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Acute Disseminated Encephalomyelitis: Clinical Features, Pathophysiology, 7 and Clinical Management

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Acute Disseminated Encephalomyelitis: Clinical Features, Pathophysiology, 7 and Clinical Management Acute Disseminated Encephalomyelitis: Clinical Features, Pathophysiology, 7 and Clinical Management Omar Hussein and Alireza Minagar Introduction ADEM is a presumably immune-mediated multifocal or diffuse inflammatory demyelinating disease of the brain and the spinal cord that, often but not always, occurs para-infection or postvaccination. It affects children more commonly than adults but that might be attributed to the more clearly defined diagnostic criteria available for children more than adults who might also have pre-existing white mat- ter lesion(s) secondary to a different pathology leading to underscoring adult ADEM [1]. From certain viewpoints, ADEM resembles MS and other demyelinating dis- eases; however, significant differences do exist. ADEM occurs worldwide and usu- ally males and females are affected equally, unlike relapsing-remitting MS that is more common among females. However few studies suggested slight male pre- dominance [2–4]. A cornerstone landmark for the diagnosis of ADEM, especially in children, is encephalopathy in the absence of fever along with other manifestation [1]. This is attributed to the early involvement of the cortical gray matter in the course of the disease unlike most other demyelinating conditions in which cortical involvement usually occurs latter as the disease progresses. Gray matter involve- ment also causes dystonia and other movement disorders [3]. ADEM rarely exists in multiphasic and recurrent forms, but if occurred, encephalopathy remains the cornerstone. To date, there is no unique biomarker that exists to distinguish ADEM from other demyelinating or non-demyelinating conditions making it mostly a diag- nosis of exclusion [3]. Pathological differences also do exist between the different autoimmune demyelinating conditions according to biopsy and postmortem tissue analysis [5]. Neuroimaging is, somehow, helpful as ADEM usually presents as mul- tifocal larger lesions or less commonly as a single large confluent white and deep O. Hussein, MD • A. Minagar, MD (*) Department of Neurology, LSU Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA e-mail: [email protected] © Springer International Publishing AG 2017 161 A. Minagar, J.S. Alexander (eds.), Inflammatory Disorders of the Nervous System, Current Clinical Neurology, DOI 10.1007/978-3-319-51220-4_7 162 O. Hussein and A. Minagar gray matter bilateral symmetrical lesion involving the basal ganglia and the thalami that, sometimes but not always, enhance. Despite of this, tumefactive MS and dif- ferent brain tumors especially gliomas can mimic this presentation making the diag- nosis and early initiation of treatment a dilemma. Recently, advances in neuroimaging including MR perfusion, spectroscopy, and susceptibility images have been used to try to differentiate between these conditions. Large randomized studies still lack regarding these attempts. The cornerstone in the treatment of ADEM is early initia- tion of pulse steroid therapy followed by oral taper. It is crucial to differentiate ADEM from other autoimmune demyelinating conditions as usually ADEM does not require long-term immune modulation or immune suppression, but in some cases, this remains difficult and thus requires close follow-ups for any relapses or new lesions to appear. In some mimicking conditions like lymphoma, early pulse steroid therapy without reaching a definite diagnosis might create a real challenge as this might mask the diagnosis of lymphoma even if brain biopsy is performed later on. Thus, in such challenging suspicious cases, brain biopsy is recommended. Clinical Features ADEM is usually a monophasic disease with acute onset. However, hyperacute and subacute cases as well as multiphasic and recurrent cases have been described [1– 4]. Patients with ADEM are mostly children with mean age between 5 and 8 years old [2, 3]. The clinical manifestations depend on the location, severity, and extent of the lesions. Clinical feature usually commences 1–4 weeks following the infection. Encephalopathy, defined as altered sensorium ranging from drowsiness to coma or just behavioral changes in the absence of fever, systemic illness, or seizure, is the key manifestation required for the diagnosis of ADEM [1]. Other neurologic pre- sentations including headache, fever, and seizures (35%) are among the common clinical manifestations. Uncommonly and depending on the location of the demye- linating lesions, optic neuritis, myelitis, ataxia, weakness and sensory abnormali- ties, abnormal involuntary movements, ataxia, falls, aphasia (uncommonly), cranial nerve palsies (apart from optic nerves), and general presentations of meningitis and encephalitis can occur. Respiratory compromise can occur if brain stem is affected. A number of patients with ADEM also develop neuropsychiatric syndrome. Signs of long tract involvement such as hyperactive reflexes as well as the presence of clonus and extensor plantar responses are also commonly present. Nevertheless, peripheral nervous system demyelination is not unusual in pediatric and adult patients [3]. The neurological manifestations of ADEM tend to fluctuate and evolve during the first 3 months of onset; thus, recurrence should not be considered before 3 months. According to the revised International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria in 2012, this is irrespective of corticosteroid use (Table 7.1) [1]. A key exclusionary criterion is the lack of clinical or imaging evidence of prior CNS lesions [6]. 7 Acute Disseminated Encephalomyelitis: Clinical Features, Pathophysiology 163 Table 7.1 Comparison of 2007 and 2012 definitions for pediatric acute demyelinating disorders of the central nervous system (CNS) Disorder 2007 2012 CIS A first monofocal or multifocal A first monofocal or multifocal CNS CNS demyelinating event; demyelinating event; encephalopathy is encephalopathy absent absent, unless due to fever Monophasic A first polysymptomatic clinical A first polyfocal clinical CNS event with ADEM event, with presumed presumed inflammatory cause inflammatory cause that affects Encephalopathy that cannot be multifocal areas of the CNS explained by fever is present Encephalopathy is present MRI typically shows diffuse, poorly MRI typically shows large, demarcated, large, 1–2 cm lesions ≥1–2 cm white matter lesion; involving predominantly the cerebral gray matter involvement white matter; TI hypointense white (thalamus or basal ganglia) is matter lesions are rare; deep gray matter frequent (e.g., thalamus or basal ganglia) can be New or fluctuating symptoms, present signs, or MRI findings within No new symptoms, signs, or MRI 3 months of the incident ADEM findings after 3 months of the incident are part of the acute event ADEM Recurrent New event of ADEM with a Now subsumed under multiphasic ADEM recurrence of the initial ADEM symptoms and signs, three or more months after the first ADEM event Multiphasic New event of ADEM, but New event of ADEM 3 months or more ADEM involves new anatomic areas of after the initial event that can be the CNS and must occur at least associated with new or reemergence of 3 months after the onset of the prior clinical and MRI findings. Timing initial ADEM event and at least in relation to steroids is no longer 1 month after completing steroid pertinent therapy MS Any of the following: Any of the following: Multiple clinical episodes of Two or more nonencephalopathic CNS demyelination separated CNS clinical events separated by in time and space more than 30 days, involving more Single clinical event which is than one area of CNS associated with 2001 Single clinical event and MRI features McDonald Brain MRI criteriaa rely on 2010 Revised McDonald for DIS and subsequent criteriab for DIS and DIT [4] (but changes on MRI consistent criteria relative for DIT for a single with criteria 2001 McDonald attack and single MRI only apply to criteria for DIT [4] children ≥12 years and only apply to An episode consistent with the cases without an ADEM onset) clinical features of ADEM ADEM followed 3 months later by a cannot be considered as the nonencephalopathic clinical event first event of MS with new lesions on brain MRI consistent with MS (continued) 164 O. Hussein and A. Minagar Table 7.1 (continued) Disorder 2007 2012 NMO All are required: All are required: Optic neuritis Optic neuritis Acute myelitis Acute myelitis At least one of two supportive At least two of three supportive criteria criteria Contiguous spinal cord MRI Contiguous spinal cord MRI lesion lesion ≥3 vertebral segments ≥3 vertebral segments Anti-aquaporin-4 IgG Brain MRI not meeting diagnostic seropositive status criteria for MS Anti-aquaporin-4 IgG seropositive status ADEM acute disseminated encephalomyelitis, CIS clinically isolated syndrome, CNS central ner- vous system, DIS dissemination in space, DIT dissemination in time, MRI magnetic resonance imaging, MS multiple sclerosis, NMO neuromyelitis optica aThe 2001 McDonald MRI criteria for DIS require three of the following four MRI features: ≥9 T2 lesions or 1 gadolinium-enhancing lesions, ≥3 periventricular lesions, ≥1 infratentorial lesion(s), and ≥1 juxtacortical lesion(s). The DIT criteria require subsequent white matter lesions whose timing depends on the temporal relation of the initial MRI with the onset of the clinical symptoms bThe 2010 Revised McDonald MRI criteria for DIS require the presence of at least two of the fol- lowing four criteria: ≥1 lesion in each of the four locations; periventricular, juxtacortical, infraten- torial,
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