2. Case presentation
A 6 year-old girl with sickle cell anemia complicated by cerebral vasculopathy received hematopoietic stem cell transplantation (HSCT) from a matched-related donor after myeloablative conditioning (Busulfan, Cyclophosphamide, Anti-T-lymphocyte globulin) (Figure 1). Graft-versus-host disease (GvHD) prophylaxia included Ciclosporin and Methotrexate. Historical timeline is presented in Figure 1.
Various infectious complications occurred around the grafting date:
After engraftment on day 20, antibiotics were stopped, mucositis and signs of HSV1 infection had fully resolved, and IV prophylactic aciclovir was started.
At day 21, she presented with bilateral facial palsy and left trigeminal hypoesthesia and swallowing impairment with voice modification. Cerebral MRI displayed T2 T2-FLAIR hypersignal of the intracranial and meatal segments of the facial nerves, with T1 Gadolinium-enhancement that also concerned the left hypoglossal nerve, without haemorrhage or cerebral ischemia nor PRES syndrome (Figure 2). First cerebrospinal fluid (CSF) examination was normal, protein level of 25 mg/dL (reference range 15-60 mg/dL), glucose level of 66 mg/dL, white blood cells 1 per µL (reference range 0-5 per µL), and without concomitant detected red blood cells. CSF Gram stain and culture were negative, and HSV, VZV, enterovirus, EBV, HHV6, HHV8, adenovirus, mycoplasma, cryptococcus and toxoplasmose PCR were negative. C-Reactive-Protein (CRP) was < 10 mg/ml.
The onset of facial diplegia was rapidly progressive, followed after 24 hours by swallowing impairment. Clinically detectable neurological damage was limited to the cranial nerves (Vst, VIIst and IXst pairs), with no evidence of limb sensory-motor deficit or areflexia. Intravenous immunoglobulins (1g/kg) were infused at day 22 and 23 without improvement. Second CSF examination was performed: protein level remained low at 30 mg/dL, glucose 63 mg/dL, and white blood cells rised at 70 per µL after immunoglobulins.
Fever and respiratory symptoms appeared secondarily at day 25 post-transplant, 4 days after diplegia, with productive cough and fever up to 40°. CRP remained negative. Chest-CT scan showed COVID-19 typical findings. SARS-Cov2 RT-PCR assay was positive in nasopharyngeal and blood, not in CSF. Acute respiratory distress syndrome led to transfer in intensive care unit.
She underwent protective mechanical ventilation and sedation for 17 days and received treatment by Remdesevir (10 days) and Tocilizumab. Neurological status could not be assessed during sedation for mechanical ventilation. Facial diplegia was persistent beyond mechanical ventilation. She received a second infusion of intravenous immunoglobulins at day 51 and 52. She showed significant clinical improvement and had normal nerve conduction study of the limbs when achievable at day 60.