Cerebellum and Ataxias最新文献

Background: Saccade slowing has been proposed as endophenotype marker in Spinocerebellar Ataxia type 2 (SCA2), nevertheless the heritability of this trait has not been properly demonstrated. Thus the present paper was aimed to assess the heritability of different saccadic parameters in SCA2.

Methods: Forty-eight SCA2 patients, 25 preclinical carriers and 24 non-SCA2 mutation carriers underwent electronystagmographical assessments of saccadic eye movements as well as neurological examination and ataxia scoring. Estimates of heritability based on the intraclass correlation coefficients were calculated for saccade velocity, accuracy and latency as well as for age at disease onset from 36, 17 and 15 sibling pairs of SCA2 patients, preclinical carriers and controls, respectively.

Results: Saccade velocity was significantly reduced in SCA2 patients and preclinical carriers, whereas decreased saccade accuracy and increased saccade latency were only observed in the patients cohort. Intraclass correlation coefficient for saccade velocity was highly significant in SCA2 patients, estimating a heritability around 94%, whereas for the age at ataxia onset this estimate was around 68%.

Conclusions: Electronystagmographical measure of saccade velocity showed higher familial aggregation between SCA2 patients leading the suitability of this disease feature as endophenotype marker, with potential usefulness for the search of modifier genes and neurobiological underpinnings of the disease and as outcome measure in future neuroprotective clinical trials.

Background: To date, 43 types of Spinocerebellar Ataxias (SCAs) have been identified. A subset of the SCAs are caused by the pathogenic expansion of a CAG repeat tract within the corresponding gene. Ethnic and geographic differences are evident in the prevalence of the autosomal dominant SCAs. Few descriptions of the clinical phenotype and molecular genetics of the SCAs are available from the African continent. Established studies mostly concern the South African populations, where there is a high frequency of SCA1, SCA2 and SCA7. The SCA7 mutation in South Africa (SA) has been found almost exclusively in families of indigenous Black African ethnic origin.

Objective: To present the results of the first clinical description of seven Zambian families presenting with autosomal dominant SCA, as well as the downstream molecular genetic analysis of a subset of these families.

Methods: The study was undertaken at the University Teaching Hospital in Lusaka, Zambia. Ataxia was quantified with the Brief Ataxia Rating Scale derived from the modified international ataxia rating scale. Molecular genetic testing for 5 types of SCA (SCA1, SCA2, SCA3, SCA6 and SCA7) was performed at the National Health Laboratory Service at Groote Schuur Hospital and the Division of Human Genetics, University of Cape Town, SA. The clinical and radiological features were evaluated in seven families with autosomal dominant cerebellar ataxia. Molecular genetic analysis was completed on individuals representing three of the seven families.

Results: All affected families were ethnic Zambians from various tribes, originating from three different regions of the country (Eastern, Western and Central province). Thirty-four individuals from four families had phenotypic features of SCA7. SCA7 was confirmed by molecular testing in 10 individuals from 3 of these families. The age of onset of the disease varied from 12 to 59 years. The most prominent phenotypic features in these families were gait and limb ataxia, dysarthria, visual loss, ptosis, ophthalmoparesis/ophthalmoplegia, pyramidal tract signs, and dementia. Affected members of the SCA7 families had progressive macular degeneration and cerebellar atrophy. All families displayed marked anticipation of age at onset and rate of symptom progression. The pathogenic SCA7 CAG repeat ranges varied from 47 to 56 repeats. Three additional families were found to have clinical phenotypes associated with autosomal dominant SCA, however, DNA was not available for molecular confirmation. The age of onset of the disease in these families varied from 19 to 53 years. The most common clinical picture in these families included a combination of cerebellar symptoms with slow saccadic eye movements, peripheral neuropathy, dementia and tremor.

Conclusion: SCA is prevalent in ethnic Zambian families. The SCA7 families in this report had similar cli

The cerebellum is a vulnerable target of autoimmunity in the CNS. The category of immune-mediated cerebellar ataxias (IMCAs) was recently established, and includes in particular paraneoplastic cerebellar degenerations (PCDs), gluten ataxia (GA) and anti-GAD65 antibody (Ab) associated-CA, all characterized by the presence of autoantibodies. The significance of onconeuronal autoantibodies remains uncertain in some cases. The pathogenic role of anti-GAD65Ab has been established both in vitro and in vivo, but a consensus has not been reached yet. Recent studies of anti-GAD65 Ab-associated CA have clarified that (1) autoantibodies are generally polyclonal and elicit pathogenic effects related to epitope specificity, and (2) the clinical course can be divided into two phases: a phase of functional disorder followed by cell death. These features provide the rationale for prompt diagnosis and therapeutic strategies. The concept "Time is brain" has been completely underestimated in the field of immune ataxias. We now put forward the concept "Time is cerebellum" to underline the importance of very early therapeutic strategies in order to prevent or stop the loss of neurons and synapses. The diagnosis of IMCAs should depend not only on Ab testing, but rather on a rapid and comprehensive assessment of the clinical/immune profile. Treatment should be applied during the period of preserved cerebellar reserve, and should encompass early removal of the conditions (such as remote primary tumors) or diseases that trigger the autoimmunity, followed by the combinations of various immunotherapies.

Background: The control of grip forces when moving a hand held object is impaired in patients with cerebellar degeneration. We asked the question whether after-effects of anodal transcranial direct current stimulation (tDCS) applied to the lateral cerebellum or M1 improved grip force control in cerebellar patients.

Methods: Grip force control while holding an object during cyclic arm movements was assessed in patients with pure cerebellar degeneration (n = 14, mean age 50.2 years ± SD 8.8 years) and age- and sex-matched control participants (n = 14, mean age 50.7 years ± SD 9.8 years). All subjects were tested before and after application of tDCS (2 mA, 22 min) in a within-subject design. Each subject received anodal tDCS applied to the cerebellum, anodal tDCS applied to M1 or sham-stimulation with a break of 1 week between the three experimental sessions.

Results: There were no clear after-effects of tDCS on grip force control neither in control participants nor in cerebellar patients. Cerebellar patients showed typical impairments with higher grip forces, a higher variability of movements.

Conclusion: In the present study, deficits in grip force control were neither improved by tDCS applied over the cerebellum nor M1 in cerebellar degeneration.

Background: Hemicerebellitisis a rare acquired condition, typical of the pediatric age. A residual switched handedness may develop after remission of acute cerebellar symptoms.

Case presentation: Herein we describe a motor functional MRI studyperformed in a 35-year old girl who had switched to left-handedness after acute right hemicerebellitis in childhood. During left hand tapping, we observed activation in the right primary sensori-motor cortex, right supplementary motor area and left superior cerebellum. During right hand tapping bilateral activations of primary sensori-motorcortex and superior cerebellum including the vermis and activation of the right supplementary motor area were observed. We speculate that during right hand tapping both the ipsilateral and contralateralpre-central gyri and the ipsilateral cerebellum would be engaged in order to recover the tapping internal model of action. From this perspective the ipsilateral pre-central gyrus might serve as are transmission station of information from the healthy cerebellum to the contralateral pre-central gyrus.

Conclusion: Selective damage of the right half of the cerebellum due to hemicerebellitis in childhood can drive shift of lateralized hand functions in the cerebrum.

Background: Damage to the cerebellum may lead to motor dysfunctions, but also to the neuropsychological deficits that comprise the Cerebellar Cognitive Affective Syndrome (CCAS). It can affect executive functions, attention, memory, visuospatial functions, language, and emotions. Our goal was to determine which neuropsychological tests could be effectively used to identify this syndrome during a short examination.

Methods: Twenty-five patients with an isolated cerebellar lesion and 25 matched healthy controls were examined using an extensive neuropsychological battery.

Results: Logistic regression models and sub-models were computed for individual tests, as well as for the full battery. The best results were produced by a model combining patient education level, the number of errors on the California Verbal Learning Test, and time on Prague Stroop Test (Dots).

Conclusions: Based on the results, we suggest that a condensed battery of neuropsychological tests can be used to detect CCAS. The tests are easy to administer and could be helpful in both research and clinical settings.

Background: Mathematicians and scientists have struggled to adequately describe the ultimate foundations of mathematics. Nobel laureates Albert Einstein and Eugene Wigner were perplexed by this issue, with Wigner concluding that the workability of mathematics in the real world is a mystery we cannot explain. In response to this classic enigma, the major purpose of this article is to provide a theoretical model of the ultimate origin of mathematics and "number sense" (as defined by S. Dehaene) that is proposed to involve the learning of inverse dynamics models through the collaboration of the cerebellum and the cerebral cortex (but prominently cerebellum-driven). This model is based upon (1) the modern definition of mathematics as the "science of patterns," (2) cerebellar sequence (pattern) detection, and (3) findings that the manipulation of numbers is automated in the cerebellum. This cerebro-cerebellar approach does not necessarily conflict with mathematics or number sense models that focus on brain functions associated with especially the intraparietal sulcus region of the cerebral cortex. A direct corollary purpose of this article is to offer a cerebellar inner speech explanation for difficulty in developing "number sense" in developmental dyscalculia.

Results: It is argued that during infancy the cerebellum learns (1) a first tier of internal models for a primitive physics that constitutes the foundations of visual-spatial working memory, and (2) a second (and more abstract) tier of internal models based on (1) that learns "number" and relationships among dimensions across the primitive physics of the first tier. Within this context it is further argued that difficulty in the early development of the second tier of abstraction (and "number sense") is based on the more demanding attentional requirements imposed on cerebellar inner speech executive control during the learning of cerebellar inverse dynamics models. Finally, it is argued that finger counting improves (does not originate) "number sense" by extending focus of attention in executive control of silent cerebellar inner speech.

Discussion: It is suggested that (1) the origin of mathematics has historically been an enigma only because it is learned below the level of conscious awareness in cerebellar internal models, (2) understandings of the development of "number sense" and developmental dyscalculia can be advanced by first understanding the ultimate foundations of number and mathematics do not simply originate in the cerebral cortex, but rather in cerebro-cerebellar collaboration (predominately driven by the cerebellum).

Conclusion: It is concluded that difficulty with "number sense" results from the extended demands on executive control in learning inverse dynamics models associated with cerebellar inner speech related to the second tier of abstraction (numbers) of the infa

Background: The pathophysiological basis for essential tremor (ET) remains unclear, although evidence increasingly links it to a disordered and perhaps degenerative cerebellum. Prior imaging studies have treated the cerebellum en bloc. Our hypothesis was that regional differences in cerebellar gray matter (GM) density may better distinguish ET cases from controls. Forty-seven ET cases and 36 control subjects were imaged using magnetic resonance imaging (MRI). The cerebellum was segmented into 34 lobes using a Spatially Unbiased Infra-Tentorial Template (SUIT) atlas within the Statistical Parametric Mapping (SPM) analysis package. Age, gender and Montreal Cognitive Assessment (MoCA) scores were regressed out from the statistical models to isolate group effects. ET cases were further stratified into phenotypically-defined subgroups. The Benjamini-Hochberg False Discovery Rate procedure (BH FDR) (α = 0.1) was used to correct for multiple comparisons.

Results: When all ET cases and controls were compared, none of the regions met the BH FDR criteria for significance. When compared with controls, ET cases with head or jaw tremor (n = 27) had significant changes in GM density in nine cerebellar lobules, with a majority in the left cerebellar region, and each meeting the BH FDR criteria. Likewise, ET cases with voice tremor (n = 22) exhibited significant changes in 11 lobules in both left and right regions and the vermis. These analyses, in sum, indicated decreases in GM density in lobules I-IV, V, VI, VII and VIII as well as the vermis. ET cases with severe tremor (n = 20) did not show regions of change that survived the BH FDR procedure when compared to controls.

Conclusions: We showed that ET cases with various forms of cranial tremor differed from controls with respect to cerebellar GM density, with evidence of GM reduction across multiple cerebellar regions. Additional work, using a lobule-by-lobule approach, is needed to confirm these results and precisely map the regional differences in ET cases, subgroups of ET cases, and controls.

Background: Multiple system atrophy (MSA) is a rare progressive neurodegenerative disorder for which brief yet sensitive scale is required in order for use in clinical trials and general screening. We previously compared several scales for the assessment of MSA symptoms and devised an eight-item pilot scale with large standardized response mean [handwriting, finger taps, transfers, standing with feet together, turning trunk, turning 360°, gait, body sway]. The aim of the present study is to investigate the validity and reliability of a simple pilot scale for assessment of multiple system atrophy symptoms.

Methods: Thirty-two patients with MSA (15 male/17 female; 20 cerebellar subtype [MSA-C]/12 parkinsonian subtype [MSA-P]) were prospectively registered between January 1, 2014 and February 28, 2015. Patients were evaluated by two independent raters using the Unified MSA Rating Scale (UMSARS), Scale for Assessment and Rating of Ataxia (SARA), and the pilot scale. Correlations between UMSARS, SARA, pilot scale scores, intraclass correlation coefficients (ICCs), and Cronbach's alpha coefficients were calculated.

Results: Pilot scale scores significantly correlated with scores for UMSARS Parts I, II, and IV as well as with SARA scores. Intra-rater and inter-rater ICCs and Cronbach's alpha coefficients remained high (> 0.94) for all measures.

Conclusion: The results of the present study indicate the validity and reliability of the eight-item pilot scale, particularly for the assessment of symptoms in patients with early state multiple system atrophy.