Main text:
To the Editor:
The 2019 novel coronavirus
(COVID-19 due to SARS-CoV-2 infection) pandemic has posed significant
challenges to the pediatric oncology population. The effects of the
virus on pediatric neurooncology patients are not yet well described. We
present the case of a pediatric patient with medulloblastoma and
SARS-CoV-2 infection (CV) who developed posterior reversible
encephalopathy syndrome (PRES) and necrotizing enterocolitis (NEC).
The patient, an 8-year-old male, was diagnosed with group 4
medulloblastoma metastatic to the brain and spine in February 2021. He
underwent debulking of the primary cerebellar tumor followed by standard
treatment as per Children’s Oncology Group protocol ACNS0332 with proton
therapy and adjuvant vincristine followed by cycles of cyclophosphamide,
cisplatin, and vincristine. His course was complicated by multiple
episodes of febrile neutropenia and significant nausea/vomiting. He was
diagnosed with peripheral neuropathy and bilateral foot drop following
cycle 3 and started on gabapentin. There were no other known
comorbidities. Post-radiation and cycle 3 chemotherapy imaging showed
excellent treatment response, the latter essentially negative for
intracranial or spinal disease.
During cycle 3, the patient presented with a 3-day history of
rhinorrhea, 1 day of fever to 101.4 ℉, neutropenia (ANC 100/microliter),
and was found to be positive for CV by viral swab PCR. He was admitted
to the pediatric oncology unit for 5 days and discharged following count
recovery. Seventeen days following diagnosis of CV, the patient began
cycle 4 chemotherapy. One week later (25 days following CV diagnosis) he
was admitted for significant vomiting, oral mucositis, and dehydration.
He was afebrile at the time but neutropenic and started on vancomycin
for two small areas of MRSA culture-positive cellulitis on his abdomen.
Following a 14-day asymptomatic period, hospital day 6 of this
admission, the patient was declared “non-infectious” for CV.
On day 7 of hospitalization, the patient was noted to have vertical
nystagmus after waking. Head CT showed no acute intracranial process.
MRI showed stippled patchy enhancement along the right medial cerebellum
consistent with encephalomalacia that was most consistent with
post-treatment change. Oxycodone (started for mucositis-related pain)
and gabapentin were both held, and the nystagmus was noted to
significantly improve over the next 48 hours.
On day 9 of hospitalization, the patient developed altered mental status
with staring spells, decreased muscle tone, and dysarthria. Head CT at
that time showed bilateral hypodense lesions in the parietal lobes.
Blood pressure at that time was noted to be in the 130s/100s with a peak
of 146/106 (previously 120s/90), and the patient was transferred to the
pediatric intensive care unit. On arrival, the patient had a generalized
seizure and was emergently intubated. MRI showed extensive new patchy
cortical and subcortical T2 hyperintensities, most pronounced in the
parietal and occipital lobes, as well as punctate foci of petechial
hemorrhage along the parietal cortex, consistent with PRES with
hemorrhagic sequelae (Fig. 1). Treatment with dexamethasone, 2
milligrams intravenous every 6 hours, was initiated. The patient
tolerated extubation the following day but had persistent altered mental
status. During this time his neutropenia resolved, and vancomycin was
discontinued.
Four days after extubation (hospital day 15), the patient’s oxygen
requirement increased and he developed abdominal distension,
bradycardia, and hypotension necessitating reintubation, multiple
vasopressors, and the initiation of broad-spectrum antibiotics. It was
at this time that the patient had a repeat nasal swab demonstrating a
positive CV result. Abdominal imaging showed multiple areas of
pneumatosis consistent with necrotizing enterocolitis (Fig. 3) and an
emergent bedside laparotomy was performed for clinical deterioration.
The cecum, ascending colon, and proximal transverse colon to the
midpoint were all necrotic with no perforation. Management consisted of
a right hemicolectomy and resection of distal small bowel with temporary
closure. On day 19, the patient was taken to the OR for an additional
hepatic flexure resection. On day 20, the patient was noted to have
decreased responsiveness, so a CT of the brain was performed which
demonstrated new multicompartmental intracranial hemorrhages, a
hypoattenuating subdural fluid collection, and 3 mm’s of leftward
midline shift. MRI additionally showed leftward shift alongside
resolution of the sulcal and cortical enhancement noted previously (Fig.
2). Despite full cardiorespiratory support the patient could not be
adequately ventilated or perfused and, in the setting of significant
intracranial insults and multisystem organ failure, the decision was
made with the team and family to withdraw care. The patient died several
hours later.
This case highlights several critical points of CV in a pediatric
neurooncology patient. As has been previously described, high CV viral
loads may persist for longer than average in immunocompromised children
[1-3]. In a retrospective study at Children’s Hospital of Colorado,
Dolen et al found that immunocompromised children with CV had prolonged
viral persistence greater than 6 weeks and moderate to high viral load
[1]. Kemp et al described a case of increased variant emergence in
an immunocompromised patient after a prolonged period of viral shedding
and management with convalescent plasma [4]. The major implications
that require further exploration of these findings include an increased
risk for CV-related sequelae and transmission to close contacts
including health care providers.
Significant neurologic manifestations have been described in CV-positive
patients both with and without comorbidities [5-7]. In a systematic
review by O’Loughlin et al, fifteen cases of severe encephalopathy were
identified after confirmatory testing of CV, while only one of them had
a preexisting neurologic condition [5].
Case reports of PRES in both a
previously healthy adult and child have also been described. In both
cases, the authors cite endothelial dysfunction triggered by CV as a
possible mechanism [6-7]. Radiation treatment and chemotherapy with
agents known to cross the blood-brain barrier are known to increase
vulnerability to PRES in pediatric neurooncology patients. Sentinel
signs and risk factors including new onset neurologic deficits and
new-onset hypertension in this patient population should be rigorously
pursued [9]. Additionally, it could be argued tighter blood pressure
control could be protective in such a vulnerable patient.
Finally, there have been increasing reports of NEC associated with CV in
both pediatric and immunocompromised populations [10-13]. In a case
report by Rohani et al, an otherwise healthy pediatric patient was
admitted for abdominal pain, fever, nausea and vomiting and found to
have pneumatosis intestinalis in the setting of acute CV. He was
medically treated for necrotizing enterocolitis with improvement
[11]. Poor prognosis in NEC is tied to the presence of perforation,
which can be minimized by early detection and management [14].
Clinicians should be on high alert for persistent viral load of COVID-19
and its sequelae including PRES and NEC in the most vulnerable pediatric
patient populations.