Dataset Information

Patients with Cerebellar Ataxia Do Not Benefit from Limb Weights.

ABSTRACT: Patients with cerebellar ataxia are sometimes treated by the addition of mass to the limbs, though this practice has received limited study. Recent work suggests that adding mass to the limbs might have predictable effects on the pattern of cerebellar dysmetria (i.e., over or undershooting) that depends on a hypothesized mismatch between the actual limb inertia and the brain's estimate of limb inertia. Based on this model, we predicted that addition of mass would only be effective in reducing dysmetria in hypometric patients. Cerebellar patients were challenged with making a single-joint, single degree of freedom reaching movement while various limb masses were tested. In this task, some single-jointed reaches were improved by adding masses that were optimized in a patient-specific manner. However, this improvement did not translate to multi-joint movements. In multi-joint movements, the "best" patient-specific masses (as determined in a single-joint task) generally exacerbated subjects' reaching errors. This finding raises questions as to the merits of adding limb weights as a therapy to mitigate the effects of dysmetria.

SUBMITTER: Zimmet AM

PROVIDER: S-EPMC6983975 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Patients with Cerebellar Ataxia Do Not Benefit from Limb Weights.

Zimmet Amanda M AM Cowan Noah J NJ Bastian Amy J AJ

Cerebellum (London, England) 20190201 1

Patients with cerebellar ataxia are sometimes treated by the addition of mass to the limbs, though this practice has received limited study. Recent work suggests that adding mass to the limbs might have predictable effects on the pattern of cerebellar dysmetria (i.e., over or undershooting) that depends on a hypothesized mismatch between the actual limb inertia and the brain's estimate of limb inertia. Based on this model, we predicted that addition of mass would only be effective in reducing dy ...[more]

PMID: 30069836

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Project description:BACKGROUND:Cerebellar damage can often result in disabilities affecting the peripheral regions of the body. These include poor and inaccurate coordination, tremors and irregular movements that often manifest as disorders associated with balance, gait and speech. The severity assessment of Cerebellar ataxia (CA) is determined by expert opinion and is likely to be subjective in nature. This paper investigates automated versions of three commonly used tests: Finger to Nose test (FNT), test for upper limb Dysdiadochokinesia Test (DDK) and Heel to Shin Test (HST), in evaluating disability due to CA. METHODS:Limb movements associated with these tests are measured using Inertial Measurement Units (IMU) to capture the disability. Kinematic parameters such as acceleration, velocity and angle are considered in both time and frequency domain in three orthogonal axes to obtain relevant disability related information. The collective dominance in the data distributions of the underlying features were observed though the Principal Component Analysis (PCA). The dominant features were combined to substantiate the correlation with the expert clinical assessments through Linear Discriminant Analysis. Here, the Pearson correlation is used to examine the relationship between the objective assessments and the expert clinical scores while the performance was also verified by means of cross validation. RESULTS:The experimental results show that acceleration is a major feature in DDK and HST, whereas rotation is the main feature responsible for classification in FNT. Combining the features enhanced the correlations in each domain. The subject data was classified based on the severity information based on expert clinical scores. CONCLUSION:For the predominantly translational movement in the upper limb FNT, the rotation captures disability and for the DDK test with predominantly rotational movements, the linear acceleration captures the disability but cannot be extended to the lower limb HST. The orthogonal direction manifestation of ataxia attributed to sensory measurements was determined for each test. TRIAL REGISTRATION:Human Research and Ethics Committee, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia (HREC Reference Number: 11/994H/16).

Project description:BackgroundSeptins are cytoskeletal proteins with filament forming capabilities, which have multiple roles during cell division, cellular polarization, morphogenesis, and membrane trafficking. Autoantibodies against septin-5 are associated with non-paraneoplastic cerebellar ataxia, and autoantibodies against septin-7 with encephalopathy with prominent neuropsychiatric features. Here, we report on newly identified autoantibodies against septin-3 in patients with paraneoplastic cerebellar ataxia. We also propose a strategy for anti-septin autoantibody determination.MethodsSera from three patients producing similar immunofluorescence staining patterns on cerebellar and hippocampal sections were subjected to immunoprecipitation followed by mass spectrometry. The identified candidate antigens, all of which were septins, were expressed recombinantly in HEK293 cells either individually, as complexes, or combinations missing individual septins, for use in recombinant cell-based indirect immunofluorescence assays (RC-IIFA). Specificity for septin-3 was further confirmed by tissue IIFA neutralization experiments. Finally, tumor tissue sections were analyzed immunohistochemically for septin-3 expression.ResultsImmunoprecipitation with rat cerebellum lysate revealed septin-3, -5, -6, -7, and -11 as candidate target antigens. Sera of all three patients reacted with recombinant cells co-expressing septin-3/5/6/7/11, while none of 149 healthy control sera was similarly reactive. In RC-IIFAs the patient sera recognized only cells expressing septin-3, individually and in complexes. Incubation of patient sera with five different septin combinations, each missing one of the five septins, confirmed the autoantibodies' specificity for septin-3. The tissue IIFA reactivity of patient serum was abolished by pre-incubation with HEK293 cell lysates overexpressing the septin-3/5/6/7/11 complex or septin-3 alone, but not with HEK293 cell lysates overexpressing septin-5 as control. All three patients had cancers (2 × melanoma, 1 × small cell lung cancer), presented with progressive cerebellar syndromes, and responded poorly to immunotherapy. Expression of septin-3 was demonstrated in resected tumor tissue available from one patient.ConclusionsSeptin-3 is a novel autoantibody target in patients with paraneoplastic cerebellar syndromes. Based on our findings, RC-IIFA with HEK293 cells expressing the septin-3/5/6/7/11 complex may serve as a screening tool to investigate anti-septin autoantibodies in serological samples with a characteristic staining pattern on neuronal tissue sections. Autoantibodies against individual septins can then be confirmed by RC-IIFA expressing single septins.

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Patients with Cerebellar Ataxia Do Not Benefit from Limb Weights.

Publications

Patients with Cerebellar Ataxia Do Not Benefit from Limb Weights.

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