Two task-specific dystonias in one hand

Contains fulltext : 127337.pdf (publisher's version ) (Open Access)BACKGROUND: Dystonia is characterized by involuntary muscle contractions that lead to abnormal postures and/or repetitive movements. Task-specific dystonia only manifests during a specific activity. CASE REPORT: We report a case of a female with writer's cramp who developed a second task-specific hand dystonia (tremor and abnormal posturing of the hand while using a computer mouse) many years after the initial onset. DISCUSSION: This observation is in agreement with the concept that task-specific hand dystonia is induced by repetitive, skilled hand movements in those who have an intrinsic vulnerability towards developing "dystonic" motor programs

Altered striatal and pallidal connectivity in cervical dystonia

Contains fulltext : 153855.pdf (publisher's version ) (Closed access)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

Expanding the phenotype in aminoacylase 1 (ACY1) deficiency: characterization of the molecular defect in a 63-year-old woman with generalized dystonia

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