Acute disseminated encephalomyelitis ADEM is also known as post-infection encephalomyelitis and post-inoculation encephalomyelitis. It is a demyelinating disease of the central nervous system caused by immune dysfunction secondary to acute rash diseases such as measles, rubella, chickenpox and smallpox, or after vaccination.
Occurrence probability
Authoritative and more comprehensive incidence statistics have not been identified.
Prior to widespread measles vaccination, neurological complications in measles patients ranged from 1 in 2000 to 1 in 800 cases; the mortality rate with neurological complications was 10% to 20%; and a similar number of patients were left with permanent neurological deficits.
Encephalomyelitis after varicella and rubella is less common, and encephalomyelitis after mumps is even less common.
Causes
1, can occur in the course of various infectious diseases, especially in children with acute rash fever. Infectious diseases leading to ADEM include measles, rubella, varicella, smallpox, mumps, influenza, parainfluenza, infectious mononucleosis, typhoid fever, mycoplasma pneumonia, many ADE patients are secondary to common respiratory infections, EBV, cytomegalovirus infections, and some occur after infections of unknown origin.
2, seen after vaccination, such as measles vaccine, mumps vaccine, rubella vaccine, varicella vaccine, sense full vaccine, rabies vaccine, smallpox vaccine, etc. Occasionally, it appears after tetanus antitoxin injection is reported.
3, taking certain drugs or food: levamisole, repellent net, compound sulfamethoxazole, fried cicada pupa, etc.
4.Very few occur in special periods: such as perinatal period, after surgery. There are also some cases without a history of pioneer infection and vaccination before the onset, which is called idiopathic ADEM.
Pathogenesis
Viral infection, vaccination, certain drugs, etc. invade the central nervous system and change its antigenicity, or cause the release of hidden antigens, which leads to the body’s immune attack against its own myelin.
ADEM is currently considered to be an autoimmune disease mediated by cellular immunity and directed against myelin basic proteins of the CNS, resulting from a delayed allergic reaction between myelin and anti-myelin antibodies.
Pathological features
A large number of widely scattered foci of demyelination in the brain and spinal cord, in some cases the lesions are limited to the cerebellum and spinal cord These lesions vary from 0.1 mm to several millimeters and are located around the small middle vein.
Inflammatory cell infiltration is evident, with inflammatory exudate in the peripheral small veins and a cellular reaction consisting of polymorphic microglia in the corresponding areas of demyelination; a perivascular set of lymphocytes and monocytes is seen; multifocal meningeal exudate is another necessary feature, but is generally not severe.
Pathologic features
The intracerebral lesions are multiple and bilaterally symmetrical, with a tendency to fuse and a predominance of hemianopiae central involvement, affecting the frontoparietal and occipital lobes as well as the insula, optic nerve, optic cross and brainstem;
The spinal cord has severe white matter loss and necrosis, involving the cervical, thoracic and lumbar segments; the lesions are equally old and new, unlike multiple sclerosis where axons and nerve cells are largely intact, with minor destruction of axons in severe lesions.
Clinical presentation
The majority of cases are in children and young adults.
The majority of cases are acute, with a few having a fulminant or subacute onset.
The disease can occur in all seasons, and most cases are disseminated.
The onset of the disease is acute 1-2 weeks after infection or vaccination and is severe, in some cases, and dangerous.
Post-rash encephalomyelitis commonly occurs 2-4 days after the rash. Patients often suddenly develop high fever, epileptic seizures, lethargy and deep coma while the rash is fading and symptoms are improving.
The disease has a monophasic course, with signs and symptoms peaking in a few days.
Clinical typology
1. Meningitis type: manifests as a meningitis syndrome, which may be an early manifestation of various clinical types, and in some cases terminates in the meningitis phase without further progression.
2, meningitis type: the first symptoms are headache, fever and confusion, in severe cases rapid coma and decerebrate tonic seizures, there may be epileptic seizures, meningeal involvement with headache, vomiting and meningeal irritation signs, limited motor and sensory impairment cross common and asymmetric. It is not uncommon to see neurological signs of optic nerve, cerebral hemisphere, brainstem or cerebellar involvement, and the clinical manifestation of ADEM is mainly acute cerebellar ataxia.
3. Myelitis: Partial or complete bradykinetic paraplegia or quadriplegia, conduction tract or lower extremity sensory deficits, pathological signs and urinary retention are common. Pain in the midline of the back can be a prominent symptom during the onset of the disease.
4, acute necrotizing hemorrhagic encephalomyelitis: also known as acute hemorrhagic leukoencephalitis, considered to be ADEM fulminant. Common in young adults, 1-2 weeks before the disease can have a history of upper respiratory tract infection, the onset of the disease is rapid, the disease is dangerous, symptoms and signs in 2-4 days to peak, high mortality. The symptoms include high fever, progressive deepening of consciousness or coma, agitation, epileptic seizures, hemiparesis or tetraplegia; increased CSF pressure, increased cell count, diffuse slow activity of EEG, and irregular hypodense areas in the brain, brainstem and cerebellar white matter seen on CT.
Auxiliary examinations
1, peripheral blood picture: leukocytosis, accelerated sedimentation.
2, cerebrospinal fluid: pressure is mostly mildly increased or normal, CSF: WBC is normal or mildly increased, protein is mildly or moderately increased, IgG is mainly increased, and oligoclonal bands can be found. Sugar and chloride are normal.
3, EEG: mostly diffuse and bilateral reciprocal abnormalities, common high voltage slow activity, “theta and σ waves”, also see spike and spike slow composite waves.
4.Brain CT: It shows diffuse multifocal large or patchy low-density areas in the white matter, with obvious enhancement effect in the acute stage.
5.Brain MRI: scattered multifocal T1 low signal and T2 high signal lesions in the white matter of the brain and spinal cord can be seen. Thalamic involvement is one of the bases for differentiating ADEM from MS.
Diagnosis- Based on typical medical history, clinical manifestations, and ancillary examinations.
Acute onset;
History of infection or vaccination before onset;
Diffuse damage to the brain and myelitis parenchyma (white matter predominant), signs of meningeal involvement;
CSF: increased WBC, non-suppurative changes;
EEG: widespread moderate abnormalities;
Autoimmune abnormal indicators: elevated IgG index, oligoclonal antibodies (+);
Clinical diagnosis can be made by CT or MRI showing multiple scattered lesions in the brain and spinal cord, etc.
Diagnosis: raising awareness
ADEM mostly starts acutely 4-14 days after viral infection or vaccination.
The disease should be considered in most patients with fever or post-vaccination headache, vomiting, confusion, convulsions, and limb paralysis.
Differential diagnosis
1. Herpes simplex virus encephalitis
It can be disseminated, with recurrent oral and lip herpes seen before or during the onset of the disease, and other prodromal symptoms are not obvious.
Psychiatric symptoms are most prominent, with symptoms such as high fever and convulsions and high cranial pressure, and can quickly fall into coma, with a high mortality rate.
Hemorrhagic changes are seen in the cerebrospinal fluid, and specific IgM antibodies can be detected.
The EEG is dominated by frontal and temporal lobe changes, which may be slow waves or epileptiform emissions, often asymmetrical bilaterally, with recurrence on one temporal lobe being more significant.
Hemorrhagic changes in the frontal and temporal lobes are seen on both CT and MRI.
The simultaneous occurrence of encephalitis and myelitis can be differentiated from viral encephalitis.
2. Epidemic B encephalitis.
Epidemic B encephalitis has a distinct epidemic season, with July – September predominating and insect-borne transmission. ADEM is sporadic.
Manifestations are high fever, headache convulsions and high cranial pressure symptoms, which can involve multiple parts of the brain, cerebellum brainstem and spinal cord.
It may show signs of systemic toxicity and increased peripheral blood leukocytes, with a predominance of neutrophils.
Cerebrospinal fluid: Neutrophilic polymorphonuclear leukocytes are predominant in the early stage, which may turn into lymphocytes after 4 – 5 days.
Specific antibodies can be detected after 2 weeks after the onset of the disease.
MRI is symmetrical bilateral thalamic and basal nucleus lesions.
3. Acute hemorrhagic white matter encephalopathy
Most scholars believe that it is a fulminant type of acute disseminated encephalomyelitis.
The onset of the disease is rapid and dangerous, and the death rate is extremely high, mostly within a few days after the onset of the disease.
Symptoms of spinal cord involvement are less common than brain symptoms or are masked by brain symptoms.
Peripheral blood and cerebrospinal fluid may show a marked increase in leukocytes, with predominantly neutrophils as a reflection of an abnormally active immune system.
Hemorrhagic foci may be seen on imaging within or around foci of softening and necrosis, and are also diffuse, mostly in a patchy distribution.
Cases of progressive progression from ADEM to acute hemorrhagic leukoencephalitis have been reported by MRI. It is possible that in more severe cases, the demyelination is accompanied by damage to the perivascular area of the microvessels, edema of the vascular matrix, and gradual fusion of the lesions to form larger lesions, leading to the development of hemorrhage. This was described in Hurst’s earliest pathological reports as erythrocyte exudation around small veins and capillaries, vessel wall necrosis, polymorphonuclear leukocyte infiltration, and glial cell reaction.
Magnetic resonance findings demonstrated acute dissemination of acute hemorrhagic leukoencephalitis.
4.Multiple sclerosis
Acute disseminated is the main difference between ADEM and MS
MS is scattered, multifocal rather than diffuse, and occurs multiple times with a relapsing-remitting course.
Some patients with MS do have an acute clinical onset and lack of relapsing-remitting features, and have a shorter course, showing a monochronic course. This type of patient is difficult to distinguish from ADEM in terms of pathogenesis, pathology and pathophysiology, and is considered by some scholars to be a transitional type.
In terms of first presentation, ADEM often presents with a more diffuse CNS disorder with coma, drowsiness, convulsions and multifocal damage involving the brain, spinal cord and optic nerve. MS often presents with a single symptom, or optic nerve damage, or subacute myelopathy.
Optic nerve damage: ADEM is mostly bilateral with simultaneous involvement, while in MS the optic nerve damage is often unilateral.
Spinal cord lesions: ADEM is mostly complete reflex loss; while MS spinal cord lesions are also often incomplete.
ADEM is often preceded by infection or vaccination, whereas MS does not always have such antecedents, but these factors make MS symptoms recur and therefore are not absolutely different.
Cerebrospinal fluid indicators are also not specific for differential diagnosis. Cellular hyperintensities may also be seen in MS.
Although oligoclonal bands are a feature of MS, they are also present in ADEM. However, the oligoclonal bands in MS can be more persistent, and follow-up observations can be meaningful in differentiating the two.
MRI: The typical ADEM is a relatively symmetrical lesion with extensive involvement of the cerebral and cerebellar white matter, and has also been reported to involve the basal nucleus, which is extremely rare in MS. MS lesions are often asymmetrical and vary in size and newness. The coexistence of old and new lesions on imaging supports the diagnosis of MS.
ADEM differs from MS in that it is monotemporal, so multiple MRI examinations during the prognosis and sequelae can help in the differential diagnosis. According to Poser’s criteria, MS is considered a relapse when symptoms reappear more than 1 month apart, thus in demyelinating disease, clinical and MRI follow-up at least every 6 months for 2 years is preferable.
5. Tuberculous meningitis
History of tuberculosis disease or exposure
Symptoms of tuberculosis toxicity: low fever in the afternoon, night sweats, loss of appetite, weakness mental depression, etc.
Early manifestations are dominated by signs of meningeal irritation, which last 1-2 weeks or longer.
Cerebrospinal fluid: increased WBC, early mixed cell reaction, and lasting for a long time.
6.Septic meningitis
Acute onset.
Severe systemic toxic symptoms such as high fever.
Headache, vomiting, neck stiffness and other signs of meningeal irritation, may have impaired consciousness, irritability, convulsions, etc.
Cerebrospinal fluid: cloudy, WBC significantly increased, more than 1000, even up to 10000, mainly neutrophils. High protein quantification and hypoglycemic chloride.
Also to be considered are.
1) extensive invasion of the CNS by multiple metastases and hematologic tumors, etc.
2) rare diseases such as acute encephalopathy associated with vitamin deficiency.
While considering neurological diseases do not ignore the possible influence of medical diseases.
Treatment
1, acute phase: early and adequate application of adrenocortical steroid hormone class is the main measure of ADEM treatment.
1) Methylprednisolone shock – prednisone oral therapy.
Methylprednisolone 20mg/kg.d for 3-5 days;
Prednisone 1.5-2mg/kg/d, × 15 days; 1mg/kg/d, × 4-6 weeks; tapered dose to 0.5mg/kg/d; total duration of prednisone treatment 3-6 months.
2) Dexamethasone 20mg/d, oral prednisone, use as above.
3)Gammaglobulin intravenous drip or plasma exchange: small sample study found to be effective and can be considered for steroid hormone treatment ineffective.
Gammaglobulin 0.4g/kg/d for 3-5 days; oral prednisone, as above.
4) Combined application of azathioprine may also be used to control the progression of the disease as soon as possible.
2. Symptomatic treatment.
Mannitol to reduce high intracranial pressure.
Antibiotics to treat pulmonary and other infections.
Passive exercise of limbs to prevent joint and muscle contractures and prevent decubitus ulcers, etc.
3.Recovery period: use of cerebrofacial, cytarabine and vitamin B drugs.
Prognosis
ADE is a monophasic disease that lasts for several weeks, with the acute phase usually lasting for 2 weeks.
Depending on the severity of the disease and the causative factors, the outcome of treatment is not uniform.
Most patients recover considerably after treatment, but some patients may have significant functional impairment. Most adult patients recover well. In children, recovery may be accompanied by persistent behavioral abnormalities, mental retardation, or seizures.
Microcephaly is benign and recovery is usually complete within a few months.
The morbidity and mortality rate is 5% to 30%.
Regardless of the clinical form, aggressive disseminated encephalomyelitis has a high mortality rate and leaves survivors with permanent neurological deficits.
Prevention There are no effective preventive methods for autoimmune diseases.
Prevention of infections, colds, and triggers such as cold or heat are the main focus of prevention and treatment.
Further improvement of the vaccine preparation process to both preserve better antigenicity and reduce the role of provoking or inducing preventive inoculation encephalomyelitis.
Changes in prevention methods, etc. can all reduce the occurrence of post-vaccination encephalomyelitis.