The cerebellum
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Spinocerebellar ataxias are autosomal dominant diseases, associated in some types with a CAG repeat expansion, and characterised by a progressive loss of motor function. Currently, as there is no cure for most ataxias, treatment predominantly involves physical therapy. Various symptomatic drug treatments have been tried; however, published clinical studies have provided inconsistent results, likely due to small sample sizes, mixed patient populations and insensitive or subjective assessment scales. ⋯ Following each dose, mice were assesed for motor function on the accelerating rotor-rod. None of the four drugs attenuated motor deficts in SCA1(154Q) mice at any dose; at FDA equivalent and higher dose administration of zolpidem and buspirone led to sedation in both strains. Our results suggest that the aforementioned drugs are likely to be ineffective for symptomatic treatment of SCA1 and most other ataxic patients and emphasise the need for comphrehensive drug studies prior to clinical use.
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Heart failure (HF) patients show an inability to regulate autonomic functions, a characteristic which is associated with increased mortality. These autonomic deficits may stem from earlier demonstrated injury to central autonomic regulatory areas, providing a structural basis for the autonomic abnormalities. However, knowledge of structural injury provides insufficient insights into timing and magnitude of signal patterns within affected areas which lead to impaired autonomic outflow. ⋯ However, all structures, except the left crus II, showed altered responses in HF during the recovery period. Crus II patterns reflected a failure of HF subjects to demonstrate the normal lateralized responses, while in the insula, HF subjects exhibited abnormal left-right patterns, relative to controls. The abnormal timing and response patterns in these injured areas critical for autonomic regulation likely contribute to the enhanced sympathetic outflow and autonomic dysfunction characteristic of HF.
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Spinocerebellar ataxias (SCAs) constitute a heterogeneous group of more than 30 autosomal-dominant genetic and neurodegenerative disorders. SCAs are generally characterized by progressive ataxia and cerebellar atrophy. Although all SCA patients present with the phenotypic overlap of cerebellar atrophy and ataxia, 17 different gene loci have so far been implicated as culprits in these SCAs. ⋯ We argue that disruptions in Purkinje cell calcium signaling lead to initial cerebellar dysfunction and ataxic sympoms and eventually proceed to Purkinje cell death. Here, we discuss a calcium hypothesis of Purkinje cell neurodegeneration in SCAs by primarily focusing on an example of spinocerebellar ataxia 2 (SCA2). We will also present evidence linking deranged calcium signaling to the pathogenesis of other SCAs (SCA1, 3, 5, 6, 14, 15/16) that lead to significant Purkinje cell dysfunction and loss in patients.
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Multicenter Study Comparative Study
Spinocerebellar ataxia types 1, 2, 3 and 6: the clinical spectrum of ataxia and morphometric brainstem and cerebellar findings.
To assess the clinical spectrum of ataxia and cerebellar oculomotor deficits in the most common spinocerebellar ataxias (SCAs), we analysed the baseline data of the EUROSCA natural history study, a multicentric cohort study of 526 patients with either spinocerebellar ataxia type 1, 2, 3 or 6. To quantify ataxia symptoms, we used the Scale for the Assessment and Rating of Ataxia (SARA). The presence of cerebellar oculomotor signs was assessed using the Inventory of Non-Ataxia Symptoms (INAS). ⋯ Cerebellar oculomotor deficits were most frequent in SCA6 followed by SCA3, whereas these abnormalities were less frequent in SCA1 and SCA2. Our data suggest that vestibulocerebellar, spinocerebellar and pontocerebellar circuits in SCA1, SCA2, SCA3 and SCA6 are functionally impaired to almost the same degree, but at different anatomical levels. The seemingly low prevalence of cerebellar oculomotor deficits in SCA1 and SCA2 is most probably related to the defective saccadic system in these disorders.
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A persistent trigeminal artery (PTA) is the most common anastomosis between the carotid and vertebrobasilar system. A PTA variant (PTAV) is a rare anomaly in which the cerebellar artery arises from the internal carotid artery (ICA) without connection with the basilar artery (BA). I present what I believe is the first report of bilateral PTAVs diagnosed using magnetic resonance (MR) angiography and briefly discuss the embryology of this rare anomaly. ⋯ The MR angiographic demonstration of bilateral anterior inferior cerebellar arteries arising from the precavernous segment of the ICA without anastomosis to the BA indicated bilateral PTAVs. This is the first report of bilateral PTAVs diagnosed by MR angiography. The literature review indicates that an estimated prevalence of bilateral PTAVs is about 0.0012%.