Adem: literature review and case report of acute psychosis presentation

doi:10.1016/S0887-8994(99)00116-2

Pediatric Neurology

Volume 22, Issue 1, January 2000, Pages 8-18

https://doi.org/10.1016/S0887-8994(99)00116-2 Get rights and content

Abstract

Acute disseminated encephalomyelitis is a monophasic, immune-mediated disorder that produces multifocal demyelinating lesions within the central nervous system. It is characterized clinically by the acute onset of neurologic abnormalities, including varying degrees of mental state changes ranging from drowsiness to coma. It is unusual for the illness to present as an isolated acute psychosis. The case of a 14-year-old female with biopsy-confirmed acute disseminated encephalomyelitis, who was initially diagnosed with an acute psychiatric disorder, is presented, and published reports on this unusual manifestation are reviewed. A Medline database search was performed from 1965 to 1999, using the terms acute disseminated encephalomyelitis, postvaccinal encephalomyelitis, postinfectious encephalomyelitis, and measles encephalomyelitis, combined with the terms psychosis, psychiatric disorder, and behavioral disorder. Selected cross-referenced reports were also reviewed. Nine patients were identified who presented with acute psychosis. We conclude that, although rare, acute disseminated encephalomyelitis can present as an acute psychosis. This immune-mediated condition should be included in the differential diagnosis of neurologic disorders presenting as a psychiatric illness.

Introduction

Acute disseminated encephalomyelitis (ADEM) is a monophasic, polysymptomatic disorder involving central nervous system (CNS) white matter. This immune-mediated inflammatory process can follow infection, which is generally viral, or vaccination. The multifocal symptoms reflect demyelinating lesions and consist of various combinations of motor, sensory, gait, visual, and memory disturbances. There are examples of ADEM presenting as a purely psychiatric illness. We report a 14-year-old female who presented with acute psychosis. Published reports are reviewed of this disease, its atypical presentations, its diagnostic evaluation, with special emphasis on the role of magnetic resonance imaging (MRI), and current therapeutic approaches.

Section snippets

Case report

The patient was a 14-year-old right-handed Hispanic female who was transferred to University Hospital on October 2, 1997 for evaluation of an acute-onset psychiatric syndrome. Her symptoms began 18 days earlier, when she was observed at school acting strangely. Later that day she became irritable and paranoid, fearing that people would hurt her. At home, she became agitated and unmanageable and was admitted to a nearby community hospital. Before this episode, she had been healthy, with no

Definition

ADEM is an acute inflammatory and demyelinating disease of the brain and spinal cord. It usually occurs a few days to weeks after systemic viral infection [1]. Most cases have been associated with exanthematous diseases, such as measles, varicella, vaccinia, and rubella, or with vaccinations for smallpox and rabies [2]. Discontinuation of vaccination against smallpox, as well as the use of the trivalent measles-mumps-rubella vaccine to reduce natural infections, have significantly decreased the

Epidemiology

A significant proportion of acute encephalitis cases are postinfectious. At London Hospital, ADEM comprised up to one third of all encephalitis cases admitted between 1963 and 1978 [6]. ADEM occurs after one of every 1,000 cases of measles [7], with a fatality rate of 20%. The next most common triggers are rabies vaccine, varicella, and rubella, with a widely variable rate reported after vaccination (Table 1). The mortality rate ranges from 5% to 20%. The age of onset of ADEM reflects that of

Clinical manifestations

The hallmark of the disease is, as implied by the name, the acute development of a multifocal neurologic disorder, accompanied by generalized complaints of headache, fever, nausea, vomiting, and mental state changes. Occasionally, there is a prodromal illness, with several days of fever, malaise, and myalgias. ADEM usually begins 1-3 weeks after a systemic infection, but it can occur sooner after an exanthematous infection such as measles. The onset is abrupt compared with a viral encephalitis,

Pathologic features

ADEM has uniform pathologic features, independent of the inciting agent and similar to other demyelinating CNS diseases. The pathologic finding is predominantly white matter disease, with perivenular inflammation and demyelination. This finding differs from acute viral encephalitis, which mainly involves the gray matter, with perivascular and parenchymal infiltration of inflammatory cells and neuronophages [2]. Gross pathologic changes include brain congestion and swelling, with engorged white

Diagnosis

Although the clinical picture is usually suggestive, biopsy allows definite diagnosis. Biopsy is rarely necessary, however. Diagnostic aids include electrophysiologic tests, CSF analysis, and neuroimaging.

Differentiation between ADEM and MS

ADEM and MS have many common clinical features, including the possibility of a discrete infectious trigger. Both are believed to involve an immune attack on myelin, with alteration of the blood-brain barrier. ADEM can even be multiphasic [50], and episodes may recur within 18 months of the initial attack without the patient going on to develop MS with long-term follow-up [51], [52]. These similarities make it more difficult to differentiate between the two diseases solely on a clinical basis.

Treatment

No reliable documented therapies for ADEM are available. Aside from supportive care, many agents and techniques that target the immune system have been used and reported anecdotally to be effective. These include glucocorticoids, adrenocorticotropin (ACTH), intravenous immunoglobulin, plasmapheresis, and glatiramer acetate (Table 4). Glucocorticoids are considered effective because of their anti-inflammatory and immunosuppressant effects, with an additional beneficial effect on cerebral edema.

Pathogenesis

The pathogenesis of ADEM is believed to involve autoimmune mechanisms: specifically, an immune response to CNS myelin. There are several explanations for how this autoimmune response might occur. One is molecular mimicry, where a specific peptide, carbohydrate, or lipid epitope of an infecting agent is similar to an antigenic epitope of myelin. Such mimicry occurs in PNS demyelination syndromes, in which there is shared antigenicity between the ganglioside GQ1b and Campylobacter jejuni in

Conclusions

ADEM is an acute inflammatory and demyelinating disease distinguished pathologically by numerous foci of demyelination scattered throughout the brain and spinal cord. The clinical picture reflects the diffuse CNS involvement and is characterized by the acute onset of headache, fever, stiff neck, confusion, and focal neurologic signs often corresponding to the location of the lesions. Convulsions are not uncommon, and severe cases may present with stupor and coma. Uncommon presentations include

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The 2018 measles outbreak in Israel affected >2000 people in Jerusalem. The aim of the study was to describe clinical features and complications of hospitalized measles patients in Jerusalem, as related to age group and risk factors.
All individuals hospitalized with measles in the three main hospitals in Jerusalem during March 2018 to February 2019 were included. Demographic, clinical and laboratory data were analysed.
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Of the three major therapeutic classes – biopharmaceuticals, synthetic therapeutic peptides, and chemically synthesized small-molecule (SMOL) pharmaceuticals – only SMOLs, which currently comprise over 80% of licensed therapeutics, have the potential to meet each of these requirements [39]. As a second conceivable indication in addition to use in PEP, a measles therapeutic may be beneficial for improved management of validated, rare measles complications such as acute demyelinating encephalomyelitis (ADEM) [40], measles inclusion body encephalitis (MIBE) [41], and subacute sclerosing panencephalitis (SSPE) [42,43]. Of these, MIBE and SSPE are associated with prolonged phases of viral replication in the brain, and both are ultimately fatal due to neurological damage.
Measles caused an estimated minimum of one million fatalities annually before vaccination. Outstanding progress towards controlling the virus has been made since the measles vaccine was introduced, but reduction of measles case-fatalities has stalled at around 100,000 annually for the last decade and a 2019 resurgence in several geographical regions threatens some of these past accomplishments. Whereas measles eradication through vaccination is feasible, a potentially open-ended endgame of elimination may loom. Other than doubling-down on existing approaches, is it worthwhile to augment vaccination efforts with antiviral therapeutics to solve the conundrum? This question is hypothetical at present, since no drugs have yet been approved specifically for the treatment of measles, or infection by any other pathogen of the paramyxovirus family. This article will consider obstacles that have hampered anti-measles and anti-paramyxovirus drug development, discuss MeV-specific challenges of clinical testing, and define drug properties suitable to address some of these problems.
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Acute disseminated encephalomyelitis (ADEM) is characterized by abrupt and diffuse demyelination within the CNS due to T cell–mediated targeting of myelin. Typically, symptoms occur after an infection (measles) or vaccination (small pox or rabies).34 Estimated occurrence of ADEM is approximately 0.4 per 100,000 of those under 20 years old with a mortality rate of 2%.35
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In previous literature, the majority of ADEM cases have been described with multiple focal symptoms and multiple neurologic deficits (1–4,9,10). Of the sparse cases that have been documented with an atypical presentation, only a few publications have described cases with similar symptoms of sole acute urinary retention (5,6,11–14). To our knowledge, all of the cases have been described in literature outside of emergency medicine.
Urinary retention in an otherwise healthy adolescent is a concerning symptom, in which etiology can range from an extracystic mass to central nervous system involvement (CNS). One possibility is acute disseminated encephalomyelitis (ADEM), a rare inflammatory autoimmune disease that affects the CNS via demyelination. The disease usually is preceded by an acute viral infection, and commonly presents with multifocal neurological deficits. The diagnosis for ADEM is made based on clinical presentation, correlating with findings characterized on magnetic resonance imaging (MRI) in the CNS.
Our case involves a 16-year-old boy who presented to the Emergency Department (ED) with urinary retention. The patient was an otherwise healthy adolescent who was experiencing intermittent fevers for 1 week, and was found to be monospot positive when seen by his pediatrician. When presenting to the ED, the patient's primary complaint was urinary retention, which he experienced acutely in the middle of the night. Due to the suspicious nature of the patient's symptoms and history of present illness, the patient received a thorough workup including magnetic resonance imaging (MRI) of the patient's brain and spinal cord, which demonstrated findings consistent with ADEM.
There is very little literature describing a case of ADEM in the ED where the primary manifesting symptom was urinary retention. In addition, it is important that clinicians address acute urinary retention in an otherwise healthy adolescent as a red flag, with the need to rule out concerning etiology.
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Review ArticlesAdem: literature review and case report of acute psychosis presentation

Abstract

Introduction

Section snippets

Case report

Definition

Epidemiology

Clinical manifestations

Pathologic features

Diagnosis

Differentiation between ADEM and MS

Treatment

Pathogenesis

Conclusions

Mayo Clin Proc

J Neurol Sci

J Neurol Sci

Pediatr Neurol

J Neuroimmunol

Magn Reson Imaging

Brain Dev

J Neurol Sci

Adv Immun

J Neuroimmunol

Parainfectious encephalomyelitis and related syndromes

J Med

The pathogenesis of acute viral encephalitis and postinfectious encephalomyelitis

J Infect Dis

Postinfectious encephalomyelitis

Semin Neurol

Neurological aspects of Mycoplasma pneumoniae

Acta Neurol Scand

Acute viral encephalitis. Its diagnosis and outcome

Brain

Acute disseminated encephalomyelitis

Measles encephalomyelitis—Clinical and immunological studies

N Engl J Med

MeaslesSummary of worldwide impact

Rev Infect Dis

Cranial MRI in acute disseminated encephalomyelitis

Neurology

Guillain-Barré syndrome and acute disseminated encephalomyelitis (ADEM)

Clin Neurol

A case of acute disseminated encephalomyelitis associated with demyelinating peripheral neuropathy

Brain Nerve

A case of acute disseminated encephalomyelitis with pathologically proven acute demyelinating lesion in the peripheral nervous system

Clin Neurol

Inflammatory demyelinating polyradiculitis in a patient with acute disseminated encephalomyelitis (ADEM)

J Neurol Neurosurg Psychiatry

Guillain-Barré syndrome (GBS) with bilateral optic neuritis and central white matter disease

Neurology

Acute severe combined demyelination

Childs Nerv Syst

Acute disseminated encephalomyelitis presenting as an acute psychotic state

J Nerv Ment Dis

Acute disseminated encephalomyelitisMRI findings and distinction from multiple sclerosis

Brain

Acute physically based psychosis after Malaria tropica

Nervenarzt

Acute disseminated encephalomyelitis in middle aged or elderly patients

Eur Neurol

Korsakoff’s syndrome as the first clinical manifestation of acute disseminated encephalomyelitis

Behav Neurol

Acquired reversible autistic syndrome in acute encephalopathic illness in children

Arch Neurol

Subtle encephalomyelitis in childrenA variant of acute disseminated encephalomyelitis

J Child Neurol

Multiple sclerosis presenting with acute remitting psychiatric symptoms

J Neurol Neurosurg Psychiatry

Childhood psychosis and Schilder’s leukoencephalitis

Rev Neuropsychiatry Infant

The neuropsychiatry of adult-onset adrenoleukodystrophy

J Neuropsychiatry Clin Neurosci

Subacute sclerosing panencephalitis presenting as schizophreniform psychosis

Br J Psychiatry

Spindle coma and alternating pattern in the course of measles encephalitis

Clin Electroencephalogr

Computed tomography in acute disseminated encephalomyelitis

Ann Neurol

Viral infections of the CNS in childrenImaging features

Review Articles
Adem: literature review and case report of acute psychosis presentation