Opsoclonus–myoclonus–ataxia syndrome in children

Journal of Neurology - Opsoclonus–myoclonus–ataxia syndrome is a rare neuroimmunologic disorder typically presenting in previously healthy infants and toddlers. It is characterized by a...     

HIV-related opsoclonus–myoclonus–ataxia syndrome: Report on two cases

Opsoclonus–myoclonus–ataxia (OMA) syndrome is a rare neurological disorder, characterized by a rapid onset of generalized myoclonus in association with chaotic multi-directional eye movements and, less frequently, cerebellar ataxia. OMA is commonly related to a paraneoplastic process, specifically neuroblastoma in children and lung or breast cancer in adults. Nevertheless, OMA may occur in association with various infectious agents, such as Coxsackie virus B3, Epstein-Barr virus, mumps, enterovirus, and streptococcus. We recently encountered two cases of HIV-related OMA syndrome. The first patient developed a sudden onset of OMA at the time of HIV seroconversion. The second patient experienced severe ataxia with a mild degree of myoclonus and opsoclonus, associated with an elevated CD4 count following the initiation of highly active antiretroviral therapy (HAART). We suggest that OMA syndrome may be another rare manifestation of HIV infection at the time of seroconversion or during an immune restoration period.     

The opsoclonus–myoclonus syndrome

The opsoclonus–myoclonus syndrome is a rare and distinct neurological disorder characterised by rapid multidirectional conjugate eye movements (opsoclonus), myoclonus and ataxia, along with behavioural changes in adults and irritability in children. Sometimes it is due to a self-limiting presumed para-infectious brainstem encephalitis but it may also represent a non-metastatic manifestation of neuroblastoma in children and small cell carcinoma of the lung in adults. In this article, we will describe the clinical features, diagnosis, pathogenesis and management.     

Update on opsoclonus–myoclonus syndrome in adults

Journal of Neurology - Opsoclonus–myoclonus syndrome in adults is a rare and heterogeneous disorder with the clinical features of opsoclonus, myoclonus, ataxia, and behavioral and sleep...     

Opsoclonus—myoclonus—dysequilibrium syndrome: cytological and immunological dynamics in the serial cerebrospinal fluid in two patients

Abstract. A peculiar clinical presentation characterized by the triad of opsoclonus,myoclonus and ataxia, mainly in a form of dysequilibrium, is usually associated with infectious or paraneoplastic processes. Serial cerebrospinal fluid (CSF) analysis in two patients with opsoclonus-myoclonus-dysequilibrium syndrome suggestive of viral encephalitis were performed from disease onset for up to 8 months. A cell count, cytology, total protein and glucose concentrations in CSF, the blood-CSF barrier function, intrathecal synthesis of immunoglobulins (Ig) in class M, G and A expressed as IgM, IgG and IgA indices and oligoclonal IgG bands were monitored. Cellular and humoral alterations in both patients were slight at the onset becoming more pronounced a month later. The kinetics of the CSF changes mirrored the subacute clinical deterioration and subsequent recovery. The delayed response in the CSF measures and the gradual clinical deterioration suggest the development of subacute brain inflammation. A mononuclear pleocytosis, including macrophages and plasma cells, increased within the first month and then normalized during the following weeks. Intrathecally synthesized IgM occurred only transiently after one month of illness, whereas intrathecal IgG production increased during the first month and persisted for at least eight months. An increasing number of oligoclonal IgG bands during the course, indicative of expanding local intrathecal synthesis, was noted. The dynamics of these CSF changes supports the hypothesis that opsoclonus-myoclonus syndrome is a post-infectious immune- mediated condition.     

Large SGCE deletion contributes to Taiwanese myoclonus–dystonia syndrome

We report three novel deletions of the SGCE gene in three families with myoclonus–dystonia (M–D) syndrome in Taiwan. Their clinical characteristics included: early onset, dominant myoclonus and dystonia in the neck, trunk and upper limbs. By direct sequencing of the SGCE gene coding regions, we identified a small heterozygous deletion (c.842delA) in exon 7 of the three sibs and asymptomatic father in the first family and an eight-base heterozygous deletion (c.524_531del) in exon 5 of the mother and a daughter in the second family. Using multiple ligation-dependent probe amplification (MLPA), a large heterozygous deletion of 2–11 exons was identified in the father and a son in the third family which was undetected by initial sequencing. It is the largest intragenic deletion ever reported. In conclusion, we have identified three novel mutations of SGCE in the respective three M–D families. The large deletion was responsible for one third of these M–D families which might implicate an important contribution to Taiwanese M–D syndrome. We suggest that the contribution of large deletion should be further verified in a large cohort of patients with M–D syndrome in Han Chinese.     

Progressive gait ataxia and intention tremor in a case of Bing–Neel syndrome

Journal of Neurology -     

Progressive myoclonus ataxia: Time for a new definition?

Background: The clinical demarcation of the syndrome progressive myoclonus ataxia is unclear, leading to a lack of recognition and difficult differentiation from other neurological syndromes. Objectives: The objective of this study was to apply a refined definition of progressive myoclonus ataxia and describe the clinical characteristics in patients with progressive myoclonus ataxia and with isolated cortical myoclonus. Methods: A retro‐ and prospective analysis was performed in our tertiary referral center between 1994 and 2014. Inclusion criteria for progressive myoclonus ataxia patients were the presence of myoclonus and ataxia with or without infrequent (all types, treatment responsive) epileptic seizures. Inclusion criteria for isolated cortical myoclonus was the presence of isolated cortical myoclonus. Clinical and electrophysiological characteristics data were systematically scored. Results: A total of 14 progressive myoclonus ataxia patients (males, 7; females, 7), median age 14.5 years, and 8 isolated cortical myoclonus patients (males, 2; females, 6), median age 23.5 years, were identified. In 93% of the progressive myoclonus ataxia patients, ataxia started first (median 2 years) followed by myoclonus (4 years) and finally infrequent epilepsy (9.3 years), with a progressive course in 93%. In 64% of the progressive myoclonus ataxia patients, a genetic underlying etiology was identified, including 3 not earlier reported causative progressive myoclonus ataxia genes. In isolated cortical myoclonus patients, myoclonus started at (median) 12 years with progression over time in 63% and a single epileptic seizure in 1 patient. No genetic causes were identified. Conclusion: Using a refined definition, we could create a rather homogenous progressive myoclonus ataxia group. Patients with isolated cortical myoclonus have a different course and do not appear to evolve in progressive myoclonus ataxia. The refined progressive myoclonus ataxia definition is a successful first step toward creating a separate syndrome for both clinical practice and future genetic research. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.     

Opsoclonus�Cmyoclonus syndrome caused by varicella-zoster virus

Opsoclonus–myoclonus syndrome (OMS) is a rare condition that has been reported from all parts of the world. It is well recognized as a paraneoplastic syndrome in children with neuroblastoma and in adults with small-cell carcinoma of lung and some other cancers. It may also occur in association with various central nervous system infections. We report a case of OMS in a patient with varicella zoster virus infection. IgM antibody for varicella-zoster virus was detected in the serum and the cerebrospinal fluid. The patient improved after treatment with clonazepam and was asymptomatic at 1-month follow-up.     

Myoclonus and tremor response to thalamic deep brain stimulation parameters in a patient with inherited myoclonus–dystonia syndrome

We present a 74-year-old woman with inherited myoclonus–dystonia, with predominant myoclonus and a novel mutation in the ?-sarcoglycan gene. The patient reports a life-long history of rapid, jerking movements, most severe in the upper extremities as well as a postural and action tremor. Bilateral deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus was performed, and the patient demonstrated moderate clinical improvement in myoclonus. We studied the effects on myoclonus and tremor of varying DBS frequency and amplitude. The frequency tuning curve for myoclonus was similar to that of tremor, suggesting similar mechanisms by which DBS alleviates both disorders.     

Peripheral polyneuropathy in children and young adults with ataxia–telangiectasia

Background and purpose

Ataxia–telangiectasia (A-T) is a rare, autosomal recessive, multisystem disorder that leads to progressive neurodegeneration with cerebellar ataxia and peripheral polyneuropathy. Cerebellar neurodegeneration is well described in A-T. However, peripheral nervous system involvement is an underdiagnosed but important additional target for supportive and systemic therapies. The aim of this study was to conduct neurophysiological measurements to assess peripheral neurodegeneration and the development of age-dependent neuropathy in A-T.

Methods

In this prospective study, 42 classical A-T patients were assessed. The motor and sensory nerve conduction of the median and tibial nerves was evaluated. Data were compared to published standard values and a healthy age- and gender-matched control group of 23 participants. Ataxia scores (Klockgether, Scale for the Assessment and Rating of Ataxia) were also assessed.

Results

In A-T, neurophysiological assessment revealed neuropathic changes as early as the first year of life. Subjective symptomatology of neuropathy is rarely described. In the upper extremities, motor neuropathy was predominantly that of a demyelinating type and sensory neuropathy was predominantly that of a mixed type. In the lower extremities, motor and sensory neuropathy was predominantly that of a mixed type. We found significant correlations between age and the development of motor and sensory polyneuropathy in A-T compared with healthy controls (p < 0.001).

Conclusions

In A-T, polyneuropathy occurs mostly subclinically as early as the first year of life. The current study of a large national A-T cohort demonstrates that development of neuropathy in A-T differs in the upper and lower extremities.     

Polycranial neuropathy and sensory ataxia with IgG anti-GD1a antibody as a variant of Guillain–Barré syndrome

Immunoglobulin G (IgG) anti-GD1a ganglioside antibody is an important marker of Guillain–Barré syndrome (GBS). This antibody is highly associated with disease severity, the need for mechanical ventilation, and axonal degeneration of peripheral nerves. We report a 46-year-old female patient manifesting the IgG anti-GD1a antibody with polycranial neuropathy and sensory ataxia as a variant of GBS. She presented with slurred speech, swallowing difficulties, and gait disturbance following diarrhea. Decreased sensations of vibration and position were found in her distal limbs and she had an ataxic gait with a positive Romberg sign. Her serum was positive for IgG anti-GD1a ganglioside antibody (1:640). Her neurological examination at the third month after intravenous Ig treatment showed complete recovery.