A 4-year-old previously healthy boy presented with a 3-week history of progressive gait difficulties. He was observed to have gait incoordination for a few days before he started complaining of neck and lower extremity pain. On the day of presentation, he was unable to move his legs upon awakening. There was no history of bladder or bowel dysfunction. Family members confirmed that he had not been recently ill or received any recent vaccinations. On examination, he was alert and oriented. He did not have any cranial nerve deficits. He had full upper extremity strength with the exception of mild bilateral grip weakness. He did not have any antigravity movements in the lower extremities. His sensory examination was remarkable for minimal withdrawal to pain bilaterally, increased tone in the left lower extremity, a right hemisensory deficit (to light touch) up to second thoracic dermatomes, and diminished pain sensation in both lower extremities. Deep tendon reflexes were 3+ at quadriceps, and sustained clonus was noted at the left ankle along with bilaterally positive Babinski reflex. Magnetic resonance imaging (MRI) of the neuroaxis showed an abnormal appearance of the cervical and thoracic spinal cord with expansion and irregular areas of enhancement (Figure 1). Initial MRI brain was unremarkable (Figure 2A and B). Routine serum and cerebrospinal fluid studies were performed to look for infectious, autoimmune, inflammatory, and neoplastic etiologies. Routine cerebrospinal fluid studies showed a WBC count of 20/muL (66% lymphocyte), 1 RBC, glucose of 30 mg/dL, and protein of 5875 mg/dL. Infectious workup (including HSV, HHV6, enterovirus, EBV, mycoplasma, Bartonella polymerase chain reactions, and screening tests for tuberculosis) was unremarkable. Autoimmune (ANA, anticardiolipin, antiphospholipids) and central nervous system inflammatory workup (MS profile, AQ4 Ab, ACE level ) were also unrevealing. Cerebrospinal fluid flow cytometry did not show abnormal cells. Given the difficulty in determining an exact onset of symptoms and that apparent abruptness of loss of function, a biopsy was deferred, and on hospital day 2, the patient was started on high-dose intravenous methylprednisolone (30 mg/kg/d) which was continued for a total of 7 days. On the third day of admission, the patient developed respiratory failure requiring intubation and mechanical ventilation along with further progression of muscle weakness in upper extremities. Given the lack of response to treatment, a thoracic cord biopsy was performed (hospital day 4). Preliminary pathological examination was indeterminate, requiring consultation with outside pathologists and taking several weeks for a definitive diagnosis. Therefore, the patient was started on a steroid taper, received intravenous immunoglobulin, and underwent plasma exchange without significant improvement, due to a remote possibility of the lesion being autoimmune. After several weeks, the pathology specimen examination revealed the diagnosis of diffuse midline glioma (World Health Organization [WHO] grade IV; Figure 3). Radiation and chemotherapy with temozolomide and bevacizumab (Avastin) were initiated. Subsequently, the child regained some upper extremity muscle power (coinciding with some improvement in spinal imaging showed in Figure 4), but still remained profoundly weak in his lower extremities. The patient also required a tracheostomy to maintain the airway but died within 4 months after diagnosis as a result of intracranial spread of this metastatic disease (Figure 2C and D).