Acute disseminated encephalomyelitis and transverse myelitis following COVID-19 vaccination - A self-controlled case series analysis.

Acute Disseminated Encephalomyelitis (ADEM) and Transverse Myelitis (TM) are within the group of immune mediated disorders of acquired demyelinating syndromes. Both have been described in temporal association following various vaccinations in case reports and case series and have been evaluated in observational studies. A recent analysis conducted by The Global Vaccine Data Network (GVDN) observed an excess of ADEM and TM cases following the adenoviral vectored ChAdOx1 nCoV-19 (AZD1222) and mRNA-1273 vaccines, compared with historically expected background rates from prior to the pandemic. Further epidemiologic studies were recommended to explore these potential associations. We utilized an Australian vaccine datalink, Vaccine Safety Health-Link (VSHL), to perform a self-controlled case series analysis for this purpose. VSHL was selected for this analysis as while VSHL data are utilised for GVDN association studies, they were not included in the GVDN observed expected analyses. The VSHL dataset contains vaccination records sourced from the Australian Immunisation Register, and hospital admission records from the Victorian Admitted Episodes Dataset for 6.7 million people. These datasets were used to determine the relative incidence (RI) of G040 (ADEM) and G373 (TM) ICD-10-AM coded admissions in the 42-day risk window following COVID-19 vaccinations as compared to control periods either side of the risk window. We observed associations between ChAdOx1 adenovirus vector COVID-19 vaccination and ADEM (all dose RI: 3.74 [95 %CI 1.02,13.70]) and TM (dose 1 RI: 2.49 [95 %CI: 1.07,5.79]) incident admissions. No associations were observed between mRNA COVID-19 vaccines and ADEM or TM. These findings translate to an extremely small absolute risk of ADEM (0.78 per million doses) and TM (1.82 per million doses) following vaccination; any potential risk of ADEM or TM should be weighed against the well-established protective benefits of vaccination against COVID-19 disease and its complications. This study demonstrates the value of the GVDN collaboration leveraging large population sizes to examine important vaccine safety questions regarding rare outcomes, as well as the value of linked population level datasets, such as VSHL, to rapidly explore associations that are identified.

Background incidence rates of adverse events of special interest related to COVID-19 vaccines in Ontario, Canada, 2015 to 2020, to inform COVID-19 vaccine safety surveillance.

BACKGROUND: Background incidence rates are critical in pharmacovigilance to facilitate identification of vaccine safety signals. We estimated background incidence rates of 11 adverse events of special interest related to COVID-19 vaccines in Ontario, Canada. METHODS: We conducted a population-based retrospective observational study using linked health administrative databases for hospitalizations and emergency department visits among Ontario residents. We estimated incidence rates of Bell's palsy, idiopathic thrombocytopenia, febrile convulsions, acute disseminated encephalomyelitis, myocarditis, pericarditis, Kawasaki disease, Guillain-Barré syndrome, transverse myelitis, acute myocardial infarction, and anaphylaxis during five pre-pandemic years (2015-2019) and 2020. RESULTS: The average annual population was 14 million across all age groups with 51% female. The pre-pandemic mean annual rates per 100,000 population during 2015-2019 were 191 for acute myocardial infarction, 43.9 for idiopathic thrombocytopenia, 28.8 for anaphylaxis, 27.8 for Bell's palsy, 25.0 for febrile convulsions, 22.8 for acute disseminated encephalomyelitis, 11.3 for myocarditis/pericarditis, 8.7 for pericarditis, 2.9 for myocarditis, 2.0 for Kawasaki disease, 1.9 for Guillain-Barré syndrome, and 1.7 for transverse myelitis. Females had higher rates of acute disseminated encephalomyelitis, transverse myelitis and anaphylaxis while males had higher rates of myocarditis, pericarditis, and Guillain-Barré syndrome. Bell's palsy, acute disseminated encephalomyelitis, and Guillain-Barré syndrome increased with age. The mean rates of myocarditis and/or pericarditis increased with age up to 79 years; males had higher rates than females: from 12 to 59 years for myocarditis and ≥12 years for pericarditis. Febrile convulsions and Kawasaki disease were predominantly childhood diseases and generally decreased with age. CONCLUSIONS: Our estimated background rates will permit estimating numbers of expected events for these conditions and facilitate detection of potential safety signals following COVID-19 vaccination.

Acute disseminated encephalomyelitis: A retrospective study of 20 children in a pediatrics department in Tunisia.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disorder of the central nervous system. Little information is available about the clinical and neuroradiological profile or the follow-up of this disease in Tunisian children. AIM: To determine the clinical, laboratory, and radiological features and the outcome of ADEM in children admitted to the pediatrics department of a university hospital in Tunisia. METHODS: All children ≤ 18 years old presenting with ADEM and admitted to the tertiary referral center for pediatrics at Sahloul University Hospital from January 2000 to December 2020 were included in the study. The diagnosis of ADEM was confirmed according to the international pediatric multiple sclerosis study group criteria. RESULTS: A total of 20 patients (13 girls and 7 boys) fulfilled the diagnostic criteria for ADEM. The mean age at diagnosis was 5.6 years. The clinical presentation included polyfocal neurological signs such as cranial hypertension (45%), seizures (35%), and motor weaknesses (55%). Pyramidal tract signs and cranial nerve palsies were noted in 55% of cases. Brain magnetic resonance imaging showed particular features, namely, a relapsing tumor-like form in one case, and optic neuritis and demyelinating lesions of the white matter in the brain and the spinal cord with gadolinium cerebral ring-like enhancement in another case. The treatment consisted of intravenous immunoglobulin in 16 cases (80%) and corticosteroid in 19 cases (95%). Plasmapheresis was used for one patient. Complete recovery was observed in 12 patients (60%); 19 patients (95%) had a monophasic course of the disease while only one patient developed multiphasic ADEM. CONCLUSIONS: ADEM remains a difficult diagnosis in children. Nevertheless, after prompt diagnosis and adequate treatment, most children with ADEM have a favorable outcome with restitutio ad integrum.

Spectrum of anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated diseases: an Indian perspective.

Myelin oligodendrocyte glycoprotein antibody (MOG-Ab) is involved in the pathogenesis of central nervous system (CNS) demyelination disorders. We aimed to explore the spectrum of MOG-Ab-associated diseases in eastern India. A single-center, prospective observational study was done over a period of 2 years in a tertiary care hospital of eastern India. Patients with CNS demyelination disorders who tested positive for MOG-Ab using live cell-based assay were included in the study; while, those with age less than 1 year, documented preexisting CNS structural lesions, developmental delays or diagnosed multiple sclerosis were excluded. Demographic profile, clinical spectrum, disease course, radiological features as well as response to treatment were analyzed among included patients. Twenty MOG-Ab-positive patients were included (M:F 1:1.85). The median age of symptom onset was 10.5 years. The median follow-up of patients was 13 months. Acute disseminated encephalomyelitis (ADEM) was the commonest presentation at first attack (55%), followed by optic neuritis (ON) (45%). Patients with ADEM had a significantly lower age at first attack (p = 0.025). Monophasic and relapsing disease courses were seen in 45% and 55% patients, respectively. While all patients with only ADEM had a monophasic course, 77.8% with ON had a relapsing course. Among patients who presented with isolated transverse myelitis, 75% had a monophasic course and all had disease confined to the spinal cord. Good response to corticosteroids was seen in majority of participants. Second-line drugs were needed in 55% patients, rituximab being the commonest second-line agent used. 35% patients had significant disability (EDSS > 4) at last follow-up. MOG-Ab-associated diseases have diverse clinical phenotypes characterized by age-dependent pattern-specific courses.

Pediatric autoimmune encephalitis: Recognition and diagnosis.

OBJECTIVE: The aims of this study were (1) to describe the incidence of autoimmune encephalitis (AIE) and acute disseminated encephalomyelitis (ADEM) in children, (2) to validate the currently used clinical criteria to diagnose AIE, and (3) to describe pitfalls in the diagnosis of pediatric autoimmune (AI) and inflammatory neurologic disorders. METHODS: This study cohort consists of 3 patient categories: (1) children with antibody-mediated AIE (n = 21), (2) children with ADEM (n = 32), and (3) children with suspicion of an AI etiology of their neurologic symptoms (n = 60). Baseline and follow-up clinical data were used to validate the current guideline to diagnose AIE. In addition, patient files and final diagnoses were reviewed. RESULTS: One-hundred three of the 113 included patients fulfilled the criteria of possible AIE. Twenty-one children had antibody-mediated AIE, of whom 19 had anti-N-methyl-D-aspartate receptor (NMDAR), 1 had anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, and 1 had anti-leucine-rich glioma-inactivated protein 1 encephalitis. Finally, 34 children had ADEM, and 2 children had Hashimoto encephalopathy. Mean incidence rates were 1.54 children/million (95% CI 0.95-2.35) for antibody-mediated AIE and 2.49 children/million (95% CI 1.73-3.48) for ADEM. Of the other 48 children, treating physicians' diagnoses were reviewed. In 22% (n = 6) of children initially diagnosed as having an AI/inflammatory etiology (n = 27), no support for AI/inflammation was found. CONCLUSION: Besides anti-NMDAR encephalitis and ADEM, other AIEs are rare in children. The current guideline to diagnose AIE is also useful in children. However, in children with nonspecific symptoms, it is important to review data critically, to perform complete workup, and to consult specialized neuroinflammatory centers.

Acute Demyelinating Events Following Vaccines: A Case-Centered Analysis.

BACKGROUND: Case reports have suggested that vaccines may trigger transverse myelitis (TM) or acute disseminated encephalomyelitis (ADEM), but the evidence for a causal association is inconclusive. We analyzed the association of immunization and subsequent development of TM or ADEM. METHODS: We identified all cases of TM and ADEM in the Vaccine Safety Datalink population. Using a case-centered method, we compared vaccination of each case to vaccination of all matched persons in the study population, who received the same type of vaccine, with respect to whether or not their vaccination occurred during a predetermined exposure interval. We calculated a risk difference (excess risk) of TM and ADEM for each vaccine. RESULTS: Following nearly 64 million vaccine doses, only 7 cases of TM and 8 cases of ADEM were vaccinated during the primary exposure window 5-28 days prior to onset. For TM, there was no statistically significant increased risk of immunization. For ADEM, there was no statistically significant increased risk following any vaccine except for Tdap (adolescent and adult tetanus, reduced diphtheria, acellular pertussis) vaccine. Based on 2 exposed cases, the odds ratio for Tdap exposure 5-28 days prior to ADEM onset was 15.8 (95% confidence interval [CI], 1.2-471.6; P = .04), and the estimated excess risk was 0.385 (95% CI, -.04 to 1.16) cases per million doses. CONCLUSIONS: We found no association between TM and prior immunization. There was a possible association of ADEM with Tdap vaccine, but the excess risk is not likely to be more than 1.16 cases of ADEM per million vaccines administered.

Nationwide Incidence of Acquired Central Nervous System Demyelination in Icelandic Children.

INTRODUCTION: Recognizing acquired demyelinating syndromes and multiple sclerosis is important to commence early treatment. The objective of this study was to describe the incidence of acquired demyelinating syndromes and multiple sclerosis among the entire Icelandic pediatric population according to recently promoted criteria. PATIENTS AND METHODS: The study included all children in Iceland (<18 years) with acquired demyelinating syndromes and multiple sclerosis from 1990 to 2009 with a minimum of 5-year follow-up. Clinical data were gathered and radiological images reviewed. The cohort included all patients with acquired demyelinating syndromes and multiple sclerosis in the Icelandic pediatric population. RESULTS: Eighteen patients with acquired demyelinating syndromes and multiple sclerosis were included, the total annual incidence being 1.15/100,000 (acquired demyelinating syndromes 1.02 and multiple sclerosis 0.45/100,000). The median age at diagnosis was 14.25 years (range 1.25-17.5 years). Thirteen patients were initially diagnosed with clinically isolated syndrome, two had acute disseminated encephalomyelitis, two had multiple sclerosis, and one had neuromyelitis optica. Seven children were diagnosed with multiple sclerosis; three patients with clinically isolated syndrome developed multiple sclerosis after the age of 18 and were not included in the multiple sclerosis group. The gender ratio was equal. Of the nine girls, seven were diagnosed with clinically isolated syndrome. Most patients (11 of 18) were diagnosed during the period January through March. Oligoclonal bands in cerebrospinal fluid were exclusively found in patients with multiple sclerosis and clinically isolated syndrome and 13 of 14 available magnetic resonance images revealed clear abnormalities. CONCLUSION: The annual incidence of acquired demyelinating syndromes and multiple sclerosis in Iceland was 1.15/100,000 children. The risk of progression from clinically isolated syndrome to multiple sclerosis was high. There was no female preponderance.

Virus and Immune-Mediated Encephalitides: Epidemiology, Diagnosis, Treatment, and Prevention.

Virus encephalitis remains a major cause of acute neurological dysfunction and permanent disability among children worldwide. Although some disorders, such as measles encephalomyelitis, subacute sclerosing panencephalitis, and varicella-zoster virus-associated neurological conditions, have largely disappeared in resource-rich regions because of widespread immunization programs, other disorders, such as herpes simplex virus encephalitis, West Nile virus-associated neuroinvasive disease, and nonpolio enterovirus-induced disorders of the nervous system, cannot be prevented. Moreover, emerging viral disorders pose new, potential threats to the child's nervous system. This review summarizes current information regarding the epidemiology of virus encephalitis, the diagnostic methods available to detect central nervous system infection and identify viral pathogens, and the available treatments. The review also describes immune-mediated disorders, including acute disseminated encephalomyelitis and N-methyl-D-aspartate receptor antibody encephalitis, conditions that mimic virus encephalitis and account for a substantial proportion of childhood encephalitis.

Anti-MOG antibodies plead against MS diagnosis in an Acquired Demyelinating Syndromes cohort.

BACKGROUND: Acquired demyelinating syndromes (ADS) in children are a group of distinct first immune-mediated demyelinating events of the central nervous system (CNS). Predictive biomarkers for future diagnosis are lacking. A putative target antigen is myelin oligodendrocyte glycoprotein (MOG). We analyzed the presence of MOG antibodies in a cohort of ADS patients in The Netherlands. METHODS: Using a cell-based assay, we analyzed 117 children with ADS from a nationwide cohort, whom were divided into five groups: optic neuritis (ON; n = 20), transverse myelitis (TM; n = 7), other monofocal ADS (n = 22), polyfocal ADS without encephalopathy (n = 44) and polyfocal ADS with encephalopathy (n = 24). Additionally, we tested children with other neurological diseases (OND; n = 13), healthy children (n = 31) and adult polyfocal ADS plus encephalopathy (ADEM) patients (n = 29). RESULTS: We found that 21 of the 117 children with ADS tested anti-MOG seropositive (18%). The group of patients with ADEM had the highest prevalence of anti-MOG seropositivity (42% versus 18% in the non-encephalopathic polyfocal ADS patients). Although 47 ADS children had a final diagnosis of multiple sclerosis (MS), in only one of them were MOG antibodies detected (2%), with only borderline positivity. Only 1 out of the 29 adult ADEM patients tested anti-MOG seropositive. CONCLUSIONS: MOG antibodies are strongly skewed towards ADS children that present with an ADEM-like disease onset. The presence of such antibodies pleads against a future diagnosis of MS.

[Analysis of a series of cases with an initial diagnosis of acute disseminated encephalomyelitis over the period 2000-2010]. / Análisis de una serie de casos con diagnostico inicial de encefalomielitis aguda diseminada en el periodo 2000-2010.

INTRODUCTION: Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease that essentially affects the white matter of the central nervous system. The diagnosis is based on clinical-imaging and developmental findings. Magnetic resonance imaging of the brain is the most useful diagnostic tool. The disease course is usually monophasic and the preferred initial treatment is with corticoids. PATIENTS AND METHODS: We conducted a retrospective study of 18 patients with a presumptive diagnosis of ADEM. Symptoms, imaging findings, progress and treatment were analysed. The definitive diagnosis was established in 12 patients, excluding one patient with positive polymerase chain reaction for herpes simplex virus in cerebrospinal fluid, one with a clinical picture that was consistent but normal magnetic resonance imaging of the brain, and four with an onset that was similar to ADEM whose definitive diagnoses were: Rassmusen's syndrome, haemophagocytic syndrome, brain tumour, and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). RESULTS: The median age was 31 months with no predominance of either sex. Infection of the upper respiratory tract was the most frequent cause in children over 2 years of age and of the gastrointestinal tract in those under the age of 2. All of them presented altered levels of consciousness and multifocal neurological deficits. The most frequent imaging finding was multifocal alteration of the white matter in both hemispheres. Corticoids were the preferred treatment in most cases. Progression was favourable in nearly all patients except for two, who were left with important sequelae. CONCLUSIONS: ADEM may present at any age, including in infants. There are a number of conditions that can mimic ADEM in the early stages.

TITLE: Analisis de una serie de casos con diagnostico inicial de encefalomielitis aguda diseminada en el periodo 2000-2010.Introduccion. La encefalomielitis aguda diseminada (EMAD) es una enfermedad desmielinizante que afecta fundamentalmente a la sustancia blanca del sistema nervioso central. El diagnostico se basa en hallazgos clinicorradiologicos y evolutivos. La resonancia magnetica cerebral es la herramienta diagnostica mas util. El curso suele ser monofasico y el tratamiento inicial de eleccion, los corticoides. Pacientes y metodos. Estudio retrospectivo de 18 pacientes con diagnostico de sospecha inicial de EMAD. Se analizo la sintomatologia, los hallazgos radiologicos, la evolucion y el tratamiento. El diagnostico definitivo se establecio en 12 pacientes, excluyendo un paciente con reaccion en cadena de la polimerasa positiva para el virus herpes simple en el liquido cefalorraquideo, uno con clinica compatible pero resonancia magnetica cerebral normal, y cuatro con inicio similar a EMAD cuyos diagnosticos definitivos fueron: sindrome de Rassmusen, sindrome hemofagocitico, tumor cerebral y MELAS (encefalomiopatia mitocondrial con acidosis lactica y accidentes cerebrovasculares). Resultados. La mediana de edad fue de 31 meses, sin predominio de sexo. La infeccion de la via respiratoria superior fue la causa mas frecuente en niños mayores y la gastrointestinal, en menores de 2 años. Todos presentaron alteracion en el nivel de conciencia y deficits neurologicos multifocales. El hallazgo radiologico mas frecuente fue la alteracion multifocal bihemisferica de la sustancia blanca. Los corticoides fueron el tratamiento de eleccion en la mayoria. La evolucion fue favorable en casi todos los pacientes excepto en dos, que tuvieron secuelas importantes. Conclusiones. La EMAD puede presentarse a cualquier edad, incluyendo lactantes. Hay multiples entidades que pueden simular una EMAD en un inicio.

Lights and shades on an historical vaccine canine distemper virus, the Rockborn strain.

Both egg- and cell-adapted canine distemper virus (CDV) vaccines are suspected to retain residual virulence, especially if administered to immuno-suppressed animals, very young pups or to highly susceptible animal species. In the early 1980s, post-vaccine encephalitis was reported in dogs from various parts of Britain after administration of a particular batch of combined CDV Rockborn strain/canine adenovirus type-1 vaccine, although incrimination of the Rockborn strain was subsequently retracted. Notwithstanding, this, and other reports, led to the view that the Rockborn strain is less attenuated and less safe than other CDV vaccines, and the Rockborn strain was officially withdrawn from the markets in the mid 1990s. By sequencing the H gene of the strain Rockborn from the 46th laboratory passage, and a commercial vaccine (Candur(®) SH+P, Hoechst Rousell Vet GmbH), the virus was found to differ from the commonly used vaccine strain, Onderstepoort (93.0% nt and 91.7% aa), and to resemble more closely (99.6% nt and 99.3% aa) a CDV strain detected in China from a Lesser Panda (Ailurus fulgens). An additional four CDV strains matching (>99% nt identity) the Rockborn virus were identified in the sequence databases. Also, Rockborn-like strains were identified in two vaccines currently in the market. These findings indicate that Rockborn-like viruses may be recovered from dogs or other carnivores with distemper, suggesting cases of residual virulence of vaccines, or circulation of vaccine-derived Rockborn-like viruses in the field.

Encefalopatía desmielinizante aguda en el adulto: presentación y algoritmo diagnóstico / Acute disseminated encephalomyelitis in the adulthood

Objetivo: estandarizar la metodología diagnóstica diferencial de lesiones pseudotumorales. Analizar a partir de este caso la aparición de esta entidad poco habitual en la población adulta. Material y métodos: se realiza historia epidemiológica de un paciente masculino de 51 años de edad que concurre a través de consultorios externos presentando inestabilidad en la marcha y diparesia braquial de 7 días de evolución. Como antecedentes refiere episodio febril de origen desconocido y resolución espontánea 20 días previos. Resultados: se realizaron estudios de tomografía axial computada y resonancia magnética nuclear de encéfalo evidenciando lesiones bilaterales. Se completa estudios con screening oncológico negativo. Líquido cefalorraquídeo: bandas oligoclonales negativas, proteinorraquia, PCR + para VEB. PESS, PEV, PEA: negativos. Se somete a tratamiento médico con metilprednisolona 1 gramo diario durante 3 días. Conclusiones: el ADEM (Encefalopatía Desmielinizante Aguda) es una entidad inflamatoria inmunomediada de diversas formas de presentación. Cumple un rol importante en el diagnóstico, la correlación de antecedentes epidemiológicos del paciente como así también la evolución progresiva del cuadro clínico y estudios complementarios.

Objective: To standardize the differential diagnosis method of pseudotumoral lesions. To analyze from this case the occurrence of this unusual condition in adults. Material and methods: An epidemilogical history is conducted in a 51 year old male patient who comes to the out-patient offices showing walking instability and brachial cliparesis during 7 days. The patient reports a febrile state with spontaneous resolution 20 days before the consultation as background. Results: A computerized axial tomography and an encephalic nuclear magnetic resonance were performed showing bilateral lesions. The studies were complete with an oncologic screening of negative results. Cephalorachidian liquid: negative oligocional bands, proteinorachia, detection of EBV (Epstein-Barr Birus) by PCR (Polymerase Chain Reaction). SEPs (Somatosensitive Evoked Potentials), VEP (Visual Evoked Potentials), PEA (Auditory Evoked Potentials): NEGATIVE. The patient receives medical treatment with 1 gram daily methylprednisolone for 3 days. Conclusions: ADEM (Acute Disseminated Encephalomyelitis) is an immune mediated inflammatory condition that can appear in several ways. The patient's epidemiological background correlation, as well as the progressive evolution of the medical condition and complementary analyses play an important role in diagnosis.

Acquired demyelinating disorders of childhood in the Western Cape, South Africa.

In a retrospective review of patients with acquired demyelinating disorders of the central nervous system, 19 children (0.6%) were identified from the Paediatric Neurology database of 3159 patients; 7 had acute disseminated encephalomyelitis, 1 had Schilder's disease, 5 had multiple sclerosis, and 6 had acute transverse myelitis. The median age of presentation was 83 months, with increased incidence during the summer and winter months. The commonest presentation was hemiparesis. The commonest regions of magnetic resonance imaging (MRI) abnormalities were the deep white matter (68%) and cerebellum (48%).The patients with multiple sclerosis had more monosymptomatic presentations (P < .02), raised cerebrospinal fluid protein (P = .022), and contrast enhancement of lesions (P = .05) compared with the acute disseminated encephalomyelitis group. Neuroepidemiological published surveillances of African children provide no data about these disorders. The prevalence of acquired demyelinating disorders in resource-poor settings is under-estimated because of the large burden of infections and limited access to neuroimaging.

Clinical study of childhood acute disseminated encephalomyelitis, multiple sclerosis, and acute transverse myelitis in Fukuoka Prefecture, Japan.

Acute disseminated encephalomyelitis (ADEM) has recently been studied in several countries owing to the development and wide spread use of imaging technology, but few epidemiological studies of childhood ADEM have been undertaken in Asian countries. To perform a comprehensive survey of ADEM and related diseases in Japanese children, we conducted a multicenter, population-based study on childhood ADEM, multiple sclerosis, and acute isolated transverse myelitis in Fukuoka Prefecture, Japan. We identified 26 children with ADEM, 8 with multiple sclerosis, and 4 with acute transverse myelitis during 5 years between September 1998 and August 2003. The incidence of childhood ADEM under the age of 15 years was 0.64 per 100,000 person-years, mean age at onset was 5.7 years, and male-female ratio was 2.3:1. The prevalence of childhood multiple sclerosis was 1.3 per 100,000 persons. The mean age at onset of multiple sclerosis, 9.3 years, was significantly higher than that of ADEM. Nineteen (73%) and four (15%) patients with ADEM experienced antecedent infectious illnesses and vaccinations, respectively, within 1 month before the onset. Clinical and radiological findings of ADEM revealed that the frequency of seizures, mean white blood cell counts in cerebrospinal fluid, and the frequency of subcortical lesions in Fukuoka study, seemed to be higher than those in previous non-Asian studies. These findings suggest that there are ethnic or geographical differences in the incidence and clinical features of ADEM, and that there might be potent genetic or environmental risk factors for ADEM distinct from those for multiple sclerosis.

Incidence of acquired demyelination of the CNS in Canadian children.

BACKGROUND: The incidence of acquired demyelination of the CNS (acquired demyelinating syndromes [ADS]) in children is unknown. It is important that physicians recognize the features of ADS to facilitate care and to appreciate the future risk of multiple sclerosis (MS). OBJECTIVE: To determine the incidence, clinical features, familial autoimmune history, and acute management of Canadian children with ADS. METHODS: Incidence and case-specific data were obtained through the Canadian Pediatric Surveillance Program from April 1, 2004, to March 31, 2007. Before study initiation, a survey was sent to all pediatric health care providers to determine awareness of MS as a potential outcome of ADS in children. RESULTS: Two hundred nineteen children with ADS (mean age 10.5 years, range 0.66-18.0 years; female to male ratio 1.09:1) were reported. The most common presentations were optic neuritis (ON; n = 51, 23%), acute disseminated encephalomyelitis (ADEM; n = 49, 22%), and transverse myelitis (TM; n = 48, 22%). Children with ADEM were more likely to be younger than 10 years, whereas children with monolesional ADS (ON, TM, other) were more likely to be older than 10 years (p < 0.001). There were 73 incident cases per year, leading to an annual incidence of 0.9 per 100,000 Canadian children. A family history of MS was reported in 8%. Before study initiation, 65% of physicians indicated that they considered MS as a possible outcome of ADS in children. This increased to 74% in year 1, 81% in year 2, and 87% in year 3. CONCLUSION: The incidence of pediatric acquired demyelinating syndromes (ADS) is 0.9 per 100,000 Canadian children. ADS presentations are influenced by age.

Smallpox and smallpox vaccination: neurological implications.

Compulsory vaccination was discontinued in the U.S. in 1972; the world was declared free of smallpox infection in 1980. Since that time, no new smallpox infections have been recognized, and only limited numbers of military and laboratory personnel have been vaccinated. As a result, the majority of the U.S. and the world population have no or diminished immunity to smallpox. Widespread vaccination, beginning with the military and health care workers, is now being undertaken. Public health strategies for immunizing the general population include preexposure voluntary vaccination, case surveillance with ring vaccination, and mass vaccination at the time of attack. Cutaneous complications of vaccination occur in immunosuppressed subjects and in those with atopic dermatitis. Among the most serious complications is postvaccinal encephalomyelitis (PVEM). A related condition, postvaccinial encephalopathy (PVE), may be seen in children less than two years of age. There are no markers to predict who will develop PVEM. In the past, mortality was high, ranging from 10 to 50%. The neuropathology of PVEM suggested an immune-mediated attack on the CNS, but the target of the immune response is unknown. Comprehensive programs are needed for surveillance and confirming case definitions for neurologic complications. Multi-institutional controlled trials of antiviral and immune modulating therapy of PVEM should be considered. Neurologists should be actively involved in the planning process for vaccination programs and in the treatment of neurologic complications.

ADEM: literature review and case report of acute psychosis presentation.

Acute disseminated encephalomyelitis is a monophasic, immune-mediated disorder that produces multifocal demyelinating lesions within the central nervous system. It is characterized clinically by the acute onset of neurologic abnormalities, including varying degrees of mental state changes ranging from drowsiness to coma. It is unusual for the illness to present as an isolated acute psychosis. The case of a 14-year-old female with biopsy-confirmed acute disseminated encephalomyelitis, who was initially diagnosed with an acute psychiatric disorder, is presented, and published reports on this unusual manifestation are reviewed. A Medline database search was performed from 1965 to 1999, using the terms acute disseminated encephalomyelitis, postvaccinal encephalomyelitis, postinfectious encephalomyelitis, and measles encephalomyelitis, combined with the terms psychosis, psychiatric disorder, and behavioral disorder. Selected cross-referenced reports were also reviewed. Nine patients were identified who presented with acute psychosis. We conclude that, although rare, acute disseminated encephalomyelitis can present as an acute psychosis. This immune-mediated condition should be included in the differential diagnosis of neurologic disorders presenting as a psychiatric illness.

Survey of herpes simplex virus infections of the central nervous system, including acute disseminated encephalomyelitis, in the Kyushu and Okinawa regions of Japan.

We analysed data from 27 patients with herpes simplex virus (HSV) infections of the central nervous system (CNS) found in a 1990-1992 survey in Kyushu and Okinawa, Japan. Patients ranged in age from one year to 70 years, with peaks seen in the 20s and 50s. Temporal lobe-limbic encephalitis was the most common HSV infection (13 patients), followed by meningitis (5), diffuse encephalitis (4), disseminated encephalomyelitis (ADEM) (3) and brain stem encephalitis (2). Another three patients with non-herpetic, non-paraneoplastic acute limbic encephalitis were presented. Our study indicates that HSV infection can course ADEM, although temporal lobe-limbic encephalitis or meningitis are more common. The early diagnosis of HSV-related ADEM is important because of the efficacy of the timely administration of corticosteroids.

A virological study of post-vaccinal encephalitis.

In the province of Voyvodina 18 cases of post-vaccinal encephalitis have been recorded, three of which were fatal.The estimated morbidity rate was 0.6 per 10(5) after revaccination, and 3.9 per 10(5) after primary vaccination. The virological studies described, as well as other findings referred to in this report, are consistent with the possibility of an autoimmune aetiology of the post-vaccinal encephalitis cases observed.