PRRT2 mutations and paroxysmal disorders

In the past year, mutations in the PRRT2 gene have been identified in patients with paroxysmal kinesigenic dyskinesia and other paroxysmal disorders. We conducted a review of the literature on PRRT2 mutation‐associated disorders. Our objectives were to describe the wide clinical spectrum associated with PRRT2 mutations, and to present the current hypotheses on the underlying pathophysiology. PRRT2 mutations are associated with a wide range of clinical syndromes: the various paroxysmal dyskinesias, infantile seizures, paroxysmal torticollis, migraine, hemiplegic migraine, episodic ataxia and even intellectual disability in the homozygous state. The PRRT2 protein, through its interaction with SNAP‐25, could play a role in synaptic regulation in the cortex and the basal ganglia. The pathogenesis may be caused by PRRT2 loss of function, which may induce synaptic deregulation and neuronal hyperexcitability. However, this does not explain the phenotypic variability, which is likely modulated by environmental factors, modifier genes or age‐dependent expression. The clinical spectrum of PRRT2 mutations has expanded among paroxysmal disorders and beyond. Unraveling the molecular pathways linking the genetic defect to its clinical expression will be crucial for the diagnosis and treatment of these disorders.     

Rare association of central pontine myelinolysis with infantile tremor syndrome

Central pontine myelinolysis (CPM) is an acute demyelination within the central basis pontis. Though exact mechanism is not known it is seen commonly with rapid correction of hyponatremia and also with pontine ischemia or infarction, demyelinating diseases, pontine neoplasm and different metabolic diseases. We report a rare association of CPM in a patient of Infantile Tremor Syndrom (ITS). ITS is a syndrome of tremor, mental and physical retardation, pigmentary changes of hair and skin and anemia in malnourished children. Though first reported in Indian subcontinent many identical cases were reported from around the world. Our case is a 15 month old child with generalized tremor, mild hepatosplenomegaly with features of grade II malnutrition including skin and hair changes. All the signs and symtoms of tremor improved after treatment with the World Health Organization (WHO) protocol for protein energy malnutrition (PEM) and administration of propranolol without any side effects.     

Inflammatory mediators in human epilepsy: A systematic review and meta-analysis

BackgroundAccumulating evidence suggests a role for inflammation in the pathophysiology of epilepsy.MethodsWe performed a systematic review and meta-analysis of studies that investigated inflammatory mediators in human epilepsy. Studies reporting on inflammatory mediators in serum, cerebrospinal fluid or brain tissue of epilepsy patients were included. Studies comparing patients to controls were included in a meta-analysis.Results66 articles reporting on 1934 patients were included. IL-1ra, IL-1β, IL-6, IL-10, IFN-γ and TNF-α were the most extensively investigated proteins. Elevated levels for IL-1ra, IL-1β, IL-6 and CXCL8/IL-8 were reported in several different epilepsy etiologies and media, while other proteins were specifically increased for one etiology. IL-1α, IL-7 and IL-13, as well as the chemokines CCL2-5, −19 and −22, were increased exclusively in brain tissue. In an aggregate meta-analysis, we found significantly different protein levels for serum IL-6, IL-17 and CSF IL-1β and IL-10.ConclusionInflammatory pathways are involved in epilepsy. Future studies may further clarify their role, and prove potential of targeted anti-inflammatory treatment.     

Pharmacological approaches to restoring lens transparency: Real world applications

Cataract is the most common cause of blindness and a major cause of visual impairment worldwide. As the world’s population ages, cataract-induced visual impairment is of increasing prevalence, and treatment is limited to those with access to surgical care. While cataracts are mainly a disease of the elderly, infantile cataracts lead to lifelong visual impairment if untreated. Even in those with surgical treatment early in life, visual prognosis is often guarded. Consequently, there is an increasing impetus for alternative therapeutic modalities. Makley and Zhao utilize two different experimental approaches to identify novel pharmacological substances able to improve lens transparency by reducing aggregation of crystalline proteins. These data support an alternative to surgical correction that may be applied to adult patients without access to surgical care as well as address the unique challenges of infantile cataracts.     

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??Abstract??Wheeze is a common symptom in infants and pre-school children characterized by chronic inflammation of the airway. The management of infantile wheeze focuses on anti-inflammatory agents including corticosteroids?? bronchodilators?? leukotriene receptor antagonists?? antihistamine drugs and macrolides. Here we reviewed the current medications of infantile wheeze and propose a de-escalation combined therapy based on our long-term practice.     

Treatment of drug-resistant epilepsy in patients with periventricular nodular heterotopia using RNS® System: Efficacy and description of chronic electrophysiological recordings

ObjectivesDescribe changes in clinical seizure frequency and electrophysiological data recorded in patients with medically-intractable seizures and periventricular nodular heterotopias (PVNH) treated with the RNS® System (NeuroPace, Inc., Mountain View, CA).MethodsClinical seizures from eight patients (mean follow-up of 10.1 years) were analyzed pre- and post-treatment. Chronic ambulatory electrocorticograms (ECoGs) recorded from PVNHs, hippocampus and neocortex were evaluated to identify the earliest electrographic seizure onset type, pattern of spread, and interictal characteristics.ResultsMean reduction in disabling seizures was 85.7 % (n = 8); seven patients had >50% seizure reduction and two were seizure-free in the final year of analysis. Seizure rate showed a progressive reduction over the course of the study with the highest rate of improvement in the first two to three years after implantation. Four of seven patients with one PVNH lead and a second lead in the hippocampus or neocortex had some electrographic seizures first recorded at either lead location, suggesting two foci or seizure propagation patterns. Low voltage fast type activity was the prominent seizure onset pattern. Interictal ECoG power was lower in PVNH than hippocampus.ConclusionsRNS® System treatment substantially reduced clinical seizure frequency in patients with PVNH. Analysis of ictal ECoG records suggests PVNH may be involved in seizure generation.SignificanceChronic ECoG recordings suggest PVNH tissue can actively participate in epileptogenic networks. Direct brain-responsive neurostimulation is a safe and effective treatment option in such patients, progressively reducing seizure rate over a period of years.     

Neonatal seizure automatism and human inborn pattern of quadrupedal locomotion

Seizures in newborns do not always show a clear electro-clinical correlation. The real epileptic nature of some stereotyped rhythmic movements, included in the ‘subtle seizures’ and considered as brainstem release phenomena, is still debated. We report a brain injured newborn, who displayed several episodes of repetitive limb movements. The ictal EEG discharge, during one of these episodes, was associated with a motor pattern modification, which was endowed with quadrupedal locomotion kinematic features. This might represent an indirect evidence of cervical and lumbar Central Pattern Generators interconnection with in-phase coordination between diagonal limbs since the first hours of life in humans.     

布洛芬混悬滴剂和对乙酰氨基酚治疗小儿热性惊厥的疗效观察

目的 观察布洛芬混悬滴剂和对乙酰氨基酚治疗小儿热性惊厥(FS)的疗效。方法 选取2017年4月—2019年4月于本院就诊的FS患儿80例,随机分为对照组与观察组,每组40例,均进行抗惊厥、物理降温等常规治疗,在此基础上,对照组采用对乙酰氨基酚治疗,观察组采用布洛芬混悬滴剂治疗,观察2组临床疗效、退热效果、实验室检查结果(血红蛋白、血钠、血钙)及不良反应情况。结果 对照组治疗总有效率为77.5%,观察组为95%,差异有统计学意义(P<0.05);治疗后1 h,2组患儿体温差异无统计学意义(P>0.05),治疗后3 h、6 h,2组体温均低于服药前,观察组患儿体温低于对照组,差异有统计学意义(P<0.05);治疗后,2组血红蛋白、血钠、血钙浓度较服药前均显著升高(P<0.05),且观察组高于对照组(P<0.05);对照组不良反应率为7.5%,观察组为5%,差异无统计学意义(P>0.05)。结论 布洛芬混悬滴剂对小儿热性惊厥临床症状改善作用显著,值得推介。