History and Physical
A 4-year-old girl presented with prolonged fever, weight loss, leukocytosis, and vomiting for one month. She was diagnosed with croup 2 weeks prior to presentation and received MMR vaccination one week prior to presentation. Subsequently, she developed lethargy, irritability, abdominal pain, and musculoskeletal pain. She was initially diagnosed and treated for Clostridium difficile infection, but her fever returned about 3 weeks later. She was found to have elevated white blood cell (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). She then reported bilateral eye pain and had difficulty walking, hyperphagia, constipation, and bladder issues. During her hospitalization, she continued to have hypersomnolence and developed hypopnea and desaturations during sleep. Exam was significant for encephalopathy, allodynia, lower extremity weakness, and diffuse hyperreflexia with upgoing toes.
Diagnostic Workup
Brain MRI with and without contrast revealed diffuse T2/FLAIR hyperintense signal abnormalities. There were patchy and confluent foci throughout all cerebral lobes. Involvement was most severe in the bilateral mesial temporal lobes. There was also involvement of the deep gray structures including the putamina and thalami, as well as brainstem structures including superior cerebellar peduncles and dorsal midbrain. White matter involvement included the periventricular regions, corona radiata, and centrum semiovale. The optic chiasm was thickened with similar signal alterations that extended posteriorly into the optic tract and inferiorly into the hypothalamus ( Fig. 52.1 ). There was no associated diffusion restriction or contrast enhancement. MRS was normal.
ADEM. Brain MRI, axial FLAIR, shows patchy hyperintensity throughout the (A-B) cerebral cortex and subcortical white matter, (C) mesial temporal lobes, (D) thalami, and (E) optic pathway. ADEM , Acute disseminated encephalomyelitis; FLAIR , fluid-attenuated inversion recovery.
Spinal MRI was significant for multifocal edema throughout the cord ( Fig. 52.2 ). There was no associated enhancement.
ADEM. Spine MRI, (A) sagittal and (B) axial T2, show multifocal lesions involving the majority of the cord cross-section. No definite enhancement was seen. ADEM , Acute disseminated encephalomyelitis; MOGAD , myelin oligodendrocyte glycoprotein-antibody disease.
The patient underwent an extensive workup and was found to have elevated inflammatory markers, including absolute neutrophil count (ANC), platelet (PLT), ESR, and CRP. Creatinine kinase (CK), complement, lactate dehydrogenase (LDH), and rheumatoid factor (RF) were normal. Broad infectious workup was negative. Hormonal screening was unrevealing including thyroid stimulating hormone (TSH). Autoimmune workup for systemic lupus erythematosus (SLE) and sarcoidosis with dsDNA and angiotensin-converting enzyme (ACE) was negative. Lumbar puncture (LP) revealed an elevated cell count (45) and protein (123). AQP-4 antibody testing was negative. Myelin oligodendrocyte glycoprotein (MOG) antibody obtained during a subsequent bout of optic neuritis was positive. She was started on steroids with significant clinical improvement, and treatment was tapered off over 2 months. Follow-up MRI 6 months later was normal. She had long-term sequelae including distal lower extremity spasticity and recurrent urinary tract infections.
Clinical Differential Diagnoses
A patient presenting with subacute onset of fever, altered mental status, and signs of myelitis raises concern for various metabolic, infectious, endocrinologic, and autoimmune processes.
The presence of encephalopathy narrows the clinical differential from various causes of myelitis to those that may mimic acute disseminated encephalomyelitis (ADEM). These include thyroid (Hashimoto) encephalopathy and CNS infections, particularly given her fever: Epstein-Barr virus (EBV)/CMV, Lyme, HIV, human herpesvirus 6 (HHV-6), and Powassan virus.
Multiple sclerosis (MS) can present with myelitis and optic neuritis but is much less likely to have associated encephalopathy with extensive cord, hypothalamic, and chiasm involvement.
Several autoimmune conditions can present with altered awareness, such as autoimmune encephalitis and Rasmussen encephalitis.
CNS vasculitis can present acutely with altered awareness and neurologic deficits.
Imaging Differential Diagnoses
There is a broad differential for multifocal T2/FLAIR-hyperintense lesions involving both white and gray matter. Autoimmune encephalitides can show cortical/subcortical abnormalities and meningeal enhancement. Limbic encephalitides affect limbic structures including hippocampus, amygdala, claustrum, and mesial temporal lobe. There may be additional involvement of basal ganglia, brainstem, and neocortex. Rasmussen encephalitis can present with more asymmetric abnormalities, including unilateral cerebral and basal ganglia atrophy, T2/FLAIR-hyperintense signal in cortex/subcortical white matter, and ex vacuo ventriculomegaly ( Fig. 52.3 ).
