Acute Disseminated Encephalomyelitis Clinical Trial
Official title:
Management of Acute Disseminated Encephalomyelitis in Neurology Unit of Assiut University Children Hospital
Acute disseminated encephalomyelitis is an immune-mediated inflammatory demyelinating disease of the central nervous system, which is typically transitory and self-limiting. It is characterized by an acute or subacute encephalopathy with neurological deficits, and magnetic resonance imaging evidence of widespread demyelination that predominantly involves the white matter of the brain and spinal cord. In the absence of specific biological markers, the diagnosis of Acute disseminated encephalomyelitis is still based upon a combination of clinical and neuro imaging features and exclusion of diseases that mimic Acute disseminated encephalomyelitis
Acute disseminated encephalomyelitis can occur at any age, but usually affects children and
young adults. The mean age of clinical presentation in pediatric cohorts ranges from 5 to 8
years. The annual incidence of Acute disseminated encephalomyelitis is reported to be 0.4-0.8
per 100,000 and the disease more commonly affects children and young adults, probably related
to the high frequency of exanthematous and other infections and vaccination in this age
group.Initial symptoms and signs of Acute disseminated encephalomyelitis usually begin within
2 days to 4 weeks after a viral infection or vaccination, and include a rapid onset
encephalopathy (behavioral change or altered consciousness) associated with a combination of
multifocal neurological deficits, leading to hospitalization within a week. Typically Acute
disseminated encephalomyelitis presents with systemic symptoms such as fever, malaise,
headache, nausea, and vomiting, which may occur shortly before the appearance of neurological
signs and symptoms. The clinical course is rapidly progressive, developing maximum deficits
within a few days (mean 4.5 days) . A wide variety of neurological deficits have been
described in pediatric patients with Acute disseminated encephalomyelitis, including:
obtundation and depressed consciousness (invariable); unilateral or bilateral long tract
signs (60-95%); acute hemiplegia (76%); ataxia (18-59%); meningismus (26-31%); seizures
(13-35%); spinal cord involvement (24%); visual involvement (7-23%); and speech impairment or
aphasia (5-21%). Cerebellar mutism and prolonged focal motor seizures in the context of Acute
disseminated encephalomyelitis have been mainly reported in children younger than 5 years of
age.Acute combined peripheral nervous system demyelination is not rare in children with Acute
disseminated encephalomyelitis whereas it is more frequently described in adult patients,
with a reported frequency of 44% in one study. A particular Acute disseminated
encephalomyelitis phenotype affecting young children has been reported in association with
group A beta hemolytic streptococcal infection. Prominent behavioral disturbances, dystonic
movements, and basal ganglia abnormalities on MRI (in addition to typical white matter
lesions) characterize this syndrome.
Supportive care in the acute stage is critical and early antiviral treatment with acyclovir
(30 mg/kg/ day) is highly recommended on admission, considering that viral encephalitis and
particularly herpes simplex encephalitis is the usual primary diagnosis in a child with
fever, encephalopathy, seizures, and focal neurological signs. The treatment for Acute
disseminated encephalomyelitis includes primarily the management of acute attacks.
Corticosteroid treatment at high doses is the most widely reported therapy. Most authors
recommend a brief (3-5 days) high-dose intravenous steroid course, usually methylprednisolone
given at 20-30 mg/kg/day to a maximum dose of 1 g/day, or dexamethasone given at 1 mg/kg/day,
followed by oral prednisone taper for 4-6 weeks . Reported treatment approaches show a wide
variety in the specific steroid formulation employed, as well as in the dosing, routes of
administration, and tapering regimens. Treatment with corticosteroids requires careful
monitoring of blood pressure, urine glucose, and serum potassium, and administration of
gastric protection. The use of immunoglobulin has been reported in several case studies
either alone or in combination with corticosteroids. The recommended total dose of
immunoglobulin is 2 g/kg, administered over 2-5 days. The usefulness of immunoglobulin has
been reported both as a second-line treatment in steroid-unresponsive Acute disseminated
encephalomyelitis cases and in patients showing recurrent or steroid-dependent demyelination.
The use of plasma exchange has been recently established as possibly effective and it may be
considered as escalation therapy for steroid-unresponsive acute fulminant demyelinating
diseases including Acute disseminated encephalomyelitis, multiple sclerosis, and transverse
myelitis, . Plasmapheresis should be started as soon as the treatment failure is recognized.
The use of this procedure in Acute disseminated encephalomyelitis has been reported in only a
small number of severe cases. A median number of seven exchanges (range 2 to 20) were
reported in one study. Moderate to severe anemia, symptomatic hypotension, hypocalcemia,
potential transfusion reactions or transmission of transfusion-related diseases, and
heparin-associated thrombocytopenia have been described in relation to therapeutic plasma
exchange. There is also a risk of catheter-related complications, including thrombosis,
septic infections or pneumothorax.
Acute hemorrhagic leukoencephalitis is often considered the most acute and severe form of
Acute disseminated encephalomyelitis, with a universally fatal course within hours to days
after the onset of neurological symptoms without treatment. Survival in pediatric patients
has been reported with combined therapy including high-dose intravenous corticosteroid,
immunoglobulin, Therapeutic plasma exchange, and decompressive craniotomies. Aggressive
treatment strategies such as surgical decompression have to be considered and performed in
patients with fulminant variants of Acute disseminated encephalomyelitis, with evidence of
continued clinical deterioration due to increased intracranial pressure, unresponsive to
conventional medical treatment and critical care measures.
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