Daniel Tibussek

Anti–Myelin Oligodendrocyte Glycoprotein Antibodies in Pediatric Patients With Optic Neuritis

OBJECTIVE To study the humoral immune response directed at myelin oligodendrocyte glycoprotein (MOG)in pediatric patients with isolated and recurrent optic neuritis(ON). DESIGN Observational prospective case series. SETTING Six pediatric hospitals in Germany and Austria. PATIENTS Thirty-seven patients 18 years or younger with single or recurrent episodes of ON were recruited from 6 different hospitals. MAIN OUTCOME MEASURES Clinical features, magnetic resonance imaging findings, intrathecal IgG synthesis,and outcome were recorded. A live cell–based immunofluorescence assay was used to measure serum IgG antibodies to MOG and aquaporin 4. RESULTS A single episode of ON was observed in 10 patients,and 15 experienced 2 to 12 episodes. The acute episode of ON was part of a clinically isolated syndrome in 12 patients, of whom 8 were subsequently classified as having multiple sclerosis. High-titer serum MOG-IgG antibodies (1:160) were detected in 17 patients (46%).In addition, high titers of MOG-IgG antibodies were more frequently observed in 12 of the 15 patients with recurrent episodes of ON (80%; median titer, 1:640)compared with 2 of the 10 patients with monophasic ON(20%; median titer, 0) and 3 of the 12 patients with ON as part of a clinically isolated syndrome (25%; median titer, 0). CONCLUSION High-titer MOG-IgG antibodies are predominantly detected in pediatric patients with recurrent ON, indicating that anti-MOG-specific antibodies may exert a direct role in the pathogenesis of ON in this subgroup.

Rituximab as a highly effective treatment in a female adolescent with severe multiple sclerosis

Michael Karenfort MD, Bernd C Kieseier MD, Daniel Tibussek MD, Birgit Assmann MD, Joerg Schaper MD, Ertan Mayatepek MD 1 Department of General Pediatrics, Heinrich-Heine-University, D sseldorf, Germany. 2 Department of Neurology, Heinrich-Heine-University, D sseldorf, Germany. 3 Department of Diagnostic Radiology, Heinrich-Heine-University, D sseldorf, Germany. Correspondence to: michael.karenfort@med.uni-duesseldorf.de

Gadolinium Brain Deposition after Macrocyclic Gadolinium Administration: A Pediatric Case-Control Study

Purpose To determine whether signal intensity (SI) in T1 sequences as a potential indicator of gadolinium deposition increases after repeated administration of the macrocyclic gadolinium-based contrast agents (GBCAs) gadoteridol and gadoterate meglumine in a pediatric cohort. Materials and Methods This retrospective case-control study of children with brain tumors who underwent nine or more contrast material-enhanced brain magnetic resonance (MR) imaging studies from 2008 to 2015 was approved by the local ethics board. Informed consent was obtained for MR imaging. Twenty-four case patients aged 5-18 years and appropriate control patients with nonpathologic MR neuroimaging findings (and no GBCA administration), matched for age and sex, were inculded. SI was measured on unenhanced T1-weighted MR images for the following five regions of interest (ROIs): the dentate nucleus (DN), pons, substantia nigra (SN), pulvinar thalami, and globus pallidus (GP). Paired t tests were used to compare SI and SI ratios (DN to pons, GP to thalamus) between case patients and control patients. Pearson correlations between relative signal changes and the number of GBCA administrations and total GBCA dose were calculated. Results The mean number of GBCA administrations was 14.2. No significant differences in mean SI for any ROI and no group differences were found when DN-to-pons and GP-to-pulvinar ratios were compared (DN-to-pons ratio in case patients: mean, 1.0083 ± 0.0373 [standard deviation]; DN-to-pons ratio in control patients: mean, 1.0183 ± 0.01917; P = .37; GP-to-pulvinar ratio in case patients: mean, 1.1335 ± 0.04528; and GP-to-pulvinar ratio in control patients: mean, 1.1141 ± 0.07058; P = .29). No correlation was found between the number of GBCA administrations or the total amount of GBCA administered and signal change for any ROI. (Number of GBCA applications: DN: r = -0.254, P = .31; pons: r = -0.097, P = .65; SN: r = -0.194, P = .38; GP: r = -0.175, P = .41; pulvinar: r = -0.067, P = .75; total amount of administered GBCA: DN: r = 0.091, P = .72; pons: r = 0.106, P = .62; SN: r = -0.165, P = .45; GP: r = 0.111, P = .61; pulvinar: r = 0.173, P = .42.) Conclusion Multiple intravenous administrations of these macrocyclic GBCAs in children were not associated with a measurable increase in SI in T1 sequences as an indicator of brain gadolinium deposition detectable by using MR imaging. Additional imaging and pathologic studies are needed to confirm these findings.

Seasonal Variation and Atypical Presentation of Idiopathic Intracranial Hypertension in Pre-Pubertal Children

Idiopathic intracranial hypertension is an enigmatic disorder of elevated cerebrospinal fluid pressure. In adulthood, patients are typically obese women of childbearing age; however, in young children the clinical picture is strikingly different, indicating age-related differences in the aetiology of idiopathic intracranial hypertension. To investigate this phenomenon, we analysed the clinical details of 15 pre-pubertal children with the diagnosis of idiopathic intracranial hypertension. Evaluating the date of initial presentation, we discovered a distinct seasonal variation. Ten patients presented between November and March, thus coinciding with the typical season of paediatric viral and bacterial infections in Germany. Therefore, we suggest an association between intracranial hypertension and possibly concurrent infections in these children. Moreover, eight children presented only with ophthalmologic findings without any other obvious symptoms, raising questions regarding the incidence of undetected cases, particularly in this age group.

Severe Cerebral Vasospasm and Childhood Arterial Ischemic Stroke After Intrathecal Cytarabine

We report on 2 patients who developed widespread cerebral vasospasm and arterial ischemic strokes (AIS) after application of intrathecal (IT) cytarabine. In a 3-year-old child with acute lymphoblastic leukemia (ALL), left leg weakness, hyperreflexia, and clonus were noted 4 days after her first dose of IT cytarabine during the induction phase of her chemotherapy. Cerebral MRI revealed multiple acute cerebral ischemic infarcts and widespread cerebral vasospasm. A 5-year-old girl complained of right arm and leg pain and began limping 11 days after IT cytarabine. Symptoms progressed to right dense hemiplegia, left gaze deviation, headache, and speech arrest. MRI revealed 2 large cortical areas of diffusion restriction in the right frontal and left parietal lobes. Cerebral magnetic resonance angiography (MRA) showed irregular narrowing affecting much of the intracranial arterial circulation. Although the first child fully recovered from her neurologic symptoms, the second patient had persistent hemiplegia on follow-up. Including this report, there are now 4 pediatric ALL cases of severe cerebral vasospasm and AIS in the context of IT cytarabine administration, strongly suggesting a true association. Differential diagnosis and management issues are discussed. Along with the more widespread use of MRI and MRA, the true frequency of this severe adverse effect will become clearer in future. For any child with neurologic symptoms within hours or days of receiving IT cytarabine, a low threshold for cerebral imaging with MRI and MRA is recommended.

Baby-walkers: an avoidable source of hazard

Correspondence to: Daniel Tibussek, Department of General Pediatrics, University Childrens Hospital, Heinrich Heine University, Moorenstraβe 5, D-40225 Dusseldorf, Germany

Treatment of Infantile Spasms: Report of the Interdisciplinary Guideline Committee Coordinated by the German-Speaking Society for Neuropediatrics.

Objectives This report aims to define treatment goals, to summarize the evidence level (EL) of different treatment options for infantile spasms (IS), both in terms of efficacy and adverse effect, and to give recommendations for the management of IS. Methods The Cochrane and Medline (1966-July 2014) databases were searched. Literature known to the guideline working group and identified through citations was also considered. The results of previously published guidelines were taken into account in our analysis. Rating the level of evidence followed the Scottish Intercollegiate Guidelines Network. Recommendations If IS are suspected, electroencephalogram (EEG) should be performed within a few days and, if confirmed, treatment should be initiated immediately. Response to first-line treatments should be evaluated clinically and electroencephalographically after 14 days.Adrenocorticotropic hormone, corticosteroids, and vigabatrin are the first-line drugs for the treatment of IS. In children with tuberous sclerosis complex, vigabatrin is the treatment of first choice. Ketogenic diet, sulthiame, topiramate, valproate, zonisamide, and benzodiazepines can be used when first-line drugs have proved ineffective. Children refractory to drug therapy should be evaluated for epilepsy surgery, especially if focal brain lesions are present.Regular follow-up controls, including EEG (preferably sleep EEG) and standardized developmental assessment are recommended.

Paraneoplastic limbic encephalitis with SOX1 and PCA2 antibodies and relapsing neurological symptoms in an adolescent with Hodgkin lymphoma

BACKGROUND Immune cross-reactivity between malignant and normal tissues causes the rare, so called paraneoplastic syndrome (PS). In approximately 60% of the patients, various onconeural antibodies are detectable in the cerebrospinal fluid (CSF) and are associated with typical tumour entities. METHODS We report an unusual case of paraneoplastic limbic encephalitis (PLE) in a 17-year-old adolescent with classical Hodgkin lymphoma. RESULTS He presented with a variety of neurologic and neuropsychiatric symptoms, profound B-symptoms and typical MRI findings including hyperintense lesions with contrast enhancement in the medial temporal lobe and limbic system. Under immunosuppressive therapy and subsequently chemotherapy the neurological situation only temporarily improved and worsened again after interruption of immunosuppression several times. Thus, multiple courses of multidrug immunosuppressive therapy were administered. To date, five years after initial presentation, the young man is able to walk with walking aids and orthoses and is still on oral prednisolone therapy. Analyses of the CSF and serum revealed anti SOX-1 antibodies at initial presentation but PCA-2 antibodies seven months after diagnosis. CONCLUSION Neurologic and/or neuropsychiatric symptoms combined with typical MRI findings should raise the suspicion of PS and lead to further diagnostics for an underlying tumour even in children.

Post stroke hemi-dystonia in children: a neglected area of research

BackgroundChildhood arterial ischemic stroke (CAIS) is increasingly recognized as an important cause of significant long-term morbidity in the pediatric population. Post stroke movement disorders, above all hemi-dystonias, are much more common in children after stroke compared to adults. However, research in this field is largely lacking. By highlighting some important knowledge gaps, we aim to encourage future collaborative research projects in this particular field.FindingsPost stroke-dystonia seems to be much more common among children than adults. However, no reliable epidemiological data of post-stroke movement disorders in childhood are available, and differentiation between spasticity and dystonia can be challenging. Pharmacotherapy for dystonia is limited by lack of effect, especially in the long-term treatment. The pathophysiology of dystonia is complex and incompletely understood. Recent findings from functional imaging studies suggest that dystonia does not result from a single lesion but rather network dysfunctions and abnormalities in functional connectivity. However, very few patients with post stroke dystonia have been studied, and it is not clear to what extent pathophysiology of primary and post stroke ischemia shares common characteristics on network level. In general, progress in understanding the nature of childhood dystonia lags far behind adult onset CNS diseases.ConclusionsDystonia after CAIS is a common yet insufficiently understood and poorly studied clinical challenge. Studies to improve our understanding of the underlying pathophysiology and consequently the development of instruments for early prediction as well as targeted treatment of dystonia should become a high priority in collaborative childhood stroke research.

PP04.10 – 2544: Trichothiodystrophy presenting with cardiomyopathy and recurrent arterial ischemic strokes

Objective Considerable differences exist between arterial ischemic stroke (AIS) in childhood and adults. Among others, a wider spectrum of rare etiologies has to be considered in children. Trichothiodystrophy (TTD) is a rare genetic syndrome characterized by typical hair texture, variable photosensitivity, xerosis cutis, short stature and psychomotor retardation. We report a child with TTD and recurrent AIS. Methods Case report. Results A 3-year-old boy presented with acute onset of left hemiparesis and facial nerve palsy. Brain magnetic resonance imaging (MRI) revealed an extensive acute ischemic infarction involving the right middle cerebral artery (MCA) territory with sparing of the basal ganglia. Intravenous thrombolysis with tPA within 3 hours after onset led to recanalisation and dramatic clinical improvement. Aspirin treatment was initiated for secondary stroke prevention. However, on day 7 a focal epileptic seizure occurred. MRI showed acute DWI/ADC positive lesions in the left MCA territory. Intravenous thrombolysis was administered again, however, without success. Two days later he suffered from reinfarction involving his right MCA and left posterior cerebral artery. There was no evidence of thrombophilia, dyslipidaemia, sickle cell disease, metabolic or autoimmune disease. His past medical history was relevant for developmental delay and dilated cardiomyopathy of unknown origin. A dilated left ventricle but no thrombi could be detected with echocardiography. Since birth he had been suffering from dry, scaly skin. A striking hair texture with brittle, short hair with patchy thinning and alopecic areas was found. Electron and polarization microscopy confirmed TTD. Conclusion This is the second documented case of AIS associated with TTD (Toelle et al., 2001). Uncommon hair structure in combination with cardiomyopathy and stroke should lead to investigations for TTD. Although AIS secondary to cardiac embolism has been suggested, the aggressive course in our patient led us to speculate that additional factors inherent in TTD might have contributed.