Delayed cerebellar ataxia complicating falciparum malaria: A clinical study of 74 patients

We report the clinical features of 74 patients with delayed cerebellar ataxia (DCA) following falciparum malaria, who were prospectively followed up at two centres. This unusual complication has an acute onset, with signs suggesting a predominantly midline cerebellar lesion without any evidence of cerebral involvement. There was a delay of a median 13 days between the onset of fever and the onset of ataxia. DCA has a good prognosis, with spontaneous and complete recovery within 3 months. In our opinion, it is an example of a post-infective neurological syndrome possibly mediated via an immune mechanism.     

Absence of mutations in ATM, the gene responsible for ataxia telangiectasia in patients with cerebellar ataxia

Ataxia-telangiectasia (AT) is an autosomal recessive multisystent disorder presenting in childhood with progressive cerebellar ataxia, oculocutaneous telangiectasia, immune deficiency, radiosensitivity, and cancer predisposition. The gene for AT, designated ATM (AT, mutated) encodes a protein with a carboxy-terminal phosphoinositide-3 kinase domain which is involved in cell cycle checkpoints and other responses to genotoxic stress. Most of the patients with the classical AT phenotype are homozygous or compound heterozygous for severe mutations causing truncation or destabilization of the ATM protein. Patients with a milder forms of disease, called AT variants, have been found to be either homozygous for milder mutations or compound heterozygotes for null alleles and mild mutations. In order to define the clinical phenotype of patients homozygous (or compound heterozygotes) for other, milder mutations, we decided to search for ATM mutations in patients with either sporadic or familial idiopathic ataxia. Thirty-four patients with idiopathic cerebellar ataxia, aged 3–77 years, were screened for mutations in the ATM coding region. There were 12 familial cases. None of the patients had abnormal immunoglobulin or α-fetoprotein levels, and none had mutations in the ATM coding region. In this heterogeneous group of patients with cerebellar ataxia we found no mutations in the ATM gene. We conclude that mutations in the ATM gene are probably not a common cause for cerebellar ataxia other than AT. Received: 29 October 1998 Received in revised form: 5 February 1999 Accepted: 7 February 1999     

Paraneoplastic cerebellar syndromes associated with antibodies against Purkinje cells

The paraneoplastic cerebellar syndrome presents as severe neuroimmunological disease associated with malignancies. Antibodies against antigens expressed by tumor cells cross-react with proteins of cerebellar Purkinje cells leading to neuroinflammation and neuronal loss. These antineuronal antibodies are preferentially investigated by serological analyses while examination of the cerebrospinal fluid is only performed infrequently.

We retrospectively investigated 12 patients with antineuronal antibodies against Purkinje cells with a special focus on cerebrospinal fluid.

Our results confirm a subacute disease with a severe cerebellar syndrome in 10 female patients due to anti-Yo antibodies associated mostly with gynecological malignancies. While standard cerebrospinal fluid parameters infrequently revealed pathological results, all patients presented oligoclonal bands indicating intrathecal IgG synthesis. Analyses of anti-Yo antibodies in cerebrospinal fluid by calculating the antibody specific index revealed intrathecal synthesis of anti-Yo antibodies in these patients. In analogy to anti-Yo syndrome, an intrathecal production of anti-Tr antibodies in one patient who presented with a paraneoplastic cerebellar syndrome was detected. In an additional patient, anti-Purkinje cell antibodies of unknown origin in the cerebrospinal fluid but not in serum were determined suggesting an isolated immune reaction within the central nervous system (CNS) and underlining the importance of investigating the cerebrospinal fluid.

In conclusion, patients with a cerebellar syndrome display a distinct immune reaction within the cerebrospinal fluid including intrathecal synthesis of disease-specific antibodies. We emphasize the importance of a thorough immunological work up including investigations of both serum and cerebrospinal fluid.     

Increased enolase activity in erythrocytes in a family with cerebellar ataxia

ABSTRACT- We have studied erythrocyte metabolism in a family affected by cerebellar ataxia. 3 of the subjects showed a severe clinical picture, and 3 were clinically normal. In all 6 subjects, we have revealed an increase in enolase activity in erythrocytes. These findings may be relevant for early diagnosis of the disease.     

康复综合疗法治疗小脑共济失调一例

正患者女性,29岁。主因言语不清、双侧肢体活动失衡3月余,于2014年10月10日入天津市环湖医院就诊。患者入院前4个月顺产一女婴,产褥期第10天出现发热,体温37.3~38.6℃,伴乏力,经当地医院退热处理后体温降至37.3~37.6℃,乏力症状稍有缓解;产褥期第14天体温突然升至41℃,伴寒战和意识不清,遂入外院急救中心重症监护病房(ICU)抢救。考虑为中暑,并可疑颅内感染、缺氧缺血性脑病(HIE)、代谢性脑病;脓毒血症;肺炎;双     

Regressive dystonia and cerebellar ataxia: two unusual symptoms in central pontine myelinolysis

Two patients with central pontine myelinolysis who presented with dystonia are described. In one, it was associated with cerebellar ataxia which spontaneously improved. In the second, dystonia progressively disappeared 6 months later. In both cases magnetic resonance imaging (MRI) revealed characteristic pontine lesions. Extrapontine myelinolysis involving the putamen was also observed in one patient. Even when the basal ganglia seem to be spared on MRI, dystonia is probably due to their involvement by myelinolysis. Cerebellar ataxia may be related to peduncular or cerebellar lesions or both.     

Clinical and genetic analysis of three German kindreds with autosomal dominant cerebellar ataxia type I linked to the SCA2 locus

The detailed clinical, electrophysiological and imaging data of three German autosomal dominant cerebellar ataxia (ADCA) families are reported. Linkage to SCA2 was established using microsatellite markers D12S105, D12S1339(1328), D12S1340(1329) yielding a lod score exceeding +3.0 for the combined data. Analysis of the pedigree data provided evidence of anticipation as observed in other neurodegenerative disorders due to polyglutamine expansion encoded by a CAG repeat. This hypothesis was confirmed by the detection of the SCA2-specific pathological protein using the 1C2 monoclonal antibody which selectively recognizes large polyglutamine expansions and the characterization of a CAG expansion in the patients. Clinically, the families were characterized by progressive ataxia of stance, gait and limbs. Saccade velocity was markedly reduced in SCA2. Further oculomotor findings were gaze palsy, impaired smooth pursuit and reduced optokinetic reflex. Dementia and pyramidal tract signs were rather rare, while peripheral involvement (reduced or absent ankle reflexes, fasciculation-like movements, amyotrophy) was a prominent feature. Electrophysiological investigations provided evidence of sensory neuropathy of the axonal type and degeneration of the posterior columns. Imaging studies demonstrated severe shrinkage of brain-stem structures even in early stages of the disease. Received: 10 September 1996 Accepted: 8 December 1996     

Slowly progressive cerebellar ataxia and cervical dystonia: Clinical presentation of a new form of spinocerebellar ataxia?

We describe 5 cases with a rare combination of young-onset, slowly progressive cerebellar ataxia and cervical dystonia. Two were sporadic, whereas the other 3 were familial, including 2 from one family. The age of onset of these cases was between 16 and 37 years. The presenting symptom was cervical dystonia and/or dystonic head tremor in 3 patients and hand or lower limb tremor in 2. In 2 cases, cervical dystonia and/or dystonic head tremor developed approximately 6 to 10 years before cerebellar dysfunction, and in three they developed at the same time. Apart from cervical dystonia, there was mild dystonic limb involvement in 2 cases, but generalized dystonia was not seen. Cerebellar ataxia was slowly progressive. A literature search showed 10 cases of cervical dystonia associated with genetically undetermined (n = 5) or genetically proven (n = 5) spinocerebellar ataxia (SCA). When the genotype was known, these patients had either SCA3, 6, 7, or 12. However, our 5 cases (or their first-degree relatives) tested negative for SCA1, 2, 3, 6, and 7, and in the 4 cases (or their first-degree relatives) tested for SCA12, the result was negative. We propose that this rare phenotype manifesting as a combination of cerebellar ataxia and cervical dystonia may represent one or more new, as yet uncharacterized, genotypes of inherited young-onset spinocerebellar ataxia. Copyright Movement Disorder Society     

小脑共济失调大鼠模型中ATM及p53的表达水平变化

目的 探讨小脑共济失调大鼠模型中共济失调毛细血管扩张突变(Ataxia telangiectasia-mutated,ATM)蛋白和p53的表达水平变化。方法 采用3-乙酰吡啶(3-acetylpyridine,3-AP)和烟酸诱导SD大鼠小脑共济失调,观察大鼠行为学变化; HE染色观察大鼠小脑组织中神经元的形态学变化; 尼氏染色观察小脑组织中神经元的缺失; 免疫组化观察小脑神经元中ATM、p53的表达水平。结果 模型组大鼠厌食,体重减轻,步态异常,平衡障碍,表型观察符合小脑共济失调模型特征; 模型组小脑组织中神经元细胞核固缩深染,且存在炎性细胞浸润分子,颗粒细胞减少,浦肯野细胞形态异常甚至缺失,神经元中ATM及p53表达水平升高,且呈现出一定的时间依赖性。结论 小脑共济失调大鼠模型小脑组织出现神经元退行性病变,可能是通过激活ATM/p53信号通路来修复细胞损伤。     

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.     

Recurrent acute cerebellar ataxia associated with anti-cardiolipin antibodies

Various autoantibodies are detected in patients with acute cerebellar ataxia (ACA). Although an autoimmune process may contribute to the mechanism of ACA, its pathophysiology is not completely understood. We report a girl with recurrent ACA and anti-cardiolipin antibodies. Her cerebral blood flow imaging showed hypoperfusion in the cerebellum, which improved when the anti-cardiolipin antibodies disappeared. Our case suggests that vasculopathy or non-vascular neurotoxicity in the cerebellum caused by antiphospholipid antibodies leads to acute cerebellar ataxia.     

A case of chronic recurrent cerebellar ataxia responding to steroid therapy

We present a 25-month-old female having unusual cerebellar ataxia responsive to steroid therapy. She had suddenly suffered from action tremor and trunkal ataxia, following antecedent mild respiratory infection. These symptoms lasted for a month, and therefore she was referred to our hospital. No abnormal findings were disclosed for cerebrospinal fluid or MR images, but anti-glutamate receptor delta2 antibodies were detected in serum. MR spectroscopy of the cerebellum revealed a decrease in the N-acethylasparate/creatine ratio, suggesting micro-neuronal damage. She had quickly responded to high-dose methylpredonisolone therapy and the effectiveness of this steroid was reproducible in the subsequent relapses of ataxia. This clinical course seemed to be unique and was characterized as chronic recurrent cerebellar ataxia responding to steroid therapy.     

Statin-associated cerebellar ataxia. A Brazilian case series

BackgroundDrug-induced cerebellar ataxias (DICA) represent an important group of secondary cerebellar ataxias. Herein, we reported a case series of progressive cerebellar ataxia induced by HMG-CoA reductase inhibitors (statins).MethodsObservational study with a Brazilian case series of patients with cerebellar ataxia due to statins use.ResultsWe described four patients with cerebellar ataxia, predominantly gait ataxia, due to statins use. Mean age was 67.5 years old, predominantly male, with several comorbidities, such as dyslipidemia, diabetes mellitus, hypertension, and myocardial revascularization. After statin withdrawal, and treatment with coenzyme Q10 in some patients, progressive improvement of gait ataxia was observed.DiscussionWe presented a case series of four patients with cerebellar ataxia due to statins use, which represents a new rare side-effect of statins, probably related to coenzyme Q10 deficiency.     

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。     

An 8-year-old boy with vertebral artery dissection with cerebellar ataxia featuring suspected vertebral artery hypoplasia

We report an 8-year-old boy with left vertebral artery dissection featuring cerebellar ataxia in which congenital vertebral artery hypoplasia was suspected as a predisposing factor in the dissection. The patient suddenly suffered from vertigo and vomiting while swimming, and he was brought to our department. The initial brain Computed Tomography (CT) demonstrated no abnormalities, and his symptoms disappeared the next morning. However, one month after onset, brain Magnetic Resonance Imaging (MRI) revealed ischemic changes (infarction) in the left cerebellum. Transfemoral angiography showed complete occlusion at the C2 portion of the left vertebral artery, suggesting dissection and diffuse narrowing of the proximal segment of the occlusion site. Three-dimensional CT angiography also revealed diffuse narrowing of the left vertebral artery from the bifurcation of the subclavian artery. He has since been living daily life without any difficulties. The detailed etiology of cerebral artery dissection remains unknown, but arterial anomalies should be considered as a predisposing factor.     

Spinocerebellar ataxia type 15

Spinocerebellar ataxia type 15 (SCA15) was first reported in 2001 on the basis of a single large Anglo-Celtic family from Australia, the locus mapping to chromosomal region 3p24.2-3pter. The characteristic clinical feature was of very slow progression, with two affected individuals remaining ambulant without aids after over 50 years of symptoms. Head and/or upper limb action tremor, and gaze-evoked horizontal nystagmus were seen in several persons. MRI brain scans showed predominant vermal atrophy, sparing the brainstem. In 2004, a Japanese pedigree was reported, which displayed very similar clinical features to the original SCA15 family, and which mapped to an overlapping candidate region. These two families might plausibly reflect a locus homogeneity, but for the present this remains an open question.     

神经系统副肿瘤综合征34例临床特点分析

目的:分析34例神经系统副肿瘤综合征患者的临床特点。方法:对1990年至2005年收治的34例神经系统副肿瘤综合征患者的临床资料进行回顾性分析。结果:副肿瘤综合征的临床类型有周围神经病15例、Lambert-Eaton肌无力综合征5例、多发性肌炎和皮肌炎3例、进行性小脑变性2例、运动神经元病3例、进行性多灶性白质脑病1例、亚急性坏死性脊髓病1例、脑干脑炎2例、边缘系统脑炎2例。结论:神经系统副肿瘤综合征临床表现形式多样,容易误诊,临床早期确诊对于隐匿肿瘤的发现和治疗非常重要。     

Case report: immune-mediated cerebellar ataxia secondary to anti-PD-L1 treatment for lung cancer

Abstract

Case presentation: A 66-year-old gentleman with metastatic non-small-cell lung cancer developed a wide-based gait following treatment on a clinical trial with cytotoxic chemotherapy and an anti-PD-L1 drug. He had no other significant past medical history of note. Brain imaging, blood tests and lumbar puncture did not reveal a structural, biochemical, paraneoplastic or infective cause. The main differential diagnoses were immune-mediated toxicity or a paraneoplastic syndrome. He was started on prednisolone on the suspicion that his symptoms represented an immune-mediated toxicity. His condition improved following this and his immunotherapy treatment was discontinued. Upon steroid withdrawal, his symptoms recurred and responded to further prednisolone.

Conclusions: Immune-mediated toxicities can affect any part of the nervous system and should form part of the differential diagnosis for new neurological symptoms in a patient receiving immunotherapy. Corticosteroids should be the first-line treatment of immune-mediated toxicities. Immunotherapy should be permanently discontinued following severe toxicities.     

The cerebellar form of acquired hepatocerebral degeneration: The hepatic ataxia

This article reports a patient with acquired hepatocerebral degeneration that presented with progressive cerebellar ataxia, cerebellar atrophy, and middle cerebellar peduncle lesions. He had a marked improvement after liver transplantation. We reinforce that hepatic failure should be investigated in patients with pure cerebellar syndrome, resembling neurodegenerative diseases.