A Teen’s Battle With Ataxia and Brain Swelling After URI

Differential Diagnosis

The initial differential diagnosis for acute ataxia was broad, including intracranial tumors, abscesses, intoxication, metabolic disorders, hereditary degenerative diseases, meningitis, encephalitis, acute cerebellar ataxia, and acute disseminated encephalomyelitis (ADEM). ¹

Meningitis was initially suspected, as CSF analysis demonstrated pleocytosis consistent with inflammation; however, the meningitis PCR panel returned negative. After obtaining cultures, empiric therapy with vancomycin, ceftriaxone, and acyclovir was initiated and maintained until an infectious cause was considered unlikely. In the context of MRI findings demonstrating cerebellar swelling and hydrocephalus, acute cerebellitis emerged as the leading diagnosis, given its potential to compress posterior fossa structures, acute hydrocephalus, and intracranial hypertension.^2-4

The Condition: Acute Cerebellitis

Acute cerebellitis is a rare condition in children and adolescents, often triggered by infection or immune-mediated processes. The clinical presentation can range from mild, self-limiting symptoms to fulminant cerebellitis, which carries a higher risk of morbidity and mortality. Common symptoms include ataxia, dysmetria, dysarthria, nystagmus, tremors, slurred speech, and elevated intracranial pressure, resulting in headaches, vomiting, and changes in consciousness.^4-9

The cause of acute cerebellitis remains unknown in nearly two-thirds of cases. However, infections, particularly viral agents, are responsible for about one-third of cases. Common pathogens include Epstein-Barr virus (EBV), Coxsackie B3, and respiratory syncytial virus (RSV). Bacteria, such as Streptococcus pneumoniae and Mycoplasma pneumoniae, have also been implicated. Other infectious agents include varicella zoster virus (VZV), herpes simplex virus-1 (HSV-1), influenza, rotavirus, cytomegalovirus (CMV), West Nile virus, Borrelia burgdorferi, and Salmonella typhi.^1,4,9-12

Emerging evidence supports immune-mediated pathogenesis in some cases. Autoantibodies against neuronal antigens such as metabotropic glutamate receptor 1 (mGluR1), glutamate receptor delta 2 (GluRδ2), and myelin-oligodendrocyte glycoprotein antibody-associated diseases (MOGAD) have been identified in serum and CSF. These findings suggest post-infectious immune activation may contribute to cerebellar inflammation, often following respiratory or viral illness such as pharyngitis, although the pathogenic role of some autoantibodies remains under investigation and not all are clearly disease causing.^13-15

Although many cases of acute cerebellitis are mild and self-limited, approximately 10% to 25% follow a moderate-to-severe course, with a subset developing life-threatening complications such as obstructive hydrocephalus, brainstem compression, or herniation due to increased intracranial pressure.^5,16-18 Hospitalists should monitor for altered mental status, progressive ataxia, or new cranial nerve deficits by serial neurological examination.

The management of cerebellitis in children remains an area of ongoing discussion, with treatment strategies generally focused on addressing the underlying pathophysiology. This often includes the use of steroids and/or intravenous immunoglobulin (IVIG) to manage cerebellar swelling. In more severe cases, surgical interventions such as ventriculostomy, external ventricular drainage, ventriculoperitoneal shunt placement, or posterior fossa decompression may be necessary, particularly in the presence of obstructive hydrocephalus. Early administration of steroids may help prevent the need for surgical intervention. However, there is no established consensus regarding the type, dosage, and duration of steroid therapy.^6,19-24

In addition, broad-spectrum antibiotics and/or antivirals are commonly administered to treat any potential concurrent central nervous system infections.

Hospital Course

In this case, an extensive workup was performed to evaluate potential infectious, autoimmune, and malignancy-related causes. Cerebrospinal fluid testing for cryptococcal antigen was negative, and serological tests for Bartonella, syphilis, and M pneumoniae were also negative. However, serum Mycoplasma IgG and IgM were positive, indicating a recent infection, although PCR for M pneumoniae in the CSF was negative. Initial blood cultures grew coagulase-negative staphylococci, but contamination was suspected, and repeat cultures were negative. Polymerase chain reaction tests for respiratory viruses, including HSV, CMV, and VZV, were all negative.

To assess an autoimmune process, tests for myelin oligodendrocyte glycoprotein (MOG-IgG1), neuromyelitis optica spectrum disorder NMO (NMOSD)/Aqp4 associated with aquaporin-4 (AQP4) antibodies, and glutamic acid decarboxylase (GAD65) were conducted, which showed negative findings. These studies were intended to exclude key entities within the differential diagnosis rather than to provide a comprehensive evaluation for autoimmune encephalitis or autoimmune cerebellitis. Notably, the patient’s clinical presentation, imaging findings, and overall course were not suggestive of autoimmune encephalitis based on the evaluation from the pediatric neurology team. Given the low clinical suspicion, additional neuronal antibody testing was not pursued, as it was unlikely to change diagnostic assessment or management. Furthermore, the pathogenic role of several reported neuronal autoantibodies remains incompletely established, and not all are clearly disease causing. The presence of cerebellar edema and hydrocephalus raised concerns for malignancy, such as lymphoma. To rule this out, an MRI of the cervical, thoracic, and lumbar spine was performed, which showed no abnormal enhancement in the spinal canal.

Final Diagnosis

Despite negative Mycoplasma CSF PCR, the positive serum Mycoplasma IgG and IgM suggested an acute infection. Schmucker et al ²⁵ have reported cases of cerebellitis associated with M pneumoniae based on serology despite negative CSF PCR, highlighting the importance of serological testing in such cases.

Al-Zaidy et al ²⁶ propose 2 mechanisms for M pneumoniae-associated neurological disease: direct central nervous system (CNS) infection and an immune-mediated response. Komatsu et al ²⁷ have also suggested that antiganglioside antibodies may play a role in the immune-mediated mechanism. Since this patient had positive serology and these findings, it supports the diagnosis of post-infectious cerebellitis likely via immune-mediated response of M pneumoniae rather than direct CNS infection or primary autoimmune encephalitis.

The patient was treated empirically with vancomycin, ceftriaxone, and acyclovir until infectious studies returned negative. Following the initiation of IV methylprednisolone, there was significant clinical improvement, with resolution of headache, nausea, vomiting, and ataxia. After 5 days of IV methylprednisolone, a follow-up MRI showed complete resolution of cerebellar edema and fourth ventricular effacement. The patient returned to baseline and did not require rehabilitation.

Unfortunately, there was insufficient CSF to run additional autoimmune or encephalitis panels. Given the patient’s improvement and the resolution of inflammation on imaging, further lumbar puncture was deemed unnecessary. If symptoms recur, additional testing, including a repeat lumbar puncture, will be considered.