common across all forms of adult-onset isolated dystonia. New research avenues should explore and plan the development of pathways of care targeting these important non-motor features.

Background Normosmic Parkinson's disease (PD) might be a unique clinical phenotype with a more benign course when compared with hyposmic PD. Objective The objective of this study was to evaluate motor features and the acute levodopa response according to olfactory function. Methods A total of 169 de novo PD patients that underwent olfactory testing and acute levodopa challenge for clinical prediction of sustained long-term dopaminergic response were evaluated. Results The overall frequency of normosmia was 33%. Normosmic PD patients scored nonsignificantly different to hyposmic/anosmic patients on motor scale and on degree of improvement with levodopa. Motor scores at follow-up were comparable among groups. Conclusions Normal olfactory function is common in early PD and was not associated with a different motor phenotype when compared with PD patients with olfactory dysfunction. © 2016 International Parkinson and Movement Disorder Society

Fil: Terroba Chambi, Cinthia. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Fil: Terroba Chambi, Cinthia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Terroba Chambi, Cinthia. Fleni. Departamento de Neurociencias; Argentina Fil: Bruno, Veronica. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Fil: Bruno, Veronica. Fleni. Departamento de Neurociencias; Argentina Fil: Bruno, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Medina Escobar, Alex. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Fil: Medina Escobar, Alex. Fleni. Departamento de Neurociencias; Argentina Fil: Nanni, Federico. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Fil: Nanni, Federico. Fleni. Departamento de Neurociencias; Argentina Fil: Cerquetti, Daniel. Fleni. Departamento de Neurociencias; Argentina Fil: Cerquetti, Daniel. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Fil: Rossi, Malco Damián. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Fil: Rossi, Malco Damián. Fleni. Departamento de Neurociencias; Argentina Fil: Merello, Marcelo. Fleni. Departamento de Neurociencias; Argentina Fil: Merello, Marcelo. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Fil: Merello, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Abstract: Objective - To determine the utility of an electronic diary for registering motor fluctuations and dyskinesia in Parkinson disease (PD). Methods - Free, open-access touch screen software suitable for Android 4.4 or higher, with medication alarms, adjustable intervals, and medication dose settings was developed to evaluate ON-OFF periods and dyskinesia. Prospective evaluation included a first phase conducted to make adjustments concerning motor limitations when using the tablet, as well as for proper motor complication identification, and a second phase of 3 days of use at home with a prior diary training session comparing a modified paper version of Core Assessment Program for Surgical Interventional Therapies in PD and the electronic diary. Results - All patients correctly identified ON-OFF periods and dyskinesia. Rater/patient matching ON-OFF fluctuations ranged between 94% and 100% for evaluations of different motor states. Dyskinesia matching percentage was 100% for patients with dyskinesia interfering with activities of daily living and 88% for those who reported no-interference. No significant differences between paper and electronic diaries were identified when reporting ON-OFF motor states or in the number of errors when filling the diaries. Conclusions - This electronic motor diary proved to be reliable for ON-OFF state and dyskinesia identification and classification. However, no advantage to paper diary has been observed in terms of number of erroneous entries. Based on these results, to improve home motor fluctuations, detection efforts should be directed toward the development of automatic wearable devices rather than digital versions of current available ON-OFF diaries.

Dear EditorPhosphomannomutase-2 deficiency-congenital disorder of glycosylation (PMM2-CDG), congenital disorder of glycosylation type-Ia or Jaeken syndrome (MIM #601785) is an autosomal recessive inherited condition of abnormal glycosylation of N-linked oligosaccharides [1]. Disease course is variable, ranging from infantile forms with multisystem involvement and a childhood-adult ataxia-intellectual disability type with neurologic stable form [1,2]. The phenotypic spectrum includes morphological abnormalities, ataxia, developmental delay, strabismus, retinopathy, seizures, stroke-like episodes, peripheral neuropathy, hypergonadotropic hypogonadism and thrombotic events [2,3]. Brain imaging displays cerebellar and brainstem atrophy. We describe two sisters with PMM2-CDG that present with cervical dystonia that to our knowledge has not been previously reported.Thirty-three and 30-year-old sisters born to non-consanguineous healthy parents of Spanish-Italian ancestry were studied. There was no other remarkable family history (Fig. 1).Both patients were the product of an uneventful pregnancy with no delivery complications. At 4 months of age, patient III:3 showed a developmental delay. At three years-old, unsteady gait was detected. Strabismus was surgically treated. At the age of five years, action limb incoordination and tremor were recognized and from ten to twenty-one years of age, axial and appendicular ataxia increased. Since then, she began to experience progressive abnormal twisted and sustained posture of the neck with slight jerks. Currently, she is in part-time employment as assistant in a bakery and performs all activities of daily living unaided. On physical examination, she presented slight dysarthria, moderate intellectual disability, slight strabismus, abnormal subcutaneous fat tissue distribution around the hips and upper thighs, kyphoscoliosis, absent deep tendon reflexes in legs and mild limb and gait ataxia. A mild dystonic posture in both hands with dystonic tremor was also present. Slight head rotation and laterocollis to the right, mild retrocollis and dystonic jerks were present (Supplementary video 1). She obtained partial relief by sensory tricks. She denied previous exposure to neuroleptics or other drugs that can induce dystonia.Index patient III:4 showed failure to thrive and developmental delay from approximately three months of age and delayed language and unsteady gait were detected at two years-old. Axial and appendicular ataxia increased over the past ten years. On physical examination, she displayed moderate dysarthria and intellectual disability, large ears, nystagmus and mild limb and gait ataxia. A slight cervical anterior shift on the sagittal plane was observed (Supplementary video 1). No hand dystonia was present.Both patients shared the presence of hypergonadotropic hypogonadism and osteopenia. None had multisystemic affectation, seizures, retinopathy, stroke-like episodes, thromboembolic events or inverted nipples.Patient III:3 received clonazepam at 0.5 mg daily, which reduced significantly dystonic tremor in both hands. Trihexyphenidyl and levodopa (up to 1000 mg/day) were tried for six months without improvement of dystonia. Onabotulinum toxin A injections were applied to patient III:3 in seven occasions with partial but acceptable alleviation of cervical dystonia. Total Toronto Western Spasmodic Torticollis Rating Scale scores improved from 23 (worst) to 11 (best) points in the last and most effective application. Treatment in patient III:4 was not necessary due to minor affectation.Liver and renal function, antithrombin III levels, prothrombin time and immunoglobulin-A and G levels were normal in both patients. Brain MRI in patient III:3 revealed marked cerebellar and brainstem atrophy (Fig. 2). Fil: Rossi, Malco Damián. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Medina Escobar, Alex. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Ameghino, Lucia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Merello, Marcelo Jorge. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Weight loss is a multifactorial disorder commonly affecting Parkinson?s disease patients. The aim of this study was to investigate the relationship between body weight, nutritional status, physical activity, and Parkinson?s disease-related factors. A total of 114 consecutive Parkinson?s disease patients without dietary restrictions were evaluated prospectively with respect to: nutritional status (Mini Nutritional Assessment), physical activity level (Yale Physical Activity Survey), MDS-UPDRS score, olfactory function, depression, cognitive functionand impulse-control disorders, among other variables. Structural equation modeling was used to build multivariate models and to calculate standardized regression weights (srw) for pairs of variables, which are homologous to correlation coefficients, taking into account the effects of all other variables in the model. Sixty (53%) patients were males. Mean age was 66.1 ± 9.8 years and mean disease duration was 8.3 ± 5.6 years. Longer disease duration was negatively related to nutritional status (srw = −0.25; p = 0.01). UPDRS II + III score was associated with reduced cognitive function (srw = −0.39; p = 0.01), which was positivelyrelated to nutritional status (srw = 0.23; p = 0.01). Finally, nutritional status was positively related to body weight (srw = 0.22, p

Autosomal‐dominant progressive external ophthalmoplegia type 1 (adPEO1) is characterized by slowly progressive ophthalmoplegia. It can be caused by mutations in different genes, including the mitochondrial DNA polymerase γ (POLG), which results in heterogeneous clinical phenotypes associated with progressive external ophthalmoplegia, including myoclonic epilepsy,1 parkinsonism,2 and ataxia3 (Table 1). Other additional features may include premature ovarian failure and hypogonadism.2 POLG mutations causing adPEO1 can have both autosomal‐dominant or ‐recessive inheritance traits.4 Dystonia has been observed in patients with POLG mutations,5-7 however, to our knowledge, not in adPEO1. Here, we describe the first adPEO1 patient attributed to a POLG mutation showing dystonia as the presenting and core clinical feature. Fil: Rossi, Malco Damián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Medina Escobar, Alex. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Radrizzani Helguera, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina Fil: Tenembaum, Silvia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Perandones, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; Argentina Fil: Merello, Marcelo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina