Clinically, the acute disseminated encephalomyelitis (ADEM) is usually easy to distinguish from multiple sclerosis (MS) by the presence of certain clinical features, including the following:
The history of infectious diseases or vaccinations
Association with constitutional symptoms and signs such as fever
Prominence of the cortical symptoms such as changes in mental status and seizures
Relative infrequency of posterior column abnormalities that are common in MS
Age less than 11-12 years in ADEM and more than 11-12 years in MS
ADEM is more common in the winter months, with as many 65-85% of cases between October and March. The average age at presentation is approximately 7 years with a range that extends from the first year of life till adulthood. Typical cases of ADEM occur 1-20 days after an infectious childhood disease, the one which is febrile in 94% of cases.
There is usually a significant afebrile improvement period lasting 1-20 days or more before the onset of neurological symptoms. In general, patients showed a partial or complete recovery of the prodromal illness at the time of the commencement of the ADEM. The viral disease which were important in older days are not significant these days as these diseases like measles can be prevented by vaccination.
Most cases that occur now are out of the respiratory tract or gastrointestinal diseases that are believed to be viral in origin. But a particular causative virus is rarely identified. Sometimes the ADEM may occur in the course of several weeks of fever of unknown origin.
Some patients have pain in the back, before the development of ADEM associate inflammatory myelitis. Several vaccines are seen as the provocation to the cause of ADEM and can measure about 3-6% of ADEM proposed account.
Although there is clear evidence for the role of the vaccine against rabies; however roles of other vaccines are less conclusive. The overall effect of the introduction of vaccination against measles and other encephalomyelitogenic viruses saw a decline in the number of severe or fatal cases of ADEM. A minority of cases has absence of a clear prodrome.
Another subgroup with prodrome unclear and a low risk of relapse are children or adolescents manifesting subacute onset of the syndromes, neuro-psychiatric disorders and movement disorders and changes in imagining studies suggestive of ADEM. The course in these cases, which could be described as Johnson Syndrome is often prolonged or progressive and have improvement by high-dose intravenous corticosteroids.
MRI abnormalities in these cases of young people and adults as a rule are closer to the MS than characteristic typical of the ADEM and CSF immune profile test results tend to be abnormal. These patients are probably the ones to get diagnosed as MS in the coming months to years. This is especially true with posterior column signs and some cortical signs are also present. The first signs of ADEM usually include sudden onset of irritability and lethargy. The occurrence of neurological manifestations is steep in more than 95% of ADEM.
Sometimes the development of the diffuse neurological abnormalities requires only a few hours. In most cases, the signs and symptoms develop over several days and in a minority of cases show a continuing deterioration for periods as long as 4 weeks. Changes in mental status (88%) are frequently observed in ADEM. The attacks of convulsions occur around the occurrence of ADEM in as many as 25% of cases.
Meningism may be present but rarely in ADEM, except in very young children with serious illnesses. Although almost every part of the central nervous system may be involved clinically, some systems seem to be particularly susceptible to interference. Descending motor tracts of white matter, optic nerves and spinal cord are affected most often. ADEM-associated optic neuritis is usually bilateral, but the appearance in the second eye needs days to several months after first eye involvement. Bilateralism may provide some measure of comfort in relation to MS risk, because optic neuritis in MS is often one-sided. Visually evoked responses can detect anomalies in a second eye before the clinical worsening of vision is palpable. A variety of cranial nerve abnormalities can occur in addition to the optic nerve disease. Long tract signs (e.g. increased muscle stretch reflexes, upgoing plantars) are seen at the beginning of nearly 80% of cases. In some cases, the reflexes are lost at first. Sometimes this is caused by transverse myelitis. A small number of cases show loss of reflexes as a sign of peripheral nerve disease with ADEM, a condition called EMRN. Some of these cases of EMRN are associated with signs of acute infection with Epstein-Barr virus. Hemiparetic weakness is possible, so is double hemiparetic, diaparetic or generalized and symmetrical weakness. Fairly symmetrical weakness of the legs is in many cases of ADEM associated transverse myelitis with abnormalities of bowel and bladder function. Transverse myelitis may be associated with optic neuritis. This combination (Devic's syndrome) is also seen in MS, but in ADEM it is more likely to have bilateral optic neuritis.
Most presentations of ADEM can be summarized in seven clinical syndromes as follows:
- Mild encephalopathy, sometimes associated with long tract signs
- Severe encephalopathy with bilateral paresis, often with signs of brain stem, especially linked to the lower cranial nerves
- Brainstem presentation suggesting Bickerstaff brainstem encephalitis in some cases and Fisher syndrome in other cases.
- Hemiparesis, ipsilateral long tract signs with or without convulsions.
- Mainly ataxic and is different from the predominantly axial / gait ACA in that ADEM related ataxia is often with nystagmus, extremity ataxia and long tract signs.
- EMRN: Encephalo-myelo-radiculo-neuropathy is a syndrome with symptoms of upper and lower motor neuron combined. It must be differentiated from infectious diseases such as direct enterovirus 71 encephalitis. In EMRN recurrences occur.
- Some presentations are fulminant.
Fulminant ADEM is more likely to occur in children under 3 years with the rapid development of a low state of the function and demonstration on scanning of severe edema. These cases have been rare with the widespread vaccination against childhood diseases. Transverse myelitis (TM) can start quickly and cab come up in connection with a swelling, usually in the neck region. ADEM associated TM should be distinguished from TM associated with MS, stroke and direct infectious conditions, including enterovirus 71 encephalitis. It must be seen apart from neuromyelitis optica (NMO) also. Some unusual presentations of ADEM are possible. They are difficult to classify. Some of them are called acute MS or diffuse sclerosis and some are labeled necrotizing encephalopathy or encephalitis than ADEM. Some cases are labeled as acute MS that have prepubertal beginning of encephalopathy, changes in mental status from confusion to coma, convulsions and prominent pyramidal tract abnormalities.
Young children may show a rapidly progressive demyelinating disease that can kill within days to weeks and is almost everywhere with profound deficits in psychomotor functions in those who survive. Some patients with large tumor-like lesions, acute MS or Schilder disease presentations and signs during childhood or young adults improve well than adults with similar presentations. The classification of these rare severe cases in children, with features suggesting either severe acute MS or ADEM, remains doubtful. However, pathological confirmation that some of these cases are infarct MS has been published and hyper-acute cases in adults with similar clinical and radiological manifestations have been reported. Due importance should be given to the fact that scan cannot reliably differentiate every case of MS from ADEM, yet inferences can be drawn out of it.
People who have lived the typical ADEM are at risk of relapse. If this was second episode then they can meet the diagnostic criteria for MS, although this responsibility requires further investigation more in prepubertal children than in older people.
Repetition may occur during the tapering of corticosteroid therapy initiated in the ADEM. This phenomenon is not intended to represent an independent or second bout of the disease. It usually reacts to increase in the dosage of corticosteroids and prolonging the period of treatment.
The occurrence of small lesions on MRI in a month of presentation should be interpreted with caution, and it can be seen in ADEM. A rare subgroup of patients is the one in which management is difficult without anti-inflammatory therapy.
Imaging changes similar to those in typical cases of ADEM (i.e., multiple sclerosis at the gray-white cross and in the deep white matter), a feature that distinguishes these cases from chronic cases under consideration, a manifestation of Schilder disease. CSF immune profile remains normal despite the relapses although myelin basic protein can be high. Neurological abnormalities in this group show promising improvements with treatment with of intravenous methylprednisolone (20 mg / kg / day for 3 consecutive doses). It is to be followed by oral methylprednisolone (2 mg / kg / d). This is to be tapered off slowly. The problem encountered with the tapering is that each patient has his own threshold for a relapse. In most cases, this threshold is met, if the daily dose of methylprednisolone is reduced to about 12-14 mg every alternate day. Neurological deterioration improves by high doses of corticosteroids hence corticosteroids in these patients are continued for a period of up to eight years. Although prolonged steroid therapy is generally well tolerated, but patients can develop osteopenia and in minority of the cases vertebral compression fracture.