Cerebellum and Ataxias最新文献

Spinocerebellar ataxias (SCA) are highly heterogenous group of neurodegenerative diseases causing progressive cerebellar dysfunction. We report the first description of relative frequencies of the common SCA mutations and of phenotypic characteristics of SCA3 patients among Malaysians. Pooled data from adult Malaysian patients who had undergone genetic testing for SCA 1,2,3,6 and 7 at UKM Medical Centre and Institute for Medical Research from 2017 to 2020 were analysed. Fifteen patients with SCA 3 had detailed clinical phenotype evaluation using Inventory for Non -Ataxia Signs (INAS) and Ataxia Severity evaluation using the Scale for Assessment and Rating of Ataxia (SARA). Out of 152 adults patients who were tested for common SCA mutations, 64(42.1%) patients were tested positive for either SCA 1,2,3,6 or 7. Of the 64 positive cases, 44 (68.9%) patients were diagnosed with SCA 3 followed by SCA 2 in 13(20.3%) patients and SCA 1 in 5 (7.8%) patients. Our findings suggest that Malay race had the highest frequency of SCA (n = 34, 50%), followed by the Chinese (n = 16, 23.5%) and approximately 60 (93.8%) SCA patients had first degree family history. In conclusion, SCA 3 is the commonest SCA in Malaysia, followed by SCA 2 and SCA 1. It is important to develop a proper registry of SCA patients to further understand the true prevalence and local impact of the disease in Malaysia.

Aims: Micturition depends on a complex voluntary and involuntarily neuronal network located at various levels of the nervous system. The mechanism is highly dependent on the hierarchical organization of central nervous system pathways. If the role of the cortex and brainstem centres is well established, the role of other subcortical areas structures, such as the cerebellum is poorly understood. We are interested in discussing the current knowledge on the role of cerebellum in micturition.

Methods: A systematic search is performed in the medical literature, using the PubMed database with the keyword « cerebellum ». The latter is combined with «urination » OR « micturition » OR « urinary bladder ».

Results: Thirty-one articles were selected, focussing on micturition and describing the role of the cerebellum. They were grouped in 6 animal experimental studies, 20 functional brain imaging in micturition and 5 clinical studies.

Conclusions: Although very heterogeneous, experimental and clinical data clearly indicate the cerebellum role in the micturition control. Cerebellum modulates the micturition reflex and participates to the bladder sensory-motor information processing. The cerebellum is involved in the reflex micturition modulation through direct or indirect pathways to major brainstem or forebrain centres.

Objective: Essential tremor is a common movement disorder with an unclear origin. Emerging evidence suggests the role of the cerebellum and the thalamus in tremor pathophysiology. We examined the two main neurotransmitters acting inhibitory (GABA+) and excitatory (Glx) respectively, in the thalamus and cerebellum, in patients diagnosed with severe essential tremor. Furthermore, we also investigated the relationship between determined neurotransmitter concentrations and tremor severity in the essential tremor patients.

Methods: Ten essential tremor patients (prior to deep brain stimulation surgery) and six healthy controls, were scanned using a 3 T MR system. GABA+ and Glx concentrations were measured using magnetic resonance spectroscopy (MRS) performed using single voxel MEGA-PRESS. For the purpose of assessing the tremor severity, the essential tremor rating scale (ETRS) was used in accordance with Fahn, Tolosa, and Marin.

Results: We demonstrated that the cerebellar GABA+/Glx ratio was positively correlated to the ETRS (r = 0.70, p = 0.03) in essential tremor. Cerebellar and thalamic GABA+ and Glx concentrations did not show any significant difference when comparing essential tremor patients with healthy controls, at the group level.

Conclusion: We demonstrated a positive correlation between increasing tremor disability and the ratio of GABA+/ Glx in the cerebellum of essential tremor patients. This highlights the impact of an altered balance of the excitatory and inhibitory neurotransmitters in tremor severity. Rather than a change in GABA+, which was constant, we attribute this finding to an overall decrease of Glx.

Background: Spinocerebellar ataxia type 23 (SCA23) is an autosomal dominant cerebellar ataxia caused by pathogenic variants in the prodynorphin gene (PDYN). The frequency of PDYN variants is reportedly very low (~ 0.1%) in several ataxia cohorts screened to date.

Case presentations: We found five cases of SCA23 in two families (mean age at onset: 37.8 ± 5.5 years; mean age at examination: 64.2 ± 12.3 years) with a novel PDYN variant (c.644G > A:p.R215H). We identified marked heterogeneity in the clinical features in Family 1: the proband showed clinical and neuroimaging features suggestive of multiple system atrophy with predominant parkinsonism (MSA-P). Conversely, the proband's mother with the PDYN p.R215H variant had no subjective symptoms; she had not come to medical attention before our survey, although she showed apparent cerebellar atrophy on brain magnetic resonance imaging (MRI). The other two patients in Family 1 and a patient in Family 2 showed slowly progressive cerebellar ataxia.

Conclusions: We here report two Japanese families with SCA23, one of which showed considerable phenotypic variation in affected members. Our findings support that SCA23 can phenotypically overlap with MSA.

Background: Friedreich ataxia (FRDA) is the most frequent form of inherited ataxias. Vestibular and auditory assessments are not commonly part of the check up for these patients despite hearing and balance complaints. Screening of vestibular and auditory function was performed in a large group of young patients with genetically confirmed FRDA.

Methods: Our study included 43 patients (7-24 years of age). A complete vestibular assessment was performed including the canals function evaluation at 3 head velocities (bithermal caloric test, earth vertical axis rotation (EVAR) and head impulse test (HIT)) and otolith function evaluation (cervical vestibular evoked myogenic potentials). Information regarding the hearing evaluation of the patients were also retrieved including impedance tympanometry, distortion product otoacoustic emissions (DPOAEs), air and bone conduction audiometry and auditory brainstem response (ABR).

Results: Vestibular responses were impaired for canal responses (only at high and middle head velocities) and vestibulospinal otolithic responses. Abnormal neural conduction in the central auditory pathways was frequently observed. Oculomotor abnormalities were frequent, mostly hypermetric saccades and gaze instability. Inhibition of the vestibulo-ocular reflex by fixation was normal.

Conclusions: We show that Friedreich ataxia, even at onset, frequently associate saccadic intrusions, abnormal ABRs and decreased vestibulo-ocular and vestibulospinal responses progressing over time. These sensory impairments combined with ataxia further impair patient's autonomy. These vestibular, auditory and visual impairments could be used as markers of the severity and progression of the disease. Adding vestibular and auditory testing to Friedreich patient's evaluation may help physicians improve patient's management.

Background: The syndrome of oculopalatal tremor is a known consequence of lesions in the dentate-olivary pathway. Hypertrophic degeneration of the inferior olive is a recognized pathological correlate of these lesions and hypothesized to cause tremorogenic olivary hypersynchrony. However, oculopalatal tremor also occurs in Alexander disease, which produces severe inferior olive degeneration without intervening hypertrophy.

Methods: Serial clinical, imaging, video-oculography and kinematic tremor recording of a patient with oculopalatal and limb tremor.

Case study: We report an unusual presentation of oculopalatal tremor and right upper extremity myorhythmia following sequential right dorsolateral and left anteromedial medullary infarcts directly involving both inferior olives. As in adult Alexander disease, our patient did not have hypertrophic olivary degeneration during 10 years of follow-up.

Conclusion: Contemporary theories have emphasized the role of cerebellar maladaptation in "shaping" oscillations generated elsewhere, the inferior olive in particular. Our patient and published Alexander disease cases illustrate that oculopalatal tremor can occur in the absence of hypertrophic olivary degeneration. Therefore, cerebellar maladaptation to any form of olivary damage may be the critical pathophysiology in producing oculopalatal tremor.

Background: There is abundant evidence for cerebellar involvement in schizophrenia, where the cerebellum has been suggested to contribute to cognitive, affective and motor dysfunction. More recently, specific cerebellar regions have also been associated with psychotic symptoms, particularly with auditory verbal hallucinations. In contrast, little is known about cerebellar contributions to delusions, and even less is known about whether cerebellar involvement differs by delusional content.

Methods: Using structural magnetic resonance imaging at 1.0 T together with cerebellum-optimized segmentation techniques, we investigated gray matter volume (GMV) in 14 patients with somatic-type delusional disorder (S-DD), 18 patients with non-somatic delusional disorder (NS-DD) and 18 patients with schizophrenia (SZ) with persistent non-somatic delusions. A total of 32 healthy controls (HC) were included. Between-group comparisons were adjusted for age, gender, chlorpromazine equivalents and illness duration.

Results: Compared to HC, S-DD patients showed decreased GMV in left lobule VIIIa. In addition, S-DD patients showed decreased GMV in lobule V and increased GMV in bilateral lobule VIIa/crus II compared to NS-DD. Patients with SZ showed increased GMV in right lobule VI and VIIa/crus I compared to HC. Significant differences between HC and NS-DD were not found.

Conclusions: The data support the notion of cerebellar dysfunction in psychotic disorders. Distinct cerebellar deficits, predominantly linked to sensorimotor processing, may be detected in delusional disorders presenting with predominantly somatic content.

Purpose: Severe Hypomagnesaemia is a rare biochemical findings utilized for identifying the etiology of cerebellar ataxia. It requires a high degree of suspicion to diagnose. MRI findings are often nonspecific.

Methods: The author presents a case of 38 yrs. old male patient presented with vomiting, gait imabalance and nystagmus. Biochemical investigations lead to severe hypomagnesaemia. Also MRI findings were matched suggesting of hyperintesity in left cerebellar hemisphere.

Results: Patient was treated with magnesium infusion which leads to recovery of patient. Again the same symptomology was repeated after 3 months and disappearance after same treatment. Offending cause was diagnosed and proton pump inhibitors stopped.

Conclusion: Severe Hypomagnesaemia is a rare but treatable cause if diagnosed at right time. It requires a high degree of suspicion to diagnose it. Measurement of serum magnesium levels should always be kept in back of mind if definite management of cerebellar symptoms has to be done.

Background: The recessive ataxia ARCA2 is a rare disorder characterized by Coenzyme Q10 (CoQ10) deficiency due to biallelic mutations in ADCK3 gene. Despite the pathophysiological role, available data are not univocal on clinical efficacy of CoQ10 supplementation in ARCA2. Here we described the long-term motor outcome of 4 untreated ARCA2 patients prospectively followed-up for one year after starting CoQ10 oral supplementation (15 mg/kg/day).

Methods: Clinical rating scales (SARA; 9 holes peg test; 6 min walking test; Timed 25-Foot Walk) and videoelectronic gait analysis were performed at baseline and every 6 months (T0, T1, T2) to evaluate the motor performances. Since two patients discontinued the treatment at the 7th month, we could provide comparative analysis between longer and shorter supplementation.

Results: At T2, the gait speed (Timed 25-Foot Walk test) significantly differed between patients with long and short treatment; overall, the clinical condition tended to be better in patients continuing CoQ10.

Conclusions: Although preliminarily, this observation suggests that only prolonged and continuous CoQ10 supplementation may induce mild clinical effects on general motor features of ARCA2. Dedicated trials are now necessary to extend and validate such observation.