A Multinational Survey on Actual Diagnostics and Treatment of Subacute Sclerosing Panencephalitis.

Subacute sclerosing panencephalitis (SSPE) is a chronic infection of the central nervous system caused by the measles virus (MV). Its prevalence remains high in resource poor countries and is likely to increase in the Northern Europe as vaccination rates decrease. Clinical knowledge of this devastating condition, however, is limited. We therefore conducted this multinational survey summarizing experience obtained from more than 500 patients treated by 24 physicians in seven countries. SSPE should be considered in all patients presenting with otherwise unexplained acquired neurological symptoms. In most patients, the diagnosis will be established by the combination of typical clinical symptoms (characteristic repetitive myoclonic jerks), a strong intrathecal synthesis of antibodies to MV and typical electroencephalogram findings (Radermecker complexes). Whereas the therapeutic use of different antiviral (amantadine, ribavirin) and immunomodulatory drugs (isoprinosine, interferons) and of immunoglobulins has been reported repeatedly, optimum application regimen of these drugs has not been established. This is partly due to the absence of common diagnostic and clinical standards focusing on neurological and psychosocial aspects. Carbamazepine, levetiracetam, and clobazam are the drugs most frequently used to control myoclonic jerks. We have established a consensus on essential laboratory and clinical parameters that should facilitate collaborative studies. Those are urgently needed to improve outcome.

Intracerebral Hemorrhage in a Child with Renal Artery Stenosis and COVID-19.

Pediatric intracerebral hemorrhage is a rare condition among children. We discuss the case of a 7-year-old Filipino male with generalized tonic seizures and diagnosed to have both SARS-CoV-2 infection and hypertension secondary to renal arterial stenosis. The occurrence of intracerebral hemorrhage in children, though commonly caused by arteriovenous malformations, may be secondary to an acute hypertensive episode. In this case, the presence of COVID-19 in the patient may have been contributory to the development of spontaneous intracerebral hemorrhage due to its direct endothelial effects, as well as its dysregulatory action on the renin-angiotensin-aldosterone system.

PD1 as a common candidate susceptibility gene of subacute sclerosing panencephalitis.

Although the exact pathogenesis of subacute sclerosing panencephalitis (SSPE) remains to be determined, our previous data suggested a genetic contribution to the host susceptibility to SSPE. During chronic viral infection, virus-specific cytotoxic T lymphocytes display poor effector functions. Since co-inhibitory molecules are involved in the suppression of T lymphocytes, we investigated whether single nucleotide polymorphisms (SNPs) of genes encoding co-inhibitory molecules contributed to a susceptibility to SSPE. Association studies on a total of 20 SNPs in 8 genes (CTLA4, CD80, CD86, PD1, PDL1, PDL2, BTLA and HVEM) and subsequent haplotype analysis of 4 SNPs in the PD1 genes were performed in Japanese and Filipino SSPE patients and controls. Then, we investigated a functional difference in promoter activity of two haplotypes and compared the expression levels of PD1 between SSPE and controls. The frequency of GCG(C) haplotype of PD1 containing -606G allele was significantly higher in SSPE patients than in controls both in Japanese and in Filipinos. The promoter activity was significantly higher in the construct with -606G allele than in that with -606A allele. The expression levels of PD1 were significantly higher in SSPE patients than in the controls. Our results suggested that the PD1 gene contributed to a genetic susceptibility to SSPE.

Effectiveness of botulinum toxin A for upper and lower limb spasticity in children with cerebral palsy: a summary of evidence.

Botulinum toxin type A (BoNT-A) therapy has gained wide acceptance in the management of spasticity in cerebral palsy (CP). Clinical experience from numerous case reports and series, retrospective and prospective open label cohort studies, and randomized controlled trials (RCT) has grown over the past 10 years. Several independent systematic reviews on the role of BoNT-A for upper and lower limb spasticity have been written by various authors. The objective of this paper is to summarize past systematic reviews and recent RCT not yet included in the systematic reviews that assess the effectiveness of BoNT-A in upper and lower limb spasticity in children with CP. We reviewed four Class II RCT discussed in five independent systematic reviews and two new Class II trials on the use of BoNT-A alone or with occupational therapy compared to placebo or occupational therapy alone in children with upper limb spasticity. There were 229 children recruited in these six trials and of those, 115 children received BoNT-A in the upper limbs. Five of six RCT showed a time limited decrease in muscle tone most especially at the wrist. Four of six trials showed improvement of hand function on a few specific functional tests. Four systematic reviews concluded that there is insufficient and inconsistent evidence to support or refute the effectiveness of BoNT-A in upper limb spasticity but one recent review recommended that BoNT-A should be considered as a treatment option in upper limb spasticity. For lower limb spasticity, we reviewed 13 RCT discussed in six systematic reviews and two new trials comparing BoNT-A with placebo or other rehabilitation modalities such as physiotherapy, occupational therapy, casting or electrical stimulation. In these studies, 617 children were recruited and of those, 360 children received BoNT-A in the lower limbs. There were six Class I and nine Class II trials. Three Class I trials documented significant improvement in gait pattern in children with gastrocnemius spasticity and one Class I study showed significant reduction in tone in the hip adductors. The most recent review establishes BoNT-A as an effective treatment for equinovarus deformity. Adverse events in these trials were mild and self-limited. The most common complaints were pain in the injection sites and transient weakness. BoNT-A is considered safe for use in children. In conclusion, there is now growing convincing evidence for the time limited beneficial effect of BoNT-A in decreasing muscle tone in children with upper and lower limbs spasticity associated with CP. Decrease muscle tone in the lower limbs translates to improved gait in CP children with spastic equinovarus however more systematic studies are necessary to show sufficient evidence for improved hand function from BoNT-A injection in the upper limbs.