Novel Influenza A (H1N1)-Associated Acute Necrotizing Encephalopathy: A Case Report
A 4-year-old girl with normal neurodevelopmental aspects was diagnosed with H1N1 infection by real-time polymerase chain reaction test from nasopharyngeal swabs and given Tamiflu. On the following day, she was presented with generalized tonic-clonic type seizure and neurologic deterioration, requiring intensive care. Cerebrospinal fluid (CSF) analysis revealed an increase in protein level (88 mg/dL) and a normal glucose level (46 mg/dL), but negative results in bacterial antigen test with no pleocytosis. Gram staining and cultures of CSF and blood were negative. The C-reactive protein value was normal (<1 mg/L) and the blood leukocyte count was elevated (15.69×103/µL). Serum aminotransferases was elevated (83 IU/L), but blood ammonia (41 µg/dL) and renal function tests were normal. There was no definite abnormality in electroencephalogram. Initial magnetic resonance image (MRI) demonstrated enhancing lesions in the bilateral thalami, pons, and left basal ganglia that suggested sequelae of previous viral infection, which were findings compatible with ANE (). Based on the CSF study, viral and bacterial encephalitis were excluded. Hypoxia, intoxication, hemolytic-uremic syndrome, metabolic disease, Leigh syndrome and other encephalopathies with thalamic involvement, such as Wernicke encephalopathy, thalamic infarction, and deep cerebral vein thrombosis were excluded by laboratory data, clinical course, and MRI findings. As a result, ANE caused by H1N1 infection was diagnosed according to the previously suggested diagnostic criteria [,]. One month after disease onset, the patient was transferred to the department of rehabilitation medicine. Although the precise muscle strength could not be measured due to altered mental status and young age, antigravity muscle activities were observed in all four extremities. Neurologic signs implicating upper motor neuron damages, such as Hoffmann's sign, ankle clonus, Babinski's sign or hyperactive deep tendon reflexes were not observed. She could not sit, stand, walk, or grasp an object. She could make sounds, but could not speak words. Strabismus due to the left abducens nerve palsy was observed (). The Gross Motor Function Measure (GMFM)-88 was 15.16%, and the Functional Independence Measure for children (WeeFIM) score was 18 of 126. Her social age (SA) was 1.08 years and social quotient (SQ) was 22.73. On the 18F-fluorodeoxyglucose positron emission tomography brain scan, glucose uptake increased diffusely in the bilateral basal ganglia and mildly in the bilateral thalami, but decreased diffusely in the bilateral cerebral hemispheres (). Physical, occupational, and speech therapy ensued. On discharge, 77 days after onset, she was able to walk on an even surface under supervision and her GMFM-88 was 78.81%. The SA was 3.0 years and SQ was 62.11. Follow-up MRI showed a decrease in the extent of the lesions involving the bilateral thalami and brainstem, with remaining hemorrhagic residue ().\nThe patient continued rehabilitative management via the outpatient clinic. Four months after initial evaluation, she could walk independently and ascend and descend stairs, but showed ataxia. She mainly used her right hand and suffered from intention tremor in the left hand. Although the degree of left abducens nerve palsy was improved, it is still present (). The International Cooperative Ataxia Rating Scale [] was 50 and Scale for the Assessment and Rating of Ataxia [] was 14, which corresponds to moderate ataxia. Her GMFM-88 had improved to 92.59% and the WeeFIM score was 70; SA was 4.07 years and SQ was 91.08. A follow-up MRI taken on April 29, 2010 showed no interval change of the hemorrhagic residue in the dorsal brain stem and bilateral thalami (). Intentional tremor of the left hand, ataxic walking pattern, and left abducens nerve palsy were still observed 2 years after onset.