Predicting Cognitive Rehabilitation Needs in Patients with Central Nervous System Infections Using Montreal Cognitive Assessment

Cognitive impairments are reported in some patients with central nervous system (CNS) infections after discharge. Our objectives were to evaluate the prevalence of CNS patients in need of rehabilitation after discharge and to assess whether the Montreal Cognitive Assessment (MoCA) could be used as a screening tool to identify these patients. CNS patients admitted during a 2-year study period were included. The need for rehabilitation was assessed by physicians with the aid of an occupational therapy assessment, after which a MoCA was performed. The prevalence of needing rehabilitation was 58% among CNS patients. An abnormal MoCA score \u3c 26 was the only variable strongly associated with higher odds of needing rehabilitation. In 42% of the CNS patients in need of rehabilitation, the MoCA score was ≥ 26, and most of these patients were aged 16 to 43 years (young adults). There is a need for rehabilitation among CNS patients after discharge. As a screening tool, MoCA was able to identify patients in need of rehabilitation. In young adults, MoCA scores were often normal despite a need for rehabilitation. Thus, MoCA cannot stand alone as a screening tool for identifying young adults in need of rehabilitation following CNS infection

Human SNORA31 variations impair cortical neuron-intrinsic immunity to HSV-1 and underlie herpes simplex encephalitis

International audienceHerpes simplex virus-1 (HSV-1) encephalitis (HSE) is typically sporadic. Inborn errors of TLR3- and DBR1-mediated central nervous system cell-intrinsic immunity can account for forebrain and brainstem HSE, respectively. We report five unrelated patients with forebrain HSE, each heterozygous for one of four rare variants of SNORA31, encoding a small nucleolar RNA of the H/ACA class that are predicted to direct the isomerization of uridine residues to pseudouridine in small nuclear RNA and ribosomal RNA. We show that CRISPR/Cas9-introduced bi- and monoallelic SNORA31 deletions render human pluripotent stem cell (hPSC)-derived cortical neurons susceptible to HSV-1. Accordingly, SNORA31-mutated patient hPSC-derived cortical neurons are susceptible to HSV-1, like those from TLR3- or STAT1-deficient patients. Exogenous interferon (IFN)-β renders SNORA31- and TLR3- but not STAT1-mutated neurons resistant to HSV-1. Finally, transcriptome analysis of SNORA31-mutated neurons revealed normal responses to TLR3 and IFN-α/β stimulation but abnormal responses to HSV-1. Human SNORA31 thus controls central nervous system neuron-intrinsic immunity to HSV-1 by a distinctive mechanism