Transient symptomatic worsening by atropine in opsoclonus–myoclonus syndrome

Opsoclonus–myoclonus syndrome (OMS) is characterized by abnormal eye and systemic involuntary movements, as well as cerebellar ataxia. Some sedatives and anesthetics worsen movements associated with OMS, while there is no known report of a negative effect of atropine. We report on sedation in two patients with OMS. Involuntary movements were transiently worsened after using atropine with midazolam or thiamylal in both, but were not seen when atropine was not used. We speculated that atropine has the potential to exacerbate involuntary movements in OMS due to vulnerability to this agent via unknown mechanisms.     

Opsoclonus–myoclonus syndrome following rotavirus gastroenteritis

Opsoclonus–myoclonus syndrome (OMS) is a rare neurologic disorder characterized by opsoclonus, myoclonus, ataxia and behavioral disturbance. In the pathogenesis, an autoimmune process with infectious or paraneoplastic trigger has been suggested. We describe the case of a 22‐month‐old girl with OMS following rotavirus gastroenteritis. Rotavirus should be considered in the differential diagnosis of OMS in children.     

Multifactorial analysis of opsoclonus‐myoclonus syndrome etiology (“Tumor” vs. “No tumor”) in a cohort of 356 US children

1 Background

Pediatric opsoclonus‐myoclonus syndrome (OMS) presents a paradox of etiopathogenesis: A neuroblastic tumor (NB) is found in only one half of the cases, the others are ascribed to infections or designated as idiopathic.

2 Method

From an IRB‐approved observational study of 356 US children with OMS, secondary analysis of “etiology” and related factors was performed on a well‐characterized cohort. The “Tumor” (n = 173) and “No Tumor” groups (n = 183), as defined radiologically, were compared according to multiple factors considered potentially differentiating. Data were analyzed retrospectively using parametric and nonparametric tests as indicated.

3 Results

Patients with NB were not distinguishable by prodromal symptoms, OMS onset age, gender, race/ethnicity, OMS severity, rank order of neurological sign appearance, or geographic distribution. Various CSF immunologic biomarker abnormalities of OMS did not vary in the presence or absence of a detectable tumor: frequency of six lymphocyte subsets, or concentrations of 18 cytokines/chemokines, cytokine antagonists, chemokine receptors, cell adhesion molecules, or neuronal/glial markers. Prior responsiveness to conventional immunotherapy was not contingent on tumor/no tumor designation.

4 Conclusions

Multiple convergent factors provide compelling empirical evidence and rationalize the concept that OMS is one neurological disorder, regardless of apparent etiology. Limitations to the current clinical etiologic classifications as paraneoplastic, parainfectious/post‐infectious, and idiopathic etiology require antigen‐based biological solutions to tease out the molecular pathophysiology of viral/tumoral mechanisms. Systematic studies, regardless of presumed etiology, will be necessary to find the highest‐yield combination of imaging approaches, screening for infectious agents, and new biomarkers. Two testable hypotheses for future research are presented.     

WASP–WIP complex in the molecular pathogenesis of Wiskott–Aldrich syndrome

Wiskott–Aldrich syndrome (WAS) is an X‐linked primary immunodeficiency disease characterized by recurrent infection, thrombocytopenia, and eczema. The gene responsible for X‐linked WAS encodes the Wiskott–Aldrich syndrome protein (WASP), which is expressed in hematopoietic cells and which regulates T‐cell activation and cytoskeletal reorganization in T‐cell receptor (TCR) signaling. Here, I review my recent research on WASP and the WASP‐interacting protein (WIP) complex in T cells. I and my colleagues first established a diagnostic screening method using flow cytometry and genetic analysis, and elucidated the molecular pathogenesis in WAS patients with unique clinical manifestations. We investigated the mechanisms by which WASP is recruited to lipid rafts following TCR stimulation and to immunological synapses between antigen‐presenting cells and T cells. Subsequently, we elucidated the molecular mechanisms by which WASP is degraded by calpain and ubiquitinated by Cbl‐family proteins, which terminate WASP activation. More importantly, we found that WIP plays a critical role in WASP stability in T cells. These results provide new insights into the molecular pathogenesis of X‐linked WAS and have facilitated the identification of WIP deficiency as an autosomal recessive form of WAS.     

Paraneoplastic opsoclonus myoclonus syndrome associated with inflammatory myofibroblastic tumor in a pediatric patient

Opsoclonus myoclonus syndrome (OMS) is a rare neurological syndrome caused by a paraneoplastic autoimmune process that affects children with neuroblastic tumors. Treatment includes corticosteroids, intravenous gamma globulin (IVIG), rituximab, and other immunosuppressive therapies. Here, we describe a patient diagnosed with OMS associated with a localized inflammatory myofibroblastic tumor. The patient has no evidence of tumor recurrence following surgical resection with 8‐month follow‐up. The neurologic symptoms resolved with corticosteroids and IVIG. This case demonstrates that in children, neoplasms other than neuroblastoma may be associated with this paraneoplastic syndrome, and highlights the importance of evaluating patients with OMS for underlying malignancies.     

Acquired facial palsy with hypertension secondary to Guillain–Barre syndrome

Most cases of facial nerve paresis are idiopathic (Bell's palsy). However, rare and potentially dangerous conditions may present in this manner. We report 2 children presenting with unilateral lower motor neuron facial nerve palsy and hypertension. A diagnosis of Guillain‐Barre syndrome was made in both; literature linking facial nerve palsy in childhood with hypertension and Guillain‐Barre syndrome is reviewed.     

Gastric leiomyoma in a child with Gorlin–Goltz syndrome: First pediatric case

Gorlin–Goltz syndrome (GGS), also known as nevoid basal cell carcinoma syndrome (MIM 109 400), is a rare genetic condition with a prevalence between 1/56 000 and 1/256 000. Clinical presentation is usually characterized by multiple basal cell carcinomas, odontogenic jaw keratocysts, palmar or plantar pitting and skeletal anomalies. It is furthermore associated with the development of various tumors beside basal cell carcinoma, among which medulloblastoma is the most frequent. Increased incidence of other mesenchymal neoplasms, however, is also well known: recently the first adult case of gastric leiomyoma in GGS was reported, and the inclusion of “fibromas and leiomyomas of other organs” in the minor criteria for the diagnosis was suggested. We report the first case of a pediatric patient with GGS who also developed a gastric leiomyoma: the present case illustrates the need for this change to the diagnostic criteria to encompass the highly variable presentations and phenotype in GGS.     

Systemic and maxillofacial characteristics of 11 Japanese children with Russell–Silver syndrome

Russell–Silver syndrome (RSS) is a congenital anomaly characterized by intrauterine and postnatal growth retardation, typical facial features, fifth‐finger clinodactyly, and skeletal asymmetry. Although data on intrauterine and postnatal growth retardation have been reported, there are few reports concerning the typical maxillofacial morphology in individuals with RSS. The aim of this study was to describe the details of this systemic condition and to characterize maxillofacial morphology based on cephalograms in 11 Japanese patients (age range, 3.9–12.0 years) with RSS. All 11 individuals had intrauterine and postnatal growth retardation. In addition, most showed mandibular retrognathia and relative macrocephaly. Lateral cephalogram measurements showed that mandibular retrognathia resulted from short mandibular body length, whereas the depth of the cranial base was close to normal. Although asymmetry of hand, foot, and limb length were present in most individuals, obvious facial asymmetry was not common. Differences between left and right skeletal and dental age were not observed, indicating that children with RSS might show asymmetry because of quantitative differences in skeletal growth rather than delayed growth rate. Our findings not only provide important information about the maxillofacial characteristics of RSS, but also help to clarify the association between these characteristics and genetics, which will add to the body of information on clinical symptoms.     

Neonatal urethral polyps associated with Beckwith–Wiedemann syndrome

We report the first case of Beckwith–Wiedemann syndrome without urinary obstruction, but with a congenital urethral polyp as a tumor protruding from the external urinary meatus. The present case suggests a possible relation between Beckwith–Wiedemann and the onset of fibroepithelial polyps in the reno‐urinary system during the neonatal period.     

Living donor liver transplantation using a graft from a donor with Dubin–Johnson syndrome

Liu C, Niu D‐M, Hsia C‐Y, Loong C‐C, Lin N‐C, Tsai H‐L, Tsou M‐Y, Chin T. Living donor liver transplantation using a graft from a donor with Dubin–Johnson syndrome.
Pediatr Transplantation 2012: 16: E25–E29. © 2010 John Wiley & Sons A/S. Abstract: DJS is an autosomal recessive disorder that causes an increase in conjugated bilirubin without elevation of liver enzymes. Most patients are asymptomatic and have normal life spans, but to the best of our knowledge, their livers have never been reported to be grafts in liver transplantation. Herein, we report an infant patient with MMA that received a partial liver graft from his mother, who had DJS. A biliary anastomosis stricture was noted five months after transplantation and was successfully treated with radiological interventions. Otherwise, the patient’s liver functions were normal, and a liver biopsy showed a pathognomonic picture of DJS nine months after the transplantation. The patient was followed for one yr, and the results were satisfactory for an increase in oral intake and protein uptake, no recurrence of metabolic stroke and there was a gradual catch‐up with regard to physical development despite having a persistently abnormal profile of amino acid analysis. From the experience of our case, we suggest that a liver from a donor with DJS can be used as a graft for liver transplantation, although long‐term follow‐up is mandatory to examine the grafted liver under the use of immunosuppressive medications.