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 [14]. 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 presentations 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 abnormalities, 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].

Table 7.1 Comparison of 2007 and 2012 definitions for pediatric acute demyelinating disorders of the central nervous system (CNS)

(continued)

Table 7.1 (continued)

ADEM acute disseminated encephalomyelitis, CIS clinically isolated syndrome, CNS central nervous 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 following four criteria: >1 lesion in each of the four locations; periventricular, juxtacortical, infratentorial, and spinal cord. The 2010 Revised McDonald MRI criteria for DIT can be satisfied either by the emergence of newT2 lesions (with or without enhancement) on serial scan(s) or can be met on a single baseline scan if there exists simultaneous presence of a clinically silent gadoliniumenhancing lesion and a nonenhancing lesion

While ADEM is generally considered a monophasic disease, patients with ADEM and multiphasic course or recurrent attacks exist as mentioned above [1]. According to the revised IPMSSG criteria, recurrent ADEM is now subsumed under multiphasic ADEM. Thus, multiphasic ADEM is now defined as new event of ADEM 3 months or more after the initial event that can be associated with new or reemergence of prior clinical and MRI findings [1].

After publishing the initial IPMSSG in 2007, few prospective studies are conducted to evaluate the predictive value of such criteria in predicting relapse of the first episode of ADEM to MS. For this to occur, the second episode was defined as nonencephalopathic event with new MRI finding consistent with dissemination in space occurring at least 3 months after the first episode. A second relapse consistent with MS rather than multiphasic ADEM was detected in 2-18%. Of all relapses, 80% occurred with 2 years of the first event [2, 4].

Acute hemorrhagic leukoencephalitis (AHLE) is rare variant of ADEM (< 2%) commonly presenting with fever, neck stiffness, seizures, and/or focal neurological deficits following upper respiratory infection with more rapid progression within days leading to coma and death in some cases due to increased cerebral edema and herniation if untreated urgently. It is considered the most aggressive of all demyelinating diseases. Areas of hemorrhage and necrosis along a massive white matter involvement are evident on the MRI. Many cases are diagnosed on postmortem autopsy [7].