Cerebellum and Ataxias最新文献

Background: Cognitive decline is a common non-motor feature characterizing Spinocerebellar Ataxia type 2 (SCA2) during the prodromal stage, nevertheless a reduced number of surrogate biomarkers of these alterations have been described.

Objective: To provide insights into cognitive dysfunction in SCA2 patients using P300 event-related potentials (ERP) and to evaluate these measures as biomarkers of the disease.

Methods: A cross-sectional study was performed with 30 SCA2 patients, 20 preclinical carriers and 33 healthy controls, who underwent visual, auditory P300 ERPs, and neurological examinations and ataxia scoring.

Results: SCA2 patients showed significant increase in P300 latencies and decrease of P300 amplitudes for visual and auditory stimuli, whereas preclinical carriers exhibit a less severe, but significant prolongation of P300 latencies. Multiple regression analyses disclosed a significant effect of SARA score on visual P300 abnormalities in patients as well as of the time to ataxia onset on visual P300 latencies in preclinical carriers.

Conclusions: This paper demonstrated the role of P300 ERP for the study of attentional, discriminative and working memory abnormalities in SCA2 patients and for the search of surrogate biomarkers from prodromal to the symptomatic stages. Moreover, our findings provide psychophysiological evidences supporting the cerebellar involvement in cognitive processes and allows us to identify promising outcome measures for future trials focusing on cognitive dysfunction.

Eye movements are frequently considered diagnostic markers indicating involvement of the cerebellum. Impaired amplitude of saccades (saccade dysmetria), impaired gaze holding function (horizontal or downbeat nystagmus), and interrupted (choppy) pursuit are typically considered hallmarks of cerebellar disorders. While saccade dysmetria is a frequently considered abnormality, the velocity of saccades are rarely considered part of the constellation of cerebellar involvement. Reduced saccade velocity, frequently called "slow saccades" are typically seen in a classic disorder of the midbrain called progressive supranuclear palsy. It is also traditionally diagnostic of spinocerebellar ataxia type 2. In addition to its common causes, the slowness of vertical saccades is not rare in cerebellar disorders. Frequently this phenomenology is seen in multisystem involvement that substantially involves the cerebellum. In this review we will first discuss the physiological basis and the biological need for high saccade velocities. In subsequent sections we will discuss disorders of cerebellum that are known to cause slowing of saccades. We will then discuss possible pathology and novel therapeutic strategies.

Background: In Patients with spinocerebellar ataxia type 6 (SCA6) are often treated by transcranial magnetic stimulation (TMS) over the motor cortex and cerebellum. However, few reports have examined effective therapeutic modalities for diplopia in SCA6 patients. In the current case, we applied single-pulse TMS over the motor cortex and cerebellum to improve ataxia, and observed an unexpected improvement of diplopia.

Case presentation: A 62-year-old Japanese male with spinocerebellar ataxia type 6 (SCA6) was admitted to our hospital for exacerbation of ataxia. We administered single-pulse transcranial magnetic stimulation (TMS) over the hand motor area and the cerebellum with a circular coil to reduce ataxia. After the initiation of TMS, since diplopia unexpectedly improved, we started a quantitative assessment of diplopia by counting the number of fixation spots that he observed in his visual field. This assessment suggested that TMS had an immediate and cumulative effect on diplopia. We also delivered more localized stimulation only over the motor cortex with a Figure-8 coil, and diplopia improved immediately. Additionally, we administered a sham stimulation before the real stimulation over the motor cortex and the cerebellum. The sham stimulation improved diplopia, and greater improvement was observed with subsequent real stimulation. We also used a Hess chart examination and video recordings of binocular gross appearance to elucidate the changes in ocular movement objectively. However, these examinations did not reveal any obvious oculomotor changes.

Conclusions: We applied single-pulse TMS to a SCA6 patient with diplopia, which improved without any adverse effects. TMS may have potential for the treatment of diplopia in SCA6 patients.

Background: Many children with neurofibromatosis type 1 (NF1) have focal abnormal signal intensities (FASI) on brain MRI, whose full clinical impact and natural history have not been studied systematically. Our aims are to describe the clinical and neuroradiological features in children with NF1 and cerebellar FASI, and report on the natural history of FASI that display atypical features such as enhancement and mass effect.

Method: A retrospective review of the hospital charts and brain MRIs was performed on children from Manitoba diagnosed between 1999 and 2008 with NF1, who also had cerebellar FASI on MRI.

Results: Fifty patients (mean age: 16.1y, minimum-maximum: 6.4 - 30y, 27 M) were identified. Mean duration of follow up was 10.1y. Developmental delay, learning disabilities, tumors, and visual signs occurred commonly. Cerebellar signs were not reported. Mean age of the patients at baseline MRI was 7.8 (SD: 4.5) years. FASI occurred in several brain locations and were rarely confined to the cerebellum. FASI displayed mass effect and enhancement infrequently but were associated with malignancy only once. The number of FASI at baseline MRI was significantly less in patients with attention deficient hyperactivity disorder and more if a first degree relative had NF1 or if they had decreased visual acuity.

Discussion: Patients with NF1 and cerebellar FASI do not have motor or consistent non-motor (e.g. developmental delay or learning disabilities) cerebellar features. The number of FASI may correlate with some clinical features. FASI may display enhancement and mass effect but they rarely become malignant.

Background: Focal abnormal signal intensities (FASI) on brain MRI occur commonly in patients with neurofibromatosis type 1 (NF1). The natural history of cerebellar FASI and their correlation with clinical features have not been studied comprehensively. Our aims are to describe the natural history of cerebellar FASI on repeat MRI scans and correlate the findings with the clinical features in children with NF1 and cerebellar FASI.

Method: A retrospective review of 226 brain MRI scans and hospital charts was performed in 50 patients with cerebellar FASI, who were diagnosed with NF1 during their childhood between 1999 and 2008.

Results: Mean age at the end of the study period was 16.1 years. There were 27 males. Mean duration of clinical follow up was 10.1 years. Mean duration between the first and the last MRI was 6.6 years (n = 36, SD: 2.8 years). FASI were rarely confined to the cerebellum. The number of FASI was highest in early childhood and decreased significantly on subsequent MRI scans in most brain regions with the exception of the cerebrum, where a fewer number of patients with a smaller number of FASI were seen. Four patterns of change in FASI size over time were determined, none correlated with the clinical features.

Conclusions: In patients with NF1, the natural history of FASI including their number, age at onset, rate of size changes, and resolution if any, varies by brain region. FASI patterns of change over time showed no clinical correlate.

Background: Riboflavin transporter deficiency (Brown-Vialetto-Van Laere syndrome) is a rare recessive neurodegenerative disorder that can present with gait ataxia, primarily due to sensory neuropathy as well as cerebellar involvement. Although sensorineural hearing loss, bulbar palsy, and optic atrophy are typical, presentation may be variable and an atypical condition may be difficult to recognize clinically.

Case presentation: Here we report a patient presenting at age 8 with progressive ataxia since the age of 2.5 years with cerebellar atrophy and peripheral polyneuropathy. Whole exome sequencing identified a known pathogenic mutation in the SLC52A2 gene consistent with a diagnosis of Brown-Vialetto-Van Laere syndrome despite the absence of common symptoms including motor neuropathy, bulbar palsy, optic atrophy, and sensorineural hearing loss. High-dose riboflavin therapy was initiated, symptoms stabilized, metabolic abnormalities resolved, and the patient is doing well with a near-normal examination at age 15.

Conclusions: Riboflavin transporter deficiency can be fatal if left untreated. The excellent outcome of this case illustrates the importance of identifying this potentially treatable neurologic condition. In this patient, clinical diagnosis was limited by an atypical presentation lacking several common features which was overcome through the use of genomic sequencing identifying the pathogenic mutation enabling correct diagnosis and subsequent treatment. Riboflavin transporter deficiency should be considered early in the diagnostic evaluation as a treatable form of ataxia in children, even if patients lack typical features.

Background: Though the cerebellum's role in visuospatial and fine motor functioning has been well-established over the last several years, the role of the cerebellum in emotion has more recently been a focus of scientific inquiry. Cerebellar impairment has been associated with deficits in emotional processing and is linked to a wide range of clinical behaviors including social withdrawal, blunted emotional expression, and impulsivity. In addition, cerebellar impairments have been associated with the onset of psychiatric disorders including major depressive disorder and, more recently, obsessive-compulsive disorder.

Case presentation: We describe a 32-year-old patient who presented to our clinic for a neuropsychological evaluation with a childhood history of a cerebellar brain tumor and detail-oriented, perfectionistic tendencies. Neuropsychological assessment data revealed impairments in visuospatial processing and in fine motor skills, likely stemming from the cerebellar tumor. Clinical assessment led to a diagnosis of obsessive-compulsive personality disorder and also suggested impairments in socio-emotional processing.

Conclusions: Our findings lend support to recent data which has suggested the impact of cerebellar impairment on emotional processing and related domains. Unlike many previous studies, however, our report focuses on an individual who, despite having marked impairments in certain domains, demonstrates a high level of functioning. We believe that this report holds important clinical relevance for proper diagnosis of cerebellar-related impairment and for the necessity of early intervention.

[This corrects the article DOI: 10.1186/s40673-018-0088-8.].

Background: We seeked for specific cerebellar contribution within the dorsal attentional network (DAN), using Independent Component Analysis (ICA).

Methods: ICA-based analysis was performed on brain resting-state functional images of 19 volunteers.

Results: We confirmed that DAN includes bilaterally: lobules VI-VII (crus I) and VIIB-VIIIA, as previously reported by Region-Of-Interest (ROI)-based functional connectivity studies. We also found that lobule IX (tonsillae), and as well as the superior and, likely, inferior colliculi. Also belong to DAN. The part of lobule IX in relation to DAN is located more caudally and laterally, and less extensive than the more rostral part of this lobule belonging to the default-mode network (DMN).

Conclusion: Rostral and caudal tonsillae partake in the DMN and DAN, respectively. The latter could subserve either eye movement control in relation to the oculomotor parieto-frontal network, partially congruent with the DAN, or more cognitive functions due to functional reallocation within the DAN.