Showing papers by "Marie Vidailhet published in 2011"

Large-scale screening of the Gaucher's disease-related glucocerebrosidase gene in Europeans with Parkinson's disease

Abstract: Pathogenic variants in the glucocerebrosidase gene (GBA) encoding the enzyme deficient in Gaucher's disease (GD) are associated with Parkinson's disease (PD). To investigate the sequence variants, their association with PD and the related phenotypes in a large cohort of European, mostly French, patients and controls, we sequenced all exons of GBA in 786 PD patients from 525 unrelated multiplex families, 605 patients with apparently sporadic PD and 391 ethnically matched controls. GBA mutations were significantly more frequent (odds ratio=6.98, 95% confidence interval 2.54-19.21; P=0.00002) in the PD patients (76/1130=6.7%) than in controls (4/391=1.0%) and in patients with family histories of PD (8.4%) than in isolated cases (5.3%). Twenty-eight different mutations were identified in patient and control groups, including seven novel variants. N370S and L444P accounted for 70% of all mutant alleles in the patient group. PD patients with GBA mutations more frequently had bradykinesia as the presenting symptom and levodopa-induced dyskinesias. The phenotype was similar in patients with one, two or complex GBA mutations, although the two patients with c.1263del+RecTL and N370S/RecΔ55 mutations had signs of GD. Segregation analyses in 21 multiplex families showed that 17% of the affected relatives did not carry GBA mutations found in the given family, indicating heterogeneity of the aetiology, but 46% of the unaffected relatives were GBA mutation carriers. These genotype and clinical analyses on the largest homogeneous sample of European patients studied to date confirmed that GBA mutations are the most common genetic risk factor for PD, particularly in familial forms.

Genome-wide association study confirms BST1 and suggests a locus on 12q24 as the risk loci for Parkinson's disease in the European population

Abstract: We performed a three-stage genome-wide association study (GWAS) to identify common Parkinson's disease (PD) risk variants in the European population. The initial genome-wide scan was conducted in a French sample of 1039 cases and 1984 controls, using almost 500 000 single nucleotide polymorphisms (SNPs). Two SNPs at SNCA were found to be associated with PD at the genome-wide significance level (P < 3 × 10(-8)). An additional set of promising and new association signals was identified and submitted for immediate replication in two independent case-control studies of subjects of European descent. We first carried out an in silico replication study using GWAS data from the WTCCC2 PD study sample (1705 cases, 5200 WTCCC controls). Nominally replicated SNPs were further genotyped in a third sample of 1527 cases and 1864 controls from France and Australia. We found converging evidence of association with PD on 12q24 (rs4964469, combined P = 2.4 × 10(-7)) and confirmed the association on 4p15/BST1 (rs4698412, combined P = 1.8 × 10(-6)), previously reported in Japanese data. The 12q24 locus includes RFX4, an isoform of which, named RFX4_v3, encodes brain-specific transcription factors that regulate many genes involved in brain morphogenesis and intracellular calcium homeostasis.

Dopamine-dependent reinforcement of motor skill learning: evidence from Gilles de la Tourette syndrome

Abstract: Reinforcement learning theory has been extensively used to understand the neural underpinnings of instrumental behaviour. A central assumption surrounds dopamine signalling reward prediction errors, so as to update action values and ensure better choices in the future. However, educators may share the intuitive idea that reinforcements not only affect choices but also motor skills such as typing. Here, we employed a novel paradigm to demonstrate that monetary rewards can improve motor skill learning in humans. Indeed, healthy participants progressively got faster in executing sequences of key presses that were repeatedly rewarded with 10 euro compared with 1 cent. Control tests revealed that the effect of reinforcement on motor skill learning was independent of subjects being aware of sequence-reward associations. To account for this implicit effect, we developed an actor-critic model, in which reward prediction errors are used by the critic to update state values and by the actor to facilitate action execution. To assess the role of dopamine in such computations, we applied the same paradigm in patients with Gilles de la Tourette syndrome, who were either unmedicated or treated with neuroleptics. We also included patients with focal dystonia, as an example of hyperkinetic motor disorder unrelated to dopamine. Model fit showed the following dissociation: while motor skills were affected in all patient groups, reinforcement learning was selectively enhanced in unmedicated patients with Gilles de la Tourette syndrome and impaired by neuroleptics. These results support the hypothesis that overactive dopamine transmission leads to excessive reinforcement of motor sequences, which might explain the formation of tics in Gilles de la Tourette syndrome.

Bilateral deep brain stimulation of the pallidum for myoclonus-dystonia due to ε-sarcoglycan mutations: a pilot study.

Abstract: OBJECTIVE: To assess the efficacy of bilateral deep brain stimulation of the internal pallidum in patients with myoclonus-dystonia due to genetically proved e-sarcoglycan (SGCE-M-D) deficiency. DESIGN: Patients with documented SGCE-M-D undergoing bilateral deep brain stimulation of the internal pallidum were recruited. Standardized assessments of M-D were videorecorded before surgery and 6 to 9 months and 15 to 18 months after surgery, using the movement and disability subscales of the Burke-Fahn-Marsden Dystonia Rating Scale and the Unified Myoclonus Rating Scale. The analysis was based on blinded evaluation of the recordings. SETTING: Movement disorder unit in a university hospital in Paris. PATIENTS: Five consecutive patients with documented SGCE-M-D. MAIN OUTCOME MEASURES: Myoclonus and dystonia scores at follow-up. RESULTS: The median myoclonus score decreased from 76 before surgery (range, 38-116) to 10 at 6 to 9 months after surgery (range, 6-31). The median dystonia score decreased from 30.0 before surgery (range, 18.5-53.0) to 4.5 after surgery (range, 3.5-16.0). Disability was also improved and symptoms remained stable between the postoperative evaluations. No adverse effects occurred. CONCLUSIONS: Bilateral deep brain stimulation of the internal pallidum is safe and highly effective in this homogeneous population of patients with SGCE-M-D. This therapeutic option should therefore be considered for patients with severe, drug-resistant forms of the disorder.

The COMT Val158Met polymorphism affects the response to entacapone in Parkinson's disease: a randomized crossover clinical trial.

Abstract: Objective In Parkinson disease (PD), the selective C-O-methyltransferase (COMT) inhibitor entacapone prolongs the effect of levodopa on motor symptoms (ON time) by increasing its bioavailability. The COMT Val158Met polymorphism is equally distributed in PD patients and modulates COMT activity, which can be high (Val/Val, COMTHH), intermediate (Val/Met, COMTHL), or low (Met/Met, COMTLL). The objective of this study was to determine the response to entacapone in COMTHH and COMTLL PD patients. Methods Thirty-three PD patients, homozygous for the COMT alleles COMTHH (n = 17) and COMTLL (n = 16), were randomized in a double-blind crossover trial consisting of 2 successive acute levodopa challenges associated with 200mg entacapone or placebo. The primary endpoint was the gain in the best ON time. Secondary endpoints were levodopa pharmacokinetics and COMT activity in red blood cells. Results The gain in the best ON time was higher in COMTHH than in COMTLL patients (39 ± 10 vs 9 ± 9 minutes, p = 0.04, interaction between treatment and genotype). Area under the concentration over time curve of levodopa increased more after entacapone in COMTHH than in COMTLL patients (+62 ± 6% vs +34 ± 8%, p = 0.01). COMT inhibition by entacapone was higher in COMTHH than in COMTLL patients (−0.54 ± 0.07 vs −0.31 ± 0.06 pmol/min/mg protein, p = 0.02). Interpretation The COMTHH genotype in PD patients enhances the effect of entacapone on the pharmacodynamics and pharmacokinetics of levodopa. The response to entacapone after repeated administrations and in heterozygous patients remains to be determined. ANN NEUROL 2011;;69:111–118.

Early postoperative management of DBS in dystonia: programming, response to stimulation, adverse events, medication changes, evaluations, and troubleshooting.

Abstract: Early postoperative management in deep brain stimulation-treated patients with dystonia differs from that of patients with essential tremor and Parkinson's disease, mainly due to the usually delayed effects of deep brain stimulation and the heterogenous clinical manifestation and etiologies of dystonia. The present chapter summarizes the available data about and concentrates on practical clinical aspects of early postoperative management in deep brain stimulation-treated patients with dystonia.

Malignant catatonia due to anti-NMDA-receptor encephalitis in a 17-year-old girl: case report

Abstract: Anti-NMDA-Receptor encephalitis is a severe form of encephalitis that was recently identified in the context of acute neuropsychiatric presentation. Here, we describe the case of a 17-year-old girl referred for an acute mania with psychotic features and a clinical picture deteriorated to a catatonic state. Positive diagnosis of anti-NMDA-receptor encephalitis suggested specific treatment. She improved after plasma exchange and immunosuppressive therapy. Post-cognitive sequelae (memory impairment) disappeared within 2-year follow-up and intensive cognitive rehabilitation.

The improvement of movement and speech during rapid eye movement sleep behaviour disorder in multiple system atrophy

Abstract: Multiple system atrophy is an atypical parkinsonism characterized by severe motor disabilities that are poorly levodopa responsive. Most patients develop rapid eye movement sleep behaviour disorder. Because parkinsonism is absent during rapid eye movement sleep behaviour disorder in patients with Parkinson's disease, we studied the movements of patients with multiple system atrophy during rapid eye movement sleep. Forty-nine non-demented patients with multiple system atrophy and 49 patients with idiopathic Parkinson's disease were interviewed along with their 98 bed partners using a structured questionnaire. They rated the quality of movements, vocal and facial expressions during rapid eye movement sleep behaviour disorder as better than, equal to or worse than the same activities in an awake state. Sleep and movements were monitored using video-polysomnography in 22/49 patients with multiple system atrophy and in 19/49 patients with Parkinson's disease. These recordings were analysed for the presence of parkinsonism and cerebellar syndrome during rapid eye movement sleep movements. Clinical rapid eye movement sleep behaviour disorder was observed in 43/49 (88%) patients with multiple system atrophy. Reports from the 31/43 bed partners who were able to evaluate movements during sleep indicate that 81% of the patients showed some form of improvement during rapid eye movement sleep behaviour disorder. These included improved movement (73% of patients: faster, 67%; stronger, 52%; and smoother, 26%), improved speech (59% of patients: louder, 55%; more intelligible, 17%; and better articulated, 36%) and normalized facial expression (50% of patients). The rate of improvement was higher in Parkinson's disease than in multiple system atrophy, but no further difference was observed between the two forms of multiple system atrophy (predominant parkinsonism versus cerebellar syndrome). Video-monitored movements during rapid eye movement sleep in patients with multiple system atrophy revealed more expressive faces, and movements that were faster and more ample in comparison with facial expression and movements during wakefulness. These movements were still somewhat jerky but lacked any visible parkinsonism. Cerebellar signs were not assessable. We conclude that parkinsonism also disappears during rapid eye movement sleep behaviour disorder in patients with multiple system atrophy, but this improvement is not due to enhanced dopamine transmission because these patients are not levodopa-sensitive. These data suggest that these movements are not influenced by extrapyramidal regions; however, the influence of abnormal cerebellar control remains unclear. The transient disappearance of parkinsonism here is all the more surprising since no treatment (even dopaminergic) provides a real benefit in this disabling disease.

Reinforcement learning and Gilles de la Tourette syndrome: dissociation of clinical phenotypes and pharmacological treatments.

Abstract: Context Gilles de la Tourette syndrome (GTS) is a hyperkinetic movement disorder with heterogeneous phenotypic expression ranging from simple motor and vocal tics to more complex tics associated with psychiatric comorbidities. The heterogeneity of clinical phenotypes may relate to the dysfunction of distinct frontal cortex–basal ganglia circuits. Objectives To assess the hypothesis that simple motor tics and comorbid obsessive-compulsive disorders are associated with dysfunction of motor and reward circuits, respectively, and to assess the effects of various antipsychotic medications because they are known to reduce motor tics and interact with dopamine-related reward processing. Design Sixty patients with GTS were divided into different subgroups depending on their clinical phenotypes and pharmacological treatments. The GTS patients and healthy control subjects underwent functional magnetic resonance imaging while they performed an instrumental learning task that involved adjusting choices between 2 responses (left- or right-hand movements) based on outcomes (reward or no reward). Setting Reference center for GTS, Centre de NeuroImagerie de recherche (CENIR) Paris, France. Patients Sixty GTS patients and 50 controls. Results Movement-related activation in motor circuits was diminished in GTS patients with simple tics only. Reward-related activation in limbic circuits was independently reduced by the following 2 factors: the presence of associated obsessive-compulsive symptoms (mostly compulsions) and the presence of medication with typical antipsychotics (dopamine receptor antagonists). Computational modeling with standard reinforcement learning algorithms indicated that, for both factors, the diminished reward-related activation could account for the impaired choice performance. Reinforcement learning was not affected by aripiprazole, a recent medication that acts as a partial dopamine agonist. Conclusions These results support the hypothesized correspondence between clinical phenotypes and frontal cortex–basal ganglia circuits. Antipsychotic treatment effects comply with formal conceptions that dopamine serves as a teaching signal for reinforcement learning. Furthermore, we suggest that, unlike typical antipsychotics, aripiprazole may preserve reward sensitivity and hence avoid blunting motivational drives.

Long-term outcome of 32 patients with chorea and systemic lupus erythematosus or antiphospholipid antibodies.

Abstract: OBJECTIVE: The aim of this work was to describe chorea during systemic lupus erythematosus or antiphospholipid antibodies and its long-term outcome. METHODS: We retrospectively analyzed clinical features, laboratory findings, imaging characteristics, and outcome in a series of 32 patients. RESULTS: Most patients were women (28 of 32), and mean age at onset of chorea was 20.6 (9-62) years. Chorea was inaugural for 28 patients. Improvement was observed with various treatments. During follow-up (12.2 ± 11.3 years), severe manifestations of systemic lupus erythematosus were rare. Antiphospholipid antibodies were repeatedly positive for 90% of the patients. Twelve patients developed arterial thrombosis. Prophylactic treatment with antithrombotic therapy might reduce the risk of further thrombosis (8% versus 57%; P = 0.01). Cardiac valvulopathy occurred in 22 patients during follow-up. Chorea relapsed in 8 cases. CONCLUSIONS: Chorea had a good outcome in itself. This long-term follow-up shows, for the first time, that these patients have substantial risk for further arterial thrombosis.

Evidence for the re-enactment of a recently learned behavior during sleepwalking

Abstract: Animal studies have shown that sequenced patterns of neuronal activity may be replayed during sleep. However, the existence of such replay in humans has not yet been directly demonstrated. Here we studied patients who exhibit overt behaviors during sleep to test whether sequences of movements trained during the day may be spontaneously reenacted by the patients during sleep. We recruited 19 sleepwalkers (who displayed complex and purposeful behaviors emerging from non REM sleep), 20 patients with REM sleep behavior disorder (who enacted their dreams in REM sleep) and 18 healthy controls. Continuous video sleep recordings were performed during sleep following intensive training on a sequence of large movements (learned during a variant of the serial reaction time task). Both patient groups showed learning of the intensively trained motor sequence after sleep. We report the re-enactment of a fragment of the recently trained motor behavior during one sleepwalking episode. This study provides, to our knowledge, the first evidence of a temporally-structured replay of a learned behavior during sleep in humans. Our observation also suggests that the study of such sleep disorders may provide unique and critical information about cognitive functions operating during sleep.

Impaired saccadic adaptation in DYT11 dystonia

Abstract: Background Recent neuroimaging studies point to a possible pathophysiological role of cerebellar dysfunction in dystonia. The authors investigated the association between sensorimotor adaptation, cerebellar dysfunction and the myoclonus–dystonia phenotype. Methods The authors prospectively analysed reactive saccade adaptation in a genetically homogeneous group of 14 patients with DYT11 dystonia owing to a mutation of the SGCE gene. The authors used a backward reactive saccade adaptation task, a well-characterised experimental oculomotor paradigm involving the cerebellum. The principle of this paradigm is to simulate a spatial error in saccade generation by systematically shifting a visual target during saccade execution. Repetition of this systematic error induces a gradual decrease in the initial saccade amplitude, reflecting an adaptive phenomenon. Results Saccade adaptation was significantly lower in the DYT11 patients than in healthy controls (mean value: 8.9%±4.5% vs 21.6%±4.5%; p=8.3×10 −6 ). The time course of adaptation also differed between the patients and controls (p=0.002), reflecting the slower saccadic adaptation in the patients. Conclusions This study provides the first neurophysiological evidence of cerebellar dysfunction in DYT11 dystonia and supports a role of cerebellar dysfunction in the myoclonus–dystonia phenotype.

Screening of the THAP1 gene in patients with early-onset dystonia: myoclonic jerks are part of the dystonia 6 phenotype

Abstract: Mutations in the THAP1 gene are responsible for an autosomal dominant form of primary torsion dystonia 6 (DYT6) [1]. Patients with DYT6 are characterized usually by childhoodor early-adulthood-onset dystonia, affecting brachial, cervical, or cranial muscles with possible progression towards generalized dystonia [2–5]. We analyzed the three exons of the THAP1 gene by direct sequencing in 113 primary dystonia cases from France, European countries, and North Africa. Familial or isolated cases with primary dystonias with early-onset ( C/p.Ser6Pro and c.215T>G/p.Leu72Arg) which affect residues that are highly conserved across

Dystonic tremor caused by mutation of the glucose transporter gene GLUT1.

Abstract: Glucose transporter 1 deficiency syndrome (GLUT1-DS) is due to heterozygous mutation of the glucose transporter type 1 gene (GLUT1/SLC2A1). GLUT1-DS is characterized by movement disorders, including paroxysmal exercise-induced dystonia (PED), as well as seizures, mental retardation and hypoglycorrhachia. Tremor was recently shown to be part of the phenotype, but its clinical and electrophysiological features have not yet been described in detail, and GLUT1 tremor reports are rare. We describe two patients, a young woman and her mother, who were referred to us for tremor. We also systematically review published cases of GLUT1-DS with tremor (14 cases, including ours), focusing on clinical features. In most cases (10/14), the tremor, which involved the limbs and voice, fulfilled clinical criteria for dystonic tremor (DT), occurring in body areas affected by dystonia. Tremor was the only permanent symptom in 2 cases. Recordings, reported here for the first time, showed an irregular 6- to 8.5-Hz tremor compatible with DT in our two patients. These findings show that tremor, and particularly DT, may be a presenting symptom of GLUT1-DS. Patients who present with dystonic tremor, with or without mental retardation, seizures, movement disorders and/or a family history, should therefore be screened for GLUT1-DS.

Somatosensory cortical remodelling after rehabilitation and clinical benefit of in writer's cramp

Abstract: In order to explore the pathophysiological basis of a new rehabilitation therapy in writer's cramp (WC), healthy controls, untreated WC patients and WC patients who recovered a legible handwriting after rehabilitation were explored using magnetoencephalography, and the somatosensory evoked fields of fingers I, II, III and V in the sensory cortex were studied. In the cortex controlling the dystonic limb, the size of the hand representation in the trained patients was similar to that of healthy controls, and significantly different from that of untrained patients. Trained patients exhibited 'super-normal' reorganisation of the finger maps. In the cortex controlling the non-dystonic limb, there was little difference between trained and untrained patients, and the hand representation was enlarged and disorganised. The authors hypothesise that prolonged tailored rehabilitation in WC may induce long-term plasticity phenomena, lateralised to the cortex controlling the dystonic hand.

Movement disorders in 2010: Parkinson disease-symptoms and treatments.

Abstract: Research conducted in 2010 has shown that surgical and dopaminergic treatments for Parkinson disease (PD) can promote the development of nonmotor symptoms, such as impulse control disorders and apathy. Lesions in cholinergic pathways have also been shown to partly underlie deficits in gait and posture in patients with advanced PD.

Acute psychosis in anti-NMDA-receptor encephalitis

Abstract: In December 1999, a 22-year-old woman presented with stooped posture, amimia and a reduced speech fluency with disorganized content. She had complained of fatigue and headache for four weeks. Acute psychosis was diagnosed by a psychiatrist and treated with haloperidol, cyamemazine and loxapine. High-grade fever occurred and over 10 days, she became mute and akinetic, with rigidity, and catalepsy. She was intubated because of hypoventilation. Off sedation, she was unresponsive to voice and pain. She developed severe movement disorders characterized by rhythmic movements with complex patterns of mouth opening, chewing, palatal elevation and asymmetric grimacing, rotation of shoulders, elbow flexion, spreading of fingers superimposed to dystonic posturing of the right arm and neck and trunk hyperextension. Routine laboratory testing was unremarkable except for elevated blood creatine phosphokinase (CPK) level. A comprehensive blood immunological and microbiological tests panel was negative. Cerebrospinal fluid (CSF) revealed a pleocytosis (51 cells/microliter, 90% mononuclear cells) with normal protein and glucose levels. Extensive CSF analysis for bacterial, viral and fungal agents and cytology were unrevealing. Brain MRI was normal. Electroencephalogram demonstrated a 6 Hz polymorphic theta activity without epileptiform features. Neuroleptic treatment was stopped. After failure of amoxicillin and acyclovir therapy, treatment with intravenous high-dose prednisolone was started. The patient dramatically improved within a few days and was weaned from mechanical ventilation after one month. Eight months after discharge, she was under low-dose oral prednisone and had fully recovered. In June 2003, as she was treated with 7 mg prednisone daily, she had a single generalized seizure, then developed dramatic mood swings, echophenomena and orofacial dyskinesia. Brain MRI was normal. EEG showed a bitemporal polymorphic theta waves with ictal discharge in the left temporal lobe. CSF revealed an isolated pleocytosis (26 cells/microliter, 90% mononuclear cells). Treatment with intravenous methylprednisolone 500 mg/d for three days followed by prednisone 50 mg daily was started with oral methotrexate 15 mg/week. Methotrexate therapy was begun because of the severity of neurological symptoms and because of the relapse of symptoms under corticosteroid therapy. Psychiatric signs and dyskinesia improved slowly. In September 2003, she was considered normal. Methotrexate was stopped in November 2006. In January 2009, while she was treated with 5 mg/d of prednisone, there was a recurrence of emotional disturbances and depression, rapidly followed by cognitive decline and prominent schizophrenia-like symptoms. The patient was admitted in a psychiatry department and was treated with haloperidol. Psychiatric signs worsened and high-grade fever occurred. Physical examination showed generalized hypertonia, frequent facial grimacing, and intermittent dystonic postures of the arms. Brain MRI was normal. CSF analysis showed a white blood cell count of five cells/mL with normal glucose and protein levels. An 18 FDG PET-scan was not performed. The diagnosis of encephalitis associated with anti-N-methyl-D-aspartate (NMDA)-receptor antibodies was suspected. Antibodies to NMDA-receptor were disclosed in CSF [1]. Whole body CT scan and pelvic MRI were normal. At that time, evaluation of cognitive functions was not performed. Haloperidol was stopped. Intravenous immunoglobulin (IVIG) 0.4 g/kg body weight/day for five days every three weeks was started. The patient rapidly improved. After six months, psychiatric and neurological evaluation (including cognitive functions) were normal and testing for anti-NMDA-receptor was negative in CSF. Eighteen months after the third relapse of the disease, the patient was symptom-free under 10 mg/d of prednisone and has returned to full-time work.

Idiopathic adult onset action dystonia of the lower limbs: case reports.

Abstract: Lower limb dystonia (LLD) usually heralds a generalized primary dystonia syndrome in children, particularly DYT 1 [4]. In adults, the syndrome is much less common and rarely associated with a genetic cause [3, 5, 6, 10–12]. We describe two cases of idiopathic action-induced LLD. A 52-year-old woman came to our institution with a 3-year history of walking difficulties. Clinically, dystonia was observed only while walking, with worsening after a few steps. The abnormal movements consist of an initial excessive flexion of the right thigh, followed by an exaggerated external rotation of the right leg. (Video, segment 1) Neurological examination was otherwise normal. The involuntary movements were not observed while walking up stairs, down stairs, sideways, backwards, and over a straight line; deterioration was observed while running, walking fast, barefoot, and on wet floor. There was no previous exposure to dopamine antagonists, no history of psychiatric disorders, pending litigation or secondary gain at work. Blood count and hepatic function tests were normal. Genetic test for DYT 1 was negative. Electromyography (EMG) and brain MRI were normal. Lumbar spine MRI showed mild spondylosis without nerve root compression. The patient received treatment with amitriptyline, levodopa, and trihexyphenidyl, without significant improvement. A 54-year-old woman came to our institution in 1999 for evaluation of right thigh pain suggestive of sciatica. Neurological examination showed action dystonia while walking down stairs, with increased flexion of the right thigh at the beginning of the movement, accompanied by mild external rotation of the leg, foot dorsiflexion, and toe extension (Video, segment 2); these involuntary movements were first noticed in 1990, and were not disabling. Dystonia improves considerably while going up stairs, descending backwards and walking on a flat surface. The left leg was not affected. Maneuvers to test root compression were negative. There were no arguments for a psychogenic phenomenon such as influence of distraction or suggestion. There was no history of mood disorders. EMG and lumbar spine MRI showed mild root compression. She received oral analgesics and physical therapy. The thigh pain resolved 1 year later. Dystonia was left untreated due to lack of physical limitation. After 20 years, LLD has mildly improved without functional or anatomical spreading. We present two cases of a rare type of action-induced LLD, without arguments supporting a psychogenic etiology. Pure psychogenic gait disturbance resembling LLD seems to be a very rare phenomenon [1]. Adult onset LLD should ordinarily raise the suspicion of Parkinson’s disease, [2] but this seems unlikely in our patients, as both had long and stable evolutions without other extrapyramidal manifestations. Electronic supplementary material The online version of this article (doi:10.1007/s00415-011-5989-x) contains supplementary material, which is available to authorized users.

Les nouvelles approches des dystonies (clinique, génétique et hypothèses physio-pathologiques)

Abstract: RESUME La dystonie se definit par la presence de mouvements anormaux et de postures involontaires qui peuvent toucher tout (forme generalisee) ou partie (formes focales) du corps. Un grand nombre de dystonies sont identifiees a ce jour, en particulier les formes genetiques monogeniques (exemple DYT1, DYT6) et les formes liees a des causes secondaires telles que maladies metaboliques, lesions cerebrales (incluant anoxie neonatale) et causes iatrogenes (post-neuroleptiques). La presence de myoclonies (myoclonus-dystonia DYT11) ou d’un syndrome parkinsonien (rapid-onset dystonia parkinsonism DYT12) permet de distinguer des sous-types specifiques de meme que le caractere intermittent caracterise le groupe des dyskinesies paroxystiques. La demarche etiologique depend de la presentation clinique, de l’âge de debut, du mode evolutif, de la presence de signes associes et des anomalies visibles en IRM. Un dysfonctionnement des ganglions de la base et du circuit sensori-moteur constitue le cœur de la physiopathologie de la dystonie. Plus recemment des anomalies de la plasticite corticale et des dysfonctions du cervelet et des circuits cerebello-thalamiques ont ete egalement mise en evidence Cette revue a pour objectif de mettre en lumiere les caracteres principaux de differents types de dystonie tant sur le plan clinique qu’etiologique ou physiopathologique.

Medical aspects of the medical treatment in dystonia

Abstract: Dystonias encompass a wide range of movement disorders characterized mainly by abnormal postures or movements. Because of this semiological and etiological heterogeneity, robust clinical trials are rare. Specific etiological treatments are available for only a few forms (e.g. Wilson's disease and dopa-responsive dystonia), which places the emphasis on symptomatic treatment. This is based on the combinations of three complementary approaches: drug therapy (anticholinergics, tetrabenazine and benzodiazepines are first-line drugs, but many others have been tested in small clinical trials), botulinium toxin injections in case of focal dystonia or focal targets in patients with more widespread dystonia, and physiotherapy. This review provides a short overview of available treatments and proposes a basic therapeutic strategy for dystonic patients.