Acute disseminated encephalomyelitis: the importance of early magnetic resonance imaging

The diagnosis of acute disseminated encephalomyelitis (ADEM) is frequently missed or delayed with consequent delay in instituting therapy in the crucial phase of the illness. The role of MRI in the diagnosis of ADEM is well established, however, the value of its early utilization of treatment on the outcome of patients has not been adequately stressed. Three patients with ADEM are described. Delay in the diagnosis of the first was associated with severe sequelae, while in the other two early diagnosis and institution of corticosteroid therapy which was facilitated by MRI, was associated with a better outcome. MRI should be carried out early once the diagosis of ADEM is entertained.     

Evidence of axonal damage in human acute demyelinating diseases

Substantial axon damage, detected by immunostaining for beta amyloid precursor protein (betaAPP) has been demonstrated in acute demyelinating lesions in multiple sclerosis. AIMS: The present study aimed to determine if this was also the case in the other human acute demyelinating diseases, acute hemorrhagic leucoencephalitis (AHLE), acute disseminated encephalomyelitis (ADEM) and central pontine myelinolysis (CPM). METHODS: BetaAPP immunostaining was used as a marker of axonal damage in autopsy material from these conditions. RESULTS: Axonal damage was detected in all these conditions. Its extent varied within and between them. Axonal damage was largely confined to tissue adjacent to veins and venules in AHLE and ADEM but was unrelated to proximity to these vessels in CPM. CONCLUSION: Substantial axon damage occurs in fatal cases of AHLE, ADEM and CPM.     

Acute disseminated encephalomyelitis associated with hepatitis B virus reinfection – Consequence or coincidence?

Acute disseminated encephalomyelitis (ADEM) is an idiopathic inflammatory demyelinating disease of the CNS that is particularly difficult to differentiate from the first episode of multiple sclerosis. ADEM typically occurs as a post-infectious phenomenon, and usually presents a monophasic episode, but also includes recurrent and multiphasic forms. We report a case of ADEM associated with hepatitis B virus (HBV) reinfection. After steroid and IV immunoglobulin treatment, neurologic symptoms were improved. We suppose that the HBV reinfection was the cause of ADEM, but possible pathogenetic mechanism is still obscure.     

Acute hemorrhagic leukoencephalitis mimicking herpes simplex encephalitis: case report

Acute hemorrhagic leukoencephalitis (AHLE) is a more severe form of acute disseminated encephalomyelitis (ADEM) characterized by a fulminant clinical course and the presence of hemorrhagic necrosis of the white matter. We report the case of a 57-year-old woman who developed delirium following a respiratory infection. Magnetic resonance imaging of the brain disclosed signal abnormalities in the frontal and temporal lobes, usually found in herpes simplex encephalitis (HSE). Gram stain, India ink and acid-fast bacilli staining were all negative in CSF as was a polymerase chain reaction (PCR) for herpes simplex virus. A diagnosis of AHLE was made and the patient was treated with i.v. methylprednisolone 1g/day for 5 days. Despite treatment, the patient developed several neurological sequelae compatible with the severity of her illness.     

儿童急性播散性脑脊髓炎21例临床分析

目的分析儿童急性播散性脑脊髓炎(acute disseminated encephalomyelitis,ADEM)的临床特点及辅助检查特点,以提高对此病的早期诊断及治疗。方法对2008-01—2013-05我院21例ADEM患儿的临床表现、辅助检查、治疗经过及预后进行回顾性分析。结果 21例患儿中有前驱感染病史者17例(80%),接种疫苗史2例。起病方式呈急性或亚急性起病,首发症状多样。MRI主要表现为白质受累。13例患儿脑脊液检查异常(62%),主要表现为细胞数及蛋白轻度升高。所有病例予以大剂量甲泼尼龙,12例合用大剂量免疫球蛋白,病情大多明显好转。结论儿童ADEM临床症状多样,结合MRI、脑脊液检查等多种辅助检查有助于及时明确诊断,患儿预后较好。     

Idiopathic inflammatory demyelinating diseases of the central nervous system: differentiating between acute disseminated encephalomyelitis and malignant multiple sclerosis

Multiple sclerosis (MS) is the most frequent demyelinating disorder of the central nervous system (CNS). However, at presentation, it is frequently difficult to differentiate between malignant MS (MMS) and other fulminant CNS demyelinating diseases like acute disseminated encephalomyelitis (ADEM). The literature contains many case reports of ADEM but few series. We report on four representative cases of acute demyelinating diseases, together with evaluation of treatment, course and follow-up. We also present clinical, laboratory, neuropathologic, neuroimaging and data on therapeutic options, including follow-up, in order to establish distinguishing characteristics of MMS and ADEM. Good clinical outcome from a postinfectious, monophasic episode, correlating with regressive demyelinating lesions on MRI, after more than 2 years differentiate best. Therapeutic efficacy, prior infection and initial MRI lesions seem to be of limited value. Despite the advances of neuroimaging and laboratory techniques, objective parameters are still missing, but findings on basic immunologic mechanisms of humoral and cellular response might provide further insight.     

A case of ADEM with atypical MRI findings of a centrally-located long spinal cord lesion

The patient was a 14-year-old male diagnosed with acute disseminated encephalomyelitis (ADEM) with acute onset of multifocal central nervous system symptoms. He showed increased cerebrospinal fluid cell counts and high myelin basic protein levels, which responded well to steroid pulse therapy. Spinal MRI showed a centrally-located long spinal cord lesion (LCL) involving 17 vertebral bodies from C2 to T11 that later expanded into the white matter, and lesions on the ventral side of the medulla. The cause of LCL has been reported to be heterogeneous. In this case, LCL is considered to be associated with ADEM, an acute autoimmune response to myelin, and vascular inflammation of the gray matter of the spinal cord.     

Diagnostic challenges in a child with familial hemophagocytic lymphohistiocytosis type 3 (FHLH3) presenting with fulminant neurological disease

Background  Familial hemophagocytic lymphohistiocytosis (FHLH) is an autosomal recessively inherited multisystem disease characterized by fever, rash, splenomegaly, cytopenias, and variable central nervous system (CNS) manifestations. Case history  We report the case of a 3-year-old boy who presented with splenomegaly and normocytic anemia 4 months after returning to the US from a region endemic for Leishmania infection. The child later developed progressive neurological impairment and had radiologic evidence of widespread demyelinating disease. Gene studies showed homozygosity for a mutation at Munc13-4, confirming FHLH type 3. Discussion  The diagnostic uncertainty that accompanies FHLH was compounded by our patient’s travel history and CNS disease mimicking acute disseminated encephalomyelitis (ADEM). Diagnostic criteria for hemophagocytic lymphohistiocytosis were not consistently met, despite aggressive disease. Conclusions  FHLH may present with fulminant demyelinating disease, mimicking ADEM, and without necessarily meeting previously defined clinical and laboratory criteria. We strongly recommend expeditious molecular testing and genetic counseling for FHLH mutations in cases of undiagnosed inflammatory CNS disease in the pediatric population.     

Acute disseminated encephalomyelitis following nephropathia epidemica

Acute disseminated encephalomyelitis (ADEM) is an acute monophasic inflammatory and demyelinating disease of the central nervous system (CNS) occurring days to weeks after a virus infection or vaccination. Nephropathia epidemica (NE) is a haemorrhagic fever with renal syndrome caused by Puumala virus, with endemic regions in Europe, especially Scandinavia and Western Russia. We describe a case of severe nephropathia epidemica requiring dialysis, followed by severe CNS symptoms caused by ADEM. To our best knowledge this is the first case in the literature in which NE caused ADEM.     

儿童急性播散性脑脊髓炎临床分析

目的探讨儿童急性播散性脑脊髓炎(ADEM)临床特点和预后。方法回顾性分析66例ADEM患儿的临床资料。应用Kurtzke扩展残疾状况量表(EDSS)评估入院时神经功能损伤情况,应用mRS评估最后一次随访时神经功能恢复情况,并分组比较其临床资料。结果 66例ADEM患儿中42例(63. 6%)有前驱感染史,5例(7. 6%)发病于疫苗接种后。所有患儿均有脑病表现,其中有意识障碍50例(75. 8%)、认知障碍9例(13. 6%)、精神症状6例(9. 1%)、认知障碍合并精神症状1例(1. 5%)。其他临床症状包括发热46例(69. 7%),锥体束征33例(50. 0%),惊厥32例(48. 5%),头痛27例(40. 1%),共济失调26例(39. 4%),言语障碍14例(21. 2%),颅神经受累11例(16. 7%)(面神经受累7例,展神经受累1例,视神经受累2例,面神经合并视神经1例),锥体外系症状9例(13. 6%),感觉异常7例(10. 6%)。MRI病灶以皮质下白质(84. 8%)、深部核团(36. 4%)、脑干(16. 7%)及小脑(15. 2%)多见,脊髓受累(7. 6%...     

Acute disseminated encephalomyelitis: a long-term follow-up study of 84 pediatric patients

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the CNS. Few pediatric series have been published, with retrospective and short-term follow-up studies. OBJECTIVES: To describe a cohort of pediatric patients with ADEM and to determine whether clinical and neuroimaging findings predict outcome. METHODS: A prospective study was conducted between March 1988 and July 2000 on 84 consecutive children with ADEM at the National Pediatric Hospital "Dr. J. P. Garrahan." RESULTS: Mean age at onset was 5.3 +/- 3.9 years, with a significant male predominance. Sixty-two patients (74%) had a preceding viral illness or vaccination. Acute hemiparesis (76%), unilateral or bilateral long tract signs (85%), and changes in mental state (69%) were the most prominent presenting features. Four MRI groups were identified: ADEM with small lesions (62%), with large lesions (24%), with additional bithalamic involvement (12%), and acute hemorrhagic encephalomyelitis (2%). Of the 54 children whose CSF samples were analyzed, none showed intrathecal oligoclonal bands. The use of high-dose corticosteroid treatment, particularly IV methylprednisolone, was associated with good recovery and resolution of MRI lesions. After a mean follow-up of 6.6 +/- 3.8 years, 90% of children showed a monophasic course, and 10% a biphasic disease. Eighty-nine percent of patients show at present Expanded Disability Status Scale scores of 0 to 2.5. Eleven percent have disability scores of 3 to 6.5. CONCLUSIONS: Childhood acute disseminated encephalomyelitis is a benign condition, affecting boys more frequently. No association was found between MRI groups and disability. Disability was related to optic nerve involvement at presentation. Even in relapsing cases, the distinction between acute disseminated encephalomyelitis and MS was possible on the basis of long-term clinical and neuroimaging follow-up and the absence of oligoclonal bands in CSF.     

急性播散性脑脊髓炎36例临床特点分析

目的阐明急性播散性脑脊髓炎(ADEM)的临床特点及诊治方法。方法分析宣武医院2003年至2010年36例ADEM住院患者的一般临床资料、临床表现、辅助检查及治疗与预后转归情况。结果本文病例多见于儿童和青壮年,急性起病,3例复发。其常见诱因为急性上呼吸道感染、疫苗接种、麻疹、风疹、水痘、流行性腮腺炎、猩红热等共计29例,原因不明7例。实验室检查中脑脊液可出现免疫球蛋白增高,磁共振成像检查提示受累部位包括脊髓、小脑、大脑白质及脑干等,其它辅助检查如电生理和免疫学检查等可协助诊断,应用糖皮质激素治疗效果确切。结论结合临床特点、神经电生理、脑脊液免疫学及影像学检查等,临床可以作出准确诊断,及时恰当的治疗对预后极为重要。     

Rituximab was effective for acute disseminated encephalomyelitis followed by recurrent optic neuritis with anti-myelin oligodendrocyte glycoprotein antibodies

Background

The effect of rituximab on acute disseminated encephalomyelitis (ADEM) followed by recurrent optic neuritis (ON) is not yet known.

Long-Term Neurocognitive Outcome and Quality of Life in Pediatric Acute Disseminated Encephalomyelitis

BackgroundAcute disseminated encephalomyelitis is an inflammatory-demyelinating disorder of the central nervous system usually with a monophasic course and a favorable neurological outcome. Long-term neurocognitive sequelae and quality of life have not yet been fully investigated.AimTo examine neurocognitive outcome and quality of life in pediatric monophasic acute disseminated encephalomyelitis.MethodsOf the 36 patients diagnosed with acute disseminated encephalomyelitis at our institution, six were lost to follow-up and eight relapsed (two with multiphasic forms and six with multiple sclerosis). The outcome of the 22 remaining patients was evaluated using four subscales of the Wechsler Intelligence Scales for estimation of IQ, a battery of neuropsychological tests, and semistructured and PedsQL questionnaires for quality of life. The effect of age at onset, neuroradiological recovery, and time elapsed from the acute event on outcome was also investigated.ResultsEstimated IQ, neuropsychological mean group scores, and quality of life at follow-up were within the normal range, but 23% of the patients had pathological scores in various neuropsychological functions, among which attention was the most clearly affected. The neuroradiological recovery was not correlated with the result of the neuropsychological tests. Age at onset correlated with linguistic skills, whereas the time elapsed from the acute event had a significant effect on attention tasks: scores were worse in the group of patients with a follow-up shorter than 7 years.ConclusionOur results suggest that pediatric monophasic acute disseminated encephalomyelitis has a favorable neurocognitive outcome. Patients with longer follow-up had a better outcome, suggesting a neurocognitive course that is different from that of multiple sclerosis and a potential for long-term recovery of affected functions.     

Rare brain biopsy findings in a first ADEM-like event of pediatric MS: histopathologic,neuroradiologic and clinical features

Pediatric MS tends to present more often with an acute onset and a polysymptomatic form of the disease, possibly with encephalopathy and large tumefactive lesions similar to those observed in some cases of acute disseminated encephalomyelitis (ADEM), which makes it more difficult to differentiate between an explosive and severe onset of MS vs. ADEM. An ADEM-like first demyelinating event can be the first attack of pediatric MS, but international consensus definitions require two or more non-ADEM demyelinating events for diagnosis of MS. In our patient KIDMUS MRI criteria for MS (Mikaeloff et al. J Pediatr 144:246–252, 2004a; Mikaeloff et al. Brain 127:1942–1947, 2004b) were negative at first attack, but Barkhof criteria for lesion dissemination in space in adults (Barkhof et al. 120:2059–2069, 1997), Callen modified MS-criteria and Callen MS-ADEM criteria for children (Callen et al. Neurology 72:961–967, 2009a; Callen et al. Neurology 72:968–973, 2009b) were positive suggesting pediatric MS. As the clinical course was devastating with non-responsiveness upon high-dose immune modulatory therapy and due to the absence of an alternative diagnosis other than demyelinating disease brain biopsy was performed. Brain biopsy studies or autopsy case reports of fulminant pediatric MS patients are extremely rare. Histopathology revealed an inflammatory demyelinating CNS process with confluent demyelination, indicating the likelihood of a relapsing disease course compatible with an acute to subacute demyelinating inflammatory disease. This pattern was corresponding to the early active multiple sclerosis subtype I of Lucchinetti et al. (Ann Neurol 47(6):707–717, 2000).     

Pediatric glioblastoma with oligodendroglioma component: Aggressive clinical phenotype with distinct molecular characteristics

The 2007 World Health Organization classification defined a new variant of glioblastoma (GBM) containing oligodendroglioma foci as GBM with an oligodendroglioma component (GBMO), which shows a favorable clinical outcome compared with “classic” GBM. However, all of the reported cases of GBMO have been adult cases, with no previous reports of pediatric cases. In this report, we demonstrated molecular characteristics of a pediatric GBMO case, showing aggressive clinical behavior with 8‐month overall survival. The case showed neither isocitrate dehydrogenase 1/2 genes (IDH1/2) mutation nor 1p/19q co‐deletion, a hallmark of oligodendroglioal tumors. In addition, microsatellite instability, leading to the putative mechanism of temozolomide (TMZ) resistance, was frequently detected. Molecular genetic analysis may provide critical prognostic and therapeutic insights, especially for the pediatric glioma containing oligodendroglioma components.     

Severe steroid-resistant post-infectious encephalomyelitis

Based on their presumed immuno-mediated etiology, post-infectious CNS disorders are commonly treated with high-dose steroids. Factors influencing treatment effectiveness, possible alternative options for steroid-resistant cases, and their outcome profiles, remain unclear. We here describe the clinical features, the prognosis and the efficacy of i. v. immunoglobulins (IVIg) in a series of severe ADEM refractory to steroids. We performed an inception cohort study on inpatients of the Neurologic and Infectious Disease Clinics, consecutively admitted over eight years, with a minimum two-year follow-up. Nineteen patients affected by classic and site-restricted ADEM were treated with IVIg after steroid failure. Five other patients received IVIg as first-line treatment due to steroids contraindications: although not included in the analysis, they were monitored for anecdotal comparison. Steroids were administered as IV 6-methylprednisolone (6-MP) 500/1000 mg daily until a maximum dose of 6-8 g; IVIg were administered at 0.4 g/kg/day for 5 days. The outcome was assessed by the Scripps Neurological Rating Scale (SNRS) score with determined periodicity. We observed that steroid-resistant patients showed high prevalence of PNS damage (89%) and myelitis (95 %). Other features were old age, severe disability at onset, and moderate to severe blood-brain-barrier (BBB) damage on CSF. In 10/19 patients (53 %) IVIg were effective, the clinical improvement beginning within the end of the five-day cycle,without relapses. Prominent effects of IVIg were detectable on motor dysfunction. Milder onset disability (p = 0.013) and lower CSF albumin (p = 0.006) were the predictors of IVIg response. Among steroid-free patients, 3/5 were responsive to IVIg. We conclude that IVIg can be useful in a portion of patients with severe steroid-resistant ADEM and prominent motor dysfunction. Unsolved issues regard the usefulness of IVIg in less selected groups, and the spectrum of their clinical effects.     

Single photon emission computerized tomography in childhood hydrocephalus

Single photon emission computerized tomography (SPECT) is now widely used as one of the tools in evaluating cerebral blood flow (CBF). The authors report the CBF changes in childhood hydrocephalus. Five pediatric cases studied by ¹²³I-IM SPECT in children are presented. The authors counted radioactivities both in early and delayed images in each patient, and calculated the reabsorption ratio (RR). Two negative-RR cases and three positive-RR cases were found. All of the negative-RR patients had a poor prognosis, while all of the positive-RR patients had a favorable outcome.     

The clinical course of acute disseminated encephalomyelitis

The objective of this review is to describe recent advances in understanding the clinical course of pediatric and adult acute disseminated encephalomyelitis (ADEM), especially the risk of relapse and conversion to multiple sclerosis (MS). The diagnosis of ADEM is reached on clinical grounds, typically in the setting of a post-infectious meningoencephalitic syndrome associated with multifocal neurological symptoms and signs, magnetic resonance imaging (MRI) evidence of white matter lesions and exclusion of other causes. Although typically monophasic, several case series demonstrate 'multiphasic' or 'recurrent' forms of ADEM with clinical relapses occurring within a short interval of disease onset. Furthermore, the estimated risk of developing MS is substantial for both children (0-33%) and adults (approximately 35%). Advances in neuroimaging have identified some MRI features that have predictive value for a relapsing course but they are not accurate enough for therapeutic decision-making; a diagnosis of monophasic ADEM should be made with caution in all cases, especially those presenting in adulthood. Research in ADEM and related disorders remains hampered by lack of prospective studies, specific and reproducible clinical case definitions and variable follow-up methods. Standardization of these variables would facilitate identification of more accurate diagnostic and prognostic variables, discovery and testing of potential objective biomarkers that would, in turn, allow early prediction of a relapsing course and appropriate therapeutic interventions.     

Giant Cerebellar Cavernomas in Pediatric Patients: Systematic Review with Illustrative Case

IntroductionGiant cavernomas (GCMs) are angiographically occult vascular malformations of the central nervous system measuring at least 4 cm in diameter. These are rare lesions, especially in the cerebellum. As such, the clinical and radiologic features, surgical management, and outcomes of treatment for this condition are unknown.MethodsWe performed a systematic review of SCOPUS and PubMed databases for case reports and case series of histopathologically proven GCMs arising from the cerebellum in the pediatric population, and included a case managed at our center. Data on clinical presentation, imaging features, surgical treatment and outcomes of management were collected.ResultsA total of 10 cases were identified from the systematic review, including our case report. The patients’ median age was 6 months, with a slight male sex predilection (1.5:1). The most common neurologic manifestations were bulging fontanelle in infants, and headache and focal cerebellar deficits in older children. Surgical excision was done in all cases, while 50% of the cases had CSF diversion surgery done prior to excision. In cases with reported outcome, complete neurologic recovery was achieved in seven while partial recovery was reported in one case. No deaths were reported at median follow-up of 12 months.ConclusionOur case report and systematic review show that giant cerebellar cavernoma is a rare differential diagnosis for symptomatic hemorrhagic cerebellar masses in the pediatric age group. Mainstay of treatment is surgical excision, which can be associated with favorable outcome in most cases.