Background Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are identified in 30–50% of ch... more Background Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are identified in 30–50% of children with acquired demyelinating syndrome (ADS), and in relapsing syndromes such as AQP4-Ab negative neuromyelitis optica spectrum disorder (NMOSD). However, less is known about the wider spectrum and the clinical course of patients who relapse. Objective To evaluate the clinical features of children with MOG-Ab and relapsing disease. Methods Fifty three consecutive children with ADS and MOG-Ab positivity from five paediatric neurology referral centers were identified between 2011 and 2104. Clinical and neuroimaging features were reviewed and the treatment and outcomes evaluated. Results The initial presenting demyelination syndrome, clinical, radiological and investigative features could not distinguish the 13 patients that had a relapsing course from the other monophasic patients. Of the 13 relapsing patients (7 female, median 6.5 yrs; range 3–15 yrs) four presented with monophasic/recurring episodes of acute disseminated encephalomyelitis (ADEM) followed by monophasic/relapsing optic neuritis (ON); three fulfilled criteria for AQP4-Ab negative NMOSD; two had multiphasic ADEM; and four were diagnosed with relapsing remitting multiple sclerosis (RRMS). Intrathecal oligoclonal bands were only detected in 8% (1/12) tested. All 12 patients with abnormal brain MRI had brainstem and/or cerebellar lesion. Eight patients (non-MS) managed on long-term immunosuppression (n=2) and/or prompt acute treatment (n=8) made a complete clinical and radiological recovery at one year from last relapse. All patients with ON (n=8) had a complete visual recovery. Three out of four patients with RRMS are currently undergoing interferon therapy but continue to relapse. Conclusion 25% of MOG-Ab positive patients have a relapsing demyelination, often with a good clinical and radiological recovery. However, 30% (4/13) of this relapsing group may fulfill the diagnosis of MS, although may not have intrathecal bands and appear to have a poor response to MS treatment.
To identify early prognostic factors of relapse and disability in children presenting with an acu... more 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.
Objective: Acute disseminated encephalomyelitis (ADEM) is a treatable inflammatory demyelinating... more Objective: Acute disseminated encephalomyelitis (ADEM) is a treatable inflammatory demyelinating disorder seen more commonly in children than in adults. It typically presents to general paediatricians, often, like encephalitis, with non‐specific cerebrospinal fluid findings. The brain computerized tomography scan is usually normal, so is falsely reassuring and delays the diagnosis, which might result in considerable morbidity. The present study was initiated to report on the various modes of presentation and raise the awareness of the diagnosis of ADEM among general paediatricians.Methods: A retrospective review of the case notes of 18 children with a diagnosis of ADEM established in a tertiary referral centre from 1995 to 2000 was undertaken with particular reference to clinical features, investigations and treatment.Results: The most common presenting features were ataxia (10 cases), followed by headache (eight cases) and weakness (five cases). Magnetic resonance imaging (MRI) ...
Aim: The outpatient clinic visit is the major focus of the hospital medical process for most paed... more Aim: The outpatient clinic visit is the major focus of the hospital medical process for most paediatricians, children and parents. The importance of children as active participants in this interaction has been recognized. Our study aims are to describe and assess the components of doctor‐parent‐child communication in the outpatient setting. Methods: Fifty‐one medical paediatric clinic consultations were recorded on audio cassette, and communication was analysed according to quantitative methods. Questionnaires assessed parents' and children's perceptions. Results: Doctors contributed most to the conversation (61%), children only 4%. Behaviour: Doctors' communication was 84% instrumental (e.g. asking questions, giving information or instructions), 13% affective behaviour (expressing concerns and worries) and 3% social (small talk). Parents' communication included giving information (83%), seeking information (13%) and social (4%). The child asked less information (3%)...
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, 2019
Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-... more Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, inclu...
The first step in branched-chain amino acid (BCAA) catabolism is catalyzed by the two BCAA transf... more The first step in branched-chain amino acid (BCAA) catabolism is catalyzed by the two BCAA transferase isoenzymes, cytoplasmic branched-chain amino acid transferase (BCAT) 1, and mitochondrial BCAT2. Defects in the second step of BCAA catabolism cause maple syrup urine disease (MSUD), a condition which has been far more extensively investigated. Here, we studied the consequences of BCAT2 deficiency, an ultra-rare condition in humans. We present genetic, clinical, and functional data in five individuals from four different families with homozygous or compound heterozygous BCAT2 mutations which were all detected following abnormal biochemical profile results or familial mutation segregation studies. We demonstrate that BCAT2 deficiency has a recognizable biochemical profile with raised plasma BCAAs and, in contrast with MSUD, low-normal branched-chain
Background Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are identified in 30–50% of ch... more Background Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are identified in 30–50% of children with acquired demyelinating syndrome (ADS), and in relapsing syndromes such as AQP4-Ab negative neuromyelitis optica spectrum disorder (NMOSD). However, less is known about the wider spectrum and the clinical course of patients who relapse. Objective To evaluate the clinical features of children with MOG-Ab and relapsing disease. Methods Fifty three consecutive children with ADS and MOG-Ab positivity from five paediatric neurology referral centers were identified between 2011 and 2104. Clinical and neuroimaging features were reviewed and the treatment and outcomes evaluated. Results The initial presenting demyelination syndrome, clinical, radiological and investigative features could not distinguish the 13 patients that had a relapsing course from the other monophasic patients. Of the 13 relapsing patients (7 female, median 6.5 yrs; range 3–15 yrs) four presented with monophasic/recurring episodes of acute disseminated encephalomyelitis (ADEM) followed by monophasic/relapsing optic neuritis (ON); three fulfilled criteria for AQP4-Ab negative NMOSD; two had multiphasic ADEM; and four were diagnosed with relapsing remitting multiple sclerosis (RRMS). Intrathecal oligoclonal bands were only detected in 8% (1/12) tested. All 12 patients with abnormal brain MRI had brainstem and/or cerebellar lesion. Eight patients (non-MS) managed on long-term immunosuppression (n=2) and/or prompt acute treatment (n=8) made a complete clinical and radiological recovery at one year from last relapse. All patients with ON (n=8) had a complete visual recovery. Three out of four patients with RRMS are currently undergoing interferon therapy but continue to relapse. Conclusion 25% of MOG-Ab positive patients have a relapsing demyelination, often with a good clinical and radiological recovery. However, 30% (4/13) of this relapsing group may fulfill the diagnosis of MS, although may not have intrathecal bands and appear to have a poor response to MS treatment.
To identify early prognostic factors of relapse and disability in children presenting with an acu... more 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.
Objective: Acute disseminated encephalomyelitis (ADEM) is a treatable inflammatory demyelinating... more Objective: Acute disseminated encephalomyelitis (ADEM) is a treatable inflammatory demyelinating disorder seen more commonly in children than in adults. It typically presents to general paediatricians, often, like encephalitis, with non‐specific cerebrospinal fluid findings. The brain computerized tomography scan is usually normal, so is falsely reassuring and delays the diagnosis, which might result in considerable morbidity. The present study was initiated to report on the various modes of presentation and raise the awareness of the diagnosis of ADEM among general paediatricians.Methods: A retrospective review of the case notes of 18 children with a diagnosis of ADEM established in a tertiary referral centre from 1995 to 2000 was undertaken with particular reference to clinical features, investigations and treatment.Results: The most common presenting features were ataxia (10 cases), followed by headache (eight cases) and weakness (five cases). Magnetic resonance imaging (MRI) ...
Aim: The outpatient clinic visit is the major focus of the hospital medical process for most paed... more Aim: The outpatient clinic visit is the major focus of the hospital medical process for most paediatricians, children and parents. The importance of children as active participants in this interaction has been recognized. Our study aims are to describe and assess the components of doctor‐parent‐child communication in the outpatient setting. Methods: Fifty‐one medical paediatric clinic consultations were recorded on audio cassette, and communication was analysed according to quantitative methods. Questionnaires assessed parents' and children's perceptions. Results: Doctors contributed most to the conversation (61%), children only 4%. Behaviour: Doctors' communication was 84% instrumental (e.g. asking questions, giving information or instructions), 13% affective behaviour (expressing concerns and worries) and 3% social (small talk). Parents' communication included giving information (83%), seeking information (13%) and social (4%). The child asked less information (3%)...
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, 2019
Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-... more Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, inclu...
The first step in branched-chain amino acid (BCAA) catabolism is catalyzed by the two BCAA transf... more The first step in branched-chain amino acid (BCAA) catabolism is catalyzed by the two BCAA transferase isoenzymes, cytoplasmic branched-chain amino acid transferase (BCAT) 1, and mitochondrial BCAT2. Defects in the second step of BCAA catabolism cause maple syrup urine disease (MSUD), a condition which has been far more extensively investigated. Here, we studied the consequences of BCAT2 deficiency, an ultra-rare condition in humans. We present genetic, clinical, and functional data in five individuals from four different families with homozygous or compound heterozygous BCAT2 mutations which were all detected following abnormal biochemical profile results or familial mutation segregation studies. We demonstrate that BCAT2 deficiency has a recognizable biochemical profile with raised plasma BCAAs and, in contrast with MSUD, low-normal branched-chain
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Papers by E. Wassmer