Cerebellar ataxia and opsoclonus as the initial manifestations of myoclonic encephalopathy associated with neuroblastoma

Cerebellar ataxia and opsoclonus were the initial manifestations of an associated neuroblastoma in a 20-month-old girl. Two months after the initial symptomatology, a physical examination revealed an abnormal mass palpable left to the midline. Urinary catecholamines were within normal limits. The child's neurological findings improved immediately after surgery, and steroid treatment and the follow-up on her after 2 years revealed normal general nad neurological development. The syndrome of myoclonic encephalopathy including cerebellar ataxia, myoclonus and opsoclonus, and its relationship to neuroblastoma is reviewed. Failure to recognize this association can result in delays in both diagnosis and treatment and could be fatal.     

Different patterns of movement-related cortical oscillations in patients with myoclonus and in patients with spinocerebellar ataxia

ObjectiveTo assess whether different patterns of EEG rhythms during a Go/No-go motor task characterize patients with cortical myoclonus (EPM1) or with spinocerebellar ataxia (SCA).MethodsWe analyzed event-related desynchronization (ERD) and synchronization (ERS) in the alpha and beta-bands during visually cued Go/No-go task in 22 patients (11 with EPM1, 11 with SCA) and 11 controls.ResultsIn the Go condition, the only significant difference was a reduced contralateral beta-ERS in the EPM1 patients compared with controls; in the No-go condition, the EPM1 patients showed prolonged alpha-ERD in comparison with both controls and SCA patients, and reduced or delayed alpha- and beta-ERS in comparison with controls. In both conditions, the SCA patients, unlike EPM1 patients and controls, showed minimal or absent lateralization of alpha- and beta-ERD.ConclusionsEPM1 patients showed abnormal ERD/ERS dynamics, whereas SCA patients mainly showed defective ERD lateralization.SignificanceA different behavior of ERS/ERD distinguished the two patient groups: the pattern observed in EPM1 suggests a prominent defect of inhibition occurring in motor cortex contralateral to activated segment, whereas the pattern observed in SCA suggested a defective lateralization attributable to the damage of cerebello-cortical network, which is instead marginal in patients with cortical myoclonus.     

Peroneal muscular atrophy with ataxia and partial myoclonic epilepsy

Summary Two brothers, 17 and 11 years old, presented with pes cavus, absence of deep tendon reflexes, peripheral vibratory sensory loss, ataxia, tremor, nystagmus, dysarthria and partial myoclonic epilepsy. Electromyography showed severe slowing of motor conduction velocity in the lower extremities and increased distal latencies. A peroneal nerve biopsy showed absence of myelin sheath in most fibres resulting in numerous demyelinated nerve fibres. The father and seven uncles on the paternal side had pes cavus, hammer toes and moderate vibratory peripheral sensory loss. Three of seven siblings had slow motor conduction velocities on EMG. None had EEG abnormalities. Epilepsy started at an early age in both patients with myoclonic jerks of the right arm especially during sleep. EEG recordings were characterized by focal or diffuse epileptiform discharges. In the elder brother a partial motor epileptic status occurred with adversive seizures involving the right side of the body. He died of a broncopneumonia after 3 days of this epileptic status. Histopathological examination showed a severe demyelination of dentato-rubral pathways in the cerebellum and a partial degeneration of Goll and Burdach's tracts in the cervical spinal cord. The nosological classification of this syndrome is discussed and an autosomal dominant inheritance with incomplete penetrance or variable expressivity is suggested.

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Zusammenfassung Bei zwei Brüdern im Alter von 17 und 11 Jahren fanden sich Pes cavus, fehlende Muskeleigenreflexe, hochgradig gestörte Tiefensensibilität, eine Ataxie, ein Nystagmus, eine Dysarthrie und eine partielle Epilepsie mit myoklonischen Anfällen. Elektromyographisch ließ sich eine hochgradige Verlangsamung der motorischen Erregungsleitung an den unteren Extremitäten mit verlängerter distaler Latenz nachweisen. Eine Biopsie des Nervus peronaeus ergab einen vollständigen Myelinverlust zahlreicher Fasern. Sowohl der Vater wie 7 Onkel väterlicherseits hat einen Pes cavus, Hammerzehen und leichte periphere Sensibilitätsstörungen. Bei 3 von 7 Untersuchten fanden sich eine Verlangsamung der motorischen Erregungsleitung peripherer Nerven. EEG im Bereiche der Norm.Die epileptischen Anfälle manifestierten sich zunächst als Myoklonie der oberen rechten Extremitäten besonders während des Schlafes. Im EEG der beiden Exploranden zeigten sich fokale oder generalisierte epileptische Entladungen. Beim älteren der Brüder trat ein Status partialer motorischer Anfälle mit rechtsseitigen Adversiv-Attacken auf. Er starb plötzlich an einer Bronchopneumonie am 3. Tag des Status epilepticus. Die neuropathologische Untersuchung ergab eine nahezu vollständige Demyelinisierung des Tractus dentatorubralis und eine partielle Degeneration des Gollschen und Burdachschen Tractus im Halsmark. Die Zuordnung dieses Syndromes wird diskutiert und es wird eine autosomal dominante Vererbung mit unvollständiger Penetranz beziehungsweise unterschiedlicher Expressivität angenommen.

     

Progressive myoclonic epilepsy

Progressive myoclonic epilepsies (PMEs) are a group of rare disorders characterized by the occurrence of seizures, myoclonus, and progressive neurological dysfunction. This article discusses epidemiology, genetics, pathology, clinical manifestations, EEG characteristics, methods of diagnosis and treatment of the most common causes of PME, including Unverricht-Lundborg Disease (Baltic Myoclonus), MERRF, neuronal ceroid lipofuscinosis, dentatorubropallidoluysan atrophy, Gaucher disease, Lafora disease, and sialidosis. The aim of this paper is to provide clinicians with useful clinical information in order to facilitate the diagnosis and treatment of these rare diseases.     

Progressive myoclonus epilepsy is not accompanied by humoral immune response within the central nervous system

CSF and serum from five patients with progressive myoclonus epilepsy taken on two occasions with about one month's interval were examined for intrathecal humoral immune response. The CSF IgG and IgA index values were normal, and no oligoclonal bands were detectable by agarose electrophoresis or polyacrylamide isoelectric focusing (IEF). Immunofixation of IEF separated IgG with four different viruses as possible antigens, and autoradiography did not reveal any intrathecal antibody production. In contradiction to previous reports, no evidence was obtained for a local humoral immune response in progressive myoclonus epilepsy.     

多发性硬化脑脊液寡克隆区带及24小时鞘内IgG合成率检测的比较

采取垂直平板聚丙烯酰胺凝胶电泳法、火箭免疫电泳法对30例多发性硬化病人进行脑脊液寡克隆区带及24小时鞘内IgG合成率的检测,结果发现寡克隆区带、合成率与多发性硬化的发病年龄、病程、病程进展类型、病残程度无统计学上的相关性,寡克隆区带阳性率46.7％,合成率增高占60％,两者合计异常率可达73.3％,提示我国多发性硬化寡克隆区带阳性率、合成率增高均较国外低,因而在我国对多发性硬化的实验室诊断两者同时检测更有意义。     

寡克隆带和IgG鞘内合成率对多发性硬化的诊断价值

目的探讨寡克隆带(OCBs)和IgG鞘内合成率(IgGSyn)对多发性硬化(MS)诊断的敏感性、特异性,以及定性和定量指标的相关性。方法选取30例MS(MS组)、40例神经系统炎性疾病(NID组)和22例神经系统非炎性疾病(NNID组)患者,应用速率散射比浊法测定血清和脑脊液(CSF)中免疫球蛋白G(IgG)、白蛋白(Alb)水平,等电聚焦结合银染色法检测CSF中OCBs,计算IgGSyn,并对其敏感性、特异性和阳性结果似然比(PRLR)进行分析。结果OCBs阳性率和IgGSyn异常率MS组与NID组比较差异无显著性;MS组、NID组与NNID组比较差异有极显著性(均P<0.01)。MS组和NID组中,OCBs阳性者与阴性者IgGSyn值差异无显著性。对MS诊断的敏感性、特异性和PRLR,OCBs分别为63.3%、77.7%和2.8;IgGSyn为46.7%、75.2%和1.9。结论OCBs和IgGSyn检测结果的不完全一致性提示中枢神经系统内存在不同的体液免疫反应机制,综合分析OCBs和IgGSyn,对MS诊断具有参考价值。     

Clinical and CSF cyto-proteic findings in 23 patients with CSF eosinophilia

Clinical diagnosis and cerebrospinal fluid (CSF) protein pattern were studied in 23 patients who had eosinophilic granulocytes in the CSF. Clinical data revealed that an inflammatory disorder of the central nervous system (CNS) was evident in 20 cases. A lymphoid reaction and elevated CSF total protein were found in most of the cases, but the most important finding was an increase of CSF gamma-globulin in 12 patients, of whom 10 had oligoclonal patterns. Our results may give support to a relationship between intrathecal eosinophilic reaction and inflammatory diseases of the CNS with subacute or chronic course accompanied by intrathecal synthesis of immunoglobulins.     

Oligoclonal immunoglobulin bands in cerebrospinal fluid of patients with Alzheimer''s disease and vascular dementia

We examined serum and cerebrospinal fluid (CSF) of 16 patients with Alzheimer's disease (AD), 28 patients with vascular dementia (VD), their age-matched controls and multiple sclerosis (MS) patients in order to evaluate the humoral immune response within the central nervous system both quantitatively and qualitatively. Intra-blood-brain barrier (BBB) protein synthesis was calculated by CSF IgG index. The presence of oligoclonal banding (OCB) was investigated with agarose isoelectric focusing (IEF) followed by immunoblotting with antihuman IgG. No patient with AD and only 4 patients with VD had slightly elevated IgG indexes, and no statistically significant differences in the indexes were found between the two groups. No bands were found in the CSF of AD patients but 3 VD patients had OCB in both serum and CSF. One VD patient had bands in serum but no bands in CSF. No kappa or lambda free light chains were found in those demented patients with demonstrable bands in the CSF and serum. No OCB were found in control sera and CSF. For comparison, the majority of patients with MS had OCB in CSF. Thus, no consistent increase of intrathecal protein synthesis was found in patients with AD and VD. Methodological differences explain at least part of the conflicting results published earlier.     

Identification of IgG subclasses'' oligoclonal bands in multiple sclerosis CSF

IgG subclasses' oligoclonal bands in unconcentrated CSF from MS patients were detected by isoelectric focusing in agarose gel with subsequent immunoblotting using mouse monoclonal antibodies to human IgG subclasses and double-antibody avidin-biotin-alkaline phosphatase system. All MS CSF showed presence of oligoclonal bands specific to the IgG1 subclass; in addition, several of these samples also had oligoclonal bands specific to IgG3, IgG2, or IgG4, in order of decreasing frequency. Since the CSF of a greater number of MS patients showed oligoclonal bands specific to the IgG1 and IgG3 subclasses, the findings are consistent with those reported in patients with chronic viral infections and autoimmune diseases.     

High-dose intravenous-penicillin in neurosyphilis: effect on intrathecal synthesis of IgG, IgM, IgA and IgD

We evaluated occurrence and levels of intrathecal synthesis of IgG, IgM, IgA and IgD by calculating corresponding index values in 8 patients with definite and 4 with suspected or possible neurosyphilis, prior to, during and after high-dose intravenous penicillin therapy. Four patients with active neurosyphilis displayed intrathecal synthesis of IgG, IgM and IgA. Only 2 of them showed elevated IgD index, and both had taboparesis, pleocytosis and positive VDRL in CSF, and simultaneous elevation of the IgG, IgA and especially of the IgM indices. This suggests that intrathecal synthesis of IgD may occur in patients with severe CNS inflammation in response to diffuse CNS treponemal damage. Penicillin therapy incited transitory elevation of one or more of the immunoglobulin index values in most patients, possibly in response to massive treponemal lysis inside the CNS. Thereafter, the values became mostly normalized but exceptions occurred, including one patient who had elevated IgG and IgM index which persisted 31 months after therapy. Our data indicate that determinations of immunoglobulin indices performed on consecutive specimens from individual patients with neurosyphilis may be helpful in the evaluation of treatment.     

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     

Progressive myoclonic ataxia and JC virus encephalitis in an AIDS patient

A case of progressive myoclonic ataxia in an AIDS patient is described, which evolved over a 13 month period. The ataxia persisted as the only clinical finding for several months before the appearance of a severe tetraparesis and cachexia. Throughout the clinical progression, magnetic resonance imaging (MRI) revealed the presence of bilateral, progressive, isolated, and symmetrical lesions involving the red nuclei, subthalami, thalami, lenticular nuclei, and primary motor cortices. Neuropathological examination, supplemented by in situ hybridisation for JC virus DNA, confirmed that the lesions were those of progressive multifocal leucoencephalopathy (PML). The exceptional clinical presentation of PML in this case is the first report of progressive myoclonic ataxia caused by PML. The selective nature of the lesions confirms the role of the dentato-rubral-thalamo-cortical tract in the pathogenesis of progressive myoclonic ataxia. The atypical MRI findings further emphasise the need for expanded diagnostic criteria for PML in AIDS patients and support the use of more aggressive diagnostic methods as new treatments become available.     

获得性神经性肌强直的临床、电生理及其免疫学异常(附并发于肺癌且有肌无力综合征肌电图特征的神经性肌强直1例报告)

本文报告1例38岁女性肺癌患者伴进行性全身肌肉连续性抽搐、痉挛、僵硬和无力，胸片和胸部CT提示右上肺中心型肺癌、肺不张。脑脊液IgG增高，寡克隆区带阳性。肌电图呈连续性高频肌强直放电，发作间期可见束颤电位。周围神经封闭可缓解全部肌强直症状，并消除肌电图异常连续性放电。低频重复电刺激出现衰减，高频重复电刺激动作电位波幅增高300％。患者同时有神经性肌强直和肌无力综合征肌电图特征，并与中心型肺癌和神经系统免疫学异常并存。上述改变可能与肺癌有关，提示患者神经系统IgG介导的自身免疫异常在神经性肌强直的发病机理中起重要作用。     

Unusual findings in Creutzfeldt-Jakob disease. Case report

We present a definite case of Creutzfeldt-Jakob disease (CJD) with visual evoked response (VER) and CSF oligoclonal band abnormalities and discuss the neurobiological significance and diagnostic value of these findings.

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Sommario Il significato neurobiologico e il valore per la diagnosi differenziale delle alterazioni dei PEV e della presenza di bande oligoclonali nel CSF nella CJD viene discusso in un caso.

     

Cerebrospinal fluid IgG profiles and oligoclonal bands in Chinese patients with multiple sclerosis

OBJECTIVES: To investigate the significance of oligoclonal bands (OCBs) and intrathecal IgG fractions (IgGIF) for the diagnosis of multiple sclerosis (MS) in northern China. MATERIALS AND METHODS: OCBs in cerebrospinal fluid from 30 patients with MS, 34 with other inflammatory neurological diseases (IND) and 22 with non-inflammatory neurological diseases (NIND) were detected using isoelectric focusing. IgGIF was calculated based on corresponding formula. RESULTS: There was no significant difference in the frequencies of positive OCBs and elevated IgGIF between the MS group and the IND group. Compared with NIND, the MS and IND groups had a significantly higher incidence of OCBs and elevated IgGIF. The sensitivity, specificity and positive result likelihood ratio of OCBs for the diagnosis of MS were 63.3%, 74.2% and 2.5 respectively; those of IgGIF were 36.7%, 84.5% and 2.4. CONCLUSIONS: The two parameters, OCBs and IgGIF are of less diagnostic value for MS in China.     

The prevalence of oligoclonal bands in the CSF of patients with primary neurodegenerative dementia

Abstract.Background: Recent guidelines from the United States and Europe on the diagnosis and management of dementia include advice that younger patients with dementia should undergo CSF examination, which frequently includes analysis for oligoclonal bands (OCB). The presence of CNS specific OCB has traditionally been considered suggestive of an inflammatory aetiology, although the interpretation of such a finding in the presence of a normal CSF white cell count and protein is more difficult.Methods: We reviewed retrospectively the prevalence of OCB, determined using agarose isoelectric focusing, in a series of 131 well characterised patients with a final diagnosis of a degenerative dementia who had undergone CSF examination.Results: The mean age of the patients was 60.0 (SD 8.4) years. Seventy (53%) patients had Alzheimers disease (AD), forty seven (36 %) had frontotemporal lobar degeneration (FTLD), seven (5%) had Dementia with Lewy bodies and the remaining seven (5%) patients had other rarer neurodegenerative dementias. Neuropathological examination had been performed in fifteen (11%) patients. CNS specific OCB were present in nine (7%) patients in this cohort, all of whom had normal CSF white cell counts: four AD patients (a prevalence of 6%), four FTLD patients (a prevalence of 9%), and one patient with Creutzfeldt-Jakob disease (a prevalence of 25%). Investigation of these patients, including two with neuropathologically verified AD and one with post-mortem confirmed CJD, did not reveal an alternative aetiology for their dementia.Conclusion: A central immune response can occur in primary neurodegenerative dementias, albeit uncommonly.