Case 3: Acute Onset of Headache, Fever, and Right Arm Weakness in 12-year-old Boy

Field: Medicine (Health Sciences)

A previously healthy 12-year-old boy is hospitalized with headache localized to the front and back of the head of 3 days duration. He had a temperature up to 39°C (102.2°F) yesterday. He also complains of neck pain that is aggravated with neck movements. There is no history of photophobia, tinnitus, sore throat, respiratory distress, abdominal pain, rash, or head trauma. Two weeks ago he was treated with one dose of intramuscular ceftriaxone and oral amoxicillin for 5 days for otitis media. His immunizations are up-to-date. He is in sixth grade, earning average grades.Vital signs at the time of admission are: temperature 38.7°C (101.7°F), heart rate 122 beats/min, respiratory rate 22 breaths/min, blood pressure 123/73 mm Hg, and oxygen saturation 97% in room air. Physical examination reveals neck stiffness and positive Kernig sign. External ocular movements are normal and pupils are equal in size and reacting normally to light. There are no focal neurologic deficits.Laboratory results include: white blood cell count 9,800/μL (9.8 × 109/L) with 80% neutrophils, 11% lymphocytes, and 6% monocytes; hemoglobin 14 g/dL (140 g/L); and platelet count 282 × 103/μL (282 × 109/L). Serum electrolytes are normal. Cerebrospinal fluid (CSF) analysis reveals a white blood cell count of 160/μL with 1% neutrophils, 84% lymphocytes, and 15% monocytes; protein 111 mg/dL; and glucose 54 mg/dL.During his hospital stay, the boy’s headache worsens and is associated with three episodes of nonbilious and nonbloody emesis. He also continues to have temperatures up to 40°C (104°F). He develops altered sensorium, with a fluctuating level of consciousness associated with agitation, confusion, and increased somnolence. He also complains of right arm weakness and paresthesias on the third day of admission. Computed tomography scan of the brain with and without contrast yields normal results. Additional imaging studies elucidate the diagnosis.The differential diagnoses for this patient included acute central nervous system (CNS) infections such as meningitis, encephalitis, meningoencephalitis, and brain abscess; CNS vascular disorders such as stroke, mitochondrial encephalopathy with lactic acidosis, and strokelike episodes (MELAS); and intracranial mass lesions, including CNS lymphoma and multiple sclerosis.The laboratory evaluation was negative for influenza A and B (nasopharyngeal wash) and acute Epstein-Barr virus (EBV) infection serology. CSF analysis was also negative for antibodies for West Nile; polymerase chain reaction (PCR) for herpes simplex virus (HSV) 1 and 2; and latex agglutination tests for pneumococcus, meningococcus, Haemophilus influenzae type b, and cryptococcus. CSF cultures for bacteria were negative. Magnetic resonance imaging (MRI) with gadolinium contrast showed small multifocal areas of increased T2-weighted signal in the white matter of the bilateral centrum semiovale and periventricular regions (Figs 1 and 2) as well as the posterior limb of the left internal capsule, left pons, bilateral superior cerebellar peduncles, right inferior cerebellar peduncle, and midbrain (Fig 3) suggestive of acute disseminated encephalomyelitis (ADEM).ADEM is an immune-mediated monophasic multifocal inflammatory demyelinating disorder of the CNS. The average age at which this disorder occurs is 5 to 8 years, and it affects boys and girls equally. ADEM is more commonly seen in the winter months and early spring, when childhood infections generally are more common. Epidemiologic studies indicate that the incidence is 0.4 per 100,000/year among those younger than age 20 years. Retrospective clinical studies over 5 to 6 years in two different tertiary centers in the United States and Great Britain identified 18 patients with ADEM. (1)(2)(3)Clinical presentation of ADEM includes viral infection or vaccination 2 days to 4 weeks before the onset of neurologic symptoms. Generalized symptoms include persistent fevers, vomiting, headache, and irritability. Neurologic symptoms and signs include weakness, motor deficits, cranial nerve palsies, cerebellar signs, paresthesias, seizures, nystagmus, diplopia, altered sensorium, and bladder involvement. Neurologic symptoms and signs depend upon the site of demyelination.Viral organisms such influenza, measles, enterovirus, Varicella zoster, EBV, cytomegalovirus, and HSV1 and 2 have been implicated. Other infectious agents, such as Mycoplasma, Borrelia burgdorferi, Leptospira, beta-hemolytic streptococci, and certain fungi, have been associated with ADEM. Certain vaccines such as antirabies nerve sheath vaccine, hepatitis B, tetanus-pertussis-diphtheria, measles-mumps-rubella, varicella, influenza, and Japanese B encephalitis have been indicated as precipitating factors for ADEM.The pathogenesis of ADEM is not completely understood. Animal models of experimental autoimmune encephalomyelitis and post-rabies vaccination encephalomyelitis suggest an autoimmune etiology. Through molecular mimicry, viral or bacterial infections can trigger and activate myelin-reactive T cells in genetically susceptible individuals, causing ADEM. Histologic findings in ADEM include periventricular T-cell infiltration, perivenous inflammation, and “sleeves” of demyelination.The most significant laboratory study for ADEM is CSF analysis, which generally shows CSF pleocytosis with a predominance of lymphocytes and increased protein. Generally, CSF glucose values are normal. Other clinical studies, such as complete blood cell count, serum electrolytes, C-reactive protein, hepatic enzymes, and renal profile, are noncontributory. Blood and CSF analysis for bacteria, fungi, and viral organisms may lead to microbiologic diagnosis of the preceding illness. Electroencephalography shows generalized slowing activity.Magnetic resonance imaging of the brain demonstrating the demyelinating and inflammatory lesions confirms ADEM diagnosis. Lesions are identified on T1, T2, FLAIR (fluid-attenuated inversion recovery), and gadolinium-enhanced T1 images. T2/FLAIR sequences show asymmetric, multifocal, heterogeneous hyperintense lesions involving white matter of cerebral hemispheres, basal ganglia, cerebellar hemispheres, and brainstem. Gadolinium-enhanced images may show homogeneous or heterogeneous ringlike enhancing lesions when demyelination is active. Diffusion restriction is also sign of acute demyelination.No controlled clinical trials are available to guide therapy for ADEM. Because the disease is believed to be an immune-mediated inflammatory disorder, administration of high-dose corticosteroids followed by a tapered dose regimen has shown good results. Suggested regimens include methylprednisolone 10 to 30 mg/kg per day in two to three divided doses for 5 days or prednisolone 2 mg/kg per day for 5 to 7 days, followed by tapering over 1 to 2 weeks. Treatment with intravenous immunoglobulin (2 g/kg) has also shown symptomatic improvement in a few studies.Follow-up studies have shown residual neurologic deficits in only a few children in the form of weakness or bladder disturbance. Long-term follow-up evaluation suggests that affected children have subtle neurocognitive deficits and behavioral problems.Our patient was treated with intravenous methylprednisolone 250 mg four times a day for 3 days, followed by 3 weeks of oral prednisolone with a tapering dose schedule. He responded fully and has not had any relapse of his symptoms.