RESPONSE TO CASE -1 QUESTIONS
نویسنده خبر : مدیر سایت    
تاریخ درج خبر : 1397/5/9

CORRECT ANSWERES

QUESTION-1  = 3

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the nervous system.[1] It is typically a monophasic disease that occurs in prepubescent children; more than 80% of cases are reported in children <10 years of age.[2,3] The onset of ADEM usually occurs in the wake of a clearly identifiable febrile prodromal illness, especially in the form of a nonspecific upper respiratory tract infection or immunization. Most cases of ADEM are thought to occur as a result of an inflammatory response provoked by infection with a virus, viral vaccine, or other infectious agent. ADEM is more common during the winter and spring months.[4–6]

A wide array of viral and bacterial pathogens have been associated with ADEM, including viruses such as measles, coronavirus, coxsackievirusescytomegalovirus, Epstein-Barr virus, herpes simplex virushepatitis Ahuman immunodeficiency virusinfluenzarubellavaricella zoster, and West Nile virusand bacteria such as MycoplasmaLeptospiraBorreliaChlamydiaRickettsia, and beta-hemolytic streptococci.[7–9] Less than 5% of ADEM cases occur after immunization. ADEM after vaccination has been associated with immunization for measles, rabieshepatitis B, influenza, mumpsJapanese encephalitis, rubella, polio, varicella, diphtheria/pertussis/tetanus, pneumococcus, and smallpox. ADEM has rarely been reported after the administration of drugs such as sulfonamides, para-aminosalicylic acid, and streptomycin.

The neuropathogenesis of ADEM has not been fully elucidated.[1,2,3] The concepts of immune dysregulation and molecular mimicry have been implicated. T-helper cells sensitized to myelin autoantigens, such as myelin basic protein, proteolipid protein, and myelin oligodendrocyte proteins, may produce cytokines and chemokines, leading to further activation of T-cell and B-cell lines as well as phagocytes. The outcome is acute inflammatory demyelination, most often in the central neurons and rarely in the peripheral neurons. For more pathological details, see the study by Young et al.[22]

ADEM is typically monophasic, but the disease can be recurrent, relapsing, and multiphasic as well. It is mostly associated with constitutional symptoms such as fever, malaise, and lethargy. The hallmark clinical feature is encephalopathy, which ranges from simple lethargy to frank coma and seizures.[1,2,3]Encephalopathy is the first sign of ADEM in more than 94% of cases. Convulsive seizures occur around the onset of ADEM in as many as 25% of cases. Other initial features include focal and multifocal signs manifesting as isolated features or in various combinations.[4,5,6,7] These reflect cerebral, brainstem, and spinal cord dysfunction and include acute hemiparesis, aphasia, cerebellar ataxia, paraparesis and quadriparesis, cranial neuropathies, and, rarely, peripheral neuropathies.[10,11] Cranial nerve palsies are seen in 35–40% of ADEM cases. The optic nerve is most commonly involved.

Most ADEM presentations can be categorized into 7 clinical syndromes: mild encephalopathy, severe encephalopathy, predominantly brainstem presentation, hemiparesis/long tract signs, predominantly ataxic, transverse myelitis, and encephalomyeloradiculoneuropathy, which is a syndrome that combines upper and lower motor neuron signs.[1] The patient in this case had both upper and lower motor neuron involvement and was categorized as having encephalomyeloradiculoneuropathy.

Differentiating ADEM from multiple sclerosis (MS) is important.[22] History of a preceding infectious illness or immunization, association with constitutional symptoms such as fever, and prominence of cortical signs such as mental status changes and seizures all favor ADEM. Cerebellar abnormalities that are common in MS are rare in ADEM. The age of onset is younger than 11 or 12 years in ADEM and older than 11 or 12 years in MS.[12]

Early recognition is important so that appropriate therapy can be started. Laboratory studies of most patients with ADEM evidence nonspecific inflammation in the form of lymphocytosis or an increased erythrocyte sedimentation rate or C-reactive protein, although these findings can be very nonspecific. Lumbar puncture and CSF examination usually reveal a normal opening pressure with mild pleocytosis and/or a modest increase in protein concentration consistent with ongoing inflammation, as was seen in this case. In some patients, the CSF may be normal. Some patients with ADEM may have oligoclonal bands. CSF myelin basic protein levels may be increased, indicating demyelination.[1,6,7]

Electroencephalography is not diagnostic for ADEM. It may reveal increased background slow wave activity that is typical of an encephalopathy, but epileptic activity is rarely seen.[11,13] In patients with optic neuritis, visual evoked potentials may be prolonged. Nerve conduction studies are indicated in patients with lower motor neuron signs, as in this case. Patients may have a demyelinating neuropathy with prolonged F waves, slower conduction velocities, and prolonged distal latencies. Conduction blocks are usually not observed. Features consistent with an axonal neuropathy may be seen in rare cases.[10,11]

Imaging studies of the central nervous system are important in establishing the diagnosis of ADEM. MRI of the brain with contrast is the imaging modality of choice. CT scanning of the brain is less sensitive and is often normal. MRI abnormalities are best defined by T2-weighted images and FLAIR sequences. The lesions are typically bilateral and asymmetric and tend to be poorly marginated, located in the deep and subcortical white matter, and have relative periventricular sparing.[1,2,6,7] Acute lesions are sometimes enhanced by contrast. In patients with features suggestive of spinal cord dysfunction, an MRI of the spine may be helpful. It may show swelling of the cord, especially on T2-weighted sequences in cases of myelitis. Demyelinating plaques may be seen, and contrast enhancement with gadolinium may be noted.

Treatment with broad-spectrum antibiotics and acyclovir is recommended until an infectious cause is excluded. Once the diagnosis of ADEM is established, steroids remain the mainstay of treatment. High-dose intravenous (IV) corticosteroids are recommended.[1,2,6,7] Methylprednisolone should be administered at a dose of 10–30 mg/kg/day for 3–5 days. Oral steroid taper is recommended only in patients who continue to show clinical symptoms after completion of the high-dose IV glucocorticoid treatment. The chief alternative treatment option is IV immunoglobulin, given at a dose of 2 g/kg/day for 2–3 days[14–17]; this is especially preferred in cases where meningoencephalitis cannot be excluded or there is an insufficient response to corticosteroids. The role of plasmapheresis in the management of ADEM is under investigation.[18,19,20] Plasma exchange should be considered for patients who fail to respond to treatment with glucocorticoids and IV immunoglobulin. It may be of particular benefit in patients with ADEM-associated myelopathy. The preferred regimen is a total of 6 exchanges, one every other day, with each exchange consisting of 1–1.5 plasma volumes.

QUESTION-2  = 3

Treatment with broad-spectrum antibiotics and acyclovir is recommended until an infectious cause is excluded. Once the diagnosis of ADEM is established, steroids remain the mainstay of treatment. Methylprednisolone should be administered at a dose of 10-30 mg/kg/day for 3-5 days. Oral steroid taper is recommended only in patients who continue to show clinical symptoms after completion of the high-dose IV glucocorticoid treatment. IV immunoglobulin is especially preferred in cases where meningoencephalitis cannot be excluded or there is an insufficient response to corticosteroids. Plasmapheresis may be considered for patients who fail to respond to treatment with glucocorticoids and IV immunoglobulin. 

Recovery from ADEM begins within days. The patient in this case was treated with pulse steroid therapy for 5 days. At discharge, he was conscious, free of seizures, and mobile with support after a 3-week stay in the hospital. Physiotherapy and a repeat MRI of the brain after 6 weeks were advised. 

Most patients make a full recovery, usually slowly over 4-6 weeks. Relapses are rare. If they do occur, particularly after cessation of steroids, the administration of antibodies to myelin oligodendrocyte glycoprotein should be considered. At follow-up, approximately 60%-90% of patients have minimal or no neurological deficits.

QUESTION-3  = 4

The neuropathogenesis of ADEM has not been fully elucidated.[1-3] The concepts of immune dysregulation and molecular mimicry, however, are implicated. T-helper cells sensitized to myelin autoantigens, such as myelin basic protein, proteolipid protein, and myelin oligodendrocyte proteins, may produce cytokines and chemokines, leading to further activation of T-cell and B-cell lines as well as phagocytes. The outcome is acute inflammatory demyelination, most often in the central neurons and rarely in the peripheral neurons.

 

 

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