Postherpes simplex encephalitis: a case series of viral-triggered autoimmunity, synaptic autoantibodies and response to therapy.

BACKGROUND: Recent evidence suggests that patients with herpes simplex virus (HSV) encephalitis may relapse because of autoimmunity against the N-methyl-D-aspartate receptor (NMDAR). We present a case series of post-HSV relapsing encephalopathy associated with antibodies to central nervous system (CNS) synaptic antigens. PATIENT/METHODS: Sera and cerebrospinal fluid (CSF) from five patients with HSV encephalitis who relapsed after antiviral therapy were tested for anti-NMDAR, gamma-aminobutyric acid b receptor (GABAbR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), Leucine-rich, glioma inactivated 1 (LGI1), anti -contactin-associated protein-like 2 (CASPR2) and dipeptidyl-peptidase-like protein-6 (DDPX) antibodies using cell-based assays. RESULTS: Five patients (two infants, one child and two adults) developed post-HSV autoimmune encephalitis. The infants, aged 9 months and 10 months, after prompt and seemingly successful anti-HSV therapy, were readmitted with typical signs of NMDAR-encephalitis evolving within days, with NMDAR antibodies detected in both serum and CSF. Although they were promptly treated with intravenous immunoglobulin (IVIg) and with IVIg followed by rituximab, respectively, they were both left with psychomotor deficits. A 14-year-old girl with seizures due to HSV encephalitis improved with anti-HSV therapy. Later, she manifested intractable seizures and she was found positive for anti-NMDAR antibodies which persist. The two adults were women, aged 58 and 33 years. The first recovered after anti-HSV therapy and remained asymptomatic for 6 months, until she developed generalized seizures with persisting CSF anti-NMDAR antibodies; the second, who continued to be encephalopathic after 2 weeks of anti-HSV therapy, tested positive for anti-NMDAR antibodies in the serum and anti-GABAbR antibodies in the serum and CSF. She recovered fully following IVIg therapy but her serum anti-GABAbR antibodies persist 34 months later. DISCUSSION: Infection of the CNS with HSV can trigger CNS autoimmunity associated not only with anti-NMDAR but also with anti-GABAbR antibodies. These antibodies can persist in the serum, even without associated symptoms, but their presence in the CSF is firmly associated with disease development. In contrast to children and adults who responded well to therapies, the infants had an incomplete recovery with severe psychomotor deficits probably due to the interference of anti-NMDAR antibodies with neuro-developmental processes.

Sleep respiratory parameters in children with idiopathic epilepsy: A cross-sectional study.

BACKGROUND: The aim of this study is to explore and compare through polysomnography respiratory sleep parameters between children with idiopathic epilepsy and healthy children. METHODS: Our cross-sectional study included 40 children with idiopathic epilepsy and 27 healthy children, who underwent overnight polysomnography. Data about sleep respiratory parameters were obtained and statistically analyzed. The level of statistical significance was set at 0.05. RESULTS: The prevalence of Obstructive Sleep Apnea Syndrome was significantly higher in the epilepsy group (35% vs 7.4%, p<0.01). Moreover, the odds ratio of an obstructive apnea index ≥1 in the epilepsy group was 10.6 (95% Confidence Intervals: 3.08-37.08) in comparison to the control group. The mean value of the obstructive apnea-hypopnea index was significantly higher in children with epilepsy compared to healthy children (2.46±1.22 vs 1.21±0.83, p=0.027). The mean values of central apnea index and desaturation index were comparable between these two groups. Longest apnea duration was significantly higher in the group of poor seizure control. All other sleep respiratory variables did not differ significantly between children with poor and good seizure control and between children with generalized and focal epilepsy. CONCLUSIONS: Children with epilepsy seem to present more prominent sleep breathing instability in comparison to healthy children, which mainly includes a predisposition to obstructive respiratory events. More studies are needed to investigate the relationship between sleep apneas and seizure control.

Sleep apneas and epilepsy comorbidity in childhood: a systematic review of the literature.

PURPOSE: Our aim is to review studies which assess the prevalence of sleep apneas in children with epilepsy and discuss possible mechanisms linking these two conditions, as well as the impact of sleep apneas on the prognosis of these children. METHODS: PubMed was used as the medical database source, and articles were selected and classified according to their originality, level of evidence, and relevance to the broad scope of the review. RESULTS: Children with epilepsy have a higher prevalence of sleep breathing disorders in comparison to healthy children, but this prevalence varies widely depending on the methodology of each study. Major risk factors for sleep apneas in childhood epilepsy include mainly poor seizure control and antiepileptic drug polytherapy. Indeed, epilepsy can trigger sleep apneas, as abnormal electrical discharge amplifies sleep-induced breathing instability, antiepileptic drugs disturb muscle tone, and vagus nerve stimulation modulates neurotransmission to airway muscles. On the other hand, sleep apneas enhance sleep fragmentation, thus reducing the threshold for the appearance of seizures. Moreover, they have a negative effect on the neurocognitive profile of these children, as they disturb neuroplasticity mechanisms and also have a probable association with sudden unexpected death in epilepsy. The surgical treatment of sleep apneas has been found to reduce seizure frequency, and this can offer new therapeutic choices. CONCLUSIONS: Between sleep apneas and childhood epilepsy, there is a complex relationship with reciprocal interactions. The presence of sleep apneas should be taken into account when designing the management of these children, as it creates therapeutic opportunities and limitations.

Holoprosencephaly and diabetes insipidus in a 3-month-old infant.

Holoprosencephaly is a developmental defect caused by incomplete cleavage of the embryonic forebrain structures during early embryogenesis. We describe a 3-month-old boy with median cleft palate, surgically reconstructed cleft lip, hypotelorism with a flat nose, cryptorchidism, clubfoot, and microcephaly. During the laboratory investigation, his blood sodium level was 154 mmol/L and urine specific gravity was 1.007. Serum osmolarity was 317 mOsm/kg and urine osmolarity was 268 mOsm/kg. Given these findings and the clinical response to vasopressin, diagnosis of central diabetes insipidus was made. Magnetic resonance imaging revealed semilobar holoprosencephaly. The patient responded very well to vasopressin treatment with restoration of serum electrolytes, which remained within normal limits on follow-up. In case of midline facial defects accompanied by hypotelorism with or without developmental delay, the brain should be imaged to confirm its morphology and investigations should be directed by a high index of suspicion of associated endocrinologic dysfunctions.