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Objective: A severe and long-term alcohol use can have adverse effects on lower limb function. Over time, some individuals may develop gait ataxia, which refers to the impairment of controlled lower body movements that are important for walking and maintaining proper gait. Gait ataxia is well-documented in patients who have been diagnosed with alcohol-related Wernicke-Korsakoff syndrome (WKS); however, less is known on how common ataxia is among patients with alcohol use disorder (AUD) without WKS. To date, no study has systematically reviewed the evidence focusing on patients suffering only from AUD. Our aim was to perform a qualitative synthesis of the existing literature examining behavioral signs of gait ataxia among abstinent patients with AUD., Method: Two facets were created encompassing keywords for "alcohol use disorder" and "measures of gait ataxia." Databases, including EMBASE, APA PsycInfo, Medline, and Cochrane Library, were searched for studies, and a quality assessment was performed., Results: Ten studies were identified (37 ≥ n s ≤ 247), which were all rated as being of moderate ( N = 7) to good quality ( N = 3). The age range was 31.4-53.4 years (weighted mean age: 53.6 years), and 78.3% of the participants were male. Eight studies found that patients with AUD and without WKS exhibited behavioral signs of gait ataxia., Conclusions: Although there is evidence of gait ataxia among patients with AUD, heterogeneous results and methodological shortcomings such as lack of screening for neurocognitive deficits deem these findings preliminary and highlight the need for more research in the future. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Abstract: A 9-year-old girl presented with morning headaches associated with vomiting, gait ataxia, and facial and ocular motor nerve palsies. Her initial imaging was concerning for demyelinating disease. After extensive infectious and rheumatologic workup returned negative, she was treated twice with intravenous immunoglobulin and intravenous steroids with near-complete resolution each time. She returned, however, with worsening neurologic deficits and imaging revealing focal ischemic infarction in the brainstem as well as new-onset hydrocephalus. A multispecialty workup was initiated without conclusive diagnosis. A novel, noninvasive test for plasma cell-free DNA established a diagnosis of Cladophialophora bantiana that was confirmed and validated by a brain biopsy taken during a clinical decompensation. Treatment was initiated with systemic voriconazole and intraventricular amphotericin B., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by North American Neuro-Ophthalmology Society.)

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.

Several spontaneous mouse mutants with deficits in motor coordination and associated cerebellar neuropathology have been described. Intriguingly, both visible gait alterations and neuroanatomical abnormalities throughout the brain differ across mutants. We previously used the LocoMouse system to quantify specific deficits in locomotor coordination in mildly ataxic Purkinje cell degeneration mice ( pcd; Machado et al., 2015). Here, we analyze the locomotor behavior of severely ataxic reeler mutants and compare and contrast it with that of pcd . Despite clearly visible gait differences, direct comparison of locomotor kinematics and linear discriminant analysis reveal a surprisingly similar pattern of impairments in multijoint, interlimb, and whole-body coordination in the two mutants. These findings capture both shared and specific signatures of gait ataxia and provide a quantitative foundation for mapping specific locomotor impairments onto distinct neuropathologies in mice., Competing Interests: AM, HM, DD, DD No competing interests declared, MC Reviewing Editor, eLife, (© 2020, Machado et al.)

Objective: GM2 gangliosidoses are lysosomal diseases due to biallelic mutations in the HEXA (Tay-Sachs disease [TS]) or HEXB (Sandhoff disease [SD]) genes, with subsequent low hexosaminidase(s) activity. Most patients have childhood onset, but some experience the first symptoms during adolescence/adulthood. This study aims to clarify the natural history of adult patients with GM2 gangliosidosis., Methods: We retrospectively described 12 patients from a French cohort and 45 patients from the literature., Results: We observed 4 typical presentations: (1) lower motoneuron disorder responsible for proximal lower limb weakness that subsequently expanded to the upper limbs, (2) cerebellar ataxia, (3) psychosis and/or severe mood disorder (only in the TS patients), and (4) a complex phenotype mixing the above 3 manifestations. The psoas was the first and most affected muscle in the lower limbs, whereas the triceps and interosseous were predominantly involved in the upper limbs. A longitudinal study of compound motor action potentials showed a progressive decrease in all nerves, with different kinetics. Sensory potentials were sometimes abnormally low, mainly in the SD patients. The main brain magnetic resonance imaging feature was cerebellar atrophy, even in patients without cerebellar symptoms. The prognosis was mainly related to gait disorder, as we showed that beyond 20 years of disease evolution, half of the patients were wheelchair users., Interpretation: Improved knowledge of GM2 gangliosidosis in adults will help clinicians achieve correct diagnoses and better inform patients on the evolution and prognosis. It may also contribute to defining proper outcome measures when testing emerging therapies. ANN NEUROL 2020;87:609-617., (© 2020 American Neurological Association.)

Background & Aims: Celiac disease is an autoimmune disorder induced by ingestion of gluten that affects 1% of the population and is characterized by gastrointestinal symptoms, weight loss, and anemia. We evaluated the presence of neurologic deficits and investigated whether the presence of antibodies to Transglutaminase 6 (TG6) increases the risk of neurologic defects in patients with a new diagnosis of celiac disease., Methods: We performed a prospective cohort study at a secondary-care gastroenterology center of 100 consecutive patients who received a new diagnosis of celiac disease based on gastroscopy and duodenal biopsy. We collected data on neurologic history, and patients were evaluated in a clinical examination along with magnetic resonance imaging of the brain, magnetic resonance (MR) spectroscopy of the cerebellum, and measurements of antibodies against TG6 in serum samples. The first 52 patients recruited underwent repeat MR spectroscopy at 1 year after a gluten-free diet (GFD). The primary aim was to establish if detection of antibodies against TG6 can be used to identify patients with celiac disease and neurologic dysfunction., Results: Gait instability was reported in 24% of the patients, persisting sensory symptoms in 12%, and frequent headaches in 42%. Gait ataxia was found in 29% of patients, nystagmus in 11%, and distal sensory loss in 10%. Sixty percent of patients had abnormal results from magnetic resonance imaging, 47% had abnormal results from MR spectroscopy of the cerebellum, and 25% had brain white matter lesions beyond that expected for their age group. Antibodies against TG6 were detected in serum samples from 40% of patients-these patients had significant atrophy of subcortical brain regions compared with patients without TG6 autoantibodies. In patients with abnormal results from MR spectroscopy of the cerebellum, those on the GFD had improvements detected in the repeat MR spectroscopy 1 year later., Conclusions: In a prospective cohort study of patients with a new diagnosis of celiac disease at a gastroenterology clinic, neurologic deficits were common and 40% had circulating antibodies against TG6. We observed a significant reduction in volume of specific brain regions in patients with TG6 autoantibodies, providing evidence for a link between autoimmunity to TG6 and brain atrophy in patients with celiac disease. There is a need for early diagnosis, increased awareness of the neurologic manifestations among clinicians, and reinforcement of adherence to a strict GFD by patients to avoid permanent neurologic disability., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Traumatic brain injury (TBI) is the commonest cause of disability in under-40-year-olds. Vestibular features of dizziness (illusory self-motion) or imbalance which affects 50% of TBI patients at 5 years, increases unemployment threefold in TBI survivors. Unfortunately, vestibular diagnoses are cryptogenic in 25% of chronic TBI cases, impeding therapy. We hypothesized that chronic adaptive brain mechanisms uncouple vestibular symptoms from signs. This predicts a masking of vestibular diagnoses chronically but not acutely. Hence, defining the spectrum of vestibular diagnoses in acute TBI should clarify vestibular diagnoses in chronic TBI. There are, however, no relevant acute TBI data. Of 111 Major Trauma Ward adult admissions screened (median 38-years-old), 96 patients (87%) had subjective dizziness (illusory self-motion) and/or objective imbalance were referred to the senior author (BMS). Symptoms included: feeling unbalanced (58%), headache (50%) and dizziness (40%). In the 47 cases assessed by BMS, gait ataxia was the commonest sign (62%) with half of these cases denying imbalance when asked. Diagnoses included BPPV (38%), acute peripheral unilateral vestibular loss (19%), and migraine phenotype headache (34%), another potential source of vestibular symptoms. In acute TBI, vestibular signs are common, with gait ataxia being the most frequent one. However, patients underreport symptoms. The uncoupling of symptoms from signs likely arises from TBI affecting perceptual mechanisms. Hence, the cryptogenic nature of vestibular symptoms in TBI (acute or chronic) relates to a complex interaction between injury (to peripheral and central vestibular structures and perceptual mechanisms) and brain-adaptation, emphasizing the need for acute prospective, mechanistic studies.

Objective: To investigate the effects of coordination and balance problems on gait and plantar pressure distribution in multiple sclerosis patients., Methods: This was an observational, cross-sectional study. It was conducted at Necmettin Erbakan University between March and December 2017. Twenty-four individuals with coordination problems, 36 individuals with balance problems and 32 healthy individuals were included in the study. The EDSS, Functional Reach Test, Dynamic Gait Index, baropodometry and stabilometry evaluations were performed., Results: There were significant differences between the groups (velocity p=0.000, cadence p=0.000, step width p=0.018, step length p=0.000, foot angle p=0.000). Multiple comparisons demonstrated that the velocities and cadences of the coordination group were lower, while their step widths were found to be higher, compared to the balance group (p=0.012, p=0.004, p=0.017, respectively). In static plantar pressure distribution, lateral forefoot pressure, lateral hindfoot pressure and medial hindfoot pressure were significantly different between the groups (p=0.002, p=0.000, respectively) Multiple comparisons showed that the pressure on the lateral part of the hindfoot in the coordination group was found to be significantly higher compared to the balance group (p=0.002). According to the dynamic plantar pressure distribution, lateral forefoot, medial forefoot, lateral hindfoot and medial hindfoot pressures were significantly different between the groups (p<0.05)., Conclusion: Coordination and balance problems affect gait and plantar pressure distribution. The identification of these changes will help physiotherapists determine specific therapeutic targets.

Background: While accumulating evidence suggests that balance and gait impairments are commonly seen in patients with essential tremor (ET), questions remain regarding their prevalence, their relationship with normal aging, whether they are similar to the impairments seen in spinocerebellar ataxias, their functional consequences, and whether some ET patients carry greater susceptibility., Methods: We conducted a literature search (until December 2018) on this topic., Results: We identified 23 articles on gait or balance impairments in ET. The prevalence of balance impairment (missteps on tandem walk test) was seven times higher in ET patients than controls. Gait impairments in ET included reduced speed, increased asymmetry, and impaired dynamic balance. While balance and gait problems worsened with age, ET patients were more impaired than controls, independent of age. The pattern of impairments seen in ET was qualitatively similar to that seen in spinocerebellar ataxias. Balance and gait impairments resulted in greater number of near falls in ET patients. Factors associated with balance and gait impairments in ET included age, presence of tremor in midline structures, and cognitive dysfunction., Discussion: Accumulating evidence suggests that balance and gait impairments are common in ET patients and occur to a greater extent in controls. Thus, they represent a disease-associated feature. These impairments, which are qualitatively similar to those seen in spinocerebellar ataxias, are not merely subclinical but result in difficulty performing functional tasks and increase falls risk. A subset of patients is more susceptible to balance and gait impairments. The full spectrum of impairments remains to be characterized., Competing Interests: Funding: AR is supported by the US National Science Foundation (grant no. SCH-1838725). EDL is supported by the National Institutes of Health (grant nos. R01 NS086736 and R01 NS094607). Conflict of Interest: The authors report no conflict of interest. Ethics Statement: This article did not involve experimental investigation of human subjects and thus did not need to obtain informed consent. All primary research reviewed in this article included investigation that was approved by a formal ethics review committee. The study was performed in accordance with the ethical standards detailed in the Declaration of Helsinki and the reporting guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Background: Infarction of the vermis and the tonsil in the cerebellum presents as truncal and gait ataxia. Acute rotatory vertigo is often present in infarction of the nodulus in the caudal vermis, which is closely associated with the vestibular pathway, but is minor in infarction of the rostral vermis. The rostral vermis receives input from the dorsal spinocerebellar tract (DSCT) which conveys unconsciousness proprioceptive signals from the ipsilateral lower trunk and leg. The present study investigated the characteristics of infarction of the vermis and the tonsil., Patients and Methods: Neuroradiological findings of 3 patients whose lesions were located in the vermis or the tonsil were analyzed., Results: All lesions were located in the anterior lobe in the rostral vermis, the nodulus in the caudal vermis, or the tonsil. Truncal and gait ataxia were exhibited by 3 patients. Rotatory vertigo was exhibited by 2 patients whose lesions were located in the nodulus and the tonsil, but absent in a patient with infarction of the anterior lobe. Lateropulsion opposite the lesion was apparent in a patient with infarction of the tonsil. Gaze-evoked nystagmus was observed in 2 patients with infarction of the nodulus and the tonsil., Conclusions: The tonsil and the nodulus were considered to have a close relationship with the vestibular pathway. Absence of rotatory vertigo indicated impairment of the DSCT. Our data suggested that the cause of truncal and gait ataxia differed between the rostral vermis and the caudal vermis/tonsil., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Introduction and Objectives: Progressive ataxic gait is a common symptom in individuals with Familial Dysautonomia (FD). At least 50% of adults with FD require assistance with walking. Our aims were to describe the medical condition of individuals with FD (ii) compare their gait characteristics to healthy individuals, and (iii) assess correlations between gait measures, presence of unstable gait pattern and frequency of falls., Methods: Twelve subjects with FD (7 males, age 25.3±10.6 years) and 16 healthy participants (6 males, age 35.9±11.9 years) were recruited. Gait kinematics, gait symmetry, dynamic muscle activity, and foot deep vibration sensation were recorded., Results: Ataxic gait degrees were: severe (6 out of 12), moderate (4 out of 12) and low (2 out of 12). The number of falls correlated with base width asymmetry. Crouch gait was noted in 3 out of 12 of the subjects., Conclusions: In-depth quantitative gait analysis of individuals with FD revealed ataxic gait. The ataxic pattern might be a result of combined neurological deficiencies and osseous deformities. Increasing the base of support of patients with FD might increase the symmetry of the base width during gait and decrease the number of falls. Additionally, perturbation treatment and dynamic balance exercises may be recommended in order to improve compensatory strategies. Future investigation of this population should include quantification of osseous rotations of the lower limb in order to fully understand its effect on their gait pattern and falls.

Cerebellar ataxia often results in impairment in ambulation secondary to gait pattern dysfunction and compensatory gait adjustments. Pharmaceutical and therapy-based interventions with potential benefit for gait in ataxia are starting to emerge, however evaluation of such interventions is hampered by the lack of outcome measures that are responsive, valid and reliable for measurement of gait decline in cerebellar ataxia. This systematic review aimed for the first time to evaluate the psychometric properties of gait and walking outcomes applicable to individuals with cerebellar ataxia. Only studies evaluating straight walking were included. A comprehensive search of three databases (MEDLINE, CINAHL and EMBASE) identified 53 studies meeting inclusion criteria. Forty-nine were rated as 'poor' as assessed by the COnsensus-based Standards for the selection of health Measurement INstruments checklist. The primary objective of most studies was to explore changes in gait related to ataxia, rather than to examine psychometric properties of outcomes. This resulted in methodologies not specific for psychometric assessment. Thirty-nine studies examined validity, 11 examined responsiveness and 12 measured reliability. Review of the data identified double and single support and swing percentage of the gait cycle, velocity, step length and the Scale for Assessment and Rating of Ataxia (SARA) gait item as the most valid and responsive measures of gait in cerebellar ataxia. However, further evaluation to establish their reliability and applicability for use in clinical trials is clearly warranted. We recommend that inter-session reliability of gait outcomes should be evaluated to ensure changes are reflective of intervention effectiveness in cerebellar ataxia., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Cerebellar Ataxias are a group of gait disorders resulting from dysfunction of the cerebellum, commonly characterised by slowly progressing incoordination that manifests as problems with balance and walking leading to considerable disability. There is increasing acceptance of gait analysis techniques to quantify subtle gait characteristics that are unmeasurable by current clinical methods This systematic review aims to identify the gait characteristics able to differentiate between Cerebellar Ataxia and healthy controls., Methods: Following systematic search and critical appraisal of the literature, gait data relating to preferred paced walking in Cerebellar Ataxia was extracted from 21 studies. A random-effect model meta-analysis was performed for 14 spatiotemporal parameters. Quality assessment was completed to detect risk of bias., Results: There is strong evidence that compared with healthy controls, Cerebellar Ataxia patients walk with a reduced walking speed and cadence, reduced step length, stride length, and swing phase, increased walking base width, stride time, step time, stance phase and double limb support phase with increased variability of step length, stride length, and stride time., Conclusion: The consensus description provided here, clarifies the gait pattern associated with ataxic gait disturbance in a large cohort of participants. High quality research and reporting is needed to explore specific genetic diagnoses and identify biomarkers for disease progression in order to develop well-evidenced clinical guidelines and interventions for Cerebellar Ataxia., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Patients with cerebellar ataxia show increased upper body movements, which have an impact on balance and walking., Aim: In this study, we investigated the effect of using dynamic movement orthoses (DMO), designed as elastic suits, on trunk motion and gait parameters., Design: Longitudinal uncontrolled study., Setting: Outpatient rehabilitation unit., Population: Eleven patients (7 men, 4 women; mean age: 49.9±9.5 years) with degenerative cerebellar ataxia were enrolled in this study., Methods: Linear overground gait of patients was recorded by means of an optoelectronic gait analysis system before DMO use (DMO-) and during DMO use (DMO+). Time-distance parameters, lower limb joint kinematics, body sway, trunk oscillations, and gait variability (coefficient of variation [CV]) were recorded. Patient satisfaction with DMO device was measured using Quebec user evaluation of satisfaction with assistive technology., Results: When using the DMO, patients showed a significant decrease in stance phase duration, double support phase duration, swing phase CV, pelvic range of motion (ROM), body sway, and trunk ROMs. A significant increase was observed in the swing phase duration and knee joint ROM. Out of 11 patients, 10 were either quite satisfied (8 points) or very satisfied (2 points) with the assistive device., Conclusions: The DMO reduce the upper body motion and in improve balance-related gait parameters., Clinical Rehabilitation Impact: We propose use of DMO as an assistive/rehabilitative device in the neurorehabilitation of cerebellar ataxia to improve the trunk control and gait stability. DMO may be considered a prototype that can be modified in terms of material characteristics, textile layers, elastic components, and diagonal and lateral seams.

In the present study, the progression of gait impairment in a group of patients with primary degenerative cerebellar ataxias was observed over a period of 4 years. A total of 30 patients underwent an initial gait analysis study, and thereafter only 12 were evaluated because they completed the 2- and 4-year follow-up evaluations. Time-distance parameters, trunk and joint range of motion (RoM), and variability parameters (e.g., coefficients of variation) were measured at the baseline and at each follow-up evaluation. The scale for the assessment and rating of ataxia (SARA) was used to evaluate disease severity. We found a significant increase in the SARA score at both the 2- and 4-year follow-up evaluations. Almost all the gait variables changed significantly only at the 4-year follow-up. Particularly, we found a significant decrease in the step length and in the hip, knee, and ankle joint RoM values and noted a significant increase in the trunk rotation RoM and stride-to-stride and step length variability. Furthermore, a significant difference in ankle joint RoM was found between spinocerebellar ataxia and sporadic adult-onset ataxia patients, with the value being lower in the former group of patients. Our findings suggest that patients with degenerative cerebellar ataxias exhibit gait decline after 4 years from the baseline. Moreover, patients try to maintain an effective gait by adopting different compensatory mechanisms during the course of the disease in spite of disease progression.

Background: Uner Tan syndrome (UTS) cases with habitual quadrupedal locomotion (QL), impaired intelligence, and dysarthric or no speech predominantly use lateral sequence (LS) gait like nonprimates rather than the predominantly diagonal sequence (DS) gait of nonhuman primates. However, these studies neglected possible sex-related differences in these gait types., Objectives: (1) To assess the possible sex-related gait types in UTS cases, healthy infants and adults with requested QL, and the nonhuman primates. (2) To test the hypothesis that sex differences may exist in quadrupedal walking gaits in UTS cases, healthy humans, and nonhuman primates., Methods: The UTS cases were filmed, the other study groups were taken from public open 'youtube' videos, which were used to assess the walking gait types as DS and LS. The right and left hind-limb phase values were calculated separately for males and females to allow a possible sex difference in walking gaits to be determined., Results: Females predominantly used DS gait, contrary to males with predominantly LS gait., Conclusions: Consistent with the working hypothesis, the results suggested a biological sex-related trend in preferred walking gaits exists in all of the human and nonhuman primates using QL.

Pur-alpha is a highly conserved sequence-specific DNA and RNA binding protein with established roles in DNA replication, RNA translation, cell cycle regulation, and maintenance of neuronal differentiation. Prior studies have shown that mice lacking Pur-alpha (-/-) display decreased neurogenesis and impaired neuronal differentiation. We sought to examine for the first time, the behavioral phenotype and brain histopathology of mice that are heterozygous (+/-) for Pur-alpha. Standardized behavioral phenotyping revealed a decreased escape response to touch, limb and abdominal hypotonia, and gait abnormalities in heterozygous Pur-alpha (+/-) mice, compared to wild-type (+/+) littermates. Footprint pattern analyses showed wider-based steps, increased missteps and more outwardly rotated hindpaws in heterozygous Pur-alpha (+/-) mice, suggestive of cerebellar pathology. The Barnes maze and novel object location testing revealed significant memory deficits in heterozygous Pur-alpha mice, suggestive of hippocampal pathology. Quantitative immunohistochemical assays of the vermal region of the cerebellum and CA1-3 regions of the hippocampus revealed reduced numbers of neurons in general, as well as reduced numbers of Pur-alpha+-immunopositive neurons and dendrites in heterozygous Pur-alpha mice, compared to wild-type littermates. Past studies have implicated mutations in Pur-alpha in several diseases of brain development and neurodegeneration. When combined with these new findings, the Pur-alpha heterozygous knockout mice may provide an animal model to study mechanisms of and treatments for Pur-alpha-related cognitive deficiencies and neuropathology., (Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.)

Symptoms and signs of the hypothyroidism vary in relation to the magnitude and acuteness of the thyroid hormone deficiency. The usual clinical features are constipation, fatigue, cold intolerance and weight gain. Rarely it can present with neurologic problems like reversible cerebellar ataxia, dementia, peripheral neuropathy, psychosis and coma. Hypothyroidism should be suspected in all cases of ataxia, as it is easily treatable. A 40 year-old male presented with the history facial puffiness, hoarseness of voice and gait-ataxia. Investigations revealed frank primary hypothyroidism. Anti-TPO antibody was positive. Thyroxine was started and patient improved completely within eight weeks. Hypothyroidism can present with ataxia as presenting feature. Hypothyroidism should be considered in all cases of cerebellar ataxia as it is a reversible cause of ataxia.

An appropriate biomarker for spinocerebellar degeneration (SCD) has not been identified. Here, we performed gait analysis on patients with pure cerebellar type SCD and assessed whether the obtained data could be used as a neurophysiological biomarker for cerebellar ataxia. We analyzed 25 SCD patients, 25 patients with Parkinson's disease as a disease control, and 25 healthy control individuals. Acceleration signals during 6 min of walking and 1 min of standing were measured by two sets of triaxial accelerometers that were secured with a fixation vest to the middle of the lower and upper back of each subject. We extracted two gait parameters, the average and the coefficient of variation of motion trajectory amplitude, from each acceleration component. Then, each component was analyzed by correlation with the Scale for the Assessment and Rating of Ataxia (SARA) and the Berg Balance Scale (BBS). Compared with the gait control of healthy subjects and concerning correlation with severity and disease specificity, our results suggest that the average amplitude of medial-lateral (upper back) of straight gait is a physiological biomarker for cerebellar ataxia. Our results suggest that gait analysis is a quantitative and concise evaluation scale for the severity of cerebellar ataxia., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Unlabelled: The authors present a Brazilian case series of eight patients with idiopathic very-late onset (mean 75.5 years old) cerebellar ataxia, featuring predominantly gait ataxia, associated with cerebellar atrophy., Method: 26 adult patients with a diagnosis of idiopathic late onset cerebellar ataxia were analyzed in a Brazilian ataxia outpatient clinic and followed regularly over 20 years. Among them, 8 elderly patients were diagnosed as probable very late onset cerebellar ataxia. These patients were evaluated with neurological, ophthalmologic and Mini-Mental Status examinations, brain MRI, and EMG., Results: 62.5% of patients were males, mean age was 81.9 years-old, and mean age of onset was 75.5 years. Gait cerebellar ataxia was observed in all patients, as well as, cerebellar atrophy on brain MRI. Mild cognitive impairment and visual loss, due to macular degeneration, were observed in 50% of cases. Chorea was concomitantly found in 3 patients., Conclusion: We believe that this condition is similar the one described by Marie-Foix-Alajouanine presenting with mild dysarthria, associated with gait ataxia, and some patients had cognitive dysfunction and chorea.

Background: The modified Dynamic Gait Index (mDGI), developed from a person-environment model of mobility disability, measures mobility function relative to specific environmental demands. The framework for interpreting mDGI scores relative to specific environmental dimensions has not been investigated., Objective: The aim of this study was to examine the person-environmental model underlying the development and interpretation of mDGI scores., Design: This was a cross-sectional, descriptive study., Methods: There were 794 participants in the study, including 140 controls. Out of the total study population, 239 had sustained a stroke, 140 had vestibular dysfunction, 100 had sustained a traumatic brain injury, 91 had gait abnormality, and 84 had Parkinson disease. Exploratory factor analysis was used to investigate whether mDGI scores supported the 4 environmental dimensions., Results: Factor analysis showed that, with some exceptions, tasks loaded on 4 underlying factors, partially supporting the underlying environmental model., Limitations: Limitations of this study included the uneven sample sizes in the 6 groups., Conclusions: Support for the environmental framework underlying the mDGI extends its usefulness as a clinical measure of functional mobility by providing a rationale for interpretation of scores that can be used to direct treatment and infer change in mobility function., (© 2015 American Physical Therapy Association.)

Background: In the original and modified Dynamic Gait Index (mDGI), 8 tasks are used to measure mobility; however, disagreement exists regarding whether all tasks are necessary. The relationship between mDGI scores and Centers for Medicare & Medicaid Services (CMS) severity indicators in the mobility domain has not been explored., Objective: The study objectives were to examine the relationship between medical diagnoses and mDGI scores, to determine whether administration of the mDGI can be shortened on the basis of expected diagnostic patterns of performance, and to create a model in which mDGI scores are mapped to CMS severity modifiers., Design: This was a cross-sectional, descriptive study., Methods: The 794 participants included 140 people without impairments (control cohort) and 239 people with stroke, 140 with vestibular dysfunction, 100 with traumatic brain injury, 91 with gait abnormality, and 84 with Parkinson disease. Scores on the mDGI (total, performance facet, and task) for the control cohort were compared with those for the 5 diagnostic groups by use of an analysis of variance. For mapping mDGI scores to 7 CMS impairment categories, an underlying Rasch scale was used to convert raw scores to an interval scale., Results: There was a main effect of mDGI total, time, and gait pattern scores for the groups. Task-specific score patterns based on medical diagnosis were found, but the range of performance within each group was large. A framework for mapping mDGI total, performance facet, and task scores to 7 CMS impairment categories on the basis of Rasch analysis was created., Limitations: Limitations included uneven sample sizes in the 6 groups., Conclusions: Results supported retaining all 8 tasks for the assessment of mobility function in older people and people with neurologic conditions. Mapping mDGI scores to CMS severity indicators should assist clinicians in interpreting mobility performance, including changes in function over time., (© 2015 American Physical Therapy Association.)

The evident ataxic characteristics of gait in patients with cerebellar damage suggest that the cerebellum plays an important role in the neural control of gait. Ataxic features, such as increased gait variability and increased step width, are often related to gait stability. However, the link between these measures and gait stability is not straightforward. Therefore, to gain more insights into relations between gait stability, gait variability and gait ataxia, we quantified gait stability using the short-term maximum Lyapunov exponent. This is a more valid measure of gait stability, derived from dynamical systems theory. Eighteen patients with focal cerebellar lesions after tumor resection walked on an instrumented treadmill at 1.0m/s for 3min. The patients displayed relatively mild functional deficits (ICARS=6.9±6.4, range 0-20) and had a lower overground walking speed as compared to healthy controls (1.12m/s versus 1.31m/s). During treadmill walking, the short-term maximum Lyapunov exponent was higher in cerebellar patients, indicating reduced gait stability. Furthermore, step width was increased in the patient group while other spatio-temporal gait parameters were similar. Patients with the largest lesions in the vermis displayed the least stable gait pattern. These observations imply that the short-term maximum Lyapunov exponent is a sensitive measure of gait deficits in mildly ataxic cerebellar patients., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: To investigate whether prefrontal cortex (PFC) functioning during ataxic gait is linked to compensatory mechanisms or to the typical intra-subject variability of the ataxic gait., Methods: Nineteen patients with chronic ataxia and fifteen healthy subjects were evaluated. The subjects were requested to walk along a straight distance of 10 meters while PFC oxygenation and gait parameters were assessed. PFC activity was evaluated by NIRO-200 while gait analysis was performed by the SMART-D500. To investigate the intra-subject variability of gait, we calculated the coefficient of multiple correlation (CMC) of the hip, knee and ankle kinematic waveforms furthermore, we evaluated the step width., Results: We observed a positive correlation between PFC bilateral oxygenation changes and the step width (r = 0.54; p = 0.02 for the right PFC, and r = 0.50; p = 0.03 for the left PFC). No correlation was found between PFC activity and CMC of the hip, knee and ankle waveforms., Conclusions: Our results suggest that PFC activity is linked to gait compensatory mechanisms more than to the variability of the joint kinematic parameters caused by a defective cerebellar control.

Rett syndrome (RTT) is a genetic disorder characterized by a range of features including cognitive impairment, gait abnormalities and a reduction in purposeful hand skills. Mice harbouring knockout mutations in the Mecp2 gene display many RTT-like characteristics and are central to efforts to find novel therapies for the disorder. As hand stereotypies and gait abnormalities constitute major diagnostic criteria in RTT, it is clear that motor and gait-related phenotypes will be of importance in assessing preclinical therapeutic outcomes. We therefore aimed to assess gait properties over the prodromal phase in a functional knockout mouse model of RTT. In male Mecp2 knockout mice, we observed alterations in stride, coordination and balance parameters at 4 weeks of age, before the onset of other overt phenotypic changes as revealed by observational scoring. These data suggest that gait measures may be used as a robust and early marker of MeCP2-dysfunction in future preclinical therapeutic studies.

We describe a 62-year-old man with a sporadic form of hyperekplexia who presented with an unsteady gait, present since the age of 47. His clinical examination revealed an insecure broad-based gait and difficulty with tandem walking but no other abnormalities. For nearly a decade the patient was misdiagnosed with an idiopathic ataxia. A video electroencephalogram combined with an electromyogram during sudden auditory stimulus demonstrated an excessive startle response. An extensive work-up ruled out all the known causes of symptomatic hyperekplexia including anti-glycine receptor antibodies. Treatment with clonazepam markedly reduced the threshold and intensity of the startle response, enabling him to recover independence. Hyperekplexia is frequently associated with an awkward and hesitating gait, but these gait abnormalities might be confused with other causes of gait disorders if one is not aware of this disease. We report this patient to highlight that a correct diagnosis of hyperekplexia is crucial, because its treatment may change quality of life., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Studies about recovery from cerebellar stroke are rare. The present study assessed motor deficits in the acute phase after isolated cerebellar stroke focusing on postural impairment and gait ataxia and outlines the role of lesion site on motor outcome, the course of recovery and the effect of treadmill training. 23 patients with acute and isolated cerebellar infarction participated. Deficits were quantified by ataxia scores and dynamic posturography in the acute phase and in a follow up after 2 weeks and 3 months. MRI data were obtained to correlate lesion site with motor performance. Half of the patients that gave informed consent and walked independently underwent a 2-week treadmill training with increasing velocity. In the acute phase patients showed a mild to severe ataxia with a worse performance in patients with infarction of the superior in comparison to the posterior inferior cerebellar artery. However, after 3 months differences between vascular territories were no longer significant. MRI data showed that patients with larger infarct volumes had a significantly more severe ataxia. In patients with ataxia of stance, gait and lower limbs lesions were more common in cerebellar lobules IV to VI. After 3 months a mild ataxia in lower limbs and gait, especially in gait speed persisted. Because postural impairment had fully recovered, remaining gait ataxia was likely related to incoordination of lower limbs. Treadmill training did not show significant effects. Future studies are needed to investigate whether intensive coordinative training is of benefit in patients with cerebellar stroke., (Copyright © 2013. Published by Elsevier B.V.)

Objectives: In this study we evaluated the usability of the Gait Deviation Index (GDI), an index that summarizes the amount of deviation in movement from a standard norm, in adults with rheumatoid arthritis (RA). The aims of the study were to evaluate the ability of the GDI to identify gait deviations, assess inter-trial repeatability, and examine the relationship between the GDI and walking speed, physical disability, and pain., Method: Sixty-three adults with RA and 59 adults with typical gait patterns were included in this retrospective case-control study. Following a three-dimensional gait analysis (3DGA), representative gait cycles were selected and GDI scores calculated. To evaluate the effect of walking speed, GDI scores were calculated using both a free-speed and a speed-matched reference set. Physical disability was assessed using the Health Assessment Questionnaire (HAQ) and subjects rated their pain during walking., Results: Adults with RA had significantly increased gait deviations compared to healthy individuals, as shown by lower GDI scores [87.9 (SD = 8.7) vs. 99.4 (SD = 8.3), p < 0.001]. This difference was also seen when adjusting for walking speed [91.7 (SD = 9.0) vs. 99.9 (SD = 8.6), p < 0.001]. It was estimated that a change of ≥ 5 GDI units was required to account for natural variation in gait. There was no evident relationship between GDI and low/high RA-related physical disability and pain., Conclusions: The GDI seems to useful for identifying and summarizing gait deviations in individuals with RA. Thus, we consider that the GDI provides an overall measure of gait deviation that may reflect lower extremity pathology and may help clinicians to understand the impact of RA on gait dynamics.

We examined the influence of focal cerebellar lesions on working memory (n-back task), gait, and the interaction between working memory and different gait tasks in a dual-task paradigm. The analysis included 17 young patients with chronic focal lesions after cerebellar tumor resection and 17 age-matched controls. Patients have shown mild to moderate ataxia. Lesion sites were examined on the basis of structural magnetic resonance imaging. N-back tasks were executed with different levels of difficulty (n = 1-4) during sitting (baseline), treadmill walking, and treadmill tandem walking (dual-task conditions). Patients exhibited decreased n-back performance particularly at difficult n-back levels and in dual-task conditions. Voxel-based lesion-symptom mapping revealed that decreased baseline n-back performance was associated with lesions of the posterolateral cerebellar hemisphere and the dentate nucleus. By contrast, decreased n-back performance in dual-task conditions was more associated with motor-related areas including dorsal portions of the dentate and the interposed nucleus, suggesting a prioritization of the motor task. During baseline walking, increased gait variability was associated with lesions in medial and intermediate regions, whereas for baseline tandem gait, lesions in the posterolateral hemispheres and the dentate nucleus became important. Posterolateral regions overlapped with regions related to baseline n-back performance. Consistently, we observed increased tandem gait variability with growing n-back difficulty in the dual-task condition. These findings suggest that dual-task effects in cerebellar patients are at least partially caused by a common involvement of posterolateral cerebellar regions in working memory and complex motor tasks.

Adult-onset autosomal-dominant leukodystrophy (ADLD) is a progressive and fatal neurological disorder characterized by early autonomic dysfunction, cognitive impairment, pyramidal tract and cerebellar dysfunction, and white matter loss in the central nervous system. ADLD is caused by duplication of the LMNB1 gene, which results in increased lamin B1 transcripts and protein expression. How duplication of LMNB1 leads to myelin defects is unknown. To address this question, we developed a mouse model of ADLD that overexpresses lamin B1. These mice exhibited cognitive impairment and epilepsy, followed by age-dependent motor deficits. Selective overexpression of lamin B1 in oligodendrocytes also resulted in marked motor deficits and myelin defects, suggesting these deficits are cell autonomous. Proteomic and genome-wide transcriptome studies indicated that lamin B1 overexpression is associated with downregulation of proteolipid protein, a highly abundant myelin sheath component that was previously linked to another myelin-related disorder, Pelizaeus-Merzbacher disease. Furthermore, we found that lamin B1 overexpression leads to reduced occupancy of Yin Yang 1 transcription factor at the promoter region of proteolipid protein. These studies identify a mechanism by which lamin B1 overexpression mediates oligodendrocyte cell-autonomous neuropathology in ADLD and implicate lamin B1 as an important regulator of myelin formation and maintenance during aging.

Acute phase rehabilitation is an important treatment for improving the functional outcome of patients after stroke. The present cohort study analyzed the feasibility and safety of acute phase rehabilitation using the hybrid assistive limb robot suit in 22 patients, 7 males and 15 females (mean age 66.6 ± 17.7 years). Neurological deterioration, mortality, or other accidents were recorded as adverse events. Baseline characteristics of each patient were recorded at the first hybrid assistive limb rehabilitation. Hybrid assistive limb rehabilitation was conducted for 12.1 ± 7.0 days with the patients in stable condition. Acute phase hybrid assistive limb rehabilitation was performed a total of 84 times with no adverse events recorded except for orthostatic hypotension. Good functional outcomes were obtained in 14 patients. Orthostatic hypotension was observed during the first hybrid assistive limb rehabilitation in four patients, and was significantly associated with intracerebral hemorrhage (p = 0.007) and lower Brunnstrom stage (p = 0.033). Acute phase rehabilitation using the hybrid assistive limb suit is feasible and safe. Patients with intracerebral hemorrhage and lower Brunnstrom stage should be carefully monitored for orthostatic hypotension.

More sensitive assays of mouse motor ataxia may provide a better understanding of the pathological profile. Treadmill gait analysis using ventral imaging allows for unhindered access to the ambulating mouse. In contrast to genetic mutations or exogenous brain injury, ethanol (EtOH) allows for the detection of dose dependent changes in motor behavior, which can be used to assess an assay's detection sensitivity. EtOH induced ataxia was assessed in C57BL/6J (B6) and 129X1/SvJ (129) mice using the DigiGait imaging system. Gait was analyzed across EtOH dosage (1.75, 2.25 and 2.75 g/kg) in each strain using a linear mixed effects model. Overall, 129 mice displayed greater susceptibility to EtOH ataxia than their B6 counterparts. In both strains, hind paws exhibited greater sensitivity to EtOH dosage than fore paws. Across most variables analyzed, only a modest EtOH-induced change in motor behavior was observed in each strain with the 1.75 g/kg EtOH doses failing to elicit significant change. These data indicate the ability to detect motor differences between strains, yet only moderate ability to detect change across EtOH dosage using the automated treadmill. Rotarod assays, however, were able to detect motor impairment at lower doses of EtOH. The significant, but opposite changes in paw placement with increasing EtOH doses highlight strain-specific differences in biophysical adaptations in response to acute EtOH intoxication., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Ehlers-Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of inherited connective tissue disorders characterised by joint hypermobility, skin hyperextensibility and tissue fragility. It has recently been shown that muscle weakness occurs frequently in EDS, and that fatigue is a common and clinically important symptom. The aim of this study was to investigate the relationship between fatigue severity and the gait pattern using 3D Gait Analysis (GA). Eleven individuals with Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome Hypermobility type (JHS/EDS-HT) were investigated using muscle strength measured with standardised questionnaire measuring fatigue (Fatigue Severity Scale, FSS) and quantitative 3D GA. Our data showed that FSS value well correlated with the peak of vertical component of ground reaction force (r=-0.66, p<0.05). The negative correlation gives evidence that the higher the fatigue is the more reduced force is during gait. Our results showed that the ground reaction force has been applied as a functional evaluation score for detecting pathology in gait of JHS/EDS-HT participants and the found correlation between vertical force and fatigue demonstrated that muscle fatigue may be associated with a loss of proprioceptive acuity in lower limb muscles., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Due to the multisensory input into the balance system, the loss of one input, such as an ear, can generally be compensated for. However, when a mismatch or incomplete loss of inputs occurs, the ability to compensate for the stimulus misrepresentation may be compromised. The inner ear and cerebellum are important input and processing centers for balance but no genetic models have been generated to assess balance or compensation in the abnormal development of both these organs/brain areas. Important to their formation is regulation of proliferation mediated by the proto-oncogene N-Myc. Conditional knockouts (CKOs) of N-Myc using Tg(Pax2-Cre) have a misshapen and smaller ear with a fused utricle, saccule, and cochlea and absent horizontal canal, aberrant cochlear and vestibular innervations, and a size reduction in the cerebellum. CKOs are viable with obvious behavioral deficits, including circling behavior and unstable gait. To test the degree of ataxia and possible compensation of vestibular defects in these mutant mice, we use the Noldus Catwalk System to assess the gait of Tg(Pax2-Cre) N-Myc CKOs over five months. N-Myc CKOs perform worse than control littermates, in particular, in step regularity. We show that disrupting one member of the Myc family during embryonic development coincides with a differential loss of function in the cochlea compared to the vestibular apparatus. In addition, we show that the distortion in the ear morphology combined with a reduction of the cerebellum, rather than a complete loss of the vestibular-cerebellar pathway, leads to partial behavioral compensation that remains unchanged over time., ((c) 2012 APA, all rights reserved)

Purpose: 1) to verify if prefrontal cortex (PFC) is activated during over ground walking in ataxic patients, 2) to correlate the clinical parameters of gait with the PFC activation patterns., Methods: Fourteen patients and 20 healthy subjects were studied. Ataxia was assessed by the Scale for the Assessment and Rating of Ataxia (SARA). A 2-channel near-infrared system was used to investigate the changes in oxygenated ([O2Hb]t) and deoxygenated ([HHb]t) hemoglobin concentrations on the PFC during gait. [O2Hb] baseline-corrected activation values ([O2Hb]c) were calculated by the difference between [O2Hb]t and [O2Hb] during upright posture ([O2Hb]b)., Results: [O2Hb]t was increased for both channels (respectively p < 0.01 and p = 0.01) only in the patients. No variation was observed in [HHB]t. The correlation coefficient between [O2Hb]c and the SARA gait score was respectively r: 0.878 (p < 0.01) and r: 0.839 (p < 0.01) for the right and left PFC, between [O2Hb]c and the SARA stance score respectively r: 0.893 (p < 0.01) and r: 0.832 (p < 0.01)., Conclusions: During over ground gait PFC is bilaterally activated in patients with severe chronic ataxia. These findings may be associated with compensatory mechanisms which are involved in severe conditions when other nervous centers controlling balance are functionally not efficient.

Unlabelled: The "arteriosclerotic parkinsonism", which is called vascular parkinsonism (VP), was first described by Critchley'. The broad based slow gait, reduced stride lenght, start hesitation, freezing and paratonia was mentioned as "lower body parkinsonism" (LBP) which can be associated by slow speech, dysexecutive syndrome, and hand tremor of predominantly postural character. In VP the DAT-scan proved normal dopamine content of the striatum in contrast with Parkinson's disease (PD). Additionally, Lewy bodies of brainstem type were not found in VR Probability of VP increases if central type pathologic gait is prominent; the hands are slightly involved, the MRI indicates transparent periventricular white substance and/or brain atrophy. In some cases differentiation of gait apraxia and parkinsonism could be challenging. There is no rigor of the lower limbs at rest in neither of them, the disturbance of movement is evoked by the gait itself. Three subtypes of "gait ignition failure" has been recently described: (1) ignition apraxia, (2) equilibrium apraxia and (3) mixed gait apraxia. The primary progressive freesing gait was considered as a Parkinson-plus syndrome. Freesing occurs more frequently in diseases with pakinsonism than in PD. The grade of ventricle dilatation and the frontal leukoaraiosis was similar in LBP and gait apraxia. In cases of normal pressure hydrocephalus the impaired gait may mimic PD. Pathologic gait in VP can be explained by the lesions of the senso-motor association pathways in dorsal paramedian white substance within the vulnerable borderzone region. These may be colocalized with the representation of the lower extremities in the posterior third of the supplementer motor area. Rektor2 proposed to change the name of LBP to "cerebrovascular gait disorder". Notwithstandig central type gait disorder develops also in many degenerative diseases other than cerebro-vascular origin. The neuronal net controling the regulation of movement is widespread, therefore several cortical and subcortical lesions could elicit large variations of pathologic gait, ie.: ataxia, apraxia, ignition failure, akinesis etc., In Conclusion: most of the central gait disorders regarding the pathology and their appearance can not be called "parkinsonism"; these are much closer related to the localization of lesions rather than to the diagnostic categories.

The Riley-Day syndrome is the most common of the hereditary sensory and autonomic neuropathies (Type III). Among the well-recognized clinical features are reduced pain and temperature sensation, absent deep tendon reflexes and a progressively ataxic gait. To explain the latter we tested the hypothesis that muscle spindles, or their afferents, are absent in hereditary sensory and autonomic neuropathy III by attempting to record from muscle spindle afferents from a nerve supplying the leg in 10 patients. For comparison we also recorded muscle spindles from 15 healthy subjects and from two patients with hereditary sensory and autonomic neuropathy IV, who have profound sensory disturbances but no ataxia. Tungsten microelectrodes were inserted percutaneously into fascicles of the common peroneal nerve at the fibular head. Intraneural stimulation within muscle fascicles evoked twitches at normal stimulus currents (10-30 µA), and deep pain (which often referred) at high intensities (1 mA). Microneurographic recordings from muscle fascicles revealed a complete absence of spontaneously active muscle spindles in patients with hereditary sensory and autonomic neuropathy III; moreover, responses to passive muscle stretch could not be observed. Conversely, muscle spindles appeared normal in patients with hereditary sensory and autonomic neuropathy IV, with mean firing rates of spontaneously active endings being similar to those recorded from healthy controls. Intraneural stimulation within cutaneous fascicles evoked paraesthesiae in the fascicular innervation territory at normal stimulus intensities, but cutaneous pain was never reported during high-intensity stimulation in any of the patients. Microneurographic recordings from cutaneous fascicles revealed the presence of normal large-diameter cutaneous mechanoreceptors in hereditary sensory and autonomic neuropathy III. Our results suggest that the complete absence of functional muscle spindles in these patients explains their loss of deep tendon reflexes. Moreover, we suggest that their ataxic gait is sensory in origin, due to the loss of functional muscle spindles and hence a compromised sensorimotor control of locomotion.

To test for an association between the LRRK2-G2019S mutation and gait, we studied 52 first-degree relatives of patients with Parkinson's disease (PD) who carry this mutation. An accelerometer quantified gait during usual-walking, fast-walking, and dual-tasking. Noncarriers (n = 27) and carriers (n = 25) were similar with respect to age, gender, height, and gait speed during all conditions. During dual-tasking and fast-walking, gait variability and the amplitude of the dominant peak of the accelerometer signal were significantly altered among the carriers. These findings support the possibility of previously unidentified, presymptomatic motor changes among relatives who have an increased risk of developing PD., (Copyright © 2010 American Neurological Association.)

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).

Animals as well as humans adapt their locomotor patterns to suit different situations. To perform smooth and stable locomotion, they coordinate not only parts of a limb but also different limbs. The cerebellum is important for sensorimotor control and plays a crucial role in intra- and inter-limb coordination. Cerebellar gait ataxia is characterized by postural deficiencies and decomposition of movements. During locomotion, the vermis and the intermediate region of the cerebellum receive information through the spinocerebellar pathways about the ongoing activities in the spinal stepping generator and the somatosensory receptors. The information is conveyed by mossy fiber afferents to Purkinje neurons via granule cells and their axons, i.e., parallel fibers. Purkinje neurons transform the mossy fiber input signals to output signals that in turn modulate activities in the brainstem descending tract neurons of the brainstem that are involved in locomotion. Further, Purkinje neurons receive enhanced climbing fiber signals during perturbed locomotion. These climbing fiber signals may induce synaptic plasticity at the parallel fiber-Purkinje neuron synapses. Long-term depression (LTD) occurs in parallel fiber-Purkinje neuron synapses and is regarded as the cellular basis for the learning mechanism of the cerebellar neuronal circuit. The activation of parallel fibers releases glutamate and nitric oxide, and the released glutamate activates the glutamate receptors in the Purkinje neurons. mGluR1, a subtype of the metabotropic glutamate receptors, is highly expressed in Purkinje neurons. In addition, delta 2 glutamate receptor is expressed in only Purkinje neurons throughout the brain. Genetically targeted mice for these glutamate receptors and/or pharmacological blocking studies have been promoted to determine the functional linkage between the molecules at the cellular level and the adaptability of locomotion at the behavioral level. This article highlights some recent advances in the understanding of the role played by the cerebellum in the adaptive control of locomotion.

Cerebellar damage typically results in ataxia and can be caused by stroke, tumor, or one of many forms of degenerative disease. Since few pharmacological options are available, most treatments rely heavily on rehabilitation therapy. Little data exist on methods for tracking the progression of ataxia, which is critical for assessing the efficacy of current and newly developing treatments. Here, we tracked the severity of ataxia, with a particular emphasis on gait and balance dysfunction, in a group of individuals with cerebellar damage using the International Cooperative Ataxia Rating Scale (ICARS) and several instrumented laboratory measures of gait and balance impairments over 1 year. We found that the ICARS was able to distinguish between subjects with static lesions and those with degenerative disorders, was sensitive to increases in ataxia severity occurring over 1 year, and correlated well with specific instrumented measures of gait in persons with cerebellar degeneration. These results suggest the ICARS is a valuable tool for clinicians and investigators to document and track long-term changes in gait and balance performance in individuals with cerebellar degenerative disorders., (© 2010 Movement Disorder Society.)

Introduction: Brain volume shrinkage is common in treatment-seeking patients with alcohol use disorders. Whether women are more vulnerable to brain dysmorphology than men despite lower alcohol consumption levels or shorter dependency ("telescoping effect") remains controversial and has not been considered with respect to infratentorial structures or their potential contribution to ataxia., Methods: The 200 participants included 64 men and 31 women with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition alcohol dependence and 105 controls. An infratentorial region (pons, cerebellar hemispheres, vermis (anterior, posterior, and inferior sectors), fissures, cisterns, fourth ventricle) was quantified with atlas-based parcellation. To enable comparison of men and women, regional tissue volumes were expressed as ratios of tissue in the volume. Participants also completed quantitative ataxia testing., Results: Total infratentorial and vermian tissue ratios were significantly smaller in alcoholics than controls; alcoholic women did not show disproportionately greater volume deficits than alcoholic men. A re-analysis including alcoholic men and women matched in alcohol consumption, onset age, abstinence duration, and age revealed again that alcoholic women did not have disproportionately greater regional vermian volume deficits than alcoholic men. Alcoholic men and women were impaired in all measures of ataxia, which correlated with low infratentorial tissue ratios in men., Discussion: Alcoholic men showed deficits of pontocerebellar volume ratios, yet alcoholic women did not display signs of "telescoping". Further, alcoholic men and women both showed signs of ataxia of gait and balance, related to affected pontocerebellar systems in the men but not the women, suggesting the need to consider other neural substrates for ataxia in women.