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BACKGROUND: We describe a 4-generation Dutch pedigree with a unique dominantly inherited clinical phenotype of a combined progressive chorea and cervical dystonia carrying a novel heterozygous dopamine D2 receptor (DRD2) variant. OBJECTIVES: The objective of this study was to identify the genetic cause of the disease and to further investigate the functional consequences of the genetic variant. METHODS: After detailed clinical and neurological examination, whole-exome sequencing was performed. Because a novel variant in the DRD2 gene was found as the likely causative gene defect in our pedigree, we sequenced the DRD2 gene in a cohort of 121 Huntington-like cases with unknown genetic cause (Germany). Moreover, functional characterization of the DRD2 variant included arrestin recruitment, G protein activation, and G protein-mediated inhibition of adenylyl cyclase determined in a cell model, and G protein-regulated inward-rectifying potassium channels measured in midbrain slices of mice. RESULT: We identified a novel heterozygous variant c.634A > T, p.Ile212Phe in exon 5 of DRD2 that cosegregated with the clinical phenotype. Screening of the German cohort did not reveal additional putative disease-causing variants. We demonstrated that the D2S/L -I212 F receptor exhibited increased agonist potency and constitutive activation of G proteins in human embryonic kidney 239 cells as well as significantly reduced arrestin3 recruitment. We further showed that the D2S -I212 F receptor exhibited aberrant receptor function in mouse midbrain slices. CONCLUSIONS: Our results support an association between the novel p.Ile212Phe variant in DRD2, its modified D2 receptor activity, and the hyperkinetic movement disorder reported in the 4-generation pedigree. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Coreia , Distonia , Animais , Coreia/genética , Mutação com Ganho de Função , Alemanha , Camundongos , Fenótipo , Receptores de Dopamina D2/genéticaRESUMO
Cervical dystonia is a neurological disorder characterized by sustained, involuntary movements of the head and neck. Most cases of cervical dystonia are idiopathic, with no obvious cause, yet some cases are acquired, secondary to focal brain lesions. These latter cases are valuable as they establish a causal link between neuroanatomy and resultant symptoms, lending insight into the brain regions causing cervical dystonia and possible treatment targets. However, lesions causing cervical dystonia can occur in multiple different brain locations, leaving localization unclear. Here, we use a technique termed 'lesion network mapping', which uses connectome data from a large cohort of healthy subjects (resting state functional MRI, n = 1000) to test whether lesion locations causing cervical dystonia map to a common brain network. We then test whether this network, derived from brain lesions, is abnormal in patients with idiopathic cervical dystonia (n = 39) versus matched controls (n = 37). A systematic literature search identified 25 cases of lesion-induced cervical dystonia. Lesion locations were heterogeneous, with lesions scattered throughout the cerebellum, brainstem, and basal ganglia. However, these heterogeneous lesion locations were all part of a single functionally connected brain network. Positive connectivity to the cerebellum and negative connectivity to the somatosensory cortex were specific markers for cervical dystonia compared to lesions causing other neurological symptoms. Connectivity with these two regions defined a single brain network that encompassed the heterogeneous lesion locations causing cervical dystonia. These cerebellar and somatosensory regions also showed abnormal connectivity in patients with idiopathic cervical dystonia. Finally, the most effective deep brain stimulation sites for treating dystonia were connected to these same cerebellar and somatosensory regions identified using lesion network mapping. These results lend insight into the causal neuroanatomical substrate of cervical dystonia, demonstrate convergence across idiopathic and acquired dystonia, and identify a network target for dystonia treatment.
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Encéfalo/patologia , Rede Nervosa/fisiopatologia , Vias Neurais/fisiopatologia , Torcicolo/fisiopatologia , Adulto , Idoso , Gânglios da Base/fisiopatologia , Encéfalo/fisiopatologia , Cerebelo/fisiopatologia , Estudos de Coortes , Conectoma/métodos , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: Trials for additional or alternative treatments for cervical dystonia (CD) are scarce since the introduction of botulinum neurotoxin (BoNT). We performed the first trial to investigate whether dystonic jerks/tremor in patients with CD respond to the selective serotonin reuptake inhibitor (SSRI) escitalopram. METHODS: In a randomised, double-blind, crossover trial, patients with CD received escitalopram and placebo for 6 weeks. Treatment with BoNT was continued, and scores on rating scales regarding dystonia, psychiatric symptoms and quality of life (QoL) were compared. Primary endpoint was the proportion of patients that improved at least one point on the Clinical Global Impression Scale for jerks/tremor scored by independent physicians with experience in movement disorders. RESULTS: Fifty-threepatients were included. In the escitalopram period, 14/49 patients (29%) improved on severity of jerks/tremor versus 11/48 patients (23%) in the placebo period (P=0.77). There were no significant differences between baseline and after treatment with escitalopram or placebo on severity of dystonia or jerks/tremor. Psychiatric symptoms and QoL improved significantly in both periods compared with baseline. There were no significant differences between treatment with escitalopram and placebo for dystonia, psychiatric or QoL rating scales. During treatment with escitalopram, patients experienced slightly more adverse events, but no serious adverse events occurred. CONCLUSION: In this innovative trial, no add-on effect of escitalopram for treatment of CD with jerks was found on motor or psychiatric symptoms. However, we also did not find a reason to withhold patients treatment with SSRIs for depression and anxiety, which are common in dystonia. TRIAL REGISTRATION NUMBER: NTR2178.
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Citalopram/uso terapêutico , Distúrbios Distônicos/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Torcicolo/tratamento farmacológico , Tremor/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Cross-Over , Método Duplo-Cego , Distúrbios Distônicos/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Torcicolo/complicações , Resultado do Tratamento , Tremor/complicaçõesRESUMO
Aminoacylase 1 (ACY1) deficiency is an organic aciduria due to mutations in the ACY1 gene. It is considered much underdiagnosed. Most individuals known to be affected by ACY1 deficiency have presented with neurologic symptoms. We report here a cognitively normal 63-year-old woman who around the age of 12 years had developed dystonic symptoms that gradually evolved into generalized dystonia. Extensive investigations, including metabolic diagnostics and diagnostic exome sequencing, were performed to elucidate the cause of dystonia. Findings were only compatible with a diagnosis of ACY1 deficiency: the urinary metabolite pattern with N-acetylated amino acids was characteristic, there was decreased ACY1 activity in immortalized lymphocytes, and two compound heterozygous ACY1 mutations were detected, one well-characterized c.1057C>T (p.Arg353Cys) and the other novel c.325A>G (p.Arg109Gly). Expression analysis in HEK293 cells revealed high residual activity of the enzyme with the latter mutation. However, following co-transfection of cells with stable expression of the c.1057C>T variant with either wild-type ACY1 or the c.325A>G mutant, only the wild-type enhanced ACY1 activity and ACY1 presence in the Western blot, suggesting an inhibiting interference between the two variants. Our report extends the clinical spectrum of ACY1 deficiency to include dystonia and indicates that screening for organic acidurias deserves consideration in patients with unexplained generalized dystonia.
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Amidoidrolases/deficiência , Erros Inatos do Metabolismo dos Aminoácidos/genética , Distúrbios Distônicos/genética , Mutação , Amidoidrolases/genética , Análise Mutacional de DNA , Feminino , Humanos , Pessoa de Meia-Idade , FenótipoRESUMO
Previous electrophysiological and functional imaging studies in focal dystonia have reported on cerebral reorganization after botulinum toxin (BoNT) injections. With the exception of microstructural changes, alterations in gray matter volume after BoNT have not been explored. In this study, we sought to determine whether BoNT influences gray matter volume in a group of cervical dystonia (CD) patients. We analyzed whole brain gray matter volume in a sample of CD patients with VBM analysis. In patients, scans were repeated immediately before and some weeks after BoNT injections; controls were only scanned once. We analyzed 1) BoNT-related gray matter volume changes within patients; 2) gray matter volume differences between patients and controls; and 3) correlations between gray matter volume and disease duration and disease severity. The pre- and post-BoNT treatment analysis revealed an increase of gray matter volume within the right precentral sulcus, at the lateral border of the premotor cortex. In comparison to healthy controls, CD patients had reduced gray matter volume in area 45 functionally corresponding to the left ventral premotor cortex. No gray matter volume increase was found for CD patients in comparison to controls. Gray matter volume of the left supramarginal gyrus and left premotor cortex correlated positively with disease duration, and that of the right inferior parietal lobule correlated negatively with disease severity. We have identified structural, yet dynamic gray matter volume changes in CD. There were specific gray matter volume changes related to BoNT injections, illustrating indirect central consequences of modified peripheral sensory input. As differences were exclusively seen in higher order motor areas relevant to motor planning and spatial cognition, these observations support the hypothesis that deficits in these cognitive processes are crucial in the pathophysiology of CD.
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Toxinas Botulínicas/farmacologia , Córtex Cerebral/efeitos dos fármacos , Transtornos Cognitivos/tratamento farmacológico , Substância Cinzenta/efeitos dos fármacos , Neurotoxinas/farmacologia , Torcicolo/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Toxinas Botulínicas/administração & dosagem , Córtex Cerebral/patologia , Transtornos Cognitivos/patologia , Feminino , Substância Cinzenta/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora , Neurotoxinas/administração & dosagem , Percepção Espacial , Torcicolo/patologia , Resultado do TratamentoRESUMO
Simple writer's cramp (WC) is a task-specific form of dystonia, characterized by abnormal movements and postures of the hand during writing. It is extremely task-specific, since dystonic symptoms can occur when a patient uses a pencil for writing, but not when it is used for sharpening. Maladaptive plasticity, loss of inhibition, and abnormal sensory processing are important pathophysiological elements of WC. However, it remains unclear how those elements can account for its task-specificity. We used fMRI to isolate cerebral alterations associated with the task-specificity of simple WC. Subjects (13 simple WC patients, 20 matched controls) imagined grasping a pencil to either write with it or sharpen it. On each trial, we manipulated the pencil's position and the number of imagined movements, while monitoring variations in motor output with electromyography. We show that simple WC is characterized by abnormally increased activity in the dorsal premotor cortex (PMd) when imagined actions are specifically related to writing. This cerebral effect was independent from the known deficits in dystonia in generating focal motor output and in processing somatosensory feedback. This abnormal activity of the PMd suggests that the task-specific element of simple WC is primarily due to alterations at the planning level, in the computations that transform a desired action outcome into the motor commands leading to that action. These findings open the way for testing the therapeutic value of interventions that take into account the computational substrate of task-specificity in simple WC, e.g. modulations of PMd activity during the planning phase of writing.
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Distúrbios Distônicos/patologia , Distúrbios Distônicos/reabilitação , Córtex Motor/fisiopatologia , Desempenho Psicomotor/fisiologia , Redação , Adulto , Fenômenos Biomecânicos , Mapeamento Encefálico , Estudos de Casos e Controles , Eletromiografia , Feminino , Lateralidade Funcional , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/irrigação sanguínea , Movimento , Força Muscular/fisiologia , Oxigênio/sangue , Fatores de TempoRESUMO
Writer's cramp is a task-specific form of dystonia with symptoms characterized by abnormal movements and postures of the hand and arm evident only during writing. Its pathophysiology has been related to faulty sensorimotor integration, abnormal sensory processing, and impaired motor planning. Its symptoms might appear when the computational load of writing pushes a tonically altered circuit outside its operational range. Using resting-state fMRI, we tested whether writer's cramp patients have altered intrinsic functional connectivity in the premotor-parietal circuit. Sixteen patients with right-sided writer's cramp and 19 control subjects were studied. We show that writer's cramp patients have reduced connectivity between the superior parietal lobule and a dorsal precentral region that controls writing movements. This difference between patients and controls occurred in the absence of writing and only in the hemisphere contralateral to the affected hand. This finding adds a novel element to the pathophysiological substrate for writer's cramp, namely, task-independent alterations within a writing-related circuit.
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Distúrbios Distônicos/patologia , Distúrbios Distônicos/fisiopatologia , Córtex Motor/patologia , Vias Neurais/patologia , Lobo Parietal/patologia , Adulto , Idoso , Mapeamento Encefálico , Distonia/fisiopatologia , Feminino , Lateralidade Funcional/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/irrigação sanguínea , Vias Neurais/irrigação sanguínea , Oxigênio/sangue , Lobo Parietal/irrigação sanguíneaRESUMO
BACKGROUND: Current guidelines recommend that every person with Parkinson's disease (PD) should have access to Parkinson's disease nurse specialist (PDNS) care. However, there is little scientific evidence of the cost-effectiveness of PDNS care. This hampers wider implementation, creates unequal access to care, and possibly leads to avoidable disability and costs. Therefore, we aim to study the (cost-)effectiveness of specialized nursing care provided by a PDNS compared with usual care (without PDNS) for people with PD in all disease stages. To gain more insight into the deployed interventions and their effects, a preplanned subgroup analysis will be performed on the basis of disease duration (diagnosis < 5, 5-10, or > 10 years ago). METHODS: We will perform an 18-month, single-blind, randomized controlled clinical trial in eight community hospitals in the Netherlands. A total of 240 people with PD who have not been treated by a PDNS over the past 2 years will be included, independent of disease severity or duration. In each hospital, 30 patients will randomly be allocated in a 1:1 ratio to receive either care by a PDNS (who works according to a recent guideline on PDNS care) or usual care. We will use two co-primary outcomes: quality of life (measured with the Parkinson's Disease Questionnaire-39) and motor symptoms (measured with the Movement Disorders Society-sponsored revision of the Unified Parkinson's Disease Rating Scale part III). Secondary outcomes include nonmotor symptoms, health-related quality of life, experienced quality of care, self-management, medication adherence, caregiver burden, and coping skills. Data will be collected after 12 months and 18 months by a blinded researcher. A healthcare utilization and productivity loss questionnaire will be completed every 3 months. DISCUSSION: The results of this trial will have an immediate impact on the current care of people with PD. We hypothesize that by offering more patients access to PDNS care, quality of life will increase. We also expect healthcare costs to remain equal because increases in direct medical costs (funding additional nurses) will be offset by a reduced number of consultations with the general practitioner and neurologist. If these outcomes are reached, wide implementation of PDNS care will be warranted. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03830190. Registered February 5, 2019 (retrospectively registered).
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Análise Custo-Benefício/economia , Enfermagem/organização & administração , Doença de Parkinson/economia , Doença de Parkinson/enfermagem , Adaptação Psicológica/fisiologia , Adulto , Cuidadores/psicologia , Feminino , Custos de Cuidados de Saúde/tendências , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Países Baixos/epidemiologia , Qualidade da Assistência à Saúde/estatística & dados numéricos , Qualidade de Vida , Autogestão/estatística & dados numéricos , Método Simples-Cego , Inquéritos e Questionários/estatística & dados numéricosRESUMO
Dystonia is a disabling movement disorder with a significant impact on quality of life. The current therapeutic armamentarium includes various drugs, botulinum toxin injections, and occasionally (neuro)surgery. In addition, many patients are referred for paramedical (including allied health care) interventions. An enormous variation in the paramedical treatment is provided, largely because evidence-based, accepted treatment regimes are not available. We have conducted a systematic review of studies that explored the effect of various paramedical interventions in primary dystonia. Only studies that have used clinical outcome measures were included. There were no class A1 or A2 studies and therefore, level 1 or 2 practice recommendations for a specific intervention could not be deducted. Many papers were case reports, mostly with a very limited number of patients and a clear publication bias for beneficial effects of a particular paramedical intervention. Some potentially interesting interventions come from class B studies, which include physical therapy in addition to botulinum toxin injections (BoNT-A) in cervical dystonia; sensorimotor training and transcutaneous electrical nerve stimulation (TENS) in writer's cramp; and speech therapy added to BoNT-A injections in laryngeal dystonia. Good quality clinical studies are therefore warranted, which should have the aim to be generally applicable. A design in which the paramedical intervention is added to a current gold standard, for example, BoNT-A injections in cervical dystonia, is recommended.
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Distúrbios Distônicos/reabilitação , Modalidades de Fisioterapia , Bases de Dados Factuais/estatística & dados numéricos , Humanos , Terapia da Linguagem/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Fonoterapia/métodosRESUMO
In this review we explore the similarities between spinocerebellar ataxias and dystonias, and suggest potentially shared molecular pathways using a gene co-expression network approach. The spinocerebellar ataxias are a group of neurodegenerative disorders characterized by coordination problems caused mainly by atrophy of the cerebellum. The dystonias are another group of neurological movement disorders linked to basal ganglia dysfunction, although evidence is now pointing to cerebellar involvement as well. Our gene co-expression network approach identified 99 shared genes and showed the involvement of two major pathways: synaptic transmission and neurodevelopment. These pathways overlapped in the two disorders, with a large role for GABAergic signaling in both. The overlapping pathways may provide novel targets for disease therapies. We need to prioritize variants obtained by whole exome sequencing in the genes associated with these pathways in the search for new pathogenic variants, which can than be used to help in the genetic counseling of patients and their families.
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Ataxia , Distonia , Atrofia , Cerebelo , HumanosRESUMO
BACKGROUND: Acquired dystonia is caused by an acquired or exogenous event. Although the therapeutic armamentarium used in clinical practice is more or less similar to that used for inherited or idiopathic dystonia, formal proof of the efficacy of these interventions in acquired dystonia is lacking. METHODS: The authors attempt to provide a comprehensive and systematic review of the current evidence for medical and allied health care treatment strategies in acquired dystonias. The PubMed, Cochrane Library, MEDLINE, Web of Science, PiCarta, and PsycINFO databases were searched up to December 2015, including randomized controlled trials, patient-control studies, and case series or single case reports containing a report on clinical outcome. RESULTS: There are level 3 practice recommendations for botulinum toxin injections and globus pallidus pars interna deep brain stimulation for tardive dystonia and dystonic cerebral palsy as well as intrathecal baclofen for dystonic cerebral palsy. There are insufficient and conflicting data on the effect (vs. the hazard) of other pharmacological interventions, and limited work has been done on other forms of neurostimulation and allied health care. Because no class A1 or A2 studies were identified, level 1 or 2 practice recommendations could not be deducted for a specific treatment intervention. CONCLUSIONS: To improve the current medical and allied health care treatment options for patients with acquired dystonia, high-quality trials that examine the efficacy of therapies need to be performed.
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BACKGROUND: Isolated (sub)acute chorea in young patients is a relatively rare movement disorder with a broad differential diagnosis, including drug-induced, post-infectious, auto-immunological and vascular aetiologies. CASE PRESENTATION: We describe an adolescent girl with Down's syndrome presenting with chorea due to oral contraceptive usage. After discontinuation of the oral contraceptive it took several months before the symptoms disappeared. Although generally well recognised, it is important to realise this delayed effect. Rejecting the diagnosis too soon may lead to unnecessary treatment for other possible underlying aetiologies, especially in patients with Down Syndrome, known to be vulnerable for autoimmune disorders. CONCLUSION: We plead for discontinuation for at least three months before exclusion of oral contraceptives as cause of chorea.
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Coreia/induzido quimicamente , Anticoncepcionais Orais/efeitos adversos , Síndrome de Down/complicações , Distúrbios Menstruais/tratamento farmacológico , Doenças Autoimunes/diagnóstico , Coreia/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Distúrbios Menstruais/complicações , Adulto JovemRESUMO
Cervical dystonia is a neurological movement disorder characterized by involuntary, abnormal movements of the head and neck. Injecting the overactive muscles with botulinum toxin is the gold standard treatment, supported by good evidence (Delnooz and van de Warrenburg in Ther Adv Neurol Disord 5:221-240, 2012). Current views on its pathophysiology support a role for the basal ganglia, although there are probably more widespread abnormalities in brain networks in which the basal ganglia are important nodes. Their precise role in cervical dystonia is unknown. We sought to address this issue by examining alterations in the functional connectivity of the basal ganglia. Using resting-state functional MRI and functional parcellations, we investigated functional connectivity in cervical dystonia patients and age- and gender-matched healthy controls. We mapped connectivity voxel-wise across the striatum and the globus pallidus for a set of brain masks, defined from well-known resting-state networks. Scans were repeated before and after botulinum toxin injections to see whether connectivity abnormalities were perhaps restored. We found that in cervical dystonia (1) the right mid-dorsal putamen and right external globus pallidus have reduced connectivity with a network comprising left fronto-parietal regions; and (2) the bilateral anterior putamen shows a trend towards enhanced connectivity with a network comprising sensorimotor areas. We observed that botulinum toxin treatment induces reorganization between a network comprising mainly (pre)frontal areas and (1) the right mid-ventral striatum and (2) the right external globus pallidus. Cervical dystonia patients have altered functional connectivity between the basal ganglia and some cortical regions that are part of specific brain networks that in part are influenced by botulinum toxin treatment. These connectivity abnormalities may be primary as well as secondary, perhaps compensatory, phenomena.
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Mapeamento Encefálico , Corpo Estriado/irrigação sanguínea , Rede Nervosa/irrigação sanguínea , Torcicolo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Corpo Estriado/fisiopatologia , Feminino , Lateralidade Funcional , Globo Pálido/irrigação sanguínea , Globo Pálido/fisiopatologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/fisiopatologia , Oxigênio/sangue , Índice de Gravidade de Doença , Estatística como AssuntoRESUMO
Cervical dystonia is characterized by involuntary, abnormal movements and postures of the head and neck. Current views on its pathophysiology, such as faulty sensorimotor integration and impaired motor planning, are largely based on studies of focal hand dystonia. Using resting state fMRI, we explored whether cervical dystonia patients have altered functional brain connectivity compared to healthy controls, by investigating 10 resting state networks. Scans were repeated immediately before and some weeks after botulinum toxin injections to see whether connectivity abnormalities were restored. We here show that cervical dystonia patients have reduced connectivity in selected regions of the prefrontal cortex, premotor cortex and superior parietal lobule within a distributed network that comprises the premotor cortex, supplementary motor area, primary sensorimotor cortex, and secondary somatosensory cortex (sensorimotor network). With regard to a network originating from the occipital cortex (primary visual network), selected regions in the prefrontal and premotor cortex, superior parietal lobule, and middle temporal gyrus areas have reduced connectivity. In selected regions of the prefrontal, premotor, primary motor and early visual cortex increased connectivity was found within a network that comprises the prefrontal cortex including the anterior cingulate cortex and parietal cortex (executive control network). Botulinum toxin treatment resulted in a partial restoration of connectivity abnormalities in the sensorimotor and primary visual network. These findings demonstrate the involvement of multiple neural networks in cervical dystonia. The reduced connectivity within the sensorimotor and primary visual networks may provide the neural substrate to expect defective motor planning and disturbed spatial cognition. Increased connectivity within the executive control network suggests excessive attentional control and while this may be a primary trait, perhaps contributing to abnormal motor control, this may alternatively serve a compensatory function in order to reduce the consequences of the motor planning defect inflicted by the other network abnormalities.
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Antidiscinéticos/uso terapêutico , Toxinas Botulínicas/uso terapêutico , Torcicolo/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antidiscinéticos/farmacologia , Toxinas Botulínicas/farmacologia , Mapeamento Encefálico , Estudos de Casos e Controles , Cerebelo/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/fisiopatologia , Rede Nervosa/fisiopatologia , Torcicolo/tratamento farmacológico , Córtex Visual/fisiopatologiaRESUMO
Dystonia is a hyperkinetic movement disorder, characterized by involuntary and sustained contractions of opposing muscles causing twisting movements and abnormal postures. It is often a disabling disorder that has a significant impact on physical and psychosocial wellbeing. The medical therapeutic armamentarium used in practice is quite extensive, but for many of these interventions formal proof of efficacy is lacking. Exceptions are the use of botulinum toxin in patients with cervical dystonia, some forms of cranial dystonia (in particular, blepharospasm) and writer's cramp; deep brain stimulation of the pallidum in generalized and segmental dystonia; and high-dose trihexyphenidyl in young patients with segmental and generalized dystonia. In order to move this field forward, we not only need better trials that examine the effect of current treatment interventions, but also a further understanding of the pathophysiology of dystonia as a first step to design and test new therapies that are targeted at the underlying biologic and neurophysiologic mechanisms.
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We determined the extent of disease impact in 28 patients with genetically confirmed chronic progressive external ophthalmoplegia (CPEO) and compared the outcomes to those of matched myotonic dystrophy type I patients. CPEO patients reported a high frequency of severe fatigue (67.9%), pain (96.2%), depression (32.1%) and dependency in daily life (46.4%). The frequency and extent of depression were significantly higher than in DM1 patients (32.1% vs. 7.1%, p=0.040; mean Beck's depression inventory for primary care score 3.8±3.5 vs. 1.3±1.4, p=0.001), as were fatigue severity, pain intensity and extent of functional impairments. CPEO patients with polymerase gamma-1 mutations reported more functional impairments than those with mitochondrial DNA mutations. Disease impact was however not influenced by most clinical features. The present results help physicians to identify and to treat the factors that influence quality of life in CPEO patients and to provide symptomatic treatment where needed.