Miller Fischer and posterior reversible encephalopathy syndromes post COVID-19 infection

Patient information

The current report is for an 11-year-old male child who was previously healthy with an unremarkable medical history. He presented at our hospital with a history of vomiting that had started 3 weeks prior to presentation. He was vomiting approximately 4 to 6 times a day, and it was effortless and non-projectile, associated with abdominal pain and mild diarrhea for a few days without any constipation, and he had mild headache. There was no history of fever. The child was first evaluated at a primary health care facility where he had a computerized tomography (CT) brain scan, a serum electrolytes test, a renal profile, liver functions tests, a complete blood count test, an abdominal ultrasonography, and a chest x-ray. All were unremarkable except for mild hypokalemia. The child was given intravenous fluid therapy and non-specific supportive measures. There was no documentation for any COVID-19 workup at that time. The child’s condition partially responded to treatment for a few days, but shortly after, the vomiting recurred with mild headache, and he started to complain of diplopia.

Clinical findings

The initial evaluation at our hospital revealed that the boy had normal vital signs for his age, was afebrile, and was fully conscious with a Glasgow Coma Scale (GCS) score of 15/15; he had normal orientation to persons, time, and place and a normal fundus examination, although he displayed bilateral sixth nerve palsy and double vision on his lateral gaze. He had normal muscle tone and power, normal deep tendon reflexes, and the rest of his physical examination was unremarkable.

Diagnostic assessment

The initial workup included a complete blood count, a renal profile, liver function tests, an erythrocyte sedimentation rate (ESR) test, a c-reactive protein (CRP) test, and his levels of serum electrolytes and procalcitonin were measured. Magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and magnetic resonance venography (MRV) of the brain were also completed (Figure 1). The child was admitted to the pediatric intensive care unit (PICU) for close monitoring, follow-up, and management, and the hospital policy for isolation precautions was followed.

Therapeutic intervention

The child was started on intravenous immunoglobulins (IVIG) at a dose of 0.4 gm/kg/day for 5 days to treat the rare MFS variant of GBS. By the second day of hospitalization, the child’s blood pressure began fluctuating between hypertensive and hypotensive states (Figure 3). He remained afebrile, was still fully conscious with a GCS score of 15/15, and had evident bilateral ptosis and ataxic gait. Over the course of the day, his level of consciousness deteriorated to GCS 8/15 and he developed generalized tonic-clonic seizures, which were controlled with levetircetam loading, and he was kept on maintenance doses. His neurological examination revealed that his pupils were 2–3 mm in length, both were equal, and they were reactive to light. He had ophthalmoplegia, weak gag reflex, absent cough, and absent deep tendon reflexes. The child was orally intubated and connected to mechanical ventilation. His temporary hypertension episodes were managed with hydralazine (0.1 mg/kg Q 4 hours PRN).

Follow-up and outcomes

Testing for the new SARS-COVID-19 real-time polymerase chain reaction (RT-PCR) was completed, and the result was positive. Furthermore, a workup for the possibility of COVID-19 associated multisystem inflammatory syndrome in children (MIS-C) was completed, which included checking ESR, CRP, procalcitonin, serum ferritin, triglycerides, blood lactate, lactic dehydrogenase, d-dimer, cardiac troponin-t, N-terminal pro b-type natriuretic peptide (NTproBNP), and interleukin-6 (IL-6).

The diagnosis of Miller Fischer syndrome (MFS) with posterior reversible encephalopathy syndrome in association with COVID-19 infection was made based on clinical presentation, radiological features, and the findings of a nerve conduction study.

Levetiracetam was administered at a maintenance dose for control of convulsions, hydralazine was used to control blood pressure, and the child was kept on mechanical ventilation and provided with other required supportive measures according to his progress. The hospital guidelines for management of COVID-19 in pediatric age groups at that time were also followed, and this involved administering broad spectrum antibiotics (ceftriaxone and azithromycin), remdesivir (with a loading dose of 5 mg/kg and maintenance dose of 2.5 mg/kg/day for 10 days), methylprednisolone (30 mg/kg once daily for 3 days), and a small dose of acetyl salicylic acid (5 mg/day).

A lumbar puncture for cerebrospinal fluid (CSF) was carried out and showed no cells and a protein count of 0.8 mg/ml (the normal range is 0.15–0.45 mg/ml) confirming the CSF cytoalbuminous dissociation. A gram stain showed no organisms, and a later CSF culture was negative. A nerve conduction velocity study was also completed, and the results were abnormal. A chest x-ray, a CT scan of the chest, a 12-lead electrocardiogram (ECG), and an echocardiography were also carried out, and all were reported to be normal. Furthermore, an urgent MRI, MRA, and MRV of the brain were repeated and confirmed a deteriorating condition (Figure 2).

Over the following 14 days, the child’s vital signs stabilized with no further blood pressure fluctuation, he remained afebrile, the convulsions were under control, the ophthalmoplegia improved, and gag and cough reflexes were regained gradually. The child’s muscle tone showed significant improvement, and deep tendon reflexes were elicited. A follow-up RT-PCR for COVID-19 was carried out on 2 occasions, on day 5 and day 7 since the initiation of treatment, and both were negative. Follow-up MRI, MRA, and MRV brain scans indicated that the previously reported lesions had resolved. Further follow-up on inflammatory markers showed significant improvement of the initially elevated markers.

The child’s gas exchange was maintained on minimal ventilation settings, and he was successfully intubated, initially to non-invasive positive pressure support and later to simple nasal cannula oxygen. Finally, the child was discharged from the PICU to the general ward and later to home with a normal level of consciousness and orientation, no apparent cranial nerve palsy, normal muscle tone, grade 4 motor power, and normal gag and cough reflexes.