Neurological manifestations following cured malaria: don’t forget post-malaria neurological syndrome

Introduction: Cerebral malaria which occurs during the active infection is the most common neurological complication of malaria. Other complications including post-malaria neurological syndrome (PMNS) can rarely occur following complete recovery from the disease. We report a case of post-malaria neurological syndrome in a Tunisian patient. Case presentation: A 26-year-old Tunisian man with no past medical history was admitted in 2016 for a muscle weakness of the 4 limbs, seizures, tetraparesis and myoclonus which appeared after he returned from Côte d’Ivoire where he had been treated three weeks ago for Plasmodium falciparum malaria with favorable outcome. Blood smears for malaria were negative. Brain MRI showed multiple hypersignal cerebral lesions. Investigations didn’t show any infectious, metabolic, toxic, vascular or tumoral etiology. Thus, the diagnosis of PMNS was considered. The patient was treated with methylprednisolone with favorable outcome. Two years later, he was completely asymptomatic. Conclusion: PMNS should be considered in patients with neurological symptoms occurring within two months of cured acute disease in which blood smears for malaria are negative and other etiologies have been ruled out. In most cases, the disease is self-limited while in severe cases corticosteroid therapy should be prescribed with favorable outcome. Keywords: Post-malaria neurological syndrome; immunologic; corticosteroid.

A severe clinical phenotype of Noonan syndrome with neonatal hypertrophic cardiomyopathy in the second case worldwide with RAF1 S259Y neomutation

Noonan syndrome and related disorders are a group of clinically and genetically heterogeneous conditions caused by mutations in genes of the RAS/MAPK pathway. Noonan syndrome causes multiple congenital anomalies, which are frequently accompanied by hypertrophic cardiomyopathy (HCM). We report here a Tunisian patient with a severe phenotype of Noonan syndrome including neonatal HCM, facial dysmorphism, severe failure to thrive, cutaneous abnormalities, pectus excavatum and severe stunted growth, who died in her eighth month of life. Using whole exome sequencing, we identified a de novo mutation in exon 7 of the RAF1 gene: c.776C > A (p.Ser259Tyr). This mutation affects a highly conserved serine residue, a main mediator of Raf-1 inhibition via phosphorylation. To our knowledge the c.776C > A mutation has been previously reported in only one case with prenatally diagnosed Noonan syndrome. Our study further supports the striking correlation of RAF1 mutations with HCM and highlights the clinical severity of Noonan syndrome associated with a RAF1 p.Ser259Tyr mutation.