Medicamenteuze Behandeling Van Hyperkinetische Bewegingsstoornissen

Patiënten met een hyperkinetische bewegingsstoornis hebben een teveel aan bewegingen, die erg invaliderend en vaak lastig te behandelen kunnen zijn. Naast de bij voorkeur causale behandeling is de behandeling van de overtollige bewegingen voornamelijk symptomatisch. Dit artikel richt zich op de symptomatische medicamenteuze behandeling van dystonie, tremor, chorea en myoclonus. In enkele flowcharts worden de eerste stappen in de klinische beoordeling en de symptomatische behandeling van deze bewegingsstoornissen weergegeven. Hierbij was het streven zo veel mogelijk ‘evidence based medicine’ aan te houden, bij voorkeur systematische reviews en gerandomiseerde trials. Vanwege een beperkte hoeveelheid hiervoor geschikte literatuur, is dit artikel vaak gebaseerd op consensusrichtlijnen en ‘expert opinion’

How to detect late-onset inborn errors of metabolism in patients with movement disorders - A modern diagnostic approach

We propose a modern approach to assist clinicians to recognize and diagnose inborn errors of metabolism (IEMs) in adolescents and adults that present with a movement disorder. IEMs presenting in adults are still largely unexplored. These disorders receive little attention in neurological training and daily practice, and are considered complicated by many neurologists. Adult-onset presentations of IEMs differ from childhood-onset phenotypes, which may lead to considerable diagnostic delay. The identification of adult-onset phenotypes at the earliest stage of the disease is important, since early treatment may prevent or lessen further brain damage. Our approach is based on a systematic review of all papers that concerned movement disorders due to an IEM in patients of 16 years or older. Detailed clinical phenotyping is the diagnostic cornerstone of the approach. An underlying IEM should be suspected in particular in patients with more than one movement disorder, or in patients with additional neurological, psychiatric, or systemic manifestations. As IEMs are all genetic disorders, we recommend next-generation sequencing (NGS) as the first diagnostic approach to confirm an IEM. Biochemical tests remain the first choice in acute-onset or treatable IEMs that require rapid diagnosis, or to confirm the metabolic diagnosis after NGS results. With the use of careful and systematic clinical phenotyping combined with novel diagnostic approaches such as NGS, the diagnostic yield of late-onset IEMs will increase, in particular in patients with mild or unusual phenotypes.</p

Early onset ataxia with comorbid myoclonus and epilepsy:A disease spectrum with shared molecular pathways and cortico-thalamo-cerebellar network involvement

OBJECTIVES: Early onset ataxia (EOA) concerns a heterogeneous disease group, often presenting with other comorbid phenotypes such as myoclonus and epilepsy. Due to genetic and phenotypic heterogeneity, it can be difficult to identify the underlying gene defect from the clinical symptoms. The pathological mechanisms underlying comorbid EOA phenotypes remain largely unknown. The aim of this study is to investigate the key pathological mechanisms in EOA with myoclonus and/or epilepsy.METHODS: For 154 EOA-genes we investigated (1) the associated phenotype (2) reported anatomical neuroimaging abnormalities, and (3) functionally enriched biological pathways through in silico analysis. We assessed the validity of our in silico results by outcome comparison to a clinical EOA-cohort (80 patients, 31 genes).RESULTS: EOA associated gene mutations cause a spectrum of disorders, including myoclonic and epileptic phenotypes. Cerebellar imaging abnormalities were observed in 73-86% (cohort and in silico respectively) of EOA-genes independently of phenotypic comorbidity. EOA phenotypes with comorbid myoclonus and myoclonus/epilepsy were specifically associated with abnormalities in the cerebello-thalamo-cortical network. EOA, myoclonus and epilepsy genes shared enriched pathways involved in neurotransmission and neurodevelopment both in the in silico and clinical genes. EOA gene subgroups with myoclonus and epilepsy showed specific enrichment for lysosomal and lipid processes.CONCLUSIONS: The investigated EOA phenotypes revealed predominantly cerebellar abnormalities, with thalamo-cortical abnormalities in the mixed phenotypes, suggesting anatomical network involvement in EOA pathogenesis. The studied phenotypes exhibit a shared biomolecular pathogenesis, with some specific phenotype-dependent pathways. Mutations in EOA, epilepsy and myoclonus associated genes can all cause heterogeneous ataxia phenotypes, which supports exome sequencing with a movement disorder panel over conventional single gene panel testing in the clinical setting

Developmental neurobiology of cerebellar and Basal Ganglia connections

BACKGROUND: The high prevalence of mixed phenotypes of Early Onset Ataxia (EOA) with comorbid dystonia has shifted the pathogenetic concept from the cerebellum towards the interconnected cerebellar motor network. This paper on EOA with comorbid dystonia (EOA-dystonia) explores the conceptual relationship between the motor phenotype and the cortico-basal-ganglia-ponto-cerebellar network. METHODS: In EOA-dystonia, we reviewed anatomic-, genetic- and biochemical-studies on the comorbidity between ataxia and dystonia. RESULTS: In a clinical EOA cohort, the prevalence of dystonia was over 60%. Both human and animal studies converge on the underlying role for the cortico-basal-ganglia-ponto-cerebellar network. Genetic -clinical and -in silico network studies reveal underlying biological pathways for energy production and neural signal transduction. CONCLUSIONS: EOA-dystonia phenotypes are attributable to the cortico-basal-ganglia-ponto-cerebellar network, instead of to the cerebellum, alone. The underlying anatomic and pathogenetic pathways have clinical implications for our understanding of the heterogeneous phenotype, neuro-metabolic and genetic testing and potentially also for new treatment strategies, including neuro-modulation

Myoclonus-Ataxia Syndromes:A Diagnostic Approach

Item does not contain fulltextBACKGROUND: A myriad of disorders combine myoclonus and ataxia. Most causes are genetic and an increasing number of genes are being associated with myoclonus-ataxia syndromes (MAS), due to recent advances in genetic techniques. A proper etiologic diagnosis of MAS is clinically relevant, given the consequences for genetic counseling, treatment, and prognosis. OBJECTIVES: To review the causes of MAS and to propose a diagnostic algorithm. METHODS: A comprehensive and structured literature search following PRISMA criteria was conducted to identify those disorders that may combine myoclonus with ataxia. RESULTS: A total of 135 causes of combined myoclonus and ataxia were identified, of which 30 were charted as the main causes of MAS. These include four acquired entities: opsoclonus-myoclonus-ataxia syndrome, celiac disease, multiple system atrophy, and sporadic prion diseases. The distinction between progressive myoclonus epilepsy and progressive myoclonus ataxia poses one of the main diagnostic dilemmas. CONCLUSIONS: Diagnostic algorithms for pediatric and adult patients, based on clinical manifestations including epilepsy, are proposed to guide the differential diagnosis and corresponding work-up of the most important and frequent causes of MAS. A list of genes associated with MAS to guide genetic testing strategies is provided. Priority should be given to diagnose or exclude acquired or treatable disorders

Ultrasonography of the Adrenal Gland

With appropriate techniques and using liver, spleen or kidney as an acoustic window, normal adrenal gland and adrenal lesions can be delineated by ultrasonography. The right adrenal gland is usually evaluated by transverse oblique scans and coronal scans, respectively, through the anterior and middle axillary line, while the left adrenal gland is investigated by an oblique coronal scan mainly through the posterior axillary line. For adrenal lesions, ultrasonography has a sensitivity of 74–97%, a specificity of 61–96%, and an accuracy of 70–97%. The diagnostic accuracy depends on the scanning technique and expertise of the operator, the body status of the patient, the size and functional status of the lesion, and the ultrasonographic quality. Small adrenal nodules, ileus, obesity, fatty liver, and large body status account for most of the reasons for decreased accuracy. Small adrenal nodules less than 3 cm in diameter mainly comprise functioning cortical adenomas, nonfunctioning cortical adenomas, nodular hyperplasia, and metastases. Most small adrenal masses are homogeneous and hypoechoic, and the echo patterns are nonspecific. Large adrenal masses greater than 3 cm in diameter mainly include primary adrenocortical carcinoma, lymphoma, metastasis, lymphoma, and pheochromocytoma. The echogenicity of a large adrenal mass may be hyperechoic and heterogeneous because of the higher incidence of necrosis and hemorrhage. Other uncommon adrenal masses are myelolipoma, hematoma, granulomatous lesions, hemangioma, and adrenal cysts of various origins. The differential diagnoses of a hyperechoic adrenal mass include neuroblastoma, myelolipoma, and tumor with central necrosis or heterogeneity. Calcification is encountered in both benign and malignant processes. It is sometimes difficult to differentiate benign adrenal masses from malignant lesions. Dynamic computed tomography, magnetic resonance imaging, and positron emission tomography play critical complementary roles in such an instance

Fatigue, Sleep Disturbances, and Their influence on Quality of Life In Cervical Dystonia Patients

Background Nonmotor symptoms (NMS) are highly prevalent in cervical dystonia (CD). In general, fatigue and sleep are important NMS that determine a decreased health-related quality of life (HR-QoL), but their influence in CD is unknown. The authors systematically investigated fatigue, excessive daytime sleepiness (EDS), and sleep quality in patients with CD and controls and assessed the influence of psychiatric comorbidity, pain, and dystonia motor severity. They also examined the predictors of HR-QoL.  Methods The study included 44 patients with CD and 43 matched controls. Fatigue, EDS, and sleep quality were assessed with quantitative questionnaires and corrected for depression and anxiety using analysis of covariance. The Toronto Western Spasmodic Torticollis Rating Scale and the Clinical Global Impression Scale-jerks/tremor subscale were used to score motor severity and to assess whether motor characteristics could explain an additional part of the variation in fatigue and sleep-related measures. HR-QoL was determined with the RAND-36 item Health Survey, and predictors of HR-QoL were assessed using multiple regression.  Results Fatigue scores were increased independently from psychiatric comorbidity (4.0 vs. 2.7; P<0.01), whereas EDS (7.3 vs. 7.4; P=0.95) and sleep quality (6.5 vs. 6.1; P=0.73) were highly associated with depression and anxiety. In patients with CD, motor severity did not explain the variations in fatigue (change in the correlation coefficient [R-2]=0.06; P=0.15), EDS (R-2=0.00; P=0.96), or sleep quality (R-2=0.04; P=0.38) scores. Fatigue, EDS, psychiatric comorbidity, and pain predicted a decreased QoL.  Conclusion Independent from psychiatric comorbidity and motor severity, fatigue appeared to be a primary NMS. Sleep-related measures were highly associated with psychiatric comorbidity, but not with motor severity. Only NMS predicted HR-QoL, which emphasizes the importance of attention to NMS in patients with CD