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:
- Asymptomatic EBV replication 14 days before the graft leading to the
administration of one dose of rituximab infusion.
- Severe mucositis aggravated by HSV-1 infection (oral and pelvic
localization) early after conditioning treated with high-dose of
Aciclovir.
- Febrile neutropenia (48 hours) during HSV-1 reactivation without
bacterial documentation, was treated with broad spectrum antibiotics
(Tazocilline from day 0 to 20 post-transplant, Vancomycine from day 2
to 15 post-transplant and Ciprofloxacine from day 2 to 10
post-transplant).
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.