Cerebello-spinal tDCS in ataxia

Neurology ◽  
2018 ◽  
Vol 91 (12) ◽  
pp. e1090-e1101 ◽  
Author(s):  
Alberto Benussi ◽  
Valentina Dell'Era ◽  
Valentina Cantoni ◽  
Elisa Bonetta ◽  
Roberto Grasso ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Rating Scale ◽  
Double Blind ◽  
Clinical Trial Registration ◽  
Sham Stimulation ◽  
Motor Cortex Excitability ◽  
Before And After ◽  
Cerebellar Brain Inhibition

ObjectiveTo investigate whether a 2-week treatment with cerebellar anodal and spinal cathodal transcranial direct current stimulation (tDCS) could reduce symptoms in patients with neurodegenerative ataxia and could modulate cerebello-motor connectivity at the short and long terms.MethodsWe performed a double-blind, randomized, sham-controlled, crossover trial with cerebello-spinal tDCS (5 d/wk for 2 weeks) in 20 patients with neurodegenerative ataxia. Each patient underwent a clinical evaluation before and after real tDCS or sham stimulation. A follow-up evaluation was performed at 1 and 3 months with a crossover washout period of 3 months. Cerebello-motor connectivity was evaluated with transcranial magnetic stimulation at baseline and at each follow-up.ResultsCerebello-spinal tDCS showed a significant improvement in all performance scores (Scale for the Assessment and Rating of Ataxia, International Cooperative Ataxia Rating Scale, 9-Hole Peg Test, 8-m walking time), in motor cortex excitability, and in cerebellar brain inhibition compared to sham stimulation.ConclusionsA 2-week treatment with cerebello-spinal tDCS reduces symptoms in patients with ataxia and restores motor cortex inhibition exerted by cerebellar structures. Cerebello-spinal tDCS might represent a promising future therapeutic and rehabilitative approach in patients with neurodegenerative ataxia, still an orphan disorder of any pharmacologic intervention.Clinical trial registrationNCT03120013.Classification of evidenceThis study provides Class II evidence that cerebello-spinal stimulation is effective and safe in cerebellar ataxia.

scholarly journals Therapeutic Use of Cerebellar Intermittent Theta Burst Stimulation (iTBS) in a Sardinian Family Affected by Spinocerebellar Ataxia 38 (SCA 38)

2021 ◽  
Author(s):  
Angela Sanna ◽  
Paolo Follesa ◽  
Paolo Tacconi ◽  
Mariangela Serra ◽  
Maria Giuseppina Pisu ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Rating Scale ◽  
Clinical Symptoms ◽  
Therapeutic Use ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Motor Cortex Excitability ◽  
Before And After ◽  
Theta Burst ◽  
Serum Bdnf

AbstractSpinocerebellar ataxia 38 (SCA 38) is an autosomal dominant disorder caused by conventional mutations in the ELOVL5 gene which encodes an enzyme involved in the synthesis of very long fatty acids, with a specific expression in cerebellar Purkinje cells. Three Italian families carrying the mutation, one of which is of Sardinian descent, have been identified and characterized. One session of cerebellar intermittent theta burst stimulation (iTBS) was applied to 6 affected members of the Sardinian family to probe motor cortex excitability measured by motor-evoked potentials (MEPs). Afterwards, patients were exposed to ten sessions of cerebellar real and sham iTBS in a cross-over study and clinical symptoms were evaluated before and after treatment by Modified International Cooperative Ataxia Rating Scale (MICARS). Moreover, serum BDNF levels were evaluated before and after real and sham cerebellar iTBS and the role of BDNF Val66Met polymorphism in influencing iTBS effect was explored. Present data show that one session of cerebellar iTBS was able to increase MEPs in all tested patients, suggesting an enhancement of the cerebello-thalamo-cortical pathway in SCA 38. MICARS scores were reduced after ten sessions of real cerebellar iTBS showing an improvement in clinical symptoms. Finally, although serum BDNF levels were not affected by cerebellar iTBS when considering all samples, segregating for genotype a difference was found between Val66Val and Val66Met carriers. These preliminary data suggest a potential therapeutic use of cerebellar iTBS in improving motor symptoms of SCA38.

scholarly journals On the Effectiveness of Event-related Beta tACS on Episodic Memory Formation and Motor Cortex Excitability

2016 ◽  
Author(s):  
Verena Braun ◽  
Rodika Sokoliuk ◽  
Simon Hanslmayr
Keyword(s):  
Motor Cortex ◽  
Episodic Memory ◽  
Inferior Frontal Gyrus ◽  
Memory Formation ◽  
Frequency Range ◽  
Beta Oscillations ◽  
Healthy Human ◽  
Sham Stimulation ◽  
Motor Cortex Excitability ◽  
Beta Frequency

AbstractBackgroundTranscranial alternating current stimulation (tACS) is widely used to entrain or modulate brain oscillations in order to investigate causal relationships between oscillations and cognition.ObjectiveIn a series of experiments we here addressed the question of whether event-related, transient tACS in the beta frequency range can be used to entrain beta oscillations in two different domains: episodic memory formation and motor cortex excitability.MethodsIn experiments 1 and 2, 72 healthy human participants engaged in an incidental encoding task of verbal and non-verbal material while receiving tACS to the left and right inferior frontal gyrus (IFG) at 6.8Hz, 10.7Hz, 18.5Hz, 30Hz, 48Hz and sham stimulation for 2s during stimulus presentation.In experiment 3, tACS was administered to M1 at the individual motor beta frequency of eight subjects. We investigated the relationship between the size of TMS induced MEPs and tACS phase.ResultsBeta tACS did not affect memory performance compared to sham stimulation in experiments 1 and 2. Likewise, in experiment 3, MEP size was not modulated by the tACS phase.ConclusionsOur findings suggest that event-related, transient tACS in the beta frequency range cannot be used to modulate the formation of episodic memories or motor cortex excitability. These null-results question the effectiveness of event-related tACS to entrain beta oscillations and modulate cognition.

scholarly journals Is staged bilateral thalamic radiosurgery an option for otherwise surgically ineligible patients with medically refractory bilateral tremor?

2018 ◽  
Vol 128 (2) ◽  
pp. 617-626 ◽  
Author(s):  
Ajay Niranjan ◽  
Sudesh S. Raju ◽  
Edward A. Monaco ◽  
John C. Flickinger ◽  
L. Dade Lunsford
Keyword(s):  
Median Time ◽  
Rating Scale ◽  
Maximum Dose ◽  
Karnofsky Performance Status ◽  
Dominant Hand ◽  
Complete Restoration ◽  
Increased Risk ◽  
Before And After ◽  
Median Maximum

OBJECTIVEUnilateral Gamma Knife thalamotomy (GKT) is a well-established treatment for patients with medically refractory tremor who are not eligible for invasive procedures due to increased risk of compications. The purpose of this study was to evaluate whether staged bilateral GKT provides benefit with acceptable risk to patients suffering from disabling medically refractory bilateral tremor.METHODSEleven patients underwent staged bilateral GKT during a 17-year period (1999–2016). Eight patients had essential tremor (ET), 2 had Parkinson's disease (PD)–related tremor, and 1 had multiple-sclerosis (MS)–related tremor. For the first GKT, a median maximum dose of 140 Gy was delivered to the posterior-inferior region of the nucleus ventralis intermedius (VIM) through a single isocenter with 4-mm collimators. Patients who benefitted from unilateral GKT were eligible for a contralateral GKT 1–2 years later (median 22 months). For the second GKT, a median maximum dose of 130 Gy was delivered to the opposite VIM nucleus to a single 4-mm isocenter. The Fahn-Tolosa-Marin (FTM) clinical tremor rating scale was used to score tremor, drawing, and drinking before and after each GKT. The FTM writing score was assessed only for the dominant hand before and after the first GKT. The Karnofsky Performance Status (KPS) was used to assess quality of life and activities of daily living before and after the first and second GKT.RESULTSThe median time to last follow-up after the first GKT was 35 months (range 11–70 months). All patients had improvement in at least 1 FTM score after the first GKT. Three patients (27.3%) had tremor arrest and complete restoration of function (noted via FTM tremor, writing, drawing, and drinking scores equaling zero). No patient had tremor recurrence or diminished tremor relief after the first GKT. One patient experienced new temporary neurological deficit (contralateral lower-extremity hemiparesis) from the first GKT. The median time to last follow-up after the second GKT was 12 months (range 2–70 months). Nine patients had improvement in at least 1 FTM score after the second GKT. Two patients had tremor arrest and complete restoration of function. No patient experienced tremor recurrence or diminished tremor relief after the second GKT. No patient experienced new neurological or radiological adverse effect from the second GKT. Statistically significant improvements were noted in the KPS score following the first and second GKT.CONCLUSIONSStaged bilateral GKT provided effective relief for medically refractory, disabling, bilateral tremor without increased risk of neurological complications. It is an appropriate strategy for carefully selected patients with medically refractory bilateral tremor who are not eligible for deep brain stimulation.

DBS of the PSA and the VIM in essential tremor

Neurology ◽  
2018 ◽  
Vol 91 (6) ◽  
pp. e543-e550 ◽  
Author(s):  
Michael T. Barbe ◽  
Paul Reker ◽  
Stefanie Hamacher ◽  
Jeremy Franklin ◽  
Daria Kraus ◽  
...  
Keyword(s):  
Side Effects ◽  
Essential Tremor ◽  
Clinical Benefit ◽  
Double Blind ◽  
Crossover Phase ◽  
Ventral Intermediate Nucleus ◽  
Frequency Of Stimulation

ObjectiveTo evaluate deep brain stimulation (DBS) of the posterior subthalamic area (PSA) in essential tremor (ET) and compare it to the ventral intermediate nucleus of the thalamus (VIM) in terms of stimulation efficacy, efficiency, and side effects.MethodsDBS leads were implanted such that contacts were placed in the VIM, on the intercommissural line, and in the PSA. Thirteen patients with ET entered a randomized, double-blind crossover phase and completed a 1-year follow-up.ResultsPSA-DBS significantly reduced tremor severity and improved quality of life. There were no relevant differences in quality and frequency of stimulation side effects between VIM and PSA, with a tendency toward greater tremor improvement with PSA stimulation. Clinical benefit was achieved at significantly lower stimulation amplitudes in the PSA. The majority of patients remained with PSA-DBS after 1 year.ConclusionIn accordance with previous retrospective investigations, our prospective data suggest that PSA-DBS is at least equally effective as but possibly more efficient than VIM-DBS.Classification of evidenceThis study provides Class I evidence that for patients with essential tremor, PSA-DBS is not significantly different from VIM-DBS in suppressing tremor, but clinical benefit from PSA-DBS is attained at lower stimulation amplitudes.

scholarly journals BCI training to move a virtual hand reduces phantom limb pain

Neurology ◽  
2020 ◽  
Vol 95 (4) ◽  
pp. e417-e426
Author(s):  
Takufumi Yanagisawa ◽  
Ryohei Fukuma ◽  
Ben Seymour ◽  
Masataka Tanaka ◽  
Koichi Hosomi ◽  
...  
Keyword(s):  
Crossover Trial ◽  
Phantom Limb Pain ◽  
Phantom Limb ◽  
Class Iii ◽  
Limb Pain ◽  
Virtual Hand ◽  
Before And After ◽  
Hand Image

ObjectiveTo determine whether training with a brain–computer interface (BCI) to control an image of a phantom hand, which moves based on cortical currents estimated from magnetoencephalographic signals, reduces phantom limb pain.MethodsTwelve patients with chronic phantom limb pain of the upper limb due to amputation or brachial plexus root avulsion participated in a randomized single-blinded crossover trial. Patients were trained to move the virtual hand image controlled by the BCI with a real decoder, which was constructed to classify intact hand movements from motor cortical currents, by moving their phantom hands for 3 days (“real training”). Pain was evaluated using a visual analogue scale (VAS) before and after training, and at follow-up for an additional 16 days. As a control, patients engaged in the training with the same hand image controlled by randomly changing values (“random training”). The 2 trainings were randomly assigned to the patients. This trial is registered at UMIN-CTR (UMIN000013608).ResultsVAS at day 4 was significantly reduced from the baseline after real training (mean [SD], 45.3 [24.2]–30.9 [20.6], 1/100 mm; p = 0.009 < 0.025), but not after random training (p = 0.047 > 0.025). Compared to VAS at day 1, VAS at days 4 and 8 was significantly reduced by 32% and 36%, respectively, after real training and was significantly lower than VAS after random training (p < 0.01).ConclusionThree-day training to move the hand images controlled by BCI significantly reduced pain for 1 week.Classification of evidenceThis study provides Class III evidence that BCI reduces phantom limb pain.

scholarly journals Randomized trial of preladenant, given as monotherapy, in patients with early Parkinson disease

Neurology ◽  
2017 ◽  
Vol 88 (23) ◽  
pp. 2198-2206 ◽  
Author(s):  
Fabrizio Stocchi ◽  
Olivier Rascol ◽  
Robert A. Hauser ◽  
Susan Huyck ◽  
Anjela Tzontcheva ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Active Control ◽  
Rating Scale ◽  
Double Blind ◽  
Clinical Trial Registration ◽  
Link Type ◽  
Parallel Group ◽  
Number Of Patients ◽  
Disease Rating ◽  
Post Hoc

Objective:To evaluate the adenosine 2a receptor antagonist preladenant as a nondopaminergic drug for the treatment of Parkinson disease (PD) when given as monotherapy.Methods:This was a randomized, 26-week, placebo- and active-controlled, parallel-group, multicenter, double-blind trial conducted in adults diagnosed with PD for <5 years who were not yet receiving l-dopa or dopamine agonists. Patients with a Unified Parkinson’s Disease Rating Scale (UPDRS) part 3 (motor function) score ≥10 and Hoehn & Yahr score ≤3 were randomized 1:1:1:1:1 to preladenant 2, 5, or 10 mg twice daily, rasagiline 1 mg (active-control) once daily, or placebo. The primary endpoint was the change from baseline at week 26 in the sum of UPDRS parts 2 (activities of daily living) and 3 scores (UPDRS2+3).Results:The number of patients treated was 1,007. Neither preladenant nor rasagiline was superior to placebo after 26 weeks. The differences vs placebo (95% confidence interval) in UPDRS2+3 scores (with a negative difference indicating improvement vs placebo) were preladenant 2 mg = 2.60 (0.86, 4.30), preladenant 5 mg = 1.30 (−0.41, 2.94), preladenant 10 mg = 0.40 (−1.29, 2.11), and rasagiline 1 mg = 0.30 (−1.35, 2.03). Post hoc analyses did not identify a single causal factor that could explain the finding of a failed trial. Preladenant was generally well-tolerated with few patients discontinuing due to adverse events (preladenant 7%, rasagiline 3%, placebo 4%).Conclusions:No evidence supporting the efficacy of preladenant as monotherapy was observed in this phase 3 trial. The lack of efficacy of the active control rasagiline makes it difficult to interpret the results.Clinical trial registration:Clinicaltrials.gov: NCT01155479.Classification of evidence:This study provides Class I evidence that for patients with early PD, preladenant is not effective as monotherapy at the doses studied (2, 5, 10 mg).

scholarly journals The Bruton tyrosine kinase inhibitor ibrutinib improves anti-MAG antibody polyneuropathy

2020 ◽  
Vol 7 (4) ◽  
pp. e720 ◽  
Author(s):  
Francesca Castellani ◽  
Andrea Visentin ◽  
Marta Campagnolo ◽  
Alessandro Salvalaggio ◽  
Mario Cacciavillani ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Rating Scale ◽  
Kinase Inhibitor ◽  
Disability Score ◽  
Clinical Scales ◽  
Sum Score ◽  
Inflammatory Neuropathy ◽  
Bruton Tyrosine Kinase

ObjectiveTo assess whether neuropathy with anti-myelin-associated glycoprotein (MAG) antibody may improve after treatment with ibrutinib, an oral inhibitor of Bruton tyrosine kinase, we prospectively treated with ibrutinib a cohort of 3 patients with anti-MAG neuropathy and Waldenström macroglobulinemia (WM).MethodsAll 3 patients underwent bone marrow biopsy showing WM, with MYD88L265P mutated and CXCR4S338X wild type, and were started on ibrutinib 420 mg/die. Patients were assessed at baseline, at 3-6-9 months, and at 12 months in 2 patients with a longer follow-up, using Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score, INCAT sensory sum score, and Medical Research Council sum score. The modified International Cooperative Ataxia Rating Scale was performed in 2 patients, whereas it was not used in the patient with Parkinson disease as a major comorbidity. Responders were considered the patients improving by at least one point in 2 clinical scales.ResultsAll the patients reported an early and subjective benefit, consistent with the objective improvement, especially of the sensory symptoms as shown by clinical scales. Treatment was well tolerated.ConclusionThese preliminary data point to a possible efficacy of ibrutinib in anti-MAG antibody neuropathy, which is the most common disabling paraproteinemic neuropathy, where active treatment is eagerly needed.Classification of evidenceThis study provides Class IV evidence that for patients with anti-MAG antibody neuropathy, ibrutinib improves neuropathy symptoms.

scholarly journals Longitudinal follow-up with VIM thalamic deep brain stimulation for dystonic or essential tremor

Neurology ◽  
2020 ◽  
Vol 94 (10) ◽  
pp. e1073-e1084 ◽  
Author(s):  
Takashi Tsuboi ◽  
Zakia Jabarkheel ◽  
Pamela R. Zeilman ◽  
Matthew J. Barabas ◽  
Kelly D. Foote ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Essential Tremor ◽  
Brain Stimulation ◽  
Rating Scale ◽  
Statistical Significance ◽  
Ventral Intermediate Nucleus ◽  
Deep Brain

ObjectiveTo assess longitudinal tremor outcomes with ventral intermediate nucleus deep brain stimulation (VIM DBS) in patients with dystonic tremor (DT) and to compare with DBS outcomes in essential tremor (ET).MethodsWe retrospectively investigated VIM DBS outcomes for 163 patients followed at our center diagnosed with either DT or ET. The Fahn-Tolosa-Marin tremor rating scale (TRS) was used to assess change in tremor and activities of daily living (ADL) at 6 months, 1 year, 2–3 years, 4–5 years, and ≥6 years after surgery.ResultsTwenty-six patients with DT and 97 patients with ET were analyzed. Compared to preoperative baseline, there were significant improvements in TRS motor up to 4–5 years (52.2%; p = 0.032) but this did not reach statistical significance at ≥6 years (46.0%, p = 0.063) in DT, which was comparable to the outcomes in ET. While the improvements in the upper extremity tremor, head tremor, and axial tremor were also comparable between DT and ET throughout the follow-up, the ADL improvements in DT were lost at 2–3 years follow-up.ConclusionOverall, tremor control with VIM DBS in DT and ET was comparable and remained sustained at long term likely related to intervention at the final common node in the pathologic tremor network. However, the long-term ADL improvements in DT were not sustained, possibly due to inadequate control of concomitant dystonia symptoms. These findings from a large cohort of DT indicate that VIM targeting is reasonable if the tremor is considerably more disabling than the dystonic features.Classification of evidenceThis study provides Class IV evidence that VIM DBS improves tremor in patients with DT or ET.

Treatment of Poststroke Pain by Epidural Motor Cortex Stimulation With a New Octopolar Lead

2011 ◽  
Vol 68 (suppl_1) ◽  
pp. ons180-ons187 ◽  
Author(s):  
Jean-Pascal Lefaucheur ◽  
Yves Keravel ◽  
Jean-Paul Nguyen
Keyword(s):  
Motor Cortex ◽  
Rating Scale ◽  
Sickness Impact Profile ◽  
Brief Pain Inventory ◽  
Mcgill Pain Questionnaire ◽  
Motor Cortex Stimulation ◽  
Pain Questionnaire ◽  
Affective Component ◽  
Clinical Scores

Abstract BACKGROUND: Chronic, drug-resistant neuropathic pain can be treated by surgically implanted motor cortex stimulation (MCS). The leads used for MCS have not been specifically designed for this application. OBJECTIVE: To study the value of a new 8-contact lead for MCS therapy in a series of 6 patients with refractory central poststroke pain. METHODS: The study comprised a 1-month randomized phase, starting 1 month after implantation, during which the neurostimulator was switched on in one-half of the patients or remained off in the other half, followed by an open phase of 10 months, during which the stimulator was switched on in all patients. Clinical assessment was performed at baseline and 1, 2, 3, 6, and 12 months after implantation with the following scales: Visual Analog Scale, Verbal Rating Scale, Brief Pain Inventory, McGill Pain Questionnaire, Sickness Impact Profile, and Medication Quantification Scale. RESULTS: In the randomized phase, clinical scores were found to be globally reduced in the on- vs off-stimulation condition. In the open follow-up phase, all clinical scores improved significantly over time. The ratio between affective and sensory McGill Pain Questionnaire subscores decreased, suggesting a preferential effect of MCS on the affective component of pain. Compared with preoperative baseline, 2 patients were totally relieved of central poststroke pain, 3 patients were very much relieved, and 1 patient remained unchanged at the final examination. CONCLUSION: A good clinical outcome was observed in all patients except 1, suggesting that this new octopolar lead could be used for MCS therapy to treat refractory central poststroke pain.

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