ON/OFF non-motor evaluation: a new way to evaluate non-motor fluctuations in Parkinson's disease.

BACKGROUND: NMF are currently poorly evaluated in therapeutic decisions. A quantification of their severity would facilitate their integration. The objective of this study was to validate an autoquestionnaire evaluating the severity of non-motor fluctuations (NMF) in Parkinson's disease (PD). METHODS: Patients with PD were included in presurgical situation for deep brain stimulation of subthalamic nuclei. They participated in the PREDISTIM cohort (a study evaluating the predictive factors for therapeutic response of subthalamic stimulation in PD) in 17 centres in France. Our questionnaire, resulting from previous phases of development, included 11 non-motor symptoms (NMS). Their severity ranged from 0 to 10 and was assessed in OFF and then ON-Dopa to study their fluctuations. RESULTS: 310 patients were included, of whom 98.8% had NMS and 98.0% had NMF. Each NMS was significantly improved by L-Dopa (decrease in severity score ranging from 43.1% to 69.9%). Fatigue was the most frequent and most severe NMS. NMS were considered more bothersome than motor symptoms by 37.5% of patients in OFF-Dopa and 34.9% in ON-Dopa. CONCLUSIONS: This is the first questionnaire allowing a real-time quantification of the severity of NMS and their fluctuation with levodopa. It was able to confirm and measure the effect of L-dopa and show differences according to the patients and the NMS. It differs from other questionnaires by its measurement at a precise moment of the severity of the NMS, allowing its use during pretherapeutic assessments.Our questionnaire has been validated to measure the severity of NMF. It will be able to quantify the non-motor effect of anti-parkinsonian treatments and could facilitate the integration of NMF in therapeutic decisions.

Fixel-Based Analysis Reveals Whole-Brain White Matter Abnormalities in Cervical Dystonia.

BACKGROUND: Cervical dystonia (CD) is a form of isolated focal dystonia typically associated to abnormal head, neck, and shoulder movements and postures. The complexity of the clinical presentation limits the investigation of its pathophysiological mechanisms, and the neural networks associated to specific motor manifestations are still the object of debate. OBJECTIVES: We investigated the morphometric properties of white matter fibers in CD and explored the networks associated with motor symptoms, while regressing out nonmotor scores. METHODS: Nineteen patients affected by CD and 21 healthy controls underwent diffusion-weighted magnetic resonance imaging. We performed fixel-based analysis, a novel method evaluating fiber orientation within specific fiber bundles, and compared fiber morphometric properties between groups. Moreover, we correlated fiber morphometry with the severity of motor symptoms in patients. RESULTS: Compared to controls, patients exhibited decreased white matter fibers in the right striatum. Motor symptom severity negatively correlated with white matter fibers passing through inferior parietal areas and the head representation area of the motor cortex. CONCLUSIONS: Abnormal white matter integrity at the basal ganglia level may affect several functional networks involved, for instance, in motor preparation and execution, visuomotor coordination, and multimodal integration. This may result in progressive maladaptive plasticity, culminating in overt symptoms of dystonia. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

[Understanding functional neurological disorders: From biological markers to pathophysiological models]. / Étiopathogénie des troubles neurologiques fonctionnels : marqueurs biologiques et modèles théoriques.

OBJECTIVES: Functional neurological disorders have witnessed intense research activity in the fields of structural and functional neuroimaging for more than twenty years. Thus, we propose a synthesis of recent research findings and etiological hypotheses that have been proposed so far. This work should help clinicians to better understand the nature of the mechanisms involved, but also help patients to increase their knowledge about the biological features underlying their functional symptoms. METHODS: We carried out a narrative review of international publications dealing with neuroimaging and biology of functional neurological disorders, from 1997 to 2023. RESULTS: Several brain networks underlie functional neurological symptoms. These networks play a role in the management of cognitive resources, in attentional control, emotion regulation, in agency and in the processing of interoceptive signals. The mechanisms of the stress response are also associated with the symptoms. The biopsychosocial model helps to better understand predisposing, precipitating, and perpetuating factors involved. The functional neurological phenotype results from the interaction between: i) a specific pre-existing vulnerability resulting from biological background and epigenetic modifications, and ii) exposure to stress factors, according to the stress-diathesis model. This interaction causes emotional disturbances including hypervigilance, lack of integration of sensations and affects, and emotional dysregulation. These characteristics in turn impact the cognitive, motor and affective control processes related with the functional neurological symptoms. CONCLUSIONS: A better knowledge of the biopsychosocial determinants of brain network dysfunctions is necessary. Understanding them would help developing targeted treatments, but is also critical for patients care.

[Validated care programs for patients with functional neurological disorders]. / Modèles de soins validés pour les patients souffrant de troubles neurologiques fonctionnels.

Functional neurological disorder (FND) is a common cause of persistent and disabling neurological symptoms. Diagnostic delay may lead to no treatment, inappropriate treatment or even iatrogenic symptoms. Yet, several treatments significantly reduce physical symptoms and improve functioning in FND patients even though not all patients respond to the currently available treatments. This review aims to describe the range of evidence-based rehabilitative and/or psychological therapeutic approaches available for FND patients. The most effective treatments are multidisciplinary and coordinated; using an outpatient or inpatient setting. Building a network of FND-trained healthcare professionals around the patient is an essential aspect of optimal patient management. Indeed, a supportive environment coupled with a collaborative therapeutic relationship improves understanding of FND and appears to help patients engage in appropriate treatments. Patients need to be invested in their own care and have to understand that recovery may depend on their commitment. The conventional treatment combines psychoeducation, physical rehabilitation and psychotherapy (cognitive and behavioral therapy, hypnosis, psychodynamic interpersonal therapy). Early referral of patients to physical therapy is recommended; however, the optimal parameters of treatment, duration and intensity are unknown and seem to vary with the severity and chronicity of symptoms. The goal is to minimize self-awareness by diverting attention or by stimulating automatically generated movements with non-specific and gradual exercises. The use of compensatory technical aids should be avoided as much as possible. Psychotherapeutic management should encourage self-evaluation of cognitive distortions, emotional reactions and maladaptive behaviors while empowering the patient in managing symptoms. Symptom management can use anchoring strategies to fight against dissociation. The aim is to connect to the immediate environment and to enrich one's sensoriality. The psychological interventions should then be adapted to the individual psychopathology, cognitive style and personality functioning of each patient. There is currently no known curative pharmacological treatment for FND. The pharmacological approach rather consists of progressively discontinuing medication that was introduced by default and that could lead to undesirable side effects. Finally, neurostimulation (transcranial magnetic stimulation, transcranial direct current stimulation) can be effective on motor FND.

Impact of HIV impact on outcomes of deep-brain stimulation of the subthalamic nucleus for Parkinson's disease.

BACKGROUND AND PURPOSE: Middle-aged persons living with HIV (PLHIV) have a heightened risk of more concomitant age-related comorbidities that are acknowledged as signs of poorer prognosis after deep-brain stimulation of the subthalamic nucleus (STN-DBS) at younger-than-expected ages. To assess the beneficial and adverse effects of STN-DBS in PLHIV with Parkinson's disease (PD). METHODS: We retrospectively included nine PLHIV with PD who had sustained virological control. Patients were followed up for 7 ± 4 years. RESULTS: Patients' mean ages at PD onset and STN-DBS were 45 ± 15 and 53 ± 16 years, respectively. At STN-DBS, mean HIV infection and PD durations were 15 ± 12 and 8 ± 4 years, respectively. STN-DBS significantly improved 1-year Unified Parkinson's Disease Rating Scale (UPDRS)-III scores (71%), daily off-time (63%), motor fluctuations (75%) and daily levodopa-equivalent dose (68%); mean 5-year UPDRS-III score and motor fluctuation improvements remained ~45%. Impulse control disorders (affecting 6/9 patients) fully resolved after STN-DBS. Postoperative course was uneventful. No serious adverse events occurred during follow-up. CONCLUSION: Our findings indicate that STN-DBS is a safe and effective treatment for PLHIV with PD.

Early-Onset Parkinsonism Is a Manifestation of the PPP2R5D p.E200K Mutation.

PPP2R5D-related neurodevelopmental disorder is characterized by a range of neurodevelopmental and behavioral manifestations. We report the association of early-onset parkinsonism with the PPP2R5D p.E200K mutation. Clinical characterization and exome sequencing were performed on three patients, with postmortem neuropathologic examination for one patient. All patients had mild developmental delay and developed levodopa-responsive parkinsonism between the ages of 25 and 40 years. The PPP2R5D c.598G>A (p.E200K) mutation was identified in all patients. Neuropathologic examination demonstrated uneven, focally severe neuronal loss and gliosis in the substantia nigra pars compacta, without Lewy bodies. Our findings suggest the PPP2R5D p.E200K mutation to be a possible new cause of early-onset parkinsonism. ANN NEUROL 2020;88:1028-1033.

Impact of Subthalamic Deep Brain Stimulation on Impulse Control Disorders in Parkinson's Disease: A Prospective Study.

BACKGROUND: Impact of subthalamic deep brain stimulation (DBS) on impulse control disorders (ICD) in Parkinson's disease (PD) remains controversial. OBJECTIVES: The objectives of this study were to analyze the natural history of ICD between baseline and 1 year after subthalamic DBS in patients with PD and to identify predictive factors, taking into account the positions of the active contact and stimulation parameters. METHODS: We analyzed postoperative modifications of ICD based on the multicentric, prospective Predictive Factors and Subthalamic Stimulation in Parkinson's Disease cohort. ICD status and Ardouin Scale of Behaviour in PD were assessed at baseline and 1 year following subthalamic DBS. Location of active contacts within the 3 subthalamic nucleus functional territories was investigated. RESULTS: A total of 217 were patients included. Of the patients, 10.6% had ICD at baseline of which 95.6% improved at 1 year following subthalamic DBS; 3.6% of the patients experienced de novo ICD at 1 year following subthalamic DBS. Dopamine agonist dose reduction (from 309.8 to 109.3 mg) was the main driver of ICD regression (P = 0.05). Higher preoperative dyskinesias were associated with poorer ICD evolution (P = 0.04). Whereas baseline apathy was a risk factor of de novo ICD (P = 0.02), ICD improvement correlated with postoperative apathy (P = 0.004). Stimulation power and position of active contacts-mainly located within the sensorimotor part of the subthalamic nucleus-did not influence ICD. CONCLUSIONS: This 1-year, postoperative follow-up study showed ICD regression and dopaminergic drug reduction with optimal position of the active contacts within the subthalamic nucleus. Whereas patients with PD with preoperative ICD were prone to postoperative apathy, we also showed that those with preoperative apathy had a higher risk to experience postoperative de novo ICD, further highlighting the meaningful influence of postoperative management of dopaminergic medication on outcome and the continuum between apathy and ICD. © 2020 International Parkinson and Movement Disorder Society.

The supplementary motor area modulates interhemispheric interactions during movement preparation.

The execution of coordinated hand movements requires complex interactions between premotor and primary motor areas in the two hemispheres. The supplementary motor area (SMA) is involved in movement preparation and bimanual coordination. How the SMA controls bimanual coordination remains unclear, although there is evidence suggesting that the SMA could modulate interhemispheric interactions. With a delayed-response task, we investigated interhemispheric interactions underlying normal movement preparation and the role of the SMA in these interactions during the delay period of unimanual or bimanual hand movements. We used functional MRI and transcranial magnetic stimulation in 22 healthy volunteers (HVs), and then in two models of SMA dysfunction: (a) in the same group of HVs after transient disruption of the right SMA proper by continuous transcranial magnetic theta-burst stimulation; (b) in a group of 22 patients with congenital mirror movements (CMM), whose inability to produce asymmetric hand movements is associated with SMA dysfunction. In HVs, interhemispheric connectivity during the delay period was modulated according to whether or not hand coordination was required for the forthcoming movement. In HVs following SMA disruption and in CMM patients, interhemispheric connectivity was modified during the delay period and the interhemispheric inhibition was decreased. Using two models of SMA dysfunction, we showed that the SMA modulates interhemispheric interactions during movement preparation. This unveils a new role for the SMA and highlights its importance in coordinated movement preparation.

Orthostatic tremor: a cerebellar pathology?

SEE MUTHURAMAN ET AL DOI101093/AWW164 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Primary orthostatic tremor is characterized by high frequency tremor affecting the legs and trunk during the standing position. Cerebellar defects were suggested in orthostatic tremor without direct evidence. We aimed to characterize the anatomo-functional defects of the cerebellar motor pathways in orthostatic tremor. We used multimodal neuroimaging to compare 17 patients with orthostatic tremor and 17 age- and gender-matched healthy volunteers. Nine of the patients with orthostatic tremor underwent repetitive transcranial stimulation applied over the cerebellum during five consecutive days. We quantified the duration of standing position and tremor severity through electromyographic recordings. Compared to healthy volunteers, grey matter volume in patients with orthostatic tremor was (i) increased in the cerebellar vermis and correlated positively with the duration of the standing position; and (ii) increased in the supplementary motor area and decreased in the lateral cerebellum, which both correlated with the disease duration. Functional connectivity between the lateral cerebellum and the supplementary motor area was abnormally increased in patients with orthostatic tremor, and correlated positively with tremor severity. After repetitive transcranial stimulation, tremor severity and functional connectivity between the lateral cerebellum and the supplementary motor area were reduced. We provide an explanation for orthostatic tremor pathophysiology, and demonstrate the functional relevance of cerebello-thalamo-cortical connections in tremor related to cerebellar defects.

Mini-Exome Coupled to Read-Depth Based Copy Number Variation Analysis in Patients with Inherited Ataxias.

Next-generation sequencing (NGS) has an established diagnostic value for inherited ataxia. However, the need of a rigorous process of analysis and validation remains challenging. Moreover, copy number variations (CNV) or dynamic expansions of repeated sequence are classically considered not adequately detected by exome sequencing technique. We applied a strategy of mini-exome coupled to read-depth based CNV analysis to a series of 33 patients with probable inherited ataxia and onset <50 years. The mini-exome consisted of the capture of 4,813 genes having associated clinical phenotypes. Pathogenic variants were found in 42% and variants of uncertain significance in 24% of the patients. These results are comparable to those from whole exome sequencing and better than previous targeted NGS studies. CNV and dynamic expansions of repeated CAG sequence were identified in three patients. We identified both atypical presentation of known ataxia genes (ATM, NPC1) and mutations in genes very rarely associated with ataxia (ERCC4, HSD17B4). We show that mini-exome bioinformatics data analysis allows the identification of CNV and dynamic expansions of repeated sequence. Our study confirms the diagnostic value of the proposed genetic analysis strategy. We also provide an algorithm for the multidisciplinary process of analysis, interpretation, and validation of NGS data.

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

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.See Raethjen and Muthuraman (doi:10.1093/brain/awv238) for a scientific commentary on this article.

Defective cerebellar control of cortical plasticity in writer's cramp.

A large body of evidence points to a role of basal ganglia dysfunction in the pathophysiology of dystonia, but recent studies indicate that cerebellar dysfunction may also be involved. The cerebellum influences sensorimotor adaptation by modulating sensorimotor plasticity of the primary motor cortex. Motor cortex sensorimotor plasticity is maladaptive in patients with writer's cramp. Here we examined whether putative cerebellar dysfunction in dystonia is linked to these patients' maladaptive plasticity. To that end we compared the performances of patients and healthy control subjects in a reaching task involving a visuomotor conflict generated by imposing a random deviation (-40° to 40°) on the direction of movement of the mouse/cursor. Such a task is known to involve the cerebellum. We also compared, between patients and healthy control subjects, how the cerebellum modulates the extent and duration of an ongoing sensorimotor plasticity in the motor cortex. The cerebellar cortex was excited or inhibited by means of repeated transcranial magnetic stimulation before artificial sensorimotor plasticity was induced in the motor cortex by paired associative stimulation. Patients with writer's cramp were slower than the healthy control subjects to reach the target and, after having repeatedly adapted their trajectories to the deviations, they were less efficient than the healthy control subjects to perform reaching movement without imposed deviation. It was interpreted as impaired washing-out abilities. In healthy subjects, cerebellar cortex excitation prevented the paired associative stimulation to induce a sensorimotor plasticity in the primary motor cortex, whereas cerebellar cortex inhibition led the paired associative stimulation to be more efficient in inducing the plasticity. In patients with writer's cramp, cerebellar cortex excitation and inhibition were both ineffective in modulating sensorimotor plasticity. In patients with writer's cramp, but not in healthy subjects, behavioural parameters reflecting their capacity for adapting to the rotation and for washing-out of an earlier adaptation predicted the efficacy of inhibitory cerebellar conditioning to influence sensorimotor plasticity: the better the online adaptation, the smaller the influence of cerebellar inhibitory stimulation on motor cortex plasticity. Altered cerebellar encoding of incoming afferent volleys may result in decoupling the motor component from the afferent information flow, and also in maladjusted sensorimotor calibration. The loss of cerebellar control over sensorimotor plasticity might also lead to building up an incorrect motor program to specific adaptation tasks such as writing.

RAD51 deficiency disrupts the corticospinal lateralization of motor control.

Mirror movements are involuntary symmetrical movements of one side of the body that mirror voluntary movements of the other side. Congenital mirror movement disorder is a rare condition characterized by mirror movements that persist throughout adulthood in subjects with no other clinical abnormalities. The affected individuals have mirror movements predominating in the muscles that control the fingers and are unable to perform purely unimanual movements. Congenital mirror movement disorder thus provides a unique paradigm for studying the lateralization of motor control. We conducted a multimodal, controlled study of patients with congenital mirror movements associated with RAD51 haploinsufficiency (n = 7, mean age 33.3 ± 16.8 years) by comparison with age- and gender-matched healthy volunteers (n = 14, mean age 33.9 ± 16.1 years). We showed that patients with congenital mirror movements induced by RAD51 deficiency had: (i) an abnormal decussation of the corticospinal tract; (ii) abnormal interhemispheric inhibition and bilateral cortical activation of primary motor areas during intended unimanual movements; and (iii) an abnormal involvement of the supplementary motor area during both unimanual and bimanual movements. The lateralization of motor control thus requires a fine interplay between interhemispheric communication and corticospinal wiring. This fine interplay determines: (i) the delivery of appropriate motor plans from the supplementary motor area to the primary motor cortex; (ii) the lateralized activation of the primary motor cortex; and (iii) the unilateral transmission of the motor command to the limb involved in the intended movement. Our results also unveil an unexpected function of RAD51 in corticospinal development of the motor system.

[Current issues surrounding Parkinson's disease]. / Enjeux actuels autour de la maladie de Parkinson.

The number of people suffering from Parkinson's disease is constantly increasing. Diagnosis is based on the motor and non-motor symptoms present throughout the course of the disease. To preserve patient autonomy, the main therapeutic challenge is to propose a treatment adapted to each profile, in conjunction with the implementation of non-medication strategies, reflection on improved accessibility to existing medication and research into innovative therapies.

The impact of subthalamic deep-brain stimulation in restoring motor symmetry in Parkinson's disease patients: a prospective study.

BACKGROUND AND OBJECTIVES: The impact of subthalamic deep-brain stimulation (STN-DBS) on motor asymmetry and its influence on both motor and non-motor outcomes remain unclear. The present study aims at assessing the role of STN-DBS on motor asymmetry and how its modulation translates into benefits in motor function, activities of daily living (ADLs) and quality of life (QoL). METHODS: Postoperative motor asymmetry has been assessed on the multicentric, prospective Predictive Factors and Subthalamic Stimulation in Parkinson's Disease cohort. Asymmetry was evaluated at both baseline (pre-DBS) and 1 year after STN-DBS. A patient was considered asymmetric when the right-to-left MDS-UPDRS part III difference was ≥ 5. In parallel, analyses have been carried out using the absolute right-to-left difference. The proportion of asymmetric patients at baseline was compared to that in the post-surgery evaluation across different medication/stimulation conditions. RESULTS: 537 PD patients have been included. The proportion of asymmetric patients was significantly reduced after both STN-DBS and medication administration (asymmetric patients: 50% in pre-DBS MedOFF, 35% in MedOFF/StimON, 26% in MedON/StimOFF, and 12% in MedON/StimON state). Older patients at surgery and with higher baseline UPDRS II scores were significantly less likely to benefit from STN-DBS at the level of motor asymmetry. No significant correlation between motor asymmetry and ADLs (UPDRS II) or overall QoL (PDQ-39) score was observed. Asymmetric patients had significantly higher mobility, communication, and daily living PDQ-39 sub-scores. CONCLUSIONS: Both STN-DBS and levodopa lead to a reduction in motor asymmetry. Motor symmetry is associated with improvements in certain QoL sub-scores.

Subcutaneous apomorphine in the treatment of progressive supranuclear palsy and corticobasal syndrome: A preliminary study of 7 cases.

BACKGROUND: Treatment of tauopathies such as Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD) remains a major challenge. These neurodegenerative extrapyramidal movement disorders share phenotypic overlap and are usually painful. Continuous subcutaneous apomorphine infusion (CSAI) is commonly used in patients with advanced Parkinson's disease (PD) to alleviate motor and non-motor fluctuations. OBJECTIVE: We investigated the effects of CSAI especially on pain and, on quality of life in 7 patients with PSD or CBD. METHODS: This is an observational "real life" surveillance-based study. The patients received low dosages of subcutaneous apomorphine (2.24mg ± 0.8/h) in addition to their usual treatment. The Verbal Rating Scale for Pain (VRS) was used to assess changes in pain level and the clinical global impression-improvement scale (CGI-I) was used to assess changes in patient's illness during six months of treatment. RESULTS: All patients treated with apomorphine experienced an improvement of their well-being remaining stable across the study period with a CGI-I = 2.6 ± 0.5 and 2.6 ± 0.6 at 3 and 6 months, respectively. All patients experienced a significant pain reduction with a VRS = 7 ± 1 before pump, a VRS = 3.83 ± 1.83 the first month, a VRS = 3.16 ± 2.11 the third month and finally a VRS 4.2 ± 1.68 the sixth month (p = 0.0047, 0.0020 and 0.0121 respectively). CONCLUSION: Our results suggest that use of subcutaneous apomorphine at low dose may be a valuable adjunct in the treatment of PSD and CBD for which only few symptomatic treatments are effective.

Combined thalamic and pallidal deep brain stimulation for dystonic tremor.

BACKGROUND: Deep brain stimulation (DBS) has been proposed to treat disabling dystonic tremor (DT), but there is debate about the optimal target. DBS of the globus pallidus interna (GPi) may be insufficient to control tremor, and DBS of the ventral intermediate thalamic nucleus (VIM) may inadequately control dystonic features, raising the question of combining both targets. OBJECTIVES: To report the respective effects on DT symptoms of high-frequency stimulation of the VIM, the GPi and both targets simultaneously stimulated. METHODS: Three patients with DT treated by bilateral high frequency DBS of 2 targets (VIM and GPi) were assessed 12 months after surgery in 4 conditions (VIM and GPi-DBS; GPi-DBS only; VIM-DBS only; DBS switched Off for both targets) by 3 independent movement disorders specialists blinded to the condition. RESULTS: The Fahn-Tolosa-Marin-tremor-rating-scale (FTM-TRS) and Burke-Fahn-Marsden-dystonia-rating-scale (BFM-DRS) scores were more improved by combined DBS than VIM alone or GPi alone. Compared to Off/Off condition, mean total FTM-TRS score decrease was 34%, 42% and 63% respectively with VIM only, GPi only and combined VIM and GPi stimulation. Mean total BFM-DRS score decrease was 34%, 37% and 60% respectively with VIM only, GPi only and combined VIM and GPi stimulation, compared to Off/Off condition. Improvement concerned both motor, functional and activities of daily living sub-scores. No complications or adverse events were observed. CONCLUSION: Combined VIM- and GPi-DBS, by modulating the cerebello-thalamo-cortical network and the basal ganglia-thalamo-cortical network, both involved in DT pathophysiology, may be more efficient than single DBS targeting only one of them.

Somatotopy of cervical dystonia in motor-cerebellar networks: Evidence from resting state fMRI.

INTRODUCTION: Cervical dystonia is the most frequent form of isolated focal dystonia. It is often associated with a dysfunction in brain networks, mostly affecting the basal ganglia, the cerebellum, and the somatosensory cortex. However, it is unclear if such a dysfunction is somato-specific to the brain areas containing the representation of the affected body part, and may thereby account for the focal expression of cervical dystonia. In this study, we investigated resting state functional connectivity in the areas within the motor cortex and the cerebellum containing affected and non-affected body representations in cervical dystonia patients. METHODS: Eighteen patients affected by cervical dystonia and 21 healthy controls had resting state fMRI. The functional connectivity between the motor cortex and the cerebellum, as well as their corresponding measures of gray matter volume and cortical thickness, were compared between groups. We performed seed-based analyses, selecting the different body representation areas in the precentral gyrus as seed regions, and all cerebellar areas as target regions. RESULTS: Compared to controls, patients exhibited increased functional connectivity between the bilateral trunk representation area of the motor cortex and the cerebellar vermis 6 and 7b, respectively. These functional abnormalities did not correlate with structural changes or symptom severity. CONCLUSIONS: Our findings indicate that the abnormal function of the motor network is somato-specific to the areas encompassing the neck representation. Functional abnormalities in discrete relevant areas of the motor network could thus contribute to the focal expression of CD.