以小脑性共济失调为主要临床表现的神经白塞病

目的探讨以小脑性共济失调为主要临床表现的神经白塞病临床、影像学特点和治疗。方法报道1例以小脑性共济失调为主要表现的神经白塞病患者,分析其临床和影像学特征以及治疗方法。结果患者青年女性,隐袭起病,病程12年,慢性波动性,主要表现为轻度顿挫性构音障碍、四肢和躯干共济失调,同时有反复口腔溃疡、皮肤脓性丘疹、会阴部溃疡、眼睑散粒肿和心脏损害。查体发现,双眼左右视和上下视时均有水平眼震,四肢肌张力略低,肌力5级,双手指鼻和跟膝胫试验欠稳准,直线行走不能完成,双侧Barbinski征阴性。头颅MRI示小脑蚓部和双侧小脑半球萎缩;脑脊液寡克隆区带弱阳性。激素和硫唑嘌呤免疫治疗后患者皮肤、眼睑、口腔和心脏功能状态恢复正常,共济失调症状稳定,药物减量后共济失调加重,口腔溃疡和眼部炎症复发。结论神经白塞病相关小脑性共济失调是脑实质型神经白塞病的表现,患者可表现为亚急性起病慢性波动性的小脑性共济失调,脑脊液可有炎性表现,影像学表现为小脑萎缩。免疫修正治疗可以改善和延缓病情进展。     

Hashimoto’s Encephalopathy Presenting with Progressive Cerebellar Ataxia

Hashimoto’s encephalopathy is a rare neurological syndrome occurring in patients with autoimmune thyroid disease. The diagnosis of Hashimoto’s encephalopathy is based on the clinical picture with the presence of serum anti-thyroid antibodies regardless of the thyroid disorder. Acquired cerebellar ataxia associated with Hashimoto’s disease is a rare occurrence. In this article, we present a case who had progressive non-familial autoimmune pancerebellar disease in association with an increased level of thyroid peroxidase and thyroglobulin antibodies. The patient was managed aggressively with both intravenous immunoglobulins and plasma exchange, which stopped the progression of the disease and allowed for slow improvement. Early diagnosis of Hashimoto’s encephalopathy with autoimmune cerebellar ataxia and intervention with immunomodulatory therapy are of paramount importance. Close monitoring after steroid therapy is important since some patients with this rare disease might be resistant to steroid therapy and require aggressive immunomodulatory therapy.

Hashimoto’s encephalopathy is a rare neurological syndrome occurring in patients with autoimmune thyroid disease.1 The diagnosis of Hashimoto’s encephalopathy is based on the clinical picture with the presence of serum anti-thyroid antibodies regardless of the thyroid disorder.2 Acquired cerebellar ataxia associated with Hashimoto’s disease is a rare occurrence.3 In this article, we present a case who had progressive non-familial autoimmune pancerebellar disease in association with an increased level of thyroid peroxidase and thyroglobulin antibodies. The patient was managed aggressively with both intravenous immunoglobulins and plasma exchange, which stopped the progression of the disease and allowed for slow improvement.     

Pediatric manifestations of Hashimoto’s encephalopathy

Hashimoto’s encephalopathy is a steroid-responsive encephalopathy associated with elevated blood concentrations of antithyroid antibodies. The patients are usually euthyroid or mildly hypothyroid. The authors report two pediatric patients with Hashimoto’s encephalopathy and review the literature. The clinical picture in adolescents, as with adults, is pleomorphic but frequently associated with seizures, confusion, and hallucinations. Alternatively, progressive cognitive decline manifested by a drop in school performance can be observed. The diagnosis of Hashimoto’s thyroiditis is often overlooked at presentation and a high degree of suspicion is necessary for proper diagnosis.     

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.     

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.     

Wolfram's syndrome presenting as a cerebellar ataxia

INTRODUCTION: Wolfram syndrome is a genetic disease with recessive autosomic transmission, associating early-onset diabetes mellitus and bilateral optical atrophy. CASE REPORT: We report the case of a 47-year-old patient for whom we diagnosed a Wolfram syndrome in view of a late neurological syndrome in association with ataxia and bilateral horizontal nystagmus. The brain resonance magnetic imaging revealed a major atrophy of the brainstem and cerebellum. CONCLUSION: Wolfram syndrome is a rare pathology, with fatal consequences before the age of 50. The association of diabetes mellitus and optical atrophy, especially when there are other symptoms (ataxia, deafness, diabetes insipidus, neuropsychiatric manifestations or urinary tract disorders) should lead to this diagnosis and to carry out a genetic confirmation.     

Evoked potential studies in Friedreich's ataxia and progressive early onset cerebellar ataxia

We recorded somatosensory evoked potentials (SEP) in 15 patients affected by Friedreich's ataxia (FA) and in 9 patients with progressive early onset cerebellar ataxia (PEOCA). Brainstem auditory evoked potentials (BAEP) were also recorded in 14 FA patients and in five PEOCA patients. SEP results showed clear differences between groups of FA, evidence of peripheral involvement was seen in all patients, with absence of the N9 potential or a major reduction of its amplitude. In patients in whom central responses could be recorded, conduction velocity was normal or near normal up to the brainstem but was reduced from brainstem to cerebral cortex. Four patients with PEOCA had SEP abnormalities similar to those seen in FA. In the five other patients, the amplitude and latency of N9 were normal but conduction velocity was reduced from brainstem to cerebral cortex. In FA, BAEP were abnormal in all patients with a disease duration of four years or more but were normal in four of the five PEOCA patients. Systematic evoked potential recording is useful in the investigation of hereditary ataxias.     

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。     

The genetic aetiology of late-onset chronic progressive cerebellar ataxia

Background   An increasing number of dominant and recessive disorders have been associated with late onset chronic progressive ataxia (LOCA) complicating the formulation of a rational diagnostic strategy. Furthermore, there is marked geographic and ethnic variation in the relative importance of these individual disorders and the cause of such observed variation remains unexplained. Methods   We have systematically investigated a populationbased cohort of patients with chronic progressive LOCA for SCA 1,2,3,6,7,8,10,12,17, FXTAS and FRDA. In addition we have examined repeat length polymorphism in chromosomes from a genetically homogeneous and representative control population to investigate the association of high-normal repeats and disease prevalence. Results   A total of 178 patients including 55 familial cases segregating in 38 kindreds and 123 sporadic were investigated. Pathological expansions were identified in 11/38 (28.9 %) of families and in 5/123 (4.1 %) of sporadic patients. The most frequent diagnoses were SCA6 (6 families and 1 sporadic patient), DRPLA (4 families) and SCA8 (1 family). In addition, one elderly female patient was identified with “possible FXTAS”. Six (2 %) control patients were noted to have expanded SCA8 alleles. Conclusions   SCA6 and DRPLA were the most frequent genetic diagnoses identified. Patterns of highnormal allele frequency in this UK population were distinct compared to other ethnic groups but this was poorly predictive of the distribution of disease in this region. The relative contribution of new mutation formation and founder effects to the prevalence of familial ataxia is uncertain, and further exploration of these factors will require detailed analysis of disease allele haplotypes and meiotic instability of intermediate length alleles. Electronic Supplementary Material  The online version of this article (DOI) contains supplementary material, which is available to authorized users.     

Secondary amenorrhea in two sisters with hypogonadotropic hypogonadism and progressive cerebellar ataxia

The association of familial hypogonadism with progressive cerebellar ataxia is only rarely encountered. Both primary hypergonadotropic and secondary hypogonadotropic hypogonadism may appear with cerebellar ataxia. However, many of these patients suffer from a variety of neurological and/or somatic malformations. Females, which are relatively rarely affected, display primary amenorrhea. In this report, two sisters presented with secondary amenorrhea prior to the appearance of progressive cerebellar ataxia and were found to have hypogonadotropic hypogonadism. This unique family displays clinical evidence for the presence of a possible common mechanism responsible for progressive hypothalamic and cerebellar impairment of late onset.     

Early clinical features of patients with progressive supranuclear palsy with predominant cerebellar ataxia

BackgroundPatients who develop progressive supranuclear palsy with predominant cerebellar ataxia (PSP-C) develop cerebellar ataxia as the initial and principal symptom, may be misdiagnosed as having multiple system atrophy with predominant cerebellar features (MSA-C). Therefore, we investigated the clinical signs and symptoms between PSP-C and MSA-C early in their disease course.MethodsWe reviewed the medical records of 15 consecutive patients with pathologically proven PSP-C (4) and MSA-C (11). We recorded the presence or absence of clinical features that developed within 2 years of disease onset.ResultsThe age at onset of PSP-C patients was older than that of MSA-C patients (p = 0.009). The frequencies of falls were higher in PSP-C patients than in MSA-C patients (p = 0.026). Additionally, the development of supranuclear vertical gaze palsy was higher in PSP-C patients than in MSA-C patients (p = 0.011), whereas the frequency of dysautonomia was lower in PSP-C patients than in MSA-C patients (p = 0.035).ConclusionsOlder onset, early falls, and supranuclear vertical gaze palsy without dysautonomia may predict the diagnosis of PSP-C in patients with late-onset sporadic cerebellar ataxia.     

Mutation of the aprataxin gene presenting with Charcot-Marie-Tooth-like neuropathy and cerebellar ataxia

BACKGROUND: Phenotype-genotype correlations, generally based on predominant associated signs, are being increasingly used to distinguish different types of autosomal recessive cerebellar ataxias (ARCA). CASE REPORTS: Two brothers developed signs of cerebellar ataxia with peripheral axonal motor and sensory neuropathy, distal muscular atrophy, pes cavus and steppage gait as seen in Charcot-Marie-Tooth neuropathy. The examination also showed oculomotor apraxia. Sural nerve biopsy revealed conspicuous reduction in the density of myelinated fibres but preservation of unmyelinated nerve fibres. Blood tests revealed low serum albumin and elevated cholesterol. A homozygous W279X truncating mutation was identified in exon 6 of the APTX gene, confirming the diagnosis of cerebellar ataxia with oculomotor apraxia type 1 (AOA1). CONCLUSIONS: These cases illustrate the presentation of AOA1 type of ARCA and discuss the role of peripheral neuropathy in the differential diagnostic of the ARCAs variants.     

Relapsing encephalopathy with cerebellar ataxia related to an ATP1A3 mutation

ATP1A3, the gene encoding the α3‐subunit of the Na⁺/K⁺‐ATPase pump, has been involved in four clinical neurological entities: (1) alternating hemiplegia of childhood (AHC); (2) rapid‐onset dystonia parkinsonism (RDP); (3) CAPOS (cerebellar ataxia, areflexia, pes cavus, optic atrophy, sensorineural hearing loss) syndrome; and (4) early infantile epileptic encephalopathy. Here, we report on a 34‐year‐old female presenting with a new ATP1A3‐related entity involving a relapsing encephalopathy characterized by recurrent episodes of cerebellar ataxia and altered consciousness during febrile illnesses. The term RECA is suggested – relapsing encephalopathy with cerebellar ataxia. The phenotype of this patient, resembling mitochondrial oxidative phosphorylation defects, emphasizes the possible role of brain energy deficiency in patients with ATP1A3 mutations. Rather than multiple overlapping syndromes, ATP1A3‐related disorders might be seen as a phenotypic continuum.