Cerebellum最新文献

Genetic alterations in the ERCC4 gene typically cause Xeroderma pigmentosum and other nucleotide excision repair disorders. Neurologic symptoms are present in some of these patients. In rare cases, ERCC4-mutations can manifest with prominent neurologic symptoms. We report a 62-year-old woman who presented with a movement disorder caused by a homozygous pathogenic variant in the ERCC4 gene. She presented with a hyperkinetic movement disorder (chorea) that affected the distal limbs as well as facial muscles and jaw. There was no ataxia. Extensive clinical evaluation revealed predominantly fronto-parietal and cerebellar atrophy on brain MRI with sparing of the basal ganglia and mesial temporal lobe. Iron and sparse Ca²⁺ deposits were found in the basal ganglia. The detailed neuropsychological evaluation revealed deficits indicating subcortical-prefrontal, subcortical-parietal and frontotemporal dysfunction, without significant impairments in activities of daily living. The audiogram revealed mild age-related hearing impairment, electroneurography was unremarkable without signs of polyneuropathy. The dermatologic examination showed no signs of skin cancer. Knowledge about ERCC4-related neurodegeneration is limited and the disease is likely underdiagnosed. Nucleotide Excision Repair Disorder-related neurodegeneration should be considered as a differential diagnosis in patients with adult-onset neurodegenerative disorders, even if dermatologic complications are absent and the family history is negative. The preserved caudate volume in our ERCC4 patient could be a hint towards this rare condition. Treatment is symptomatic. Once the diagnosis is established, patients need to be advised to have regular medical consultations to prevent disease complications such as skin cancer.

Spinocerebellar ataxias (SCAs) types 1, 2, and 3 are the most common subtypes of SCAs. However, the atrophy patterns of these three subtypes still need to be fully clarified. In this study, a total of 130 genetically confirmed SCA patients (SCA1: n = 16; SCA2: n = 13; symptomatic SCA3: n = 76; pre-symptomatic SCA3: n = 25) along with 65 age- and sex-matched healthy controls (HCs) were enrolled. MR volumetric analysis was used to explore the different atrophied patterns in these three SCA subtypes and the associations between significant morphometry alterations and clinical variables were further analyzed. Compared with HCs, the global brain grey matter (GM) of the three SCA subtypes and white matter (WM) volumes of the SCA2 and SCA3 were significantly reduced. SCA2 had significantly more severe GM volume atrophy than symptomatic SCA3. For local GM and WM volumes, all three subtypes of SCA have significant atrophy in infra- and supratentorial areas than HCs. The pre-symptomatic SCA3 patients had already demonstrated substantial WM atrophy. The SCAs subgroup comparisons showed that compared with symptomatic SCA3, SCA1 and SCA2 demonstrated more severe atrophy in regions of the cerebral and cerebellum, but symptomatic SCA3 had significantly atrophied bilateral lenticular nuclei. Besides, no significant difference was found in the local GM or WM volume between SCA1 and SCA2. Furthermore, some affected GM and WM regions, especially the damaged cerebellar peduncles, showed significant correlations with disease duration and severity in SCA1 and symptomatic SCA3. Our research results indicate differences in MRI brain injury patterns among common SCA subtypes, which might shed light on the deeper understanding of the pathophysiological mechanisms of SCAs.

To determine predicting factors and frequency of phenoconversion from sporadic adult-onset ataxia (SAOA) to multiple system atrophy (MSA). We performed a retrospective review of all patients referred for cerebellar ataxia from 1998 to 2018 at Mayo Clinic, Minnesota. We analyzed clinical features, autonomic testing, and imaging for predictors of later diagnosis of MSA. Among 169 patients with ataxia at presentation, 60 (35.5%) phenoconverted to MSA. Clinical features in MSA phenoconverters included: early autonomic symptoms, stridor, and dream enactment behavior. Imaging features in phenoconverters included pontine atrophy and hot cross bun sign. On autonomic testing, MSA phenoconverters had higher supine blood pressures with larger drops, higher median composite autonomic severity scores, and higher percentage anhidrosis than patients with SAOA. Our findings show that at least a third of patients with SAOA phenoconverted to MSA. Clinical features, autonomic testing, and imaging at presentation may be helpful to identify such patients.

Stroke patients often experience post-stroke emotional impairments, yet the underlying pathophysiology remains unclear. At the brain level, dysregulation of socio-affective skills should be considered through alterations in brain networks instead of isolated regions. Investigating network alterations may be crucial in explaining emotional or cognitive deficits. In this context, and in line with the dysmetria of thought theory, cerebello-cortical networks' alterations could explain socio-affective functioning. To examine whether impairments in intrinsic functional networks following a cerebellar stroke are associated with poor cognitive and socio-affective performance. Thirty-six cerebellar stroke patients underwent resting-state functional MRI scans at the early stage (T1). They were assessed through a battery of clinical evaluations for cognitive and socio-affective skills. At the chronic stage (T2), evaluations were repeated with additional ecological momentary assessments (EMA) for emotional behavior. The global efficiencies of four resting-state functional brain networks associated with the cerebellum were determined. Patients were classified into subgroups of high and low functioning based on the evaluations and compared. Poorer global efficiency in the default-mode network was present in the subgroup with higher depression (T1: p = 0.034, T2: p = 0.006) and low EMA positive mood (p = 0.048), while lower efficiency in the dorsal attentional network was shown in the subgroup with lower verbal memory (T1: p = 0.004, T2: p = 0.048). Disruptions in intrinsic functional networks are linked to poorer cognition and emotion for some cerebellar stroke patients, partially supporting the theory of 'dysmetria of thought'.

Essential tremor (ET) is a common movement disorder affecting millions of people. Studies of ET patients and perturbations in animal models have provided a foundation for the neural networks involved in its pathophysiology. However, ET encompasses a wide variability of phenotypic expression, and this may be the consequence of dysfunction in distinct subcircuits in the brain. The cerebello-thalamo-cortical circuit is a common substrate for the multiple subtypes of action tremor. Within the cerebellum, three sets of cerebellar cortex-deep cerebellar nuclei connections are important for tremor. The lateral hemispheres and dentate nuclei may be involved in intention, postural and isometric tremor. The intermediate zone and interposed nuclei could be involved in intention tremor. The vermis and fastigial nuclei could be involved in head and proximal upper extremity tremor. Studying distinct cerebellar circuitry will provide important framework for understanding the clinical heterogeneity of ET.

Damage to the cerebellum results in dysfunctional standing postural control. Patients with cerebellar ataxia have a larger sway in the center of gravity (COG) while standing. Transcranial direct current stimulation (tDCS) has been applied in the rehabilitation of patients with central nervous system disorders; however, its effect on COG sway in patients with cerebellar ataxia remains unknown. We aimed to confirm the effects of anodal cerebellar tDCS (ctDCS) combined with physical therapy on COG sway in a patient with cerebellar ataxia using a retrospective ABA single-case study design. This study involved a patient with left cerebellar hemorrhage. Walking and postural balance rehabilitation were conducted in phase A. Anodal ctDCS was combined with the walking and postural balance rehabilitation in phase B. We measured COG sway in the open- and closed-eyes standing conditions daily throughout all the phases. In the open-eyes standing condition, there was no significant change in COG sway in phase B. Conversely, in the closed-eyes standing condition, the circumferential area, total sway path length, and anteroposterior sway path length decreased in phase B. No change was observed in the mediolateral sway path length. The combination of anodal ctDCS and physical therapy may decrease COG sway in patients with cerebellar ataxia in the closed-eyes standing condition, and its effect may be greater in the anteroposterior direction.

Rhombencephalosynapsis (RES) is a hindbrain malformation characterized by a missing cerebellar vermis with apposition or fusion of the cerebellar hemispheres. The present clinical case report provides a comprehensive, longitudinal overview of cognitive and affective manifestations in a 22-year-old patient with RES. The patient shows clinical signs of emotional reactivity and dysregulation, impulsivity, and impairments in executive functioning since early childhood. These features fit the constellation of neuropsychiatric symptoms observed in patients with congenital and acquired abnormalities of the posterior vermis. It is proposed that patients with RES may show affective and cognitive difficulties which increase their vulnerability to psychological stress and risk of developing mental health issues.

Fatty acids play many critical roles in brain function but have not been investigated in essential tremor (ET), a frequent movement disorder suspected to involve cerebellar dysfunction. Here, we report a postmortem comparative analysis of fatty acid profiles by gas chromatography in the cerebellar cortex from ET patients (n = 15), Parkinson's disease (PD) patients (n = 15) and Controls (n = 17). Phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI)/ phosphatidylserine (PS) were separated by thin-layer chromatography and analyzed separately. First, the total amounts of fatty acids retrieved from the cerebellar cortex were lower in ET patients compared with PD patients, including monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA). The diagnosis of ET was associated with lower cerebellar levels of saturated fatty acids (SFA) and PUFA (DHA and ARA) in the PE fraction specifically, but with a higher relative content of dihomo-γ-linolenic acid (DGLA; 20:3 ω-6) in the PC fraction. In contrast, a diagnosis of PD was associated with higher absolute concentrations of SFA, MUFA and ω-6 PUFA in the PI + PS fractions. However, relative PI + PS contents of ω-6 PUFA were lower in both PD and ET patients. Finally, linear regression analyses showed that the ω-3:ω-6 PUFA ratio was positively associated with age of death, but inversely associated with insoluble α-synuclein. Although it remains unclear how these FA changes in the cerebellum are implicated in ET or PD pathophysiology, they may be related to an ongoing neurodegenerative process or to dietary intake differences. The present findings provide a window of opportunity for lipid-based therapeutic nutritional intervention.

Motor adaptation is critical to update motor tasks in new or modified environmental conditions. While the cerebellum supports error-based adaptations, its neural implementation is partially known. By controlling the frequency of cerebellar transcranial alternating current stimulation (c-tACS), we can test the influence of neural oscillation from the cerebellum for motor adaptation. Two independent experiments were conducted. In Experiment 1, 16 participants received four c-tACS protocols (45 Hz, 50 Hz, 55 Hz, and sham) on four different days while they practiced a visuomotor adaptation task (30 degrees CCW) with variable intensity (within-subject design). In Experiment 2, 45 participants separated into three groups received the effect of 45 Hz, 55 Hz c-tACS, and sham, respectively (between-subject design), performing the same visuomotor task with a fixed intensity (0.9 mA). In Experiment 1, 45 Hz and 50 Hz of c-tACS accelerated motor adaptation when participants performed the task only for the first time, independent of the time interval between sessions or the stimulation intensity. The effect of active c-tACS was ratified in Experiment 2, where 45 Hz c-tACS benefits motor adaptation during the complete practice period. Reaction time, velocity, or duration of reaching are not affected by c-tACS. Cerebellar alternating current stimulation is an effective strategy to potentiate visuomotor adaptations. Frequency-dependent effects on the gamma band, especially for 45 Hz c-tACS, ratify the oscillatory profile of cerebellar processes behind the motor adaptation. This can be exploited in future interventions to enhance motor learning.