Presentations

Abstract

Introduction: Acute disseminated encephalomyelitis (ADEM) is a rare acute, rapidly progressive, immune-mediated demyelinating disorder of the central nervous system requiring early hospitalization. The disease is characterized by diffuse neurological symptoms such as encephalopathy unexplained by fever, extrapyramidal signs, ataxia, aphasia, nystagmus, seizures, intracranial pressure, optic neuritis, urinary retention, dysarthria, and oculomotor dysfunction. It is often monophasic and self-limiting with clinical remission as early as 4 weeks. Signs of peripheral involvement including weakness of limbs and muscle atrophy, which are considered to have worse prognosis, might be seen in some adult patients. Evidence of multifocal demyelination in the brain, spinal cord, and optic nerve is visible on neuroimaging. The clinical manifestations are often similar to multiple sclerosis or solitary lesions. More common in children, preceding infection or immunization has been reported in 50-85% of ADEM cases. Infectious etiology include cytomegalovirus, herpes simplex virus, human herpes-virus-6, Epstein-Barr virus, influenza virus, mumps, rubella, coxsackie, hepatitis A, HIV, mycoplasma pneumonia, Leptospira, beta-hemolytic streptococci, and Borrelia burgdorferi.

Case Information: A 56-year-old female with medical history of HIV on tenofovir/ emtricitabine/ cobicistat/ elvitegravir with last CD4 930 and undetectable viral load was admitted for generalized malaise, non-bloody emesis, and painful rash on right neck. On arrival, she was febrile at 101.3F, tachycardic, tachypneic, and hypertensive. CBC was unremarkable. Initial concern was for sepsis, but blood cultures were negative. Physical exam revealed right-prominent lower extremity weakness with numbness and lesions in C4-C5 dermatome distribution consistent with herpes zoster. MR lumbar spine was notable for degenerative changes. Patient was initiated on a 7-day course of acyclovir. On Day 7 of admission, she began developing right-prominent upper extremity weakness. After neurology consult, a non-contrast brain MRI was done, which initially raised concern for multifocal stroke given subacute infarcts in brainstem and left cerebrum. Subsequent contrast-enhanced brain MRI revealed increased T2 FLAIR hyperintensity with bilateral periventricular and adjacent white matter enhancements. Cervical and thoracic MRIs were significant for longitudinally extensive abnormal cord signals with associated enhancements. BioFire Respiratory panel was negative. Meningitis/Encephalitis panel including serology tests for cytomegalovirus, Epstein-Barr virus, JC virus, HTLV antibodies, varicella zoster virus, and herpes simplex virus were unremarkable. Acute myelitis, extensive ADEM, and granulomatous process were included in our differential. With high suspicion for ADEM, the patient was initiated on IV solumedrol with a 5-day course, but she experienced minimal improvement in extremity weakness with continuous fluctuation of mentation. Subsequent lumbar puncture showed open pressure of 12 mmHg, pleocytosis, and mildly elevated protein and glucose supporting the diagnosis of ADEM along with imaging studies. After the course of glucocorticoid, a 5-day regimen of intravenous immune globulin was also initiated. At discharge, the patient was afebrile, alert, and oriented, but continued to experience right upper extremity weakness with poor lower extremity strength. She was instructed to follow up with a multiple sclerosis specialist outpatient.

Discussion/Clinical Findings: ADEM is typically seen in children following an illness. Subtle MRI changes include hyperintense lesions, often with indistinct margins compared to clear-cut margins seen in multiple sclerosis. There are no specific biomarkers or confirmatory diagnostic tests for ADEM. It is a diagnosis of exclusion with supportive features of one or more supratentorial or infratentorial demyelinating lesions on brain MRI, signs of neurologic dysfunction, preceding infection, and abnormal CSF with mild lymphocytic pleocytosis and elevated protein. First-line treatment is a 5-day course of high dose methylprednisolone. Empiric treatment with acyclovir and antibiotics can be provided before infectious etiology is ruled out. If no symptomatic improvement is seen, intravenous immune globulin or plasma exchange is required.

Conclusion: This case describes a rare finding of acute monophasic ADEM likely secondary to varicella zoster virus infection in a HIV-positive, 56-year-old female with preserved immune status. Our clinical suspicion for varicella zoster-induced ADEM compared to HIV etiology was supported by symptomatic manifestation following recent herpes zoster infection. Nevertheless, more extensive research is warranted to better understand the pathophysiology and complications associated with ADEM in adult patients, especially those with HIV who have a diverse clinical spectrum. In addition, despite being a rare diagnosis in adults, ADEM should be a part of the broader differential diagnosis as it can often be misdiagnosed as multiple sclerosis or primary neurological infection.