Showing papers by "Marie Vidailhet published in 2015"

Altered structural connectivity of cortico-striato-pallido-thalamic networks in Gilles de la Tourette syndrome.

Abstract: Gilles de la Tourette syndrome is a childhood-onset syndrome characterized by the presence and persistence of motor and vocal tics. A dysfunction of cortico-striato-pallido-thalamo-cortical networks in this syndrome has been supported by convergent data from neuro-pathological, electrophysiological as well as structural and functional neuroimaging studies. Here, we addressed the question of structural integration of cortico-striato-pallido-thalamo-cortical networks in Gilles de la Tourette syndrome. We specifically tested the hypothesis that deviant brain development in Gilles de la Tourette syndrome could affect structural connectivity within the input and output basal ganglia structures and thalamus. To this aim, we acquired data on 49 adult patients and 28 gender and age-matched control subjects on a 3 T magnetic resonance imaging scanner. We used and further implemented streamline probabilistic tractography algorithms that allowed us to quantify the structural integration of cortico-striato-pallido-thalamo-cortical networks. To further investigate the microstructure of white matter in patients with Gilles de la Tourette syndrome, we also evaluated fractional anisotropy and radial diffusivity in these pathways, which are both sensitive to axonal package and to myelin ensheathment. In patients with Gilles de la Tourette syndrome compared to control subjects, we found white matter abnormalities in neuronal pathways connecting the cerebral cortex, the basal ganglia and the thalamus. Specifically, striatum and thalamus had abnormally enhanced structural connectivity with primary motor and sensory cortices, as well as paracentral lobule, supplementary motor area and parietal cortices. This enhanced connectivity of motor cortex positively correlated with severity of tics measured by the Yale Global Tics Severity Scale and was not influenced by current medication status, age or gender of patients. Independently of the severity of tics, lateral and medial orbito-frontal cortex, inferior frontal, temporo-parietal junction, medial temporal and frontal pole also had enhanced structural connectivity with the striatum and thalamus in patients with Gilles de la Tourette syndrome. In addition, the cortico-striatal pathways were characterized by elevated fractional anisotropy and diminished radial diffusivity, suggesting microstructural axonal abnormalities of white matter in Gilles de la Tourette syndrome. These changes were more prominent in females with Gilles de la Tourette syndrome compared to males and were not related to the current medication status. Taken together, our data showed widespread structural abnormalities in cortico-striato-pallido-thalamic white matter pathways in patients with Gilles de la Tourette, which likely result from abnormal brain development in this syndrome.

ADCY5-related dyskinesia: Broader spectrum and genotype-phenotype correlations.

Abstract: Objective: To investigate the clinical spectrum and distinguishing features of adenylate cyclase 5 ( ADCY5 )–related dyskinesia and genotype–phenotype relationship. Methods: We analyzed ADCY5 in patients with choreiform or dystonic movements by exome or targeted sequencing. Suspected mosaicism was confirmed by allele-specific amplification. We evaluated clinical features in our 50 new and previously reported cases. Results: We identified 3 new families and 12 new sporadic cases with ADCY5 mutations. These mutations cause a mixed hyperkinetic disorder that includes dystonia, chorea, and myoclonus, often with facial involvement. The movements are sometimes painful and show episodic worsening on a fluctuating background. Many patients have axial hypotonia. In 2 unrelated families, a p.A726T mutation in the first cytoplasmic domain (C1) causes a relatively mild disorder of prominent facial and hand dystonia and chorea. Mutations p.R418W or p.R418Q in C1, de novo in 13 individuals and inherited in 1, produce a moderate to severe disorder with axial hypotonia, limb hypertonia, paroxysmal nocturnal or diurnal dyskinesia, chorea, myoclonus, and intermittent facial dyskinesia. Somatic mosaicism is usually associated with a less severe phenotype. In one family, a p.M1029K mutation in the C2 domain causes severe dystonia, hypotonia, and chorea. The progenitor, whose childhood-onset episodic movement disorder almost disappeared in adulthood, was mosaic for the mutation. Conclusions: ADCY5 -related dyskinesia is a childhood-onset disorder with a wide range of hyperkinetic abnormal movements. Genotype-specific correlations and mosaicism play important roles in the phenotypic variability. Recurrent mutations suggest particular functional importance of residues 418 and 726 in disease pathogenesis.

Intrinsic signature of essential tremor in the cerebello-frontal network.

Abstract: See Raethjen and Muthuraman (doi:[10.1093/brain/awv238][1]) for a scientific commentary on this article. Essential tremor is a movement disorder characterized by tremor during voluntary movements, mainly affecting the upper limbs. The cerebellum and its connections to the cortex are known to be involved in essential tremor, but no task-free intrinsic signatures of tremor related to structural cerebellar defects have so far been found in the cortical motor network. Here we used voxel-based morphometry, tractography and resting-state functional MRI at 3 T to compare structural and functional features in 19 patients with essential tremor and homogeneous symptoms in the upper limbs, and 19 age- and gender-matched healthy volunteers. Both structural and functional abnormalities were found in the patients' cerebellum and supplementary motor area. Relative to the healthy controls, the essential tremor patients' cerebellum exhibited less grey matter in lobule VIII and less effective connectivity between each cerebellar cortex and the ipsilateral dentate nucleus. The patient's supplementary motor area exhibited (i) more grey matter; (ii) a lower amplitude of low-frequency fluctuation of the blood oxygenation level-dependent signal; (iii) less effective connectivity between each supplementary motor area and the ipsilateral primary motor hand area, and (iv) a higher probability of connection between supplementary motor area fibres and the spinal cord. Structural and functional changes in the supplementary motor area, but not in the cerebellum, correlated with clinical severity. In addition, changes in the cerebellum and supplementary motor area were interrelated, as shown by a correlation between the lower amplitude of low-frequency fluctuation in the supplementary motor area and grey matter loss in the cerebellum. The structural and functional changes observed in the supplementary motor area might thus be a direct consequence of cerebellar defects: the supplementary motor area would attempt to reduce tremor in the motor output by reducing its communication with M1 hand areas and by directly modulating motor output via its corticospinal projections. * Abbreviation : ALFF : amplitude of low-frequency fluctuation CDTC : cerebello-dentato-thalamo-cortical MI : primary motor cortex SMA : supplementary motor area VBM : voxel-based morphometry [1]: /lookup/doi/10.1093/brain/awv238

Sleepiness in Idiopathic REM Sleep Behavior Disorder and Parkinson Disease.

Abstract: OBJECTIVE To determine whether patients with idiopathic and symptomatic RBD were sleepier than controls, and if sleepiness in idiopathic RBD predicted earlier conversion to Parkinson disease. METHODS The Epworth Sleepiness Scale (ESS) and its determinants were compared at the time of a video-polysomnography for an RBD diagnosis in patients with idiopathic RBD, in patients with Parkinson disease, and in controls. Whether sleepiness at time of RBD diagnosis predicted an earlier conversion to neurodegenerative diseases was retrospectively analyzed in the followed-up patients. RESULTS The 75 patients with idiopathic RBD were sleepier (ESS: 7.8 ± 4.6) at the time of RBD diagnosis than 74 age- and sex-matched controls (ESS: 5.0 ± 3.6, P < 0.0001). They reached the levels of 114 patients with Parkinson disease (ESS: 8.7 ± 4.8), whether they had (n = 78) or did not have (n = 36) concomitant RBD. The severity of sleepiness in idiopathic RBD correlated with younger age, but not with sleep measures. Among the 69 patients with idiopathic RBD who were followed up for a median 3 years (1-15 years), 16 (23.2%) developed parkinsonism (n = 6), dementia (n = 6), dementia plus parkinsonism (n = 2), and multiple system atrophy (n = 2). An ESS greater than 8 at time of RBD diagnosis predicted a shorter time to phenoconversion to parkinsonism and dementia, from RBD onset, and from RBD diagnosis (when adjusted for age and time between RBD onset and diagnosis). CONCLUSIONS Sleepiness is associated with idiopathic REM sleep behavior disorder and predicts more rapid conversion to parkinsonism and dementia, suggesting it is an early marker of neuronal loss in brainstem arousal systems.

High nigral iron deposition in LRRK2 and Parkin mutation carriers using R2* relaxometry.

Abstract: Objectives The goal of this work was to investigate iron deposition in the basal ganglia and thalamus in symptomatic and asymptomatic leucine-rich repeat kinase 2 (LRRK2) and Parkin-associated Parkinson's disease (PD), using R2* relaxometry rate. Methods Twenty subjects with genetic PD (four symptomatic and two asymptomatic Parkin subjects, nine symptomatic and five asymptomatic LRRK2 subjects) were compared with 20 patients with idiopathic PD (IPD) and 20 healthy subjects. Images were obtained at 3 teslas, using multi-echo T2 and T2* sequences. R2 and R2* values were calculated in the substantia nigra (SN), the striatum, the globus pallidus, and the thalamus. Results The R2* values in the SN were increased in IPD and mutation-carrying patients as compared with controls and in mutation-carrying patients as compared with IPD. Asymptomatic mutation carriers showed higher R2* values than controls and did not differ from IPD patients. No changes were seen in the other structures or in R2 values. Conclusion These results are consistent with increased iron load in LRRK2- and Parkin-mutation carriers. The increased R2* in asymptomatic PD-mutation carriers suggests that iron deposition occurs early during the preclinical phase of the disease. R2* measurements may be used as markers for investigating nigrostriatal damage in preclinical mutation-carrying patients. © 2015 International Parkinson and Movement Disorder Society

Polymorphism of the dopamine transporter type 1 gene modifies the treatment response in Parkinson's disease.

Abstract: After more than 50 years of treating Parkinson’s disease with l-DOPA, there are still no guidelines on setting the optimal dose for a given patient. The dopamine transporter type 1, now known as solute carrier family 6 (neurotransmitter transporter), member 3 (SLC6A3) is the most powerful determinant of dopamine neurotransmission and might therefore influence the treatment response. We recently demonstrated that methylphenidate (a dopamine transporter inhibitor) is effective in patients with Parkinson’s disease with motor and gait disorders. The objective of the present study was to determine whether genetic variants of the dopamine transporter type 1-encoding gene (SLC6A3) are associated with differences in the response to treatment of motor symptoms and gait disorders with l-DOPA and methylphenidate (with respect to the demographic, the disease and the treatment parameters and the other genes involved in the dopaminergic neurotransmission). This analysis was part of a multicentre, parallel-group, double-blind, placebo-controlled, randomized clinical trial of methylphenidate in Parkinson’s disease (Protocol ID:2008-005801-20; ClinicalTrials.gov:NCT00914095). We scored the motor Unified Parkinson's Disease Rating Scale and the Stand-Walk-Sit Test before and after a standardized acute l-DOPA challenge before randomization and then after 3 months of methylphenidate treatment. Patients were screened for variants of genes involved in dopamine metabolism: rs28363170 and rs3836790 polymorphisms in the SLC6A3 gene, rs921451 and rs3837091 in the DDC gene (encoding the aromatic L-amino acid decarboxylase involved in the synthesis of dopamine from l-DOPA), rs1799836 in the MAOB gene (coding for monoamine oxidase B) and rs4680 in the COMT gene (coding for catechol-O-methyltransferase). Investigators and patients were blinded to the genotyping data throughout the study. Eighty-one subjects were genotyped and 61 were analysed for their acute motor response to l-DOPA. The SLC6A3 variants were significantly associated with greater efficacy of l-DOPA for motor symptoms. The SLC6A3 variants were also associated with greater efficacy of methylphenidate for motor symptoms and gait disorders in the ON l-DOPA condition. The difference between motor Unified Parkinson's Disease Rating Scale scores for patients with different SLC6A3 genotypes was statistically significant in a multivariate analysis that took account of other disease-related, treatment-related and pharmacogenetic parameters. Our preliminary results suggest that variants of SLC6A3 are genetic modifiers of the treatment response to l-DOPA and methylphenidate in Parkinson’s disease. Further studies are required to assess the possible value of these genotypes for (i) guiding l-DOPA dose adaptations over the long term; and (ii) establishing the risk/benefit balance associated with methylphenidate treatment for gait disorders.

Altered structure of cortical sulci in gilles de la Tourette syndrome: Further support for abnormal brain development

Abstract: Gilles de la Tourette syndrome is a neurodevelopmental disorder characterized by the presence of motor and vocal tics. We hypothesized that patients with this syndrome would present an aberrant pattern of cortical formation, which could potentially reflect global alterations of brain development. Using 3 Tesla structural neuroimaging, we compared sulcal depth, opening, and length and thickness of sulcal gray matter in 52 adult patients and 52 matched controls. Cortical sulci were automatically reconstructed and identified over the whole brain, using BrainVisa software. We focused on frontal, parietal, and temporal cortical regions, in which abnormal structure and functional activity were identified in previous neuroimaging studies. Partial correlation analysis with age, sex, and treatment as covariables of noninterest was performed amongst relevant clinical and neuroimaging variables in patients. Patients with Gilles de la Tourette syndrome showed lower depth and reduced thickness of gray matter in the pre- and post-central as well as superior, inferior, and internal frontal sulci. In patients with associated obsessive-compulsive disorder, additional structural changes were found in temporal, insular, and olfactory sulci. Crucially, severity of tics and of obsessive-compulsive disorder measured by Yale Global Tic severity scale and Yale-Brown Obsessive-Compulsive scale, respectively, correlated with structural sulcal changes in sensorimotor, temporal, dorsolateral prefrontal, and middle cingulate cortical areas. Patients with Gilles de la Tourette syndrome displayed an abnormal structural pattern of cortical sulci, which correlated with severity of clinical symptoms. Our results provide further evidence of abnormal brain development in GTS.

The long-term outcome of orthostatic tremor

Abstract: Objectives Orthostatic tremor is a rare condition characterised by high-frequency tremor that appears on standing. Although the essential clinical features of orthostatic tremor are well established, little is known about the natural progression of the disorder. We report the long-term outcome based on the largest multicentre cohort of patients with orthostatic tremor. Methods Clinical information of 68 patients with clinical and electrophysiological diagnosis of orthostatic tremor and a minimum follow-up of 5 years is presented. Results There was a clear female preponderance (76.5%) with a mean age of onset at 54 years. Median follow-up was 6 years (range 5–25). On diagnosis, 86.8% of patients presented with isolated orthostatic tremor and 13.2% had additional neurological features. At follow-up, seven patients who initially had isolated orthostatic tremor later developed further neurological signs. A total 79.4% of patients reported worsening of orthostatic tremor symptoms. These patients had significantly longer symptom duration than those without reported worsening (median 15.5 vs 10.5 years, respectively; p=0.005). There was no change in orthostatic tremor frequency over time. Structural imaging was largely unremarkable and dopaminergic neuroimaging (DaTSCAN) was normal in 18/19 cases. Pharmacological treatments were disappointing. Two patients were treated surgically and showed improvement. Conclusions Orthostatic tremor is a progressive disorder with increased disability although tremor frequency is unchanged over time. In most cases, orthostatic tremor represents an isolated syndrome. Drug treatments are unsatisfactory but surgery may hold promise.

Why do patients with neurodegenerative frontal syndrome fail to answer: 'In what way are an orange and a banana alike?'.

Abstract: Concept formation is the ability to create an abstract link between dissimilar objects or thoughts and is crucial for abstract and creative thinking. This process is related to the integrity of the prefrontal cortex, given the altered performances reported in patients with frontal damage, particularly those suffering from the behavioural variant of frontotemporal dementia. However, the cognitive mechanisms and neural bases of verbal concept formation are not clearly understood. The present study was aimed at addressing the following unresolved issues regarding concept formation in the field of neurology and cognitive neuroscience: (i) Are alterations in concept formation specific to frontotemporal dementia or are they also present in other cortical neurodegenerative disorders such as Alzheimer's disease? (ii) Is impaired performance in concept formation due to cortical lesions specific to frontotemporal dementia or to a cortico-subcortical frontal syndrome? and (iii) What are the cognitive mechanisms and neural bases underlying concept formation? To address these questions, we designed the Verbal Concept Formation Task, an experimental paradigm based on the similarities test. Patients presenting with severe frontal dysfunction (frontotemporal dementia, n = 18, and the Richardson form of progressive supranuclear palsy, n = 21) or with medial temporal pathology (amnestic mild cognitive impairment or Alzheimer's disease, n = 14) and healthy participants (n = 18) were given the Verbal Concept Formation Task and a large battery of neuropsychological tests. In addition, all participants underwent 3D T1-weighted MRI to analyse grey matter volume using voxel-based morphometry. Frontal patients were significantly impaired on the Verbal Concept Formation Task as compared to non-frontal participants (P = 0.00001). Global performance score was positively correlated with scores in cognitive tasks assessing executive functions and with grey matter volume in several areas, mostly in the frontal-basal-ganglion network. Two types of errors were observed in frontal patients. The most frequent was discriminating instead of grouping items ('linking deficit'). Patients also linked items on a concrete instead of an abstract basis ('abstraction deficit'). Linking and abstraction deficits were related to partially different areas: the linking deficit to the dorsal anterior cingulate cortex, right middle frontal gyrus and both inferior parietal lobules and the abstraction deficit to the head of the caudate nuclei and the left superior frontal gyrus. These data suggest that verbal concept formation requires the integrity of the prefrontal-basal-ganglion functional network. In addition, it can be divided into two distinct cognitive processes, which are underlain by two partially different neural networks.

A diagnostic flow chart for POLG-related diseases based on signs sensitivity and specificity

Abstract: OBJECTIVE: Diseases due to mutations of POLG gene, encoding the mitochondrial DNA polymerase, are reputed to have very diverse clinical presentations and have been proposed to cause up to 25% adult mitochondrial diseases. Our objective was the evaluation of the specificity and sensitivity of the signs encountered with POLG mutations. DESIGN: Forty-four patients out of 154 with sequenced POLG gene had mutations affecting either one (POLG(+/-) group) or two POLG alleles (POLG(+/+) group). Phenotyping included clinical signs, electroneuromyography and brain imaging while mitochondrial investigations encompassed muscle histochemistry, respiratory chain assays and search for multiple mitochondrial deletions. The specificity and sensitivity of the signs associated with POLG mutations were analysed by comparison between POLG(+/+) and patients without POLG mutation. RESULTS: High sensitivity but low specificity was observed with single signs such as axonal sensory neuropathy, cerebellar syndrome, movement disorders and weakness involving ocular, pharyngeal, axial and/or limb muscles. Specificity was increased with combination of previous signs plus psychiatric symptoms, cognitive impairment and epilepsy. High specificity and sensitivity was only obtained with sensory neuronopathy associated with one of the following signs: weakness of ocular, pharyngeal, axial and/or limb muscles. Mitochondrial investigations did not suffice for diagnosis. The widespread neuromuscular signs were often present since disease onset and were the rule above 50 years of age leading to a very low probability of POLG mutations in patients with less than three signs and absent sensory neuropathy. CONCLUSIONS: Phenotypes associated with POLG mutations follow a reproducible pattern, which allows establishing a diagnostic flow chart.

Pallidal activity in myoclonus dystonia correlates with motor signs.

Abstract: Background Myoclonus–dystonia related to epsilon-sarcoglycan gene mutations is characterized by myoclonic jerks and mild to moderate dystonia. The role of basal ganglia dysfunction in the pathogenesis is unknown. Methods Pallidal neuronal activity was recorded in six myoclonus–dystonia and six primary generalized dystonia patients operated on for internal globus pallidus deep brain stimulation. Results In myoclonus–dystonia patients compared with primary-dystonia patients, internal pallidum neurons showed higher burst frequency, lower mean burst, and pause durations. External pallidum neurons showed higher mean pause frequency. Oscillatory activity was present in 33% and 35% of internal pallidum neurons in myoclonus–dystonia and primary-dystonia patients, respectively, predominantly in the theta frequency band (3-8 Hz). In myoclonus–dystonia patients with more severe myoclonus, internal pallidum neurons exhibited a higher bursting activity with high intraburst frequency and lower oscillatory activity frequency. Conclusions Myoclonus–dystonia appears to be related to specific changes in internal pallidum activity, leading to disruption in striato-pallido-thalamo-cortical circuits. © 2015 International Parkinson and Movement Disorder Society

Pallidal stimulation for myoclonus-dystonia: Ten years' outcome in two patients

Abstract: Myoclonus-dystonia syndrome (M-D) is characterized by a variable combination of myoclonic jerks and mild to moderate dystonia. Myoclonus is usually the main and most disabling feature, predominating in the arms and axial muscles. Psychiatric disorders are occasionally part of the phenotype. Mutations or deletion in SGCE, the main culprit gene, accounts for 40% to 50% of the typical cases. Neurophysiological characteristics of the myoclonus point to a subcortical disorder, reflecting a primary dysfunction of the cerebello-thalamo-cortical pathway or of the striato-pallidothalamo-cortical pathway. In a subset of patients, the motor phenotype is severe, with a significant impact on social interactions and activities of daily living. Pharmacological treatments are usually disappointing. Bilateral deep brain stimulation of the internal globus pallidus (GPi-DBS) is a safe and effective option for patients with severe and disabling isolated primary dystonia. Although not formally evaluated, GPi-DBS seems to be at least as efficient in M-D patients as in patients with isolated primary dystonias, with a motor and functional improvement usually exceeding 60% at 12 months after surgery. This treatment is effective on both myoclonus and dystonia. The benefit over side effects ratio is likely better with GPi-DBS than with ventral intermediate nucleus DBS. Information on the very-long-term benefit of GPi-DBS in M-D patients is scarce. In the largest series reporting the effect of DBS in M-D patients, one patient had sustained benefit of GPi-DBS over 9 y. The evaluation was not blinded in this study. We report detailed results of blind evaluations on the two first M-D patients that underwent GPi-DBS in our center, 10 years ago (patients 4 and 5 in Azoulay-Zyss et al.). Two sisters with a deleterious p.Gln286X mutation in the SGCE gene had GPi-DBS to treat a severe and disabling MD syndrome that was poorly responsive to medical treatment (Table 1). The surgical procedure and evaluation of the effect were previously described. Briefly, two movement disorders experts (D.G. and M.V.) blindly evaluated standardized videotape of the patients shown in a random order. The patients were evaluated preoperatively, at 1 y and 10 y after surgery (routine follow-up) during continuous GPi neurostimulation while taking their usual medication. In both patients, myoclonus and dystonia were nearly suppressed by GPi-DBS (Table 1 and video). No residual functional impairment was seen, assessed by the disability subscore of the Burke-Fahn-Marsden Dystonia Rating Scale. Within this 10y period, no adverse effect was related to the stimulation, and no cognitive deterioration or psychiatric disorder was seen. After the initial setting within the first weeks after surgery, the amplitude was not significantly modified during the 10-y period (Table 1). Although the patients were not blinded to the stimulation condition, the amplitude of the effect and its very long duration rule out a placebo effect. This observation further indicates that SGCE M-D patients may have sustained motor and functional benefits of GPi-DBS over 10 y, thereby supporting the use of this therapeutic approach when M-D is disabling and refractory to medical treatment.

Sleep aspects on video‐polysomnography in LRRK2 mutation carriers

Abstract: Background Rapid eye movement sleep behavior disorder and sleepiness precede or accompany idiopathic Parkinson's disease (PD), but their presence in subjects with leucine-rich repeat kinase 2 mutations is unknown. Methods Ten patients with leucine-rich repeat kinase 2-associated PD, four healthy leucine-rich repeat kinase 2 mutation carriers, 20 patients with idiopathic PD, and 12 healthy controls underwent clinical assessments and a nighttime video-polysomnography. Results No sleep changes, no rapid eye movement sleep behavior disorder, or rapid eye movement sleep without atonia was found in the 14 subjects with leucine-rich repeat kinase 2mutations compared with controls, whereas 41% of patients with idiopathic PD had rapid eye movement sleep behavior disorder. Eventually, 20% of patients with leucine-rich repeat kinase 2–associated PD had abnormal periodic leg movements, a frequency similar to the idiopathic PD group frequency. Conclusions The sleep phenotype in leucine-rich repeat kinase 2 mutations parallels that of idiopathic PD, except for absent rapid eye movement sleep behavior disorder here in the presymptomatic and symptomatic stages. © 2015 International Parkinson and Movement Disorder Society

Chapter 48 – Paroxysmal Movement Disorders: Clinical and Genetic Features

Abstract: Paroxysmal movement disorders comprise paroxysmal dyskinesias and episodic ataxias of various types. They are mainly of genetic origin but are occasionally symptomatic of an underlying nongenetic disorder. Their current classification is based mainly on the phenomenology of the attacks, especially their triggering factors and duration. Basic research is providing new insights into these disorders, notably by showing that a given paroxysmal movement disorder can be caused by mutations in various genes, and that mutations of a given gene can result in various types of paroxysmal movement disorders. This chapter describes the broad clinical spectrum of paroxysmal movement disorders and their main known genetic causes. An algorithm is provided to help clinicians avoid diagnostic pitfalls.

Two cases of early dystonia of the trunk in Parkinson's disease.

Abstract: Dr. Roze is the recipient of a grant ‘‘poste d’accueil’’ APHP/CNRS. He received research support from INSERM (COSSEC), AP-HP (DRC-PHRC), Fondation pour la Recherche sur le Cerveau (FRC), the Dystonia Coalition (Pilot project), Ipsen, and Merz-Pharma, Novartis, Teva, Lundbeck, Orkyn; served on scientific advisory boards for Orkyn, Ipsen, and Merz-pharma; received speech honorarium from Novartis, Teva and Orkyn; received travel funding from Teva, Novartis, the Dystonia Coalition, the Movement Disorders Society, the World Federation of Neurology Association of Parkinsonism and Related Disorders, International Federation of Clinical Neurophysiology. Dr. M Vidailhet has been an invited speaker at ENS, EFNS and MDS International meetings. She is on the scientific advisory board of Novartis and Merz. She has received unrestricted research grants from DHOSINSERM and ANR (French National Institutes) and from AMADYS and Alliance France Dystonie (patient associations). Dystonia is frequently observed as a long-term side effect of antiparkinsonian treatment but is uncommon in drug-naive patients with Parkinson’s disease (PD). Highest risk of dystonia is observed young onset PD, mostly with exercise-induced foot dystonia [1], especially in genetic forms [2]. Dystonic features, as found in idiopathic dystonia may precede the diagnosis of PD [3], and response to L-Dopa or dopaminergic agonist therapy is variable. Truncal dystonia has not been reported as the presenting manifestation. We describe two patients with truncal dystonia as the presenting manifestation of PD. None of them had previous treatment with neuroleptics, nor family history of dystonia or parkinsonism. Case 1 A 34-year-old man had a progressive dystonia with hyperextension of the trunk associated a few months later with bilateral upper limbs dystonia (video, segment 1). Within the two following years, the patient developed a left akinetic-rigid syndrome with an intermittent action and postural tremor (video, segment 2). There were no mutations in the torsin A, GCH1 and Parkin. Search for Wilson’s disease was negative. Brain MRI was normal. Electronic supplementary material The online version of this article (doi:10.1007/s00415-015-7747-y) contains supplementary material, which is available to authorized users.

Apomorphine Therapy: The Hazard of Left Over Needles.

Abstract: A 55-year-old patient with Parkinson’s disease (PD) was seen for a shoulder abscess. This abscess was related to the presence of a subcutaneous needle that was disconnected from the tubing used for continuous apomorphine therapy. The patient recovered after abscess incision and antibiotherapy. An X-ray of the shoulders confirmed that several needles remained subcutaneously in both shoulders (Fig. 1). After changing the type of catheter, no similar event occurred. After several years with levodopa treatment, PD patients develop motor fluctuations and dyskinesia, linked to iterative stimulations of dopaminergic receptors by multiple daily intakes of dopaminergic drugs. Continuous apomorphine administration may be used as an alternative therapy either as a monotherapy or in association with L-dopa. Apomorphine reduces significantly the OFF state periods, but also dyskinesia, mainly as a monotherapy. Our case report highlights that needles may occasionally be dislocated from tubing, especially when removing the injecting system. It seems that the junction between the needle and the tubing is a weak point and uncoupling may occur, especially in patients with dyskinesia. In this situation, we recommend to use a different injecting system, such as a tangential catheter, which may be more resistant because it is flexible and therefore less breakable. Education to use the injecting system should be performed before starting apomorphine therapy, and special attention should be paid to the monitoring of local side effects in patients treated with subcutaneous apomorphine.

Essential Palatal Tremor Synchronization: A Study by Video Record Numerical Analysis.

Abstract: A 12-year-old girl presented with a 2-year history of rhythmic ear clicks. She was born 7 weeks premature with caesarean without fetal distress and had a normal psychomotor development. A strabismus was corrected by surgery. The clicks started concurrently with an acute infectious sinusitis. These involuntary clicks were not bothersome and stopped during sleep. They were present every day with a fluctuating intensity. Free intervals shorter than 2 days may rarely occur. She had no particular tricks to control the clicks, and no provoking factors were identified. Examination revealed isolated continuous rhythmic bilateral and symmetrical brisk movements of the soft palate (see Video 1). Brain MRI was normal with no hypertrophy of the inferior olive. Because the movements of the soft palate seemed quite irregular, she was referred to our neurophysiology department to determine precisely the palatal tremor (PT) frequency and to perform frequency entrainment trials in order to examine the psychogenic hypothesis.

Baseline Features Influencing the Effectiveness of Retraining Therapy for Writer's Cramp

Abstract: Background: The effectiveness of retraining therapy (RT) for writer's cramp is difficult to predict and its determinants are unknown. Methods: We examined factors potentially predicting improved legibility after RT in patients with writer's cramp (WC). We reviewed the files of 693 WC patients treated with RT from 1995 to 2009. Standardized assessments were made both at baseline and after 2 months of RT in 305 patients. The effect of RT on legibility was evaluated by using the handwriting subscore of the Burke-Fahn-Marsden (BFM) disability scale. Initial and final handwriting samples were blindly scored in random order. Associations between WC patterns and changes in legibility were identified by uni- and multivariable analyses. Results: Legibility improved by ≥1 point in the BFM handwriting subscore in 93 patients (31%). WC patients who improved were more likely to have synergic dystonic patterns involving the wrist and forearm (60% vs. 40%; P = 0.03) and less likely to have flexion of fingers F3 to F5 (19% vs. 81%; P = 0.017). Outcome was not related to gender, age, or dystonia duration. Our results confirm that retraining therapy could improve legibility in patients with writer's cramp. Conclusions: The pattern of writer's cramp can help to identify patients who are most likely to benefit from retraining therapy, regardless of age, gender, and disease duration.