Fulminant acute disseminated encephalomyelitis in children

Acute disseminated encephalomyelitis (ADEM) is a typically monophasic inflammatory demyelinating disease of the central nervous system with a favorable outcome. However, 2% of ADEM involves acute hemorrhagic leukoencephalitis (AHLE), which is a fulminant and hyperacute variant of ADEM with a poor outcome and high mortality. There are limited case reports of fulminant ADEM including AHLE in children. Herein, we report two pediatric cases of fulminant ADEM. Both cases had a rapid deterioration of consciousness, repetitive seizures, and brain edema on neuroimaging, in addition to atypical neuroradiological findings on magnetic resonance imaging (MRI), a reversible splenial lesion in case 1, and bilateral frontal and occipital cortical lesions in case 2. Both cases were treated with early high-dose methyl-prednisolone and immunoglobulin, while therapeutic hypothermia was also initiated in case 2 after the patient exhibited a decerebrate posture and irregular breathing pattern. Both cases had a favorable outcome. Further case reports on pediatric fulminant ADEM are required to clarify the various clinical types, and to examine the efficacy of various treatment modalities for fulminant ADEM and AHLE in children.     

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。     

MRI and proton MR spectroscopy in acute disseminated encephalomyelitis

Introduction Acute disseminated encephalomyelitis (ADEM) is one of a group of demyelinating disorders of the central nervous system (CNS). It is said to be attributed to an overshooting immunologic response following an infection or vaccination. The clinical course and type of manifestation is heterogeneous. The early application of corticosteroids has been shown to be beneficial to outcome; thus, an early diagnosis is highly desirable.Methods The potential diagnostic value of advanced MR techniques such as proton MR spectroscopy and diffusion-weighted imaging (DWI) was investigated in two paediatric patients with ADEM, one of whom had a remitting and relapsing clinical course and presented with additional cranial nerve involvement. Proton MR spectroscopy revealed typical signs of acute demyelination, such as increased macromolecules, not found in other forms of non-necrotising pathology.Conclusion The addition of proton MR spectroscopy and DWI adds to the diagnostic power of MRI in the setting of post-infectious demyelinating disorders of the CNS or ADEM and may obviate the need for biopsy.     

Probable acute disseminated encephalomyelitis due to Haemophilus influenzae meningitis

We report the case of a 17-year-old male on long-term steroid therapy for minimal lesion glomerulopathy who, after an upper respiratory infection, presented with Haemophilus influenzae type b meningitis. Twenty-four hours later he developed depression of consciousness which progressed to coma and left hemiparesis. Brain magnetic resonance imaging (MRI) revealed multiple lesions (hyperintense on T2 and slightly hypointense on Tl) involving mainly white matter suggestive of inflammation. MRI features were compatible with acute disseminated encephalomyelitis (ADEM), although a differential diagnosis included cerebritis or vasculitis, secondary to bacterial meningitis. The patient was treated with high-dose steroids which resulted in a gradual improvement followed by complete clinical recovery. We propose a diagnosis of ADEM was the best diagnosis because of the radiological features and response to steroids. The occurrence of ADEM associated with acute meningitis, however rare, represents an important diagnostic challenge for the clinician.     

急性播散性脑脊髓炎的临床及影像学特征

目的探讨并总结急播散性脑脊髓炎的临床表现特征、治疗策略及转归情况。方法通过收集华中科技大学附属同济医院神经内科住院治疗的急性播散性脑脊髓炎病例,详细分析患者发病的临床表现及相关辅助检查结果,并对其治疗后的转归情况进行随访调查。结果4例患者中3例为中年,1例为青壮年,均急性起病,脑和脊髓损害的表现在时间上重叠出现,有明显的脑脊液及影像学检查改变,在急性期采用甲基强的松龙冲击治疗,结合神经营养及支持治疗均好转。结论急性播散性脑脊髓膜炎临床表现多种多样,在神经内科临床工作中较易误诊及漏诊,如能早期诊断并早期应用激素治疗效果良好,可极大改善其预后。     

Recurrence of acute disseminated encephalomyelitis at the previously affected brain site

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a usually monophasic demyelinating disorder of the central nervous system. Recurrences pose a diagnostic challenge because they can be overlooked or suggest an alternative diagnosis. OBJECTIVE: To examine the frequency, nature, and outcome of recurrent ADEM. DESIGN: Review of the medical records of patients diagnosed in our institution as having ADEM between January 1, 1983, and May 31, 1998. Recurrences were defined as appearance of new symptoms and signs at least 1 month after the previous episode. RESULTS: Five (24%) of 21 patients with ADEM developed recurrent disease episodes. In all, diagnosis was confirmed by brain biopsy. One patient had 4 disease episodes, 2 had 3, and the other 2 each had 2. Recurrence appeared 1.5 to 32 months after initial presentation and involved the same brain territory in 6 of 9 recurrences in 3 of 5 patients. In 2 patients, recurrences included neuropsychiatric signs. A good response to corticosteroid therapy was observed in 10 of 13 of treated ADEM attacks: in 3 of the 4 treated initial events and in 7 of 9 recurrences. CONCLUSIONS: Recurrent ADEM may be more prevalent than previously recognized. Patients who relapse tend to have more than 1 recurrence that usually involves, clinically and radiologically, a brain territory that was affected before and can simulate a space-occupying lesion that requires histologic diagnosis. Neuropsychiatric features may be the main presentation of a relapse. Since recurrent ADEM is a corticosteroid-responsive condition, awareness and early diagnosis are mandatory.     

Multiple sclerosis and acute disseminated encephalomyelitis diagnosed in children after long-term follow-up: comparison of presenting features

The aim of this study was to compare the characteristics of the first demyelinating event between acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS). Children with acute demyelinating disease of the central nervous system and an abnormal brain magnetic resonance image (MRI) were studied. Patients were assigned a final diagnosis after long-term follow-up. Comparisons were made between the MS and ADEM groups. Proposed definitions by the Pediatric MS Study Group were applied to our cohort in retrospect and are discussed. Fifty-two children and adolescents with a documented abnormal brain MRI were identified (24 females, 28 males; mean age 10y 11mo [SD 5y 4mo] range 1y 10mo–19y 7mo). To date, 26 children have been diagnosed with MS, and 24 with ADEM. One child has relapsing neuromyelitis optica and one child has clinically isolated optic neuritis. Follow-up duration was 6 years 8 months in monophasic patients, and 5 years 6 months in relapsing patients. None of the patients with MS had encephalopathy while encephalopathy was present in 42% of patients with ADEM. Cerebrospinal fluid oligoclonal bands, an elevated immunoglobulin and the periventricular perpendicular ovoid lesions correlated with MS outcome. Several clinical characteristics differ between ADEM and MS at first presentation; encephalopathy, when present, strongly suggests the diagnosis of ADEM.     

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.     

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。     

Development of demyelinating lesions in progressive multifocal leukoencephalopathy (PML): Comparison of magnetic resonance images and neuropathology of post‐mortem brain

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder caused by opportunistic infection of JC polyomavirus (JCV). Today, increased attention has been focused on PML development in multiple sclerosis (MS) patients under disease‐modifying therapies (DMT). Although in the acquired immunodeficiency syndrome (AIDS) era, PML was thought to be a rapidly progressive disease with poor prognosis, drug‐associated PML is relatively slow in progress, and a favorable outcome may be expected with early diagnosis. However, early PML diagnosis on magnetic resonance imaging (MRI) is frequently difficult, and JCV DNA copy number in cerebrospinal fluid (CSF) is usually low. To facilitate early PML diagnosis on MRI, the pre‐mortem images were compared with neuropathology of the post‐mortem brain, and underlying pathology corresponding to the MRI findings was evaluated. As a result, PML lesions of the autopsied brain were divided into three parts, based on the disease extension patterns: (A) Progressive white matter lesion in the right frontoparietal lobe including the precentral gyrus. Huge demyelinated lesions were formed with fusions of numerous small lesions. (B) Central lesion including deep gray matters, such as the putamen and thalamus. The left thalamic lesion was contiguous with the pontine tegmentum. (C) Infratentorial lesion of brainstem and cerebellum. Demyelination in the pontine basilar region and in cerebellar white matter was contiguous via middle cerebellar peduncles (MCPs). In addition, (D) satellite lesions were scattered all over the brain. These observations indicate that PML lesions likely evolve with three steps in a tract‐dependent manner: (1) initiation; (2) extension/expansion of demyelinating lesions; and (3) fusion. Understanding of the PML disease evolution patterns would enable confident early diagnosis on MRI, which is essential for favorable prognosis with good functional outcome.     

The head MRI by fluid attenuated inversion recovery (FLAIR) was useful for diagnosis in the patient with post influenza vaccinal acute disseminated encephalomyelitis (ADEM)

A 6-year-old, previously healthy boy developed ataxia and muscle weakness, 16 days after influenza vaccination. The CSF showed an elevated level of myelin basic protein, pleocytosis and negative influenza virus isolation. The head MRI revealed an extensive high intensity area in the deep white matter, which was more clearly defined on FLAIR images. The diagnosis of post influenza vaccinal ADEM was made, and he was successfully treated by steroid pulse therapy with a monophasic course and favorable outcome.     

急性播散性脑脊髓炎12例临床分析

目的探讨急性播散性脑脊髓炎临床特点及治疗原则。方法回顾1990年5月-2010年12月住院治疗且诊断明确的急性播散性脑脊髓炎患者临床资料,结合文献分析其临床表现、实验室检查及影像学特点。结果共12例患者符合入组条件,男性10例,女性2例,年龄6～69岁(中位年龄34.50岁)。其中9例发病前出现前驱感染症状如上呼吸道感染(6例)或无诱因发热(3例),以及诱发因素如麻疹疫苗接种史(1例)或麻疹病史(1例)。临床主要表现为发热,恶心、呕吐,头痛,神经系统症状与体征以脑神经受累(展神经常见),瘫痪(偏瘫、截瘫、四肢瘫),感觉异常,膀胱功能障碍[尿失禁和(或)尿潴留],脑膜刺激征阳性,以及不同程度意识障碍为主。大剂量糖皮质激素冲击疗法或人血丙种球蛋白静脉注射治疗有效。结论尽管急性播散性脑脊髓炎发病凶险,但早期明确诊断及鉴别诊断,及时治疗,可明显改善患者预后。     

Acute disseminated encephalomyelitis: prognostic value of early follow-up brain MRI

Patients with acute disseminated encephalomyelitis (ADEM) are presumed to have radiological monophasic disease, but this is uncertain since follow-up brain MRI is not routinely performed. We aimed to ascertain combined radiological and clinical monophasic disease in ADEM patients and to assess whether performing early (<6 months) follow-up brain MRI has prognostic value for subsequent multiphasic disease. We retrospectively studied the medical records of patients initially diagnosed with ADEM (years 2000–2014) at the Massachusetts General Hospital, USA. A neuroimaging specialist, masked to clinical events, reviewed all available brain MRIs. We included 62 patients (25 male; 30 pediatric; median clinical follow-up 3 years) and classified them into two subgroups: (1) clinically monophasic (no new, recurrent or worsening neurological symptoms >3 months after onset) (n = 45), and (2) clinically multiphasic (clinical relapse >3 months after onset) (n = 17). All clinically monophasic patients with brain MRI follow-up (n = 30) also had radiological monophasic disease a median of 2 years after ADEM onset. New lesions (58 vs. 14%) and persistent lesions (100 vs. 18%) on early brain MRI [available in 40 patients (65%)], as well as clinical flares (53 vs. 20%), were more common in clinically multiphasic versus monophasic patients. These early follow-up data allowed us to predict multiphasic disease with reasonable accuracy in a multivariable model (AUC = 0.73). We conclude that performing early follow-up brain MRI routinely in ADEM patients would aid clinicians in predicting multiphasic disease and may stratify patients who would benefit from initiation of disease-modifying therapy for multiple sclerosis.     

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.     

Acute disseminated encephalomyelitis in adults: a reappraisal of clinical, CSF, EEG, and MRI findings

Objectives To establish an adequate definition of acute disseminated encephalomyelitis (ADEM) in adults, based on our clinical observations of a case-series. Methods Over a period of three years 10 adult patients with a para- or postinfectious disseminated (diffuse or multifocal) syndrome of the CNS fulfilling predefined strict criteria for the diagnosis of ADEM were encountered and systematically followed. Results The age ranged from 21 to 62 years, two were men. MRI was normal in 5 patients and only mildly abnormal in the remaining patients. CSF was normal in 5 patients and mildly abnormal in the remainder, EEG was abnormal in 7/8 patients. All patients survived and were followed over a period of 30 months (range: 8 to 48 months). Nine patients were left with some residual defects, consisting most often of a mild cognitive impairment. Conclusions The EEG as an investigation of brain function can be crucial in establishing the organic nature of disease. MRI is important to exclude other diffuse or multifocal encephalopathies. However, in contrast to previous reports in the literature abnormal MRI should not be considered mandatory in adult ADEM. Difficulties in the diagnosis of ADEM are discussed and the importance of clinical and paraclinical findings for establishing the diagnosis is outlined. Received: 20 April 2001, Received in revised form: 19 July 2001, Accepted: 25 July 2001     

Acute Disseminated Encephalomyelitis Confined to Brainstem

A 21-year-old man was troubled with a subacute history of brainstem involvement and a leukocyte pleocytosis in the cerebrospinal fluid. Magnetic resonance imaging (MRI) demonstrated a massive lesion with Gd enhancement in the pons. Steroid therapy, not antiviral drugs, was dramatically effective for the mass reduction and symptom improvement. Over 4 years no recurrence has been recognized, so this case was diagnosed to be an unusual case of acute disseminated encephalomyelitis (ADEM). ADEM must be included in the differential diagnosis for a brainstem mass in MRI.     

Childhood autoimmune neurologic diseases of the central nervous system

An autoimmune mechanism for ADEM and MS can be supported by the similar patterns of pathologic changes seen in both diseases with the animal model EAE induced by inoculating animals with nervous tissue and the occurrence of ADEM in patients exposed to nervous tissue during vaccination. Whereas there are no universally agreed-upon criteria for the diagnosis of ADEM, a combination of prodromal illness or preceding vaccination, MRI signs of demyelination, and an acute presentation of neurologic symptoms are the triad most commonly looked for in making the diagnosis of ADEM. An ever-increasing number of infections and vaccinations (nonspecific URIs being most common) has been associated with ADEM. Fever and encephalopathy are seen frequently at presentation. Seizures also are common, as are cranial nerve abnormalities and motor symptoms. A mild pleocytosis or protein elevation is found in the majority of patients with ADEM. Intrathecal IgG synthesis and oligoclonal bands are relatively infrequent but should not be considered inconsistent with the diagnosis of ADEM. White matter changes on T2 in a bilateral although asymmetric distribution with relative sparing of the periventricular region with or without deep gray matter involvement is consistent and to some a requirement for the diagnosis. Low-dose steroids have no beneficial effect in the treatment of ADEM and may be contraindicated. High-dose steroids may have a beneficial effect, particularly in more prolonged illnesses, although the evidence is primarily anecdotal. If steroids are used to improve morbidity, 30 mg/kg/d of methylprednisolone for three to five days is the dose with a six-week taper to reduce the risk of recurrence. The prodromal infection may be a major factor in the ultimate mortality and morbidity of the disease. The current mortality of ADEM is quite low. Whether or not this is an effect of different triggering agents or changes in medical care cannot be determined. In larger series of patients with ADEM, 10% to 20% of children experience some sort of recurrence with the majority occurring in the initial one to two months after the first event. This is sometimes associated with steroid withdrawal. A second group of children have a late second recurrence that clinically may not be MS but a recurrence of ADEM, although longer follow-up may change that assessment. Two months should be allowed before a second relapse is considered a manifestation of MS, whereas a second attack also may occur years after an initial attack of ADEM and still be consistent with ADEM recurrence. MS does occur during childhood, with the youngest children at the least risk, and risk increasing with age. The criteria of Poser et al can be used to diagnose MS in childhood [40]. The presentation of MS in childhood is most often sensory, motor, and brainstem signs and symptoms. A relapsing-remitting course is most common with a first relapse occurring in the year after presentation. MRI findings in MS typically show periventricular changes. Oligoclonal bands and CSF IgG synthesis are found in the majority. Treatments of childhood MS have not been studied adequately, but, when treatments studied in adults are used in children, they are well tolerated. Efficacy has not been shown. The long-term outcome of MS in childhood can be either severe or benign with no clear consensus that childhood MS is either a less or more severe disease than the adult form. ATM and ON treatments and outcomes are particularly difficult to evaluate because of the heterogeneity of populations included in case series and the small numbers reported. Steroids are used with anecdotal reports of their superiority to nontreatment. Outcome in ATM often can be poor, whereas in ON it rarely is. A multinational collaborative effort to study and collect the large numbers necessary to address the important questions in these childhood autoimmune disorders would be of great benefit and the only way likely to demonstrate good evidenced-based medicine practiced in this field.     

急性播散性脑脊髓炎的临床特点

目的探讨急性播散性脑脊髓炎（ADEM）的临床特点。方法对3例ADEM患者的临床表现、辅助检查、治疗及预后等进行回顾性分析。结果 3例ADEM中2例有前驱感染史,1例有手术史,首发症状分别为意识障碍、头晕和癫癇发作,头颅磁共振（MRI）见颅内多发长T1、长T2信号,呈环形或脑回样强化,累及双侧大脑、小脑和脑干,以双侧侧脑室旁和丘脑常见,经糖皮质激素治疗后病情迅速缓解。结论 ADEM是一种急性炎性脱髓鞘疾病,认识该病的临床及MRI特点可使患者得到及时诊治,改善预后。     

Acute disseminated encephalomyelitis in children: outcome and prognosis

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is the most common demyelinating disorder of childhood. Its clinical features, prognosis and treatment vary in different reports. OBJECTIVES: To examine a series of children with ADEM for clinical findings, course, recurrences, and possible variables affecting outcome. METHODS: Multicentric data collected from 7 tertiary referral centers were registered and evaluated in a central database in 1990 - 2001 for clinical, laboratory, and MRI features. Course and prognosis were assessed in patients with at least 12 months' follow-up. RESULTS: Forty-six patients were evaluated. Median age at onset was 8 years, M/F ratio, 1.7/1. Most common symptoms and signs pertained to the motor system and consciousness. Of 39 children with 12 months' follow-up, 71 % recovered completely. Thirteen (33 %) children had relapses. Patients who had more than one relapse (n = 4) presented with new symptoms at each attack. Treatment with high-dose methylprednisolone was associated with complete recovery, and tapering over more than 3 weeks, with a lower rate of relapses. MRI lesions could persist even in asymptomatic patients; in particular, periventricular lesions tended to disappear later than others. CONCLUSIONS: Complete clinical recovery is common and serious complications are rare in childhood ADEM, but the rate of relapses is considerable. Clinical picture at first relapse may help to identify patients likely to experience multiple relapses. The timing and duration of steroid treatment affects outcome.     

急性播散性脑脊髓炎8例临床分析

目的研究急性播散性脑脊髓炎(ADEM)的临床特点。方法对8例临床确诊为ADEM患者进行回顾及随访,并对临床和影像学表现等进行分析。结果(1)临床表现:5例病前有前驱感染或疫苗接种史,3例无明显诱因,神经系统症状多样。(2)影像学表现:主要累及脑白质的脱髓鞘病变,4例累及丘脑,2例累及脊髓。(3)治疗及预后:8例全用激素,其中7例予甲基泼尼松龙冲击。4例同时合用人血丙种球蛋白。8例均经6个月～2年随访,无复发,其中3例遗留后遗症。结论ADEM是一种中枢神经系统炎性脱髓鞘疾病,临床表现多样。MRI表现有一定的特征性,MRI检查有利于早期诊断,也是评价疗效的重要手段。