Evangeline Wassmer

Neurology, Pediatrics

37.94

Publications

  • European Journal of Paediatric Neurology 05/2015; 19:S61. DOI:10.1016/S1090-3798(15)30200-2 · 1.93 Impact Factor
  • European Journal of Paediatric Neurology 05/2015; 19:S80. DOI:10.1016/S1090-3798(15)30266-X · 1.93 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pediatric movement disorders are still a diagnostic challenge, as many patients remain without a (genetic) diagnosis. Magnetic resonance imaging (MRI) pattern recognition can lead to the diagnosis. MEGDEL syndrome (3-MethylGlutaconic aciduria, Deafness, Encephalopathy, Leigh-like syndrome MIM #614739) is a clinically and biochemically highly distinctive dystonia deafness syndrome accompanied by 3-methylglutaconic aciduria, severe developmental delay, and progressive spasticity. Mutations are found in SERAC1, encoding a phosphatidylglycerol remodeling enzyme essential for both mitochondrial function and intracellular cholesterol trafficking. Based on the homogenous phenotype, we hypothesized an accordingly characteristic MRI pattern. A total of 43 complete MRI studies of 30 patients were systematically reevaluated. All patients presented a distinctive brain MRI pattern with five characteristic disease stages affecting the basal ganglia, especially the putamen. In stage 1, T2 signal changes of the pallidum are present. In stage 2, swelling of the putamen and caudate nucleus is seen. The dorsal putamen contains an "eye" that shows no signal alteration and (thus) seems to be spared during this stage of the disease. It later increases, reflecting progressive putaminal involvement. This "eye" was found in all patients with MEGDEL syndrome during a specific age range, and has not been reported in other disorders, making it pathognomonic for MEDGEL and allowing diagnosis based on MRI findings. Georg Thieme Verlag KG Stuttgart · New York.
    Neuropediatrics 02/2015; 46(02). DOI:10.1055/s-0034-1399755 · 1.10 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: N-methyl-D-aspartate receptor antibody (NMDAR-Ab) encephalitis is a well-recognised clinico-immunological syndrome that presents with neuropsychiatric symptoms cognitive decline, movement disorder and seizures. This study reports the clinical features, management and neurological outcomes of paediatric NMDAR-Ab-mediated neurological disease in the UK. A prospective surveillance study. Children with NMDAR-Ab-mediated neurological diseases were voluntarily reported to the British Neurological Surveillance Unit (BPNSU) from November 2010 to December 2011. Initial and follow-up questionnaires were sent out to physicians. Thirty-one children fulfilled the criteria for the study. Eight presented during the study period giving an incidence of 0.85 per million children per year (95% CI 0.64 to 1.06); 23 cases were historical. Behavioural change and neuropsychiatric features were present in 90% of patients, and seizures and movement disorders both in 67%. Typical NMDAR-Ab encephalitis was reported in 24 children and partial phenotype without encephalopathy in seven, including predominantly psychiatric (four) and movement disorder (three). All patients received steroids, 22 (71%) received intravenous immunoglobulin, 9 (29%) received plasma exchange,and 10 (32%) received second-line immunotherapy. Of the 23 patients who were diagnosed early, 18 (78%) made a full recovery compared with only 1 of 8 (13%) of the late diagnosed patients (p=0.002, Fisher's exact test). Seven patients relapsed, with four needing additional second-line immunotherapy. Paediatric NMDAR-Ab-mediated neurological disease appears to be similar to adult NMDAR-Ab encephalitis, but some presented with a partial phenotype. Early treatment was associated with a quick and often full recovery. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Archives of Disease in Childhood 01/2015; 100(6). DOI:10.1136/archdischild-2014-306795 · 2.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To determine whether myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) were predictive of a demyelination phenotype in children presenting with acquired demyelinating syndrome (ADS). Sixty-five children with a first episode of ADS (12 acute disseminated encephalomyelitis, 24 optic neuritis, 18 transverse myelitis, 11 other clinically isolated syndrome) were identified from 2 national demyelination programs in the United Kingdom and France. Acute serum samples were tested for MOG-Abs by cell-based assay. Antibodies were used to predict diagnosis of multiple sclerosis (MS) at 1 year. Twenty-three of 65 (35%) children had MOG-Abs. Antibody-positive and antibody-negative patients were not clinically different at presentation, but identification of MOG-Abs predicted a non-MS course at 1-year follow-up: only 2/23 (9%) MOG-Ab-positive patients were diagnosed with MS compared to 16/42 (38%) MOG-Ab-negative patients (p = 0.019, Fisher exact test). Antibody positivity at outset was a useful predictor for a non-MS disease course, with a positive predictive value of 91% (95% confidence interval [CI] 72-99), negative predictive value of 38% (95% CI 24-54), positive likelihood ratio of 4.02 (CI 1.0-15.4), and odds ratio of 6.5 (CI 1.3-31.3). MOG-Abs are found at presentation in 35% of patients with childhood ADS, across a range of demyelinating disorders. Antibody positivity can be useful in predicting a non-MS disease course at onset.
    01/2015; 2(2):e81-e81. DOI:10.1212/NXI.0000000000000081
  • [Show abstract] [Hide abstract]
    ABSTRACT: To identify early prognostic factors of relapse and disability in children presenting with an acute idiopathic transverse myelitis (TM). Ninety-five children with acute idiopathic TM from 2 national European cohorts (France and United Kingdom) of CNS demyelinating diseases in children were identified and studied for early factors that predict relapse and disability using logistic regression models. Sixteen (17%) relapsed, with a diagnosis of multiple sclerosis in 13 (14%) and neuromyelitis optica in 3 (3%). Logistic regression revealed 2 main criteria as risk factors for relapse: female sex (odds ratio [OR] 3.21, 95% confidence interval [CI] 0.88-11.78) and presence of associated brain lesions (OR 14.0, 95% CI 2.8-69.3). Twenty-eight (30%) children had a poor outcome defined by a Kurtzke Expanded Disability Status Scale score ≥4 or an American Spinal Injury Association impairment (ASIA) scale <D at last follow-up. Five factors were associated with poor outcome: female sex (OR 5.8, 95% CI 0.99-32.7), severe ASIA scale at onset (OR 33.5, 95% CI 1.8-618), gadolinium enhancement on spinal MRI (OR 24.1, 95% CI 3.78-153.88), absence of pleocytosis (OR 4.6, 95% CI 0.87-26.0), and absence of cervical or cervico-thoracic lesion on spinal MRI (OR 3.9, 95% CI 0.78-19.6). Early predictors of relapse and disability identified in this large childhood study of acute idiopathic TM have important utility for clinical management. Larger prospective collaborative studies are required to validate these findings, which may improve the design of clinical trials. © 2014 American Academy of Neurology.
    Neurology 12/2014; 84(4). DOI:10.1212/WNL.0000000000001179 · 8.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Acute necrotising encephalopathy (ANE) is a rapidly progressive encephalopathy associated with acute viral illness. A missense mutation in nuclear pore gene RANBP2 has been identified as a major cause of familial and recurrent ANE, which is now termed as ANE1. First presentation of ANE can mimic an acute disseminated encephalomyelitis (ADEM), although ANE presents in a slightly younger age group. Identification of this disorder at radiological study is the most important determinant of the outcome. ANE1 is inherited as autosomal dominant, but shows incomplete penetrance. We report two female children who presented with atypical clinical presentation (afebrile) and atypical radiological presentation (lack of bilateral thalamic involvement), not fitting into the original diagnostic criteria for ANE1. Both received steroid therapy for a presumed diagnosis of ADEM and made good clinical recovery. We also reviewed the available literature on ANE1, including the clinical profile, MRI brain descriptions, CSF characteristics and common mutations. A total of 59 patients are reported in patients with ANE1 were identified, the incidence of ANE was higher in younger age group (<4 yrs) as compared to ADEM 5.3 yrs (3.6-7). Male and female were equally affected. High CSF protein (>0.45 g/l) was reported in 44/47 (94%) in absence CSF pleocytosis (Cells > 5 × 10(6)/L). Neuroimaging findings showed multifocal involvement across different studies, and bilateral thalamic involvement was seen in 77% of patients. Based on the literature review of ANE1 with RANBP2 mutation, we propose a threshold for RANBP2 mutation testing. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
    European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 12/2014; 19(2). DOI:10.1016/j.ejpn.2014.11.010 · 1.93 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Stroke is a major cause of mortality in children. Conditions that mimic stroke also cause severe morbidity and require prompt diagnosis and treatment. We have investigated the time to diagnosis in a cohort of children with stroke.
    Journal of Neurology Neurosurgery & Psychiatry 10/2014; DOI:10.1136/jnnp-2014-309188 · 5.58 Impact Factor
  • Michael Eyre, Michael Absoud, Evangeline Wassmer
    [Show abstract] [Hide abstract]
    ABSTRACT: CNS inflammatory demyelinating diseases (CIDD) are rare. At first presentation children are diagnosed with acute disseminated encephalomyelitis (ADEM) or a clinically isolated syndrome (CIS) such as transverse myelitis (TM) or optic neuritis (ON). Many of these disorders are monophasic, however a small number of children relapse and are diagnosed with multiple sclerosis (MS) or neuromyelitis optica (NMO). Paediatric onset Multiple Sclerosis (POMS) is a chronic inflammatory neurodegenerative demyelinating disease of the CNS that is usually relapsing-remitting at onset. There has been significant recent interest and progress in these disorders. Encephalopathy (behavioural change or altered consciousness) distinguishes ADEM from other demyelinating conditions. A high index of suspicion for CIDD is required in children presenting with neurological deficits, encephalopathy or status epilepticus. Several UK and international studies are underway to further our understanding of these diseases. There has been significant development of new treatments for MS and NMO. A national service for these rare disorders will enable better management of these well deserving patients. In this review we describe current understanding of the epidemiology, pathogenesis, clinical features, outcome and management of childhood CIDD.
    Paediatrics and Child Health 10/2014; DOI:10.1016/j.paed.2014.04.011
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A reduction of ADA2 activity due to autosomal recessive loss of function mutations in CECR1 results in a newly described vasculopathic phenotype reminiscent of polyarteritis nodosa, with manifestations ranging from fatal systemic vasculitis with multiple strokes in children to limited cutaneous disease in middle-aged individuals. Evidence indicates that ADA2 is essential for the endothelial integrity of small vessels. However, CECR1 is not expressed, nor is the ADA2 protein detectable, in cultured human endothelial cells, thus implicating additional cell types or circulating factors in disease pathogenesis.
    Pediatric Rheumatology 09/2014; 12(1):44. DOI:10.1186/1546-0096-12-44 · 1.62 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Neuromyelitis Optica (NMO) is a severe and rare inflammatory condition, where relapses are predictive of disability.
    Journal of Neurology Neurosurgery & Psychiatry 08/2014; 86(4). DOI:10.1136/jnnp-2014-308550 · 5.58 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Objective: To assess the utility and safety of rituximab in paediatric autoimmune and inflammatory disorders of the CNS. Methods: Multicentre retrospective study. Results: 144 children and adolescents (median age 8 years, range 0.7-17; 103 females) with NMDAR encephalitis (n=39), opsoclonus myoclonus ataxia syndrome (n=32), neuromyelitis optica spectrum disorders (n=20), neuropsychiatric systemic lupus erythematosus (n=18), and other neuro-inflammatory disorders (n=35) were studied at onset of neurological disease. Rituximab was given after a median duration of disease of 0.5 years (range 0.05-9.5 years). Infusion adverse events were recorded in 18/144 (12.5%) including Grade 4 (anaphylaxis) in three. 11 patients (7.6%) had an infectious adverse event (AE), including two with Grade 5 (death) and two with Grade 4 (disabling) infectious AE (median follow-up of 1.65 years (range 0.1-8.5). No patients developed progressive multifocal leukoencephalopathy. A definite, probable or possible benefit was reported in 125 of 144 (87%) patients. 17.4% of patients had a modified Rankin scale (mRS) of 0-2 at rituximab initiation, compared to 73.9% at outcome. The change in mRS 0-2 was greater in patients given rituximab early in their disease course compared to those treated later. Conclusion: While limited by the retrospective nature of this analysis, our data supports an off-label use of rituximab, although the significant risk of infectious complications suggests rituximab should be restricted to disorders with significant morbidity and mortality. Classification of Evidence: This study provides Class IV evidence that in paediatric autoimmune and inflammatory CNS disorders, rituximab improves neurologic outcomes with a 7.6% risk of adverse infections.
    Neurology 07/2014; 83(2). DOI:10.1212/WNL.0000000000000570 · 8.30 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To report the clinical and radiologic findings of children with NMDA receptor (NMDAR) antibodies and white matter disorders.
    06/2014; 1(1):e2. DOI:10.1212/NXI.0000000000000002
  • S. Jain, T. Willis, E. Wassmer, S. Agrawal
    Archives of Disease in Childhood 04/2014; 99(Suppl 1):A136-A136. DOI:10.1136/archdischild-2014-306237.314 · 2.91 Impact Factor
  • Archives of Disease in Childhood 04/2014; 99(Suppl 1):A5-A5. DOI:10.1136/archdischild-2014-306237.11 · 2.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Mitochondrial neurological disorders are known for their variable clinical presentation and diagnostic complexity. Despite an extensive battery of tests, the diagnosis may still remain unclear. We report our experience in the use of biochemical and molecular genetic testing, in the diagnostic algorithm of mitochondrial neurological disease in children. Aim: To evaluate the clinical, radiological, biochemical and molecular genetic features of cohort of children at a single centre with suspected mitochondrial neurological diseaseMethodology: We retrospectively reviewed the data of children with suspected mitochondrial neurological disorder over a 6 years period from April 2007 to 2013. Information on clinical, neuroimaging, biochemical parameters and molecular genetic diagnosis was recorded. Results: In our cohort of 105 children with suspected mitochondrial neurological disease 54 (51%) had multi organ involvement. Elevatedplasma lactate (>2.5 mmol/L) was found in 47(44%) and elevated CSF lactate in 21/41(51%). Neuroimaging revealed abnormalities of the white matter in 34/103 (32%), white matter and basal ganglia in 13 (12%). Isolated Basal ganglia abnormalities were noted in 11(10%) and atrophy in 14 (13%). Biochemical and molecular genetic confirmation was obtained in 44/105 (42%). 71 children had muscle and skin biopsy. Abnormal histopathology was noted in 13/71 (18%), enzyme abnormalities (respiratory chain complexes and pyruvate dehydrogenase) in 29/71 (40%). Fifteen of these 29 did not have a genetic diagnosis. In the whole cohort 29 children had a genetic diagnosis (23 nuclear ,6 mitochondrial DNA mutation) with predominantly white matter abnormalities in this subgroup (17/29). Conclusion- Grey Matter abnormalities have been traditionally considered to be features of mitochondrial disorders. It is interesting to note predominantly white matter abnormalities in our cohort (44%).The low diagnostic yield of biochemical and histological testing in our cohort may justify the use of exome sequencing as an early step to unravel the diagnostic maze of mitochondrial disorders.
    Developmental medicine and child neurology. Supplement 01/2014; 56(s1):4. DOI:10.1111/dmcn.12350_1
  • Developmental medicine and child neurology. Supplement 01/2014; 56(s1):7. DOI:10.1111/dmcn.12350_4
  • [Show abstract] [Hide abstract]
    ABSTRACT: Arterial ischaemic stroke is an important cause of acquired brain injury in children. Few prospective population-based studies of childhood arterial ischaemic stroke have been undertaken. We aimed to investigate the epidemiology and clinical features of childhood arterial ischaemic stroke in a population-based cohort. Children aged 29 days to less than 16 years with radiologically confirmed arterial ischaemic stroke occurring over a 1-year period (July 1, 2008, to June 30, 2009) residing in southern England (population denominator 5·99 million children) were eligible for inclusion. Cases were identified using several sources (paediatric neurologists and trainees, the British Paediatric Neurology Surveillance Unit, paediatricians, radiologists, physiotherapists, neurosurgeons, parents, and the Paediatric Intensive Care Audit Network). Cases were confirmed by personal examination of cases and case notes. Details of presenting features, risk factors, and investigations for risk factors were recorded by analysis of case notes. Capture-recapture analysis was used to estimate completeness of ascertainment. We identified 96 cases of arterial ischaemic stroke. The crude incidence of childhood arterial ischaemic stroke was 1·60 per 100 000 per year (95% CI 1·30-1·96). Capture-recapture analysis suggested that case ascertainment was 89% (95% CI 77-97) complete. The incidence of arterial ischaemic stroke was highest in children aged under 1 year (4·14 per 100 000 per year, 95% CI 2·36-6·72). There was no difference in the risk of arterial ischaemic stroke between sexes (crude incidence 1·60 per 100 000 per year [95% CI 1·18-2·12] for boys and 1·61 per 100 000 per year [1·18-2·14] for girls). Asian (relative risk 2·14, 95% CI 1·11-3·85; p=0·017) and black (2·28, 1·00-4·60; p=0·034) children were at higher risk of arterial ischaemic stroke than were white children. 82 (85%) children had focal features (most commonly hemiparesis) at presentation. Seizures were more common in younger children (≤1 year) and headache was more common in older children (>5 years; p<0·0001). At least one risk factor for childhood arterial ischaemic stroke was identified in 80 (83%) cases. Age and racial group, but not sex, affected the risk of arterial ischaemic stroke in children. Investigation of such differences might provide causative insights. The Stroke Association, UK.
    The Lancet Neurology 11/2013; 13(1). DOI:10.1016/S1474-4422(13)70290-4 · 21.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Autoantibodies to glial, myelin and neuronal antigens have been reported in a range of central demyelination syndromes and autoimmune encephalopathies in children, but there has not been a systematic evaluation across the range of central nervous system (CNS) autoantibodies in childhood-acquired demyelinating syndromes (ADS). Children under the age of 16 years with first-episode ADS were identified from a national prospective surveillance study; serum from 65 patients had been sent for a variety of diagnostic tests. Antibodies to astrocyte, myelin and neuronal antigens were tested or retested in all samples. Fifteen patients (23%) were positive for at least one antibody (Ab): AQ4-Ab was detected in three; two presenting with neuromyelitis optica (NMO) and one with isolated optic neuritis (ON). Myelin oligodendrocyte glycoprotein (MOG)-Ab was detected in seven; two with acute disseminated encephalomyelitis (ADEM), two with ON, one with transverse myelitis (TM) and two with clinically isolated syndrome (CIS). N-Methyl-D-Aspartate receptor (NMDAR)-Ab was found in two; one presenting with ADEM and one with ON. Voltage-gated potassium channel (VGKC)-complex antibodies were positive in three; one presenting with ADEM, one with ON and one with CIS. GlyR-Ab was detected in one patient with TM. All patients were negative for the VGKC-complex-associated proteins LGI1, CASPR2 and contactin-2. A range of CNS-directed autoantibodies were found in association with childhood ADS. Although these antibodies are clinically relevant when associated with the specific neurological syndromes that have been described, further studies are required to evaluate their roles and clinical relevance in demyelinating diseases.
    Journal of neurology, neurosurgery, and psychiatry 10/2013; 85(4). DOI:10.1136/jnnp-2013-306411 · 5.58 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recently, we reported a previously unrecognized symptom constellation comprising epilepsy, ataxia, sensorineural deafness, and tubulopathy (EAST syndrome) associated with recessive mutations in the KCNJ10 gene. Here, we provide a detailed characterization of the clinical features of the syndrome to aid patient management with respect to diagnosis, prognostic counselling, and identification of best treatment modalities. We conducted a retrospective review of the detailed neurological and neuroradiological features of nine children (four females, five males; age range at last examination 6-20y) with genetically proven EAST syndrome. All children presented with tonic-clonic seizures in infancy. Later, non-progressive, cerebellar ataxia and hearing loss were noted. Whilst seizures mostly responded well to treatment, ataxia proved to be the most debilitating feature, with three patients non-ambulant. All available magnetic resonance imaging (MRI) revealed subtle symmetrical signal changes in the cerebellar dentate nuclei. Moreover, four patients had a small corpus callosum and brainstem hypoplasia, and three had a small spinal cord. Regional quantitative volumetric analysis of the images confirmed the corpus callosum and brainstem hypoplasia and showed further patterns of variation from the norm. The neurological features of EAST syndrome appear to be non-progressive, which is important for prognostic counselling. The spectrum of EAST syndrome includes consistent abnormalities on brain MRI, which may aid diagnosis. Further longitudinal documentation is required to determine the true natural history of the disorder.
    Developmental Medicine & Child Neurology 09/2013; 55(9):846-56. DOI:10.1111/dmcn.12171 · 3.29 Impact Factor

47 Following View all

88 Followers View all