Year : 2006 | Volume
: 9 | Issue : 1 | Page : 20--24
Clinical features and outcome of acute disseminated encephalomyelitis (ADEM): An outlook from South India
Boby Varkey Maramattom1, C Sarada2,
1 Department of Neurology, Lourdes Hospital, Kochi - 682 023, Kerala, India
2 Department of Neurology, Sree Chitra Tirunal Institute of Medical Sciences, Thiruvananthapuram, Kerala, India
Boby Varkey Maramattom
Department of Neurology, Lourdes Hospital, Kochi - 682 023, Kerala
Introduction: Acute disseminated encephalomyelitis (ADEM) is an uncommon inflammatory demyelinating encephalomyelitis that may follow infections, vaccinations or occur spontaneously. Most of the large series of this disorder were published in the pre-MRI era. Subsequently there has been a paucity of data regarding this entity. Aims: We sought to describe our experience with ADEM across 2 hospitals from Kerala, Sree chitra tirunal institute of medical sciences, thiruvanthapuram and the Indo-american Brain and spine center, Vaikom. We wanted to look at the clinico-radiological parameters of this patient population as well as the functional outcome following ADEM. Materials and Methods: A total of 45 patients seen in these two centers over a period of 9 years from 1995 to 2003 were analyzed in a retrospective-prospective design. MRI, CT scans, laboratory investigations, nerve conduction parameters and modified rankin outcome scores at last follow up were also noted. Results: The clinico-radiological profile of our patients was comparable to that of patients described in the literature. Relapse was uncommon although transient reappearance of prior symptoms during subsequent illness was common. Possible multiple sclerosis could be diagnosed only in one patient during follow up. Mortality was low (<5%). However, most survivors were left with varying degrees of disability.
Conclusions: ADEM deserves to be distinguished from MS in our population as there seems to be a low likelihood of recurrence or relapse. Although mortality rates have improved greatly, survivors are left with a plethora of disabilities and are functionally impaired. Future studies should focus on specific disabilities and treatment options to further improve outcomes in ADEM
|How to cite this article:|
Maramattom BV, Sarada C. Clinical features and outcome of acute disseminated encephalomyelitis (ADEM): An outlook from South India.Ann Indian Acad Neurol 2006;9:20-24
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Maramattom BV, Sarada C. Clinical features and outcome of acute disseminated encephalomyelitis (ADEM): An outlook from South India. Ann Indian Acad Neurol [serial online] 2006 [cited 2020 Aug 9 ];9:20-24
Available from: http://www.annalsofian.org/text.asp?2006/9/1/20/22817
Acute disseminated encephalomyelitis (ADEM) is an acute inflammatory disease of the central nervous system and may follow systemic viral infections (post infectious encephalomyelitis), vaccination (post vaccinial encephalomyelitis), or occur spontaneously., Although there is no universal definition of ADEM, most reports have described young adults or children with an acute onset of focal or multi focal neurological symptoms and signs variably associated with a meningo-encephalitic syndrome.
A number of terminologies have been used interchangeably with ADEM in the literature including disseminated vasculomyelinopathy, microglial encephalitis, peri venous encephalitis, peri venous allergic encephalopathy, allergic neuro encephalopathies, para or post infectious encephalomyelitis, post vaccinial encephalomyelitis, acute encephalo-myeloradiculitis and acute multiple sclerosis (MS). Unlike MS, ADEM is usually a monophasic disease with acute onset focal or multi focal neurological dysfunction. There are no generally accepted diagnostic criteria for ADEM; thus, distinguishing ADEM from the first episode of MS is often difficult, albeit increasingly vital in view of the potential benefits of disease modifying therapy for MS. Currently the distinction awaits the discovery of a biological marker for either disorder. ADEM seems to be common in children, than adults. Although, two adult series on ADEM are available from Andhra Pradesh, these were published as early as 1999. Hence, we wanted to analyze our more recent clinico-radiological experience with ADEM and look at functional outcomes following this abrupt illness.
Materials and Methods
Between January 1995 and October 2003, a total of 45 patients with ADEM were identified from two institutes; the Sree Chitra Tirunal Institute of Medical sciences and Technology, Trivandrum. Kerala and the Indo-American Brain and Spine Center, Vaikom, Kerala. The study was a retrospective-prospective study. For the period from 1995 to 1999, a retrospective chart review was done (25 patients). From 1999 to 2003, twenty patients were prospectively collected by one of the authors (BV). Follow up was based on chart review as well as outpatient visits.
We used the following criteria for the diagnosis of ADEM; namely a monophasic illness, the presence of symptomatology pertaining to the cerebrum with or without spinal cord or peripheral nervous system involvement, low grade or transient fever, non lateralized EEG. An acute neurological illness without a history of previous unexplained neurological symptoms was taken as an operational criterion for the initial diagnosis of ADEM. Neuroimaging evidence of single or multiple supra- or infra-tentorial demyelinating lesions was considered corroborative. As magnetic resonance imaging (MRI) abnormalities in ADEM are variable and not well defined, more specific criteria were not available.
All patients with a diagnosis of ADEM were admitted and worked up as inpatients. Demographic information including age, gender, history of antecedent illness particularly history of recent immunizations, vaccinations or recent infections, duration of current illness and initial symptomatology including the presence of fever, behavioral alteration, seizures and headache were collected. Neurological deficits were also recorded.
There were forty patients who underwent cranial and or spinal MRI with contrast. There were thirteen patients including five of those who did not undergo MRI who had Computed Tomography (CT) scans of the brain performed. The following variables were noted from the radiological images - the number of lesions, appearance, and contrast enhancement, pattern of enhancement and sites of lesions. Most patients underwent routine hematological evaluation, renal and liver function tests, vasculitis work up, thyroid function tests and nerve conduction tests. Nerve conduction studies and electromyography were performed according to clinical suspicion. Lumbar punctures were performed at or immediately after admission in forty patients. Routine CSF analysis was performed. PCR for Mycobacterium tuberculosis was performed wherever clinical suspicion of chronic meningitis existed.
Patients were treated according to a standard protocol with intravenous methyl prednisolone 1000 mg daily for 3-5 days depending upon the clinical response. This was followed by oral steroids (prednisolone 1 mg/kg/day) for a period of 15-21 days. Patients who did not improve with IV methylprednisolone, received small volume plasma exchange (100 ml/kg total dose) (4 patients) or immunoglobulin 0.4 mg/kg/day ´ 5 days (2 patients). The length of hospital stay was noted. At follow up patients were also assessed for residual deficits or relapses. The final outcome at discharge and follow up were also assessed to estimate the burden of the disease process. Modified Rankin score (MRS) functional outcome scores were determined at last follow up.
A total of 45 patients, 16 females and 29 males, with a mean age of 30 yrs (2-68 years) were included in this analysis. Adults above the age of 18 years constituted 85% of patients but patients older than 50 year were less (17%). Antecedent infections were seen in 18 patients (40%) with a mean preceding interval of 13 days (2-60 days). Of these nonspecific febrile illnesses were seen in 22 patients (48%), preceding diarrheal illness in one patient, and vaccination with antirabies vaccine in one case. Other preceding factors like parotitis, teeth extraction and zoster ophthalmicus were each seen in one patient each. The mean interval to admission was 20 days (1-120 days). The mean length of hospital stay was 12 days (2-65 days). The duration of follow up was approximately 2.5 years (0.75-5 years).
The most common symptoms were motor weakness (65%) and cranial nerve symptoms (48%), of which blurring of vision and diplopia accounted for approximately 31%. Headache and fever were seen in 18% of patients at the onset of illness. Low grade fever which remitted within 2-3 days of admission was encountered in 5% of patients. Alteration of sensorium was seen in 29% of patients and ranged from an acute confusional state to stupor. Seizures were seen at the onset in 12% of patients and were mostly generalized seizures. Prominent sensory and bladder complaints were seen in a third of patients. Gait ataxia and limb incoordination were seen in about 15% of patients. Pyramidal signs were commonly found (71%) and were more often bilateral. Cerebellar signs were seen in 35% and sensory findings (mostly dysaesthesias) were present in 30 % of patients. Facial weakness and oculomotor weakness was found in 28% of patients. Ocular motor involvement affected the VI nerve predominantly. Bilateral optic neuritis was commoner than unilateral involvement (17 vs 2%). The severity of visual loss ranged from mild to complete visual loss (7%). Trigeminal sensory impairment and lower cranial nerve deficits were noticed in 16-21% of patients. Unilateral deafness was detected in two patients (4%). No extra pyramidal involvement was noticed. Meningism was noted in eight patients (17%).
MRI was abnormal in 90% of patients who underwent the test. 30 patients (75%) had multiple lesions (2 or more lesions) on T2 weighted MRI (T2WI). The most common findings were T2WI hyper intense lesions in the sub cortical and periventricular white matter (50%). Spinal cord involvement was observed in eight patients (20%). These eight patients also had concurrent intracranial lesions. The spinal cord showed extensive lengthwise involvement in one patient, segmental involvement in five and an ascending pattern in two patients. Brainstem lesions were observed in a third of patients (29%). Although lesions were seen in the cerebellar peduncles, the cerebellar substance was uninvolved. The deep gray matter (thalamus and basal ganglia) was involved in five patients (12%). Lesions involving the cortex were also relatively infrequent (13%). On T1 weighted imaging (T1WI), lesions appeared mildly hypo intense. TI WI enhancement was uncommon, and only seven patients (17%) demonstrated patchy contrast enhancement of lesions. Ring or nodular enhancement was seen only in one case. Only one case showed edema surrounding the lesion. MRI was normal in five patients (10%). CT scan of the brain was done in 13 patients who included five patients who had not undergone an MRI evaluation. These five patients had normal studies on CT scan. CT scans did not pick up any additional lesions and in most cases picked up less number of lesions than MRI scans (only two out of seven CT scans picked up more than two lesions). CT scan showed hypo densities on plain scans without contrast enhancement. The lesion sites corresponded to those identified on the MRI. Posterior fossa and brainstem lesions were missed by CT scanning. MRI showed a higher number of lesions and had a higher pick up rate of lesions in ADEM [Figure 1][Figure 2],[Table 1].
Nerve conduction studies
Twenty five patients underwent nerve conduction studies. Of these six patients (13%) had a demyelinating neuropathy with prolongation of F waves, slowing of conduction velocities and prolongation of distal latencies. Conduction blocks were not observed. Four patients (8%) had an axonal neuropathy. Fifteen patients (33%) had normal nerve conduction parameters.
Lumbar puncture was performed at or immediately after admission in 40 patients. The mean interval between onset and CSF examination was 15 days. Opening pressure was normal in all patients. All patients showed a lymphocytic predominant CSF with a cell count ranging from 2 to 450 cells (mean 141 cells). However, only four patients showed CSF pleocytosis over 100 cells (9%). Twenty seven patients (60%) had a CSF cell count below 5 cells/cmm 3. The CSF protein ranged from 21 to 800 mg % (mean 73 mg %). In most (72%) the protein level was normal (Secondary complications
Six patients (13%) developed complications during hospital stay. Four patients developed respiratory failure (9%) and required mechanical ventilation. All these patients had spinal cord lesions on MR imaging. One additional patient required mechanical ventilation after acquiring nosocomial pneumonia. Mild dysautonomia (tachycardia, postural hypotension) was observed but was not of clinical significance. A total of 34 patients were treated with intravenous methyl prednisolone followed by oral prednisolone.
Outcome of ADEM
Seven patients (15%) had a modified Rankin score (MRS) of 0 and had gone back to work. Residual deficits were present in 9% of patients who were able to work (MRS of 1). There were fifteen patients (33%) who had an MRS of two and were ambulant but unable to work. MRS was three (moderate disability requiring some help, but able to walk without assistance) was the outcome score for 13% of patients. There were eleven patients (24%) who were severely disabled and dependent for all activities (MRS of 5). ADEM was associated with a low mortality (4%) [Table 2].
Eighteen patients (40%) reported transient reappearance of symptoms during subsequent illnesses. Only two patients had relapses (lasting >24 h), one of them had a relapse within four months with symptoms and signs suggesting involvement of the CNS at sites different from that of previous episode. His MRI showed a number of newer lesions suggestive of multiple sclerosis. On follow up, he was left with severe disability (MRS 5) but did not go on to develop any further episodes during the rest of his follow up (14 months). The other patient went on to develop a relapse after 1½ years. As he had the same symptoms as his initial illness he was not re-imaged. This patient could be characterized as having a recurrent disseminated encephalomyelitis (RDEM). However, only these two patients demonstrated new and persistent weakness.
Our case series sums up the experience of ADEM from two centers in Kerala spanning a period of nearly nine years. The clinical presentation of ADEM in this series is by and large similar to that described earlier in the literature. The predominant clinical features were motor and cranial nerve manifestations, minimal fever or meningism, a strong association with antecedent infections and dramatic changes on MR imaging. Lumbar puncture and nerve conduction studies were helpful in characterizing the pattern of illness and excluding other causes. Florid CSF pleocytosis, high CSF proteins or altered glucose values were unusual but helpful in distinguishing ADEM from MS. A wide variety of conditions such as vasculitis, multiple thromboemobolism, meningo encephalitis, neurocysticercosis can mimic ADEM. MRI findings of porphyria may mimic ADEM.
Although cerebellar signs are common in ADEM, MRI usually reveals only involvement of the cerebellar peduncles. We did not encounter any lesions within the cerebellar white matter or cortex. It is worth noting that even in post varicella zoster cerebellitis, the MRI is usually normal. Hence, conventional imaging sequences do not reveal any involvement of cerebellar substance in ADEM.
ADEM is considered to be a monophasic illness. The natural history of ADEM appears to vary. Reappearance of earlier symptoms during subsequent illnesses is common and worrisome for patients. This should not be confused with a relapse, which refers to worsening of clinical condition or of new deficits that lasts longer than 24 h. Some of these relapses when it involves a different site indicates the evolution to MS as happened in our patients. The rate of progression to MS seemed to be very low (<2%) in this series. Hence ADEM should be considered a distinct entity from MS in our population. This is in contrast to the western population where the frequency of conversion to MS seems to be much higher.
The mortality of ADEM was relatively low (<5%) in our series. Nevertheless our treatment modalities are yet suboptimal and future studies and treatment options need to look into improving functional outcomes following this catastrophic illness. We have documented the functional outcome following ADEM to quantify the burden and impact of the disease. Only few patients were able to return to work without any disability (15%) and most are left with residual degrees of disability.
ADEM is rare in the elderly who are beleaguered more by vascular, neoplastic or degenerative processes than by inflammatory demyelinating disorders. In our series, 83% of patients were at the age less than 50 years.
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