Reduced life expectancy in 40 cases of early onset cerebellar ataxia with retained tendon reflexes: a population-based study

A survival analysis of 40 cases of early onset cerebellar ataxia (EOCA) with retained tendon reflexes was performed. They represent all cases of EOCA diagnosed between 1945 and 1990 among residents of a defined area of Northwestern Italy, followed up to December 31, 1990. The survival rates were respectively 92%, 87% and 77% at 10, 20 and 30-years, worse than expected in a disease which is usually considered benign. The relative death rate was 4 times higher than expected for the general population. Prognosis was significantly worse for males than for females, whereas the age of onset and the calendar year of onset did not affect survival.     

Friedreich''s ataxia: a clinical review of 20 childhood cases

The authors report the clinical review of 20 childhood cases with Friedreich's ataxia. The mean age at onset of symptoms was 6.1 years. The main presenting symptom was abnormal gait (100%). Ataxia of gait and limbs and depressed or absent tendon reflexes were found in all cases. Clinical findings are in accordance with the findings of Harding and Werdelin. Neurophysiological studies (especially sensory) are important in the confirmation of the diagnosis. Of the 10 cases in which sensory nerve conduction velocity measurements were performed, 7 had absent sensory action potentials, 2 had decreased potentials and one was normal. In our study, it is shown that in patients having ataxic gait, ataxia of limbs and tendon reflexes depression or loss, Friedreich's ataxia may be diagnosed with the help of electrophysiological studies.     

Early onset cerebellar ataxia with retained tendon reflexes: foot deformity in a first grade family member

Early onset cerebellar ataxia with retained tendon reflexes (EOCA) is a clinical syndrome characterised by progressive cerebellar ataxia with an onset before the age of 25 years and a wide spectrum of associated features. It is distinguished from Friedreich’s ataxia (FA) mainly by the preservation of tendon reflexes, a better prognosis, and the absence of GAA expansion in the frataxin gene. Although EOCA is thought to be a hereditary disorder with an autosomal recessive mode of inheritance, genetic heterogeneity might underlie the spectrum of clinical features. In this case report we describe a patient with EOCA accompanied by pes cavus, hammer toes and peripheral neuropathy. The patient’s father did not have any ataxia, but had the same foot deformities as his daughter and a slight peripheral neuropathy. The possible relationship between these clinical features is discussed.     

Risk factors for idiopathic cerebellar ataxia of late onset

In an attempt to identify risk factors for the development of idiopathic cerebellar ataxia (IDCA) we performed a case-control study of 59 IDCA patients. Hypertension and medicine intake were less frequent in IDCA than in neurological controls. Multiple logistic regression yielded an odds ratio (OR) for hypertension of 0.13 (95% confidence interval: 0.00–1.02, P=0.0527) and medicine intake of 0.10 (95% confidence interval: 0.00–0.72, P=0.0157). In contrast, we did not identify an association of IDCA with a number of medical diseases, head trauma, smoking, alcohol intake, rural living and well-water drinking. Some of these factors have been previously shown to be associated with other neurodegenerative diseases. In addition, serum antibody titers against neurotropic viruses were not elevated in IDCA.     

Magnetic resonance imaging in “typical” and “late onset” Friedreich''s disease and early onset cerebellar ataxia with retained tendon reflexes

MRI makes it possible to study the in vivo brain and spinal cord morphology of patients with hereditary ataxia. We performed T1-and T2-weighted studies in eleven patients with Friedreich's disease (FD), five with late onset FD and ten with early onset cerebellar ataxia with retained tendon reflexes (EOCA). Cervical cord atrophy was constant in FD and late onset FD and often associated with atrophy of the cerebellum and of the brainstem; T2-weighted studies showed posterior column degeneration in the cervical cord. The most frequent finding in EOCA was cerebellar atrophy, pure or associated with cervical cord or brainstem atrophy; the cerebellar atrophy was marked in a few cases and was related to disease duration.This study was partially supported by the CNR (Grant 91.04180) and the Ministry of Health.     

Treatable causes of cerebellar ataxia

The cerebellar ataxia syndromes are a heterogeneous group of disorders clinically characterized by the presence of cerebellar dysfunction. Initial assessment of patients with progressive cerebellar ataxia is complex because of an extensive list of potential diagnoses. A detailed history and comprehensive examination are required for an accurate diagnosis and hierarchical diagnostic investigations. Although no cure exists for most of these conditions, a small group of metabolic, hereditary, inflammatory, and immune‐mediated etiologies of cerebellar ataxia are amenable to disease‐modifying, targeted therapies. Over the past years, disease‐specific treatments have emerged. Thus, clinicians must become familiar with these disorders because maximal therapeutic benefit is only possible when done early. In this article, we review disorders in which cerebellar ataxia is a prominent clinical feature requiring targeted treatments along with specific management recommendations. © 2015 International Parkinson and Movement Disorder Society     

原发性自身免疫性小脑性共济失调的临床分析

目的 分析原发性自身免疫性小脑性共济失调（PACA）的临床特征,为对该类疾病的诊断及治疗提供经验。方法 收集2018年1月至2023年1月中南大学湘雅三医院收治的PACA患者,回顾性分析患者的临床表现、实验室检查、影像学资料等。结果 共纳入6例患者,其中男3例,女3例;中位年龄54岁。6例患者急性或亚急性起病,以步态不稳为主要症状,无前驱感染史;脑脊液常规、生化、细胞学和颅脑磁共振成像（MRI）检查基本正常;脑脊液自身免疫性小脑性共济失调抗体和血副肿瘤综合征抗体均为阴性;4例结缔组织病相关指标异常。6例患者中,4例患者接受免疫球蛋白治疗,其中2例合并激素治疗,1例合并激素及环磷酰胺治疗。6例患者经治疗后,步态不稳均有不同程度缓解,接受免疫或激素治疗患者的症状缓解明显。结论 PACA是一种免疫介导的,但未发现明确病因或特定神经元抗体的自身免疫性疾病;临床表现以共济失调为主;脑脊液及影像学检查大致正常;免疫治疗对多数患者是有效的。     

Early-onset ataxia with cardiomyopathy and retained tendon reflexes maps to the friedreich's ataxia locus on chromosome 9q

Absence of lower limb tendon reflexes has been considered an essential diagnostic criterion for Friedreich's ataxia (FA). However, preservation of knee and ankle jerks has been reported in a few patients. Linkage analysis to FA locus (FRDA) on chromosome 9q13-21.1 was performed in 11 patients from 6 families with FA phenotype, including cardiomyopathy, but retained reflexes (FARR). A maximal lod score of 3.38 at recombination fraction theta equal to 0.00 was obtained demonstrating that FARR maps to the FRDA locus. These results suggest that FARR is a variant phenotype of FA.     

无共济失调小脑梗死12例临床分析

目的:探讨无共济失调小脑梗死的临床特点、梗死区域及早期诊断对疾病预后的意义。方法:回顾性分析12例以眩晕为主要症状但无共济失调表现的小脑梗死的临床资料。结果:患者年龄58～78岁,CT检查未发现梗死灶,MRI阳性率为100%。脑梗死主要危险因素为高血压、糖尿病、高脂血症和心房颤动。11例患者小脑梗死的病灶主要位于单侧小脑半球后下部,属于小脑后下动脉(PICA)供血区域;1例小脑梗死的病灶位于小脑蚓部后部及其附近的两侧小脑半球,属于小脑后下动脉中间支(mPICA)供血区域。结论:无共济失调小脑梗死常见于PICA供血区。对于中老年眩晕患者,无论有无共济失调表现,都应完善MRI检查明确有无小脑梗死。     

High-dose piracetam is effective on cerebellar ataxia in patient with cerebellar cortical atrophy.

We describe a patient with cerebellar ataxia of degenerative nature who was administered high-dose piracetam in a single-blind trial. Piracetam was demonstrated to be highly effective on tandem gait and gait ataxia in daily doses of 60 g. We suggest piracetam has a potential anti-ataxic effect in human cerebellar ataxia when used in considerably higher doses than those indicated for other purposes.     

Clinical and genetic heterogeneity in early onset cerebellar ataxia with retained tendon reflexes.

A clinical and genetic study was performed on 20 patients affected by early onset cerebellar ataxia with retained tendon reflexes (EOCA). Mean age at onset was 8.8 (SD 6.0) years. The frequency distribution of age of onset significantly differed from the normal distribution. Consanguinity rate was 16.7% and segregation ratio 0.164. As well as ataxia, which was a constant feature, there were signs of involvement of the cortico-spinal tracts and/or peripheral nerves in most patients. Results of neurophysiological studies were not homogeneous, nor were morphological findings of the sural nerve biopsy. The data suggest that EOCA may be genetically and clinically heterogeneous.     

Neoplastic meningitis presenting with acute cerebellar ataxia

Acute cerebellar ataxia is a rare initial presenting feature of neoplastic meningitis (NM), particularly in gastric cancer. The authors report a 61-year-old woman with acute cerebellar ataxia secondary to NM from gastric cancer, which was not accompanied by other symptoms commonly associated with NM at initial presentation. It is suggested that NM should be considered in the differential diagnosis of cancer patients with acute cerebellar ataxia.     

Pharmacological treatments of cerebellar ataxia

The confirmed pharmacological treatment of cerebellar ataxia is still lacking. In a recent preliminary trial, we showed that D-cycloserine, a partial NMDA allosteric agonist, may relieve the symptoms. In this paper, major clinical trials to relieve ataxic symptoms are reviewed. Previous studies showed some efficacy of physostigmine in ataxic patients. However, physostigmine did not improve the ataxia in a recent double-blind crossover study. The replacement therapy of the deficient cholinergic system with choline or choline derivatives was tried in patients with Friedreich's ataxia and other ataxic patients, but the result was not definitive. A levorotatory form of hydroxytryptophan (a serotonin precursor), a serotoninergic 5-HT1A agonist, a serotoninergic 5-HT3 antagonist, and a serotonin reuptake inhibitor were also used for the therapy for ataxia. In a double-blind randomized study, buspirone, a 5-HT1A agonist was active in cerebellar ataxia, but the effect is partial and not major. The effects of the studies with the other serotoninergic drugs were not consistent. The effect of sulfamethoxazole-trimethoprim therapy in spinocerebellar ataxia type3/Machado-Joseph disease (MJD) was reported, although the therapy improved spasticity or rigidity, rather than ataxia. In contrast to previous studies, sulfamethoxazole-trimethoprim therapy in MJD had no effect in a 2001 double-blind crossover study. The thyrotropin-releasing hormone, D-cycloserine, and acetazolamide for SCA6 may have some efficacy. However, a well-designed double-blind crossover trial is needed to confirm the effect.     

Oral choline in cerebellar ataxia

In a double-blind crossover pilot study with placebo, choline chloride, the physiologic precursor of acetylcholine, was tested in six patients with cerebellar ataxia. Neither subjectively nor objectively could any statistical significant difference be demonstrated.     

An autopsied case of progressive supranuclear palsy presenting with cerebellar ataxia and severe cerebellar involvement

A Japanese male patient presented with gait disturbance at the age of 69 years. His principal symptom was cerebellar ataxia for several years. He was initially diagnosed as having olivopontocerebellar atrophy because dysarthria and ataxia gradually developed, and head CT scan showed apparent atrophy of the cerebellum and brainstem and dilatation of the fourth ventricle. Later, he showed vertical gaze palsy, dysphagia, retrocollis, parkinsonism, axial dominant rigidity and grasp reflex, and therefore, the diagnosis was modified to progressive supranuclear palsy (PSP). Progressive atrophy of the frontotemporal lobe, cerebellum and brainstem, and dilatation of the lateral, third and fourth ventricles were evident on MRI. Gastrostomy and tracheotomy were performed 9 and 10 years after onset, respectively, and the patient died after 11 years disease duration. At autopsy the brain weighed 1000 g and showed atrophy of the frontotemporal lobe, cerebellum and brainstem. Neurofibrillary tangles, mainly globose‐type revealed by Gallyas‐Braak silver staining, were extensively observed in the cerebral cortex and subcortical grey matter. Numerous glial fibrillary tangles, including tuft‐shaped astrocytes and coiled bodies, and extensive argyrophilic threads were also recognized, particularly in the frontal lobe, basal ganglia, cerebellar white matter, brainstem and spinal cord. The Purkinje cell layer showed severe neuron loss with Bergmann's gliosis, and the dentate nucleus showed severe neuron loss with grumose degeneration. Tau‐positive/Gallyas‐positive inclusions in the Purkinje cells and the glial cells of the Purkinje cell layer were observed. Pathological findings of the present patient were consistent with the diagnosis of PSP, but the olivopontocerebellar involvement, particularly in the cerebellum, was generally more severe, and the quantity of tau‐positive/Gallyas‐positive structures were more abundant than in typical PSP cases. The existence of a distinct, rare PSP subtype with severe olivopontocerebellar involvement, “PSP‐C“, which tends to be clinically misdiagnosed as spinocerebellar degeneration in the early disease stage, is noteworthy. The present case corresponded to this rare subtype of PSP.     

Acute cerebellar ataxia in children

Acute cerebellar ataxia is a benign syndrome usually occurring after an acute febrile disease. In a few cases neuroradiological investigations reveal cerebellar alterations. Clinical and neuroradiological involvement of the brain stem has rarely been reported in the literature. We present five cases of acute cerebellar ataxia. In two cases the cerebellar symptomatology was associated with neurological signs of brain stem involvement. CT scans did not show any pathologic findings in three patients. MRI disclosed cerebellar or brain stem alterations in all the patients. Clinical and neuroradiological findings allow differentiation of this pathologic entity from other demyelinating or dysmyelinating diseases. The value of MRI in detection and localization of the lesions and in following their evolution is emphasized. Received: 4 December 1996 Revised: 20 May 1997     

Pseudodominant Friedreich's ataxia with phenotypic heterogeneity

OBJECTIVE: A family with a clinically heterogeneous progressive ataxia in two generations is presented. METHODS: Having eliminated mutations within the known dominant spinocerebellar ataxia genes, the family was investigated for expansion at the Friedreich's gene. RESULTS: The affected members (father, son and daughter) were homozygous for the mutation at the Friedreich's gene, while the unaffected (the mother and her sister) were heterozygous. CONCLUSION: This pseudodominant form of Friedreich's ataxia should be considered in families with an apparently autosomal dominant progressive ataxia in conjunction with sensory neuropathy and pyramidal signs.     

Friedreich's ataxia presenting with pure sensory ataxia: a long-term follow-up study of two patients

We describe two patients with Friedreich's ataxia whose presenting symptomatology was for years progressive tabetic ataxia. Based upon the initial clinical, electrophysiological and nerve biopsy data, a diagnosis of idiopathic sensory neuropathy was established. Subsequent examination of the kin showed that three sisters of case 1 had Friedreich's ataxia. Upon serial clinical and electrocardiographic study, both patients eventually developed a florid Friedreich's ataxia, including cardiomyopathy. Our findings indicate that at onset Friedreich's ataxia may be indistinguishable from sensory neuropathy and also that serial examination and investigation of kinship are essential steps for accurate diagnosis.     

GAD65抗体相关性小脑性共济失调一例报道及文献复习

目的探讨抗谷氨酸脱羧酶65(glutamic acid decarboxylase,GAD65)抗体相关性小脑性共济失调的临床表现、治疗及预后。方法报道一例抗GAD65抗体相关性小脑性共济失调患者的临床资料,进行诊断、鉴别诊断、治疗及预后分析。结果患者为中老年男性,急性起病,缓慢进展,主要表现为步态不稳并渐出现复视、不能独立行走;神经系统体检发现双眼上视受限、双侧跟膝胫试验及双手轮替试验欠稳准;血清及脑脊液抗GAD65抗体阳性;头颅MRI未见异常萎缩及责任病灶;大剂量甲强龙冲击后症状明显减轻。结论抗GAD65抗体相关性小脑性共济失调可有脑干及小脑受累症状,是一种可以治疗性疾病,早期诊断并积极治疗有望改善预后。