Acute disseminated encephalomyelitis

Acute disseminated encephalomyelitis (ADEM)

Demyelinating diseases of the central nervous system

ADEM classically occurs in children and young adults. The mean age of onset is 5–15 years.
It typically follows a febrile illness with viral exanthem mainly measles, rubella, varicella and many others (Postinfectious encephalomyelitis) or vaccination mainly rabies (postvaccination encephalomyelitis) by 1–4 weeks, often after the exanthem and the initial fever subside.
Clinical features

The onset is usually with a low-grade fever and headache

drowsiness and encephalopathy
which may progress to stupor and coma.

Neurological deficits

are typically multi-focal

seizure

Ataxia,
hemiparesis
Hemisensory loss
paresthesia
Abnormal movement (choreoathetosis, myoclonus)
Visual loss
cranial
nerve palsies


These clinical features evolves rapidly over several hours, a day or two.
It is rarely fulminant, with acutely raised intracranial pressure leading to tentorial herniation and death within 72 hours. Respiratory failure resulting from brainstem involvement may also occur.

Pathogenesis

It is generally accepted that the pathogenesis of ADEM is immune-mediated, rather than caused directly by infection.
The exact mechanism of this is not clear. It has been proposed that the preceding infection or vaccine cross-activates an immune reaction to myelin through molecular mimicry.
Pathological examination of the brain in ADEM classically shows multiple peri-venous zones of demyelination in the cerebral white matter.
The lesions are generally homogeneous in appearance and appear to be of the same age.

Investigations

MRI is most useful in the diagnosis of ADEM, with abnormalities frequently evident on T2-weighted and FLAIR imaging, although MRI may be normal early in the disease. MRI show with large, multifocal, confluent and ill-defined lesion that involve both white matter, cortical grey and deep grey matter with gadolinium, reflecting their acute and synchronous development, Mass lesions, mimicking tumors occur.
Spinal cord lesions are often large, extending over several levels, with swelling and mass effect, and have a predilection for the thoracic cord.
CSF may be normal in up to 50% of patients but may reveal an elevation in the opening pressure and a mild lymphocytosis, increased protein concentration, Oligoclonal bands may be present acutely in up to 30% of patients but often disappear on repeat testing. CSF polymerase chain reaction (PCR) for viral infection may show the underlying precipitating agent.

Treatment

Supportive treatment for fever, seizure, and raised ICP preferably in the ICU.
Antibiotic and antiviral therapy to treat underlying infection.
Treatment of choice is high dose corticosteroids in a form of methylprednisolone 1g/d for 5 days (dose in children is 10-30 mg/kg/day) followed by taper prednisolone for 3-6 weeks.
If unresponsive to steroids, Plasmapheresis or IVIG may be considered, although the evidence for these is limited.


Prognosis
Prognosis is generally good as ADEM is usually a monophasic illness which is self-limiting.
Recovery takes place over weeks to months, and full recovery may occur in about 50–75% of cases.
Residual neurological deficit may occur in up to one-third of patients and mortality is approximately 5%.
Poor prognostic features include seizures and coma accompany the acute illness.

Definition

bilateral optic neuritis and severe myelitis that occurred in quick succession.
Epidemiology
NMO typically occurs in young adults (mean age 40), predominantly female (4 : 1). Familial cases have been reported in less than 5% of cases.
Classification
NMO is currently classified as being either
• monophasic (nearly simultaneous bilateral optic neuritis and myelitis with no subsequent relapses) or
• relapsing (usually, but not always, presenting with unilateral optic neuritis or myelitis, followed by relapses that can include either optic neuritis or myelitis, or less frequently cerebral involvement).
These subtypes seem to differ in important ways; the relapsing form is more commonly associated with AQP4 autoantibodies, more common in elderly and more common in women.
Neuromyelitis optica (Devic disease)


Pathophysiology NMO is a humoral mediated autoimmune disease caused by an antibodies called NMO-IgG antibodies directed towards antigen called aquaporin-4 which is present on the surface of astrocytes.
Clinical Features
The core clinical features of NMO spectrum disorders include optic neuritis, acute myelitis.
area postrema syndrome, acute brainstem syndrome, symptomatic narcolepsy or acute diencephalic clinical syndrome, and symptomatic cerebral syndrome.
the frequencies of specific presentations were as follows: 43% myelitis ,41% optic neuritis, 4% optic neuritis and simultaneous myelitis, 5% brain or brainstem presentations in isolation and 7% mixed presentations (eg, optic neuritis and brain).



Optic neuritis may be difficult to distinguish from those that occur in MS, and are variable in severity. Clinical features suggestive of NMO include:
• Bilateral.
• More severe.
• Poor response to treatment than those in MS.
• Radiologically T2 hyperintensity that is also extensive over more than half of optic nerve or involvement of chiasm.


c

myelitis in NMO is usually complete(ie, bilateral, motor, and sensory); by contrast, transverse myelitis due to MS is usually partial.
Radiologically, MRI shows central lesion that involve three or more spinal segments and may extend to area postrema called longitudinally extensive transverse myelitis (LETM), while in MS the lesion is typically short involve less than three vertebral segment and located at the dorsolateral aspect of the spinal cord.


Beside MRI brain and spinal cord, Any patient for whom the diagnosis of NMO disorder is suspected should have a serum anti-aquaporin-4 antibodies. Where available, a cell based assay is preferred because of higher sensitivity and specificity compared to alternative methods. sensitivity is 75% and Specificity is 99% for cell-based assay.
CSF analysis shows increase cell count which is predominantly neutrophils, in contrast to MS, in which lymphocytes make up the vast majority of the differential. Total protein may be elevated regardless of current disease activity. Whereas oligoclonal bands are seen in the vast majority of patients with MS (up to 90%), they are much less common in NMO disorders, accounts for approximately 25%.

Investigations

Acute attacks are typically treated with corticosteroids and, if necessary, rescue plasma exchange as outlined in the discussion of transverse myelitis.
Relapse prevention strategies are meant to reduce or eliminate the effects of pathogenic AQP4 antibodies, either directly or indirectly. Patients with established relapsing NMO and those deemed to be at high risk for relapse (eg, patients with seropositive NMO spectrum disorder such as those with first-ever LETM or optic neuritis) either oral drugs (eg, azathioprine or mycophenolate Mofetil) or parenteral drugs (eg, rituximab). These agent decrease relapses by 30-70%.
Treatment
Treatment of acute attack
Relapse preventive strategies
corticosteroids and, if necessary, rescue plasma exchange
long-term immunosuppressive therapy
Oral AZA, mycophenolate Mofetil
Parental rituximab


This syndrome results from:
• infectious (bacterial, viral, fungal, parasitic)
• noninfectious inflammatory disorders (multiple sclerosis, neuromyelitis optica, acute disseminated encephalomyelitis, systemic autoimmune diseases)
• idiopathic
Children and young adults are affected most often.
Clinical findings include bilateral sensory, motor, and autonomic deficits in the limbs and trunk; a discrete sensory level corresponding to the site of inflammation in the spinal cord.
Transverse myelitis


Most patients present with a combination of sensory, motor, and bladder or bowel-related symptoms suggestive of myelopathy.

MS-related myelitis is usually characterized by short-segment, peripheral cord lesions, whereas NMO is strongly associated with a longitudinally extensive transverse myelitis (LETM) lesion that extends contiguously over three or more vertebral segments (seen best on sagittal T2-weighted MRI) and usually affects the central cord.

Double sphincter

motor
sensory

Investigation

MRI showing an intrinsic spinal cord lesion that usually enhances with gadolinium administration. Compressive lesions of the spinal cord, such as spinal epidural abscess, must be excluded as they require specific Rx.
An inflammatory CSF profile (pleocytosis, increased protein concentration, an accompanying low CSF glucose suggests an infective cause).

Treatment

Treatment is with corticosteroids, typically methylprednisolone (1 g intravenously daily for 3-5 days).
Plasma exchange, intravenous immunoglobulin, or cyclophosphamide may be useful in steroid-unresponsive patients.
Patients tend to improve over several months, but may have residual deficits, and mortality rates in excess of 30% have been reported.

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