Rationale:
Coronavirus Disease 2019 (COVID-19) has been associated with a wide spectrum of symptoms, and neurological complications characterized by anosmia, hypogeusia, seizures, hemorrhagic stroke, neuromuscular problems, and encephalopathy have been reported in over 30% of cases.The pathogenesis is still unclear, though underlying genetic susceptibility, viral invasion, and cytokine storm may play a role. We report a pediatric patient with COVID 19 associated encephalopathy characterized by focal seizures and central apnea.
Method:
A 14-year-old girl with no prior medical history presented with six days of fever, nasal congestion, and myalgia, followed by 3 generalized tonic clonic seizures with peri-oral cyanosis. The patient was initially lethargic, but otherwise had a normal neurological examination. She had ongoing hypoxia and bilateral infiltrates on chest x-ray; she subsequently tested positive for COVID-19 polymerase chain reaction (PCR) via nasopharyngeal swab. Laboratory work was unremarkable, cerebrospinal fluid (CSF) profile and culture were normal, and CSF PCR for COVID-19 was negative. The patient was started on Levetiracetam and Remdesivir. After two days, the patient had two apneic episodes, necessitating intubation. Electroencephalography (EEG) during these periods of apnea did not show any epileptiform correlate. There were only mild elevations in inflammatory markers and serum cytokine panel was normal (Table 1). Magnetic resonance imaging (MRI) of brain and spine was normal. Over the following week, the patient remained intubated despite minimal sedation; decreasing ventilatory support resulted in rising serum carbon dioxide without any response in respiratory drive. Her mental status improved over another week and she was able to follow commands, but only rarely had spontaneous respirations on the ventilator. Caffeine was initiated, and two days later her apnea improved to 1-4 brief, self-resolved episodes daily. An apneic episode at this point was associated with lip-smacking; further EEG monitoring revealed a seizure correlate arising from right posterior temporal region. Lacosamide was added with resolution of apneic events and the patient was extubated. On follow up, the patient was doing well without further seizures.
Results:
Central apnea occurs due to impairment of a ponto-medullary pacemaker resulting in lack of activation of inspiratory thoracic muscles. Both acquired and genetic disorders can result in sleep related alveolar hypoventilation despite normal neuromuscular and pulmonary function. A congenital cause is rare, and typically attributed to central alveolar hypoventilation syndrome from PHOX2B mutations that result in abnormal respiratory drive that manifests as shallow breathing with no distress or arousal in response to hypoxemia and hypercapnia. Acquired causes of central apnea abound due to brainstem, diencephalic, or spinal cord disorders, and have been reported in cases of viral encephalitis, such as dengue. In contrast to persistent and continuous central apnea, intermittent apneic events are well known to correlate with seizures. Studies have shown that the hippocampus and amygdala are limbic breathing control regions. Sudden unexpected death in epilepsy (SUDEP) is a severe complication of patients with refractory epilepsy, often thought to be related to ictal or postictal central apnea with hypoventilation.
Conclusion:
This case brings attention to a previously unreported encephalopathy with seizures and central respiratory disturbance associated with COVID 19 in the absence of inflammatory biomarkers and normal brain MRI. It remains to be seen whether COVID-19 may precipitate an increase in SUDEP in patients with epilepsy.
Funding:
:No funding received.
FIGURES
Figure 1