The Efficacy and Safety of Transcranial Direct Current Stimulation for Cerebellar Ataxia: a Systematic Review and Meta-Analysis.

A promising new approach, transcranial direct current stimulation (tDCS) has recently been used as a therapeutic modality for cerebellar ataxia. However, the strength of the conclusions drawn from individual studies in the current literature may be constrained by the small sample size of each trial. Following a systematic literature retrieval of studies, meta-analyses were conducted by pooling the standardized mean differences (SMDs) using random-effects models to assess the efficacy of tDCS on cerebellar ataxia, measured by standard clinical rating scales. Domain-specific effects of tDCS on gait and hand function were further evaluated based on 8-m walk and 9-hole peg test performance times, respectively. To determine the safety of tDCS, the incidences of adverse effects were analyzed using risk differences. Out of 293 citations, 5 randomized controlled trials involving a total of 72 participants with cerebellar ataxia were included. Meta-analysis indicated a 26.1% (p = 0.003) improvement in ataxia immediately after tDCS with sustained efficacy over months (28.2% improvement after 3 months, p = 0.04) when compared with sham stimulation. tDCS seems to be domain-specific as the current analysis suggested a positive effect on gait (16.3% improvement, p = 0.04) and failed to reveal differences for hand function (p = 0.10) with respect to sham. The incidence of adverse events in tDCS and sham groups was similar. tDCS is an effective intervention for mitigating ataxia symptoms with lasting results that can be sustained for months. This treatment shows preferential effects on gait ataxia and is relatively safe.

Transcranial direct current stimulation (tDCS) of the cortical motor areas in three cases of cerebellar ataxia.

The excitability of the motor areas of the cerebral cortex is reduced in ataxia. Since transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique able to increase the cortical excitability, we assessed the effect of anodal tDCS over the motor cortex in three patients with ataxia. A clinical evaluation, a video-taped SARA rating scale and a gait analysis with cinematic parameters, were performed pre- and post-sham and anodal tDCS cycle. The full cycle was composed by five consecutive constant current sessions of stimulation. Anodal tDCS (2.0 mA, 20 min,max current density: 0.0278 mA/cm2, max total charge:0.033 C/cm2) was performed on the M1 area of the most affected side. The contralateral primary motor cortex underwent cathodal stimulation (2.0 mA, 20 min, max current density:0.0278 mA/cm2, max total charge: 0.033 C/cm2). After anodal tDCS, gait analysis revealed an improvement of the symmetry of step execution and reduction of base-width lasting 30 days associated to patients' perception of amelioration. No relevant changes were found after sham stimulation. Our results suggest tDCS can improve gait symmetry in patients with ataxia for a short-term period. Future researches are needed in order to standardize time, amplitude, and area of stimulation in order to reach a long lasting effect on cerebellar ataxia.

Need for prolonged immunosupressive therapy in CLIPPERS--a case report.

BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) was first described in 2010 by Pittock and colleagues. All reported patients presented with diplopia and gait ataxia and had similar typical MRI findings with punctuate gadolinium enhancement of the pons. Alternative diagnoses were excluded by means of laboratory, radiological and histological tests. All patients were successfully treated with steroids. We present a case in which the steroid therapy was switched to long term immunosuppressive therapy, leading to several severe side-effects, but sustained clinical improvement. CASE PRESENTATION: A 63-year-old male presented with sub-acute diplopia and progressive gait ataxia. During admission his neurological condition worsened and he developed multiple cranial nerve deficits, paraparesis and urine retention. MRI-findings were remarkable with punctuate enhancement with gadolinium of the pons. Cerebrospinal fluid only showed elevated protein levels and all other additional investigations were normal. The probable diagnosis of CLIPPERS was made and intravenous corticosteroids were administered. This led to rapid clinical recovery and decreased enhancement on the MRI-scan. Long-term oral immunosuppressive therapy was started. One-and-a-half year later our patient has no recurrence of neurological symptoms, however due to the side effects of the immunosuppressive therapy he was readmitted several times. CONCLUSION: CLIPPERS presents with distinctive clinical and MRI-findings and may be diagnosed after excluding other differential diagnoses. Patients are treated with corticosteroids with good clinical results. Since short term glucocorticoid treatment results into relapse of the disease, longer term immunosuppressive therapy appears to be mandatory for sustained improvement, although accompanied by severe side effects.

Gait ataxia in essential tremor is differentially modulated by thalamic stimulation.

Patients with advanced stages of essential tremor frequently exhibit tandem gait ataxia with impaired balance control and imprecise foot placement, resembling patients with a cerebellar deficit. Thalamic deep brain stimulation, a surgical therapy for otherwise intractable cases, has been shown to improve tremor, but its impact on cerebellar-like gait difficulties remains to be elucidated. Eleven patients affected by essential tremor (five females; age 69.8 ± 3.9 years; disease duration 24.4 ± 11.2 years; follow-up after surgery 24.7 ± 20.3 months) were evaluated during the following conditions: stimulation off, stimulation on and supra-therapeutic stimulation. Ten age-matched healthy controls served as the comparison group. Locomotion by patients and controls was assessed with (i) overground gait and tandem gait; (ii) balance-assisted treadmill tandem gait and (iii) unassisted treadmill gait. The two treadmill paradigms were kinematically analysed using a 3D opto-electronic motion analysis system. Established clinical and kinesiological measures of ataxia were computed. During stimulation off, the patients exhibited ataxia in all assessment paradigms, which improved during stimulation on and worsened again during supra-therapeutic stimulation. During over ground tandem gait, patients had more missteps and slower gait velocities during stimulation off and supra-therapeutic stimulation than during stimulation on. During balance-assisted tandem gait, stimulation on reduced the temporospatial variability in foot trajectories to nearly normal values, while highly variable (ataxic) foot trajectories were observed during stimulation off and supra-therapeutic stimulation. During unassisted treadmill gait, stimulation on improved gait stability compared with stimulation off and supra-therapeutic stimulation, as demonstrated by increased gait velocity and ankle rotation. These improvements in ataxia were not a function of reduced tremor in the lower limbs or torso. In conclusion, we demonstrate the impact of thalamic stimulation on gait ataxia in patients with essential tremor with improvement by stimulation on and deterioration by supra-therapeutic stimulation, despite continued control of tremor. Thus, cerebellar dysfunction in these patients can be differentially modulated with optimal versus supra-therapeutic stimulation. The cerebellar movement disorder of essential tremor is due to a typical cerebellar deficit, not to trembling extremities. We hypothesize that deep brain stimulation affects two major regulating circuits: the cortico-thalamo-cortical loop for tremor reduction and the cerebello-thalamo-cortical pathway for ataxia reduction (stimulation on) and ataxia induction (supra-therapeutic stimulation).

Chronic ataxic neuropathy mimicking dorsal midbrain syndrome.

We describe the clinical course, with special attention to the disturbance of eye movements, of a 29-year-old man with chronic ataxic neuropathy with ophthalmoplegia, IgM paraprotein, cold agglutinins and anti-GD1b disialosyl antibodies (CANOMAD). Using the magnetic search coil technique, we documented convergence during upward saccades and other features suggestive of dorsal midbrain syndrome. Thus, in common with Miller Fisher syndrome, CANOMAD may present with clinical findings implicating involvement of the central nervous system, which contains ganglioside antigens to anti-GD1b antibodies.

MR imaging findings of spinal posterior column involvement in a case of Miller Fisher syndrome.

SUMMARY: The site of lesions causing ataxia in Miller Fisher syndrome (MFS) remains in dispute. A 43-year-old man manifested rapidly progressive left-sided ptosis, bilateral abducens palsy, areflexia, and severe ataxia. Initial MR imaging showed confined lesions of the cauda equina with gadolinium enhancement. A diagnosis of MFS was made, and the patient underwent immunotherapy. His ophthalmoplegia disappeared, but other symptoms remained. Five months after onset, MR imaging disclosed lesions confined to the spinal posterior column, which were considered to result from involvement of posterior nerve roots of the cauda equina and to be responsible for his remaining severe ataxia.

Acute cerebellar ataxia in a toddler: case report and literature review.

Acute cerebellar ataxia (ACA) is an inflammatory CNS disease that is characterized by rapid onset of ataxia in a child under 6 years of age. Symptoms typically occur in association with a relatively benign viral illness and have been reported after vaccination as well. Immunological studies suggest that both involve autoimmune destruction of axon tracts, with pathological and radiographic evidence of a link with multiple sclerosis. The emergency approach should be focused on excluding more significant illnesses, such as meningitis or an intracranial mass lesion. Here we present a case of a young girl with ACA and review the relevant literature.

[A case of paraneoplastic syndrome improved following chemoradiotherapy for lung cancer].

Paraneoplastic neurosyndrome (PNS) is a group of neurological disorders caused by or associated with neoplasms that are not direct effects of the primary tumor or of a metastasis to the involved organs. Chemotherapy, radiotherapy, immunosuppressive therapy, and plasmapheresis have been performed to treat PNS, but improvement of the neurological disorder is rather rare. A 64-year-old man was referred to our hospital with dysesthesia of the extremities and ataxic gait. Small cell lung cancer was diagnosed in another hospital and chemotherapy (CDDP 80 mg/m2 + VP-16 100 mg/m2) was performed. A partial response was obtained with this treatment, but the neurological dysfunction was exacerbated. Three months later, the patient was admitted to our hospital. On treatment with CDDP 80 mg/m2 (day 1) and CPT-11 80 mg/m2 (days 1, 8 and 15) and subsequent radiation therapy (60 Gy), his neurological disorder improved. We consider that neurological symptoms are important signs of malignancy in PNS and that a full course of treatment could improve the neurological disorders.

[There is something amiss]. / Neuromuskuläre Irrwege.

We report the case of a 54-year old man with slowly progressive symmetrical weakness of the proximal legs and atactic gait. The diagnostic work-up is reviewed. It revealed the diagnosis of a Lambert-Eaton myasthenic syndrome(LEMS) and SIADH caused by a small cell lung cancer (SCLC).

Lower limb joints kinematics in essential tremor and the effect of thalamic stimulation.

Following the hypothesis that thalamic deep brain stimulation improves ataxia in patients with essential tremor by modulating the cerebello-thalamo-cortical pathway, we examined the joint kinematics of lower limbs during uninterrupted gait in eleven patients who have been treated with bilateral thalamic stimulation for 24.7±20.3 months. Patients were assessed under routine chronic stimulation, supra-therapeutic amplitude, and off stimulation by means of an infrared movement analysis system while walking on a treadmill. Chronic thalamic DBS normalized the highly variable excursion throughout the gait cycle that characterized the subgroup of patients with longest disease duration. Supratherapeutic thalamic DBS amplitude did not reproduce such improvements while, more importantly, it induced ataxic changes of joint excursion. The normalization of kinematic abnormalities argues against the hypothesis of a cerebellar neurodegeneration in ET. Moreover, these results suggest that the beneficial effect of thalamic DBS on ataxic symptoms is limited to a narrow therapeutic window.

Análisis de la marcha y fisioterapia Bobath en adultos con síndrome de Down / Gait analysis and Bobath physiotherapy in adults with Down syndrome

Introducción. El síndrome de Down (SD) es un trastorno cromosómico de expresión fenotípica variable, aunque con rasgos comunes en los distintos pacientes. Entre ellos, destaca la hipotonía, hiperlaxitud ligamentosa y el retraso en el desarrollo psicomotor. Estos rasgos mejoran con la terapia temprana, pero persisten en forma de inestabilidad de la marcha y compensaciones patológicas en el adulto. La marcha patológica en estos pacientes ha sido objeto de estudios previos, pero el tratamiento de los problemas motores no ha sido abordado desde un enfoque neurorrehabilitador, dirigido a la calidad del funcionamiento. Objetivos. El propósito del presente estudio es describir las alteraciones de la marcha en una muestra de pacientes con SD y evaluar los cambios después del tratamiento con fisioterapia Bobath. Material y métodos. Estudio prospectivo experimental de tipo ensayo no controlado. Diez personas adultas con SD (edad media: 28 años) fueron evaluadas en situación basal y después de 10 sesiones de fisioterapia Bobath. Se recogieron variables cuantitativas (como longitud del paso, velocidad de la marcha) y variables cualitativas (como calidad del braceo o inestabilidad) a través de un evaluador ciego al tratamiento fisioterápico. Resultados. Se encontraron claras desviaciones respecto a la marcha adulta normal y una tendencia a la mejoría después del tratamiento fisioterápico. Esta mejoría fue significativa en la corrección del ángulo y en la simetría del paso. Se pone de manifiesto el potencial beneficio de la fisioterapia en adultos con SD y alteraciones de la marcha, así como la necesidad de realizar más estudios en este sentido (AU)

Introduction. Down syndrome (DS) is a chromosomal disorder with variable phenotypic expression, although different patients share some common features. Among them, hypotonia, ligament laxity and delayed psychomotor development stand out. These traits can improve with early therapy, but remain as gait instability and pathologic compensatory strategies in adult patients. Pathological gait in DS patients has been studied previously, but the treatment of motor problems has not been approached from a neurological rehabilitation viewpoint, focused on quality of function. Objectives. The aim of this study was to describe the gait alterations in a sample of patients with DS and to assess changes after Bobath physiotherapy. Material and methods. An experimental prospective uncontrolled study was performed. Ten adults with DS (mean age: 28 years) were assessed at baseline and after 10 sessions of Bobath physiotherapy treatment. Quantitative data (such as step length or walking speed) and qualitative data (such as characteristics of arm movements and instability) were recorded by an evaluator blinded to the treatment received. Results. Clear deviations with respect to normal adult gait were found, and a trend towards improvement after physiotherapy treatment. The results were significant in the correction of pitch angle and its symmetry. The study has revealed the potential benefits of physiotherapy in adults with DS and the need to complete more studies in this sense (AU)

The role of gait analysis in treating gait abnormalities in cerebral palsy.

Individuals with cerebral palsy (CP) cannot take a normal activity like walking for granted. CP is the most common pediatric neurologic disorder, with an incidence of 3.6 per 1000 live births. The current trend in the treatment of individuals with CP is to perform a thorough evaluation including a complete patient history from birth to present, a comprehensive physical examination, appropriate radiographs, consultation with other medical specialists, and analysis of gait.

Immediate effect of percutaneous intramuscular stimulation during gait in children with cerebral palsy: a feasibility study.

The feasibility of percutaneous intramuscular functional electrical stimulation (P-FES) in children with cerebral palsy (CP) for immediate improvement of ankle kinematics during gait has not previously been reported. Eight children with CP (six with diplegia, two with hemiplegia; mean age 9 years 1 month [SD 1 y 4 mo; range 7 y 11 mo to 11 y 10 mo]) had percutaneous intramuscular electrodes implanted into the gastrocnemius (GA) and tibialis anterior (TA) muscles of their involved limbs. Stimulation was provided during appropriate phases of the gait cycle in three conditions (GA only, TA only, and GA/TA). immediately after a week of practice for each stimulation condition, a gait analysis was performed with and without stimulation. A significant improvement in peak dorsiflexion in swing for the more affected extremity and dorsiflexion at initial contact for the less affected extremity were found in the GA/TA condition. Clinically meaningful trends were evident for improvements in dorsiflexion kinematics for the more and less affected extremities in the TA only and GA/TA conditions. The results suggest that P-FES might immediately improve ankle kinematics in children with CP.

GALOP syndrome: case report with 7-year follow-up.

An elderly woman complaining of a gait disorder was found to have the GALOP syndrome (gait ataxia, late-onset polyneuropathy). She exhibited mild distal weakness and sensory loss in the legs, a positive Romberg, and an unsteady gait. Serum immunofixation disclosed a monoclonal IgM-kappa protein. There was specific IgM binding to galopin, a central nervous system white matter antigen. Periodic treatment with intravenous immunoglobulin has alleviated her neurologic symptoms. She has now been followed for 7 years and maintained significant improvement in neurologic symptoms and signs.

Efeito da facilitação neuromuscular proprioceptiva no equilíbrio de indivíduo com degeneraçãoespinocerebelar recessiva / The proprioceptive neuromuscular facilitation effect in fall risk in an ataxic patient

Objetivo: Avaliar os efeitos da facilitação neuromuscular proprioceptiva (PNF) no risco de queda de um paciente com degeneraçãoespinocerebelar recessiva utilizando como instrumentos de avaliaçãoa escala de equilíbrio de Berg (EEB) e a o teste time get up and go (TUG). Método: Foram realizados 10 atendimentos compostos porcinco exercícios baseados no conceito PNF cada. Antes da primeirasessão e imediatamente após a última o paciente foi avaliado atravésda EEB e, a cada sessão, era realizado ainda uma avaliação pré epós-intervenção utilizando o TUG teste para avaliar os resultados do atendimento em cada sessão. Resultados: Observou-se melhoraprogressiva no tempo de execução do TUG teste a cada atendimento e, quando comparado a primeira à última sessão, essa melhora chegou a redução de 50% do tempo inicial. Já na EEB não se observou melhoras significativas visto que o paciente não conseguiu realizar tanto no pré como no pós-testes alguns domínios da escala. Conclusão: O PNF foi efetivo no controle do equilíbrio de um pacientecom degeneração espinocerebelar.

Objective: To investigate the effects of proprioceptive neuromuscularfacilitation (PNF) in falls risk in an ataxic patient using 2 different tests: the Berg Balance Scale (BBS) and the time get up and go test (TUG). Method: 10 therapy sessions with 5 exercises each one were carried out. Before the first session and after the last onethe BBS was applied and, in each session, a pre and post-test wereperformed using the TUG test to analyze the effect of this exerciseprogram in each session. Results: There was a decrease of the timeduration of TUG test comparing the pre and post tests in each onetherapy session and it was observed an improvement of 50% whencompared the first and the last session. On the other hand, we didnot observe significant improvements in the BBS’s results becausethe patient could not realize some point of this scale either in the preor in the posttest. Conclusion: The PNF was effective in the balancerehabilitation of an ataxic patient.