Mental retardation,seizures and language delay caused by new SETD1B mutations:Three case reports

BACKGROUND The SETD1B gene is instrumental in human intelligence and nerve development.Mutations in the SETD1B gene have been linked in recent studies to neurodevelopmental disorders,seizures,and language delay.CASE SUMMARY This study aimed to analyze the clinical manifestations and treatment of three patients suffering from mental retardation,epilepsy,and language delay resulting from a new mutation in the SETD1B gene.Three individuals with these symptoms were selected,and their clinical symptoms,gene test results,and treatment were analyzed.This article discusses the impact of the SETD1B gene mutation on patients and outlines the treatment approach.Among the three patients(two females and one male,aged 8,4,and 1,respectively),all exhibited psychomotor retardation,attention deficit,and hyperactivity disorder,and two had epilepsy.Antiepileptic treatment with sodium tripolyvalproate halted the seizures in the affected child,although mental development remained somewhat delayed.Whole exome sequencing revealed new mutations in the SETD1B gene for all patients,specifically with c.5473C>T(p.Arg1825trp),c.4120C>T(p.Gln1374*,593),c.14_15insC(p.His5Hisfs*33).CONCLUSION Possessing the SETD1B gene mutation may cause mental retardation accompanied by seizures and language delay.Although the exact mechanism is not fully understood,interventions such as drug therapy,rehabilitation training,and family support can assist patients in managing their symptoms and enhancing their quality of life.Furthermore,genetic testing supplies healthcare providers with more precise diagnostic and therapeutic guidance,informs families about genetic disease risks,and contributes to understanding disease pathogenesis and drug research and development.

Neuroimaging features in a patient with non-ketotic hyperglycaemic seizures: A case report

BACKGROUND Non-ketotic hyperglycaemic(NKH)seizures are a rare neurological complication of diabetes caused by hyperglycaemia in non-ketotic and non-hyperosmotic states.The clinical characteristics of NKH seizures are atypical and lack unified diagnostic criteria,leading to potential misdiagnoses in the early stages of the disease.CASE SUMMARY This report presents a rare case of NKH seizures in a 52-year-old male patient with a history of type 2 diabetes mellitus.We performed comprehensive magnetic resonance imaging(MRI)studies at admission,12 d post-admission,and 20 d post-discharge.The imaging techniques included contrast-enhanced head MRI,T2-weighted imaging(T2WI),fluid-attenuated inversion recovery(FLAIR),diffusion-weighted imaging,susceptibility-weighted imaging,magnetic reso-nance spectroscopy(MRS),and magnetic resonance venography.At the time of admission,T2WI and FLAIR of the cranial MRI showed that the left parieto-occipital cortex had gyrus-like swelling and high signal,and subcortical stripes had low signal.MRS showed a reduced N-acetylaspartate peak and increased creatine and choline peaks in the affected areas.A follow-up MRI 20 d later showed that the swelling and high signal of the left parieto-occipital cortex had disappeared,and the low signal of the subcortex had disappeared.CONCLUSION This case study provides valuable insights into the potential pathogenesis,diagnosis,and treatment of NKH seizures.The comprehensive MRI findings highlight the potential utility of various MRI sequences in diagnosing and characterizing NKH seizures.

Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause CMT2.Mutations located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)model.In addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive control.Of these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut allele.We found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila.Flies heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal morphology.These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

Lights for epilepsy:can photobiomodulation reduce seizures and offer neuroprotection?

Epilepsy is synonymous with individuals suffering repeated“fits”or seizures.The seizures are triggered by bursts of abnormal neuronal activity,across either the cerebral cortex and/or the hippocampus.In addition,the seizure sites are characterized by considerable neuronal death.Although the factors that generate this abnormal activity and death are not entirely clear,recent evidence indicates that mitochondrial dysfunction plays a central role.Current treatment options include drug therapy,which aims to suppress the abnormal neuronal activity,or surgical intervention,which involves the removal of the brain region generating the seizure activity.However,~30%of patients are unresponsive to the drugs,while the surgery option is invasive and has a morbidity risk.Hence,there is a need for the development of an effective non-pharmacological and non-invasive treatment for this disorder,one that has few side effects.In this review,we consider the effectiveness of a potential new treatment for epilepsy,known as photobiomodulation,the use of red to near-infrared light on body tissues.Recent studies in animal models have shown that photobiomodulation reduces seizure-like activity and improves neuronal survival.Further,it has an excellent safety record,with little or no evidence of side effects,and it is non-invasive.Taken all together,this treatment appears to be an ideal treatment option for patients suffering from epilepsy,which is certainly worthy of further consideration.

Neonatal Seizures: Epidemiological, Diagnostic Aspects and Short-Term Outcome at Issaka Gazoby Maternity Hospital of Niamey, Niger

Introduction: Neonatal seizures are one of the most challenging situations for paediatricians. The objective of this work was to study the epidemiological and diagnostic aspects and short-term outcomes of neonatal seizures at Issaka Gazoby Maternity Hospital in Niamey. Patients and Methods: This was a prospective study from November 2020 to April 2021 in the neonatology department of Issaka Gazoby Maternity Hospital. All newborns aged 0 to 28 days hospitalized for seizures and/or having convulsions during hospitalization were included. Neonatal characteristics, diagnostic aspects, and their outcomes were studied. Data were analyzed using SPSS version 20 software. Results: Of the 3.068 newborns admitted, 69 cases of neonatal seizures were recorded (2.24%). The sex ratio was 1.22, and 94.2% of neonates were born at term. Generalized crises were found in 50.7%. The main etiologies were perinatal asphyxia (46.4%) and early-onset neonatal infection (40.6%). The death rate was 20.3%. Neonates died between one (1) and three (3) days of age in 42.9%. The main death causes were perinatal asphyxia (50%) and early-onset neonatal infection (21.4%). Conclusion: Neonatal seizures are uncommon frequent, with a semiology dominated by generalized seizures. Mortality is high. The reinforcement of preventive measures is necessary.

Epileptic Seizures in Neonates Treated with Hypothermia for Hypoxo-Ischemic Encephalopathy in Brazzaville, Congo: Types and Evolution

Background: Moderate to severe hypoxic-ischemic encephalopathy (HIE) in neonates is often treated with hypothermia. However, some neonates may experience epileptic seizures during therapeutic hypothermia (TH). Data on the electrophysiologic and evolutionary aspects of these seizures are scarce in African countries. Objectives: To determine the types of epileptic seizures caused by HIE in neonates in Brazzaville;to describe the evolution of background EEG activities during TH and rewarming;to report the evolution of epileptic seizures. Methods: This was a cross-sectional, descriptive study conducted from January 2020 to July 2022. It took place in Brazzaville in the Neonatology Department of the Blanche Gomez Mother and Child Hospital. It focused on term neonates suffering from moderate or severe HIE. They were treated with hypothermia combined with phenobarbital for 72 hours. Results: Among 36 neonates meeting inclusion criteria, there were 18 boys and 18 girls. Thirty-one (86.1%) neonates had grade 2 and 5 (13.9%) grade 3 HIE. In our neonates, HIE had induced isolated electrographic seizures (n = 11;30.6%), electroclinical seizures (n = 25;69.4%), and 6 types of background EEG activity. During TH and rewarming, there were 52.8% of patients with improved background EEG activity, 41.7% of patients with unchanged background EEG activity, and 5.5% of patients with worsened background EEG activity. At the end of rewarming, only 9 (25%) patients still had seizures. Conclusion: Isolated electrographic and electroclinical seizures are the only pathological entities found in our studied population. In neonates with moderate HIE, the applied therapeutic strategy positively influences the evolution of both seizures and background EEG activity. On the other hand, in neonates with severe HIE, the same therapeutic strategy is ineffective. .

Analysis of the optimal target node to reduce seizure-like discharge in networks

Network approaches have been widely accepted to guide surgical strategy and predict outcome for epilepsy treatment.This study starts with a single oscillator to explore brain activity,using a phenomenological model capable of describing healthy and epileptic states.The ictal number of seizures decreases or remains unchanged with increasing the speed of oscillator excitability and in each seizure,there is an increasing tendency for ictal duration with respect to the speed.The underlying reason is that the strong excitability speed is conducive to reduce transition behaviors between two attractor basins.Moreover,the selection of the optimal removal node is estimated by an indicator proposed in this study.Results show that when the indicator is less than the threshold,removing the driving node is more possible to reduce seizures significantly,while the indicator exceeds the threshold,the epileptic node could be the removal one.Furthermore,the driving node is such a potential target that stimulating it is obviously effective in suppressing seizure-like activity compared to other nodes,and the propensity of seizures can be reduced 60%with the increased stimulus strength.Our results could provide new therapeutic ideas for epilepsy surgery and neuromodulation.

Clinical efficacy of Baijin pills in the treatment of generalized tonicclonic seizure epilepsy with cognitive impairment

BACKGROUND The generalized tonic-clonic seizure(GTCS)is the most usual variety of epileptic seizure.It is mainly characterized by strong body muscle rigidity,loss of consciousness,a disorder of plant neurofunction,and significant damage to cognitive function.The effect of antiepileptic drugs on cognition should also be considered.At present,there is no effective treatment for patients with epilepsy,but traditional Chinese medicine has shown a significant effect on chronic disease with fewer harmful side effects and should,therefore,be considered for the therapy means of epilepsy with cognitive dysfunction.AIM To investigate the clinical efficacy of Baijin pills for treating GTCS patients with cognitive impairment.METHODS This prospective study enrolled patients diagnosed with GTCS between January 2020 and December 2023 and separate them into two groups(experimental and control)using random number table method.The control group was treated with sodium valproate,and the experimental group was Baijin pills and sodium valproate for three months.The frequency and duration of each seizure,the Montreal Cognitive Assessment Scale(MoCA),and the Quality of Life Rating Scale(QOLIE-31)were recorded before and after treatment.RESULTS There were 85 patients included(42 in the control group and 43 in the experimental group).After treatment,the seizure frequency in the experimental group was significantly reduced(P<0.05),and seizure duration was shortened(P<0.01).The total MoCA score in the experimental group significantly increased compared to before treatment(P<0.01),and the sub-item scores,except naming and abstract generalization ability,significantly increased(P<0.05),whereas the total MoCA score in the control group significantly decreased after treatment(P<0.05).The QOLIE-31 score of the experimental group increased significantly after treatment compared to before treatment(P<0.01).CONCLUSION Baijin pills have a good clinical effect on epilepsy with cognitive dysfunction.

Primary Multiple Cerebral Hydatid Cyst in 8 Year-Old Girl: A Rare Cause of Childhood Seizure

Background: Cystic echinococcosis is a zoonotic infection that occurs worldwide. Humans are infected through ingestion of parasite eggs in contaminated food, water or through direct contact with infected dogs, which are the definite host. Humans serve accidentally as intermediate host, and occurrences are common in children and young adults. Cystic echinococcosis is endemic in Mediterranean, South American, Middle Eastern, Central Asia, East Africa countries and Australia. Multiple cerebral hydatid cysts are very rare with only a few reports in the literature. Case Description: We present the case of an 8-year-old girl who presented with focal seizures, hemiparesis, headache, vomiting and bilateral optic atrophy. Diagnostic workup was performed, and magnetic resonance imaging revealed multiple intracranial cysts predominantly in the right frontal region with significant mass effect. A total of 11 intracranial cysts were removed surgically, and the child recovered uneventfully. Conclusion: Neurosurgeons should keep hydatidosis in the list of differentials when evaluating patients with cystic diseases of the brain. Although the removal of such cysts is challenging, outcomes are excellent when cysts are evacuated without rupture and patients show complete resolution of symptoms.

Diagnosis of neurocysticercosis among patients with seizures in northern coastal districts of Andhra Pradesh, India

Objective: To report cases of neurocysticercosis(NCC) from three neighboring districts of Andhra Pradesh state in India where NCC burden was never explored before.Methods: A total of 160 patients presenting with recent onset seizures were recruited from neurology, general medicine, and pediatric outpatient clinics of a local major tertiary care teaching hospital serving above districts during the period 2011–2014. Brain imaging was performed in all the above cases. A commercial immunoglobulin G-ELISA kit(sensitivity = 85%; specificity = 94%) was employed for the serological diagnosis of NCC.Results: The recruited patients presented with generalized, simple partial, and complex partial seizures(55%, 31.25% and 13.75% respectively). NCC was diagnosed in 44 of160(27.5%) seizure cases based on imaging characteristics, and a positive serum antibody ELISA. No association was detected between seropositivity with the number and location of the lesion(s) in the brain.Conclusions: The possible potentiality of NCC could be identified as an underlying cause of the recent onset of seizures in this region as explored in the present study. It is recommended that NCC should be suspected as one of the major differential in every recent onset seizure with or without a radio imaging supportive diagnosis, especially in areas endemic for taeniasis/cysticercosis.

Glucocorticoid receptor expression in neonatal rat cortex following recurrent seizures The role in developing brain injury

BACKGROUND： Studies have explored changes in neonatal rat glucocorticoid receptor （GR） expression changes following mature brain injury. OBJECTIVE： To investigate the temporal and special changes of GR during brain development in rats with recurrent seizures. DESIGN, TIME AND SE＇n＇ING： A randomized, controlled animal experiment was performed at the Department of Pediatrics, Second Xiangya Hospital of Central South University, from February 2008 to March 2009. MATERIALS： Rabbit anti-rat GR monoclonal antibody was purchased from Santa Cruz Biotechnology, USA; goat anti-rabbit IgG was purchased from Zhongshan Goldenbridge Biotechnology, China. METHODS： A total of 48 Sprague-Dawley rats, 7 days old, were randomly assigned to control and seizure groups, with 24 animals in each group. Seizures were induced by inhalant flurothyl. MAIN OUTCOME MEASURES： Changes in GR protein expression in the rat cerebral cortex were detected by Western blotting analysis and immunohistochemistry. RESULTS： GR expression in the cerebral cortex of control rats significantly increased with aging （P 〈 0.05）, and varied in the frontal lobe, temporal lobe, and parietal lobe. GR was predominantly expressed in the cytoplasm early and rapidly increased in the nuclei. GR protein expression in the cerebral cortex after seizure was lower in the cytoplasm at 15 days and in nuclear protein at 19 days. CONCLUSION： GR expression displayed temporal and spatial changes in brain development. Recurrent seizures in neonatal rats cause abnormal GR expression and might play an important role in developing brain injury.

Microglial displacement of GABAergic synapses has endogenous protective function in generation of complex febrile seizures

OBJECTIVE Microglia-mediated dis-placement of synapses has been reported in the setting of experimental neuroinflammation,but its role in neurological disorders is poorly understood.Complex febrile seizures(FS) are the most common infantile seizures,yet its pathological progress is largely unknown.METHODS Mice pups(postnatal 8-10 d) were posted to 43℃ hyperthermia condition to develop FS,and then the latency and threshold of seizures were determined.The displacement of synapses was observed through immunofluorescence staining.We researched whether microglial displacement of GABAergic synapses will influence complex FS-induced increase in GABAergic neurotransmission and neuronal excitability with patch-clamp electrophysiology.Moreover,we used the CD11 bD TR mice to selective ablation of microglia or pharmacological inhibition of microglia to observe their effects on susceptibility to FS and synaptic stripping.RESULTS GABAergic presynaptic terminals surrounding neuronal soma and GABAergic transmissions were increased in complex FS.Meanwhile,the activated microglia ensheathe glutamatergic neuronal soma to displace,but do not phagocytize,GABAergic presynaptic terminals.Patch-clamp electrophysiology established that the microglial displacement of GABAergic synapses reduced complex FS-induced increase in GABAergic neurotransmission and neuronal excitability,while GABA exerts excitatory action in this immature stage.Moreover,pharmacological inhibition of microglial displacement of GABAergic synapses or selective ablation of microglia in CD11 bDTR mice promoted the generation of complex FS.CONCLUSION Displacement of GABAergic synapses by microglia is a protective event in the pathological progress of complex FS.

Models and detection of spontaneous recurrent seizures in laboratory rodents

Epilepsy, characterized by spontaneous recurrent seizures （SRS）, is a serious and common neurological disorder afflicting an estimated 1% of the population worldwide. Animal experiments, especially those utilizing small laboratory rodents, remain essential to understanding the fundamental mechanisms underlying epilepsy and to prevent, diagnose, and treat this disease. While much attention has been focused on epileptogenesis in animal models of epilepsy, there is little discussion on SRS, the hallmark of epilepsy. This is in part due to the technical difficulties of rigorous SRS detection. In this review, we comprehensively summarize both genetic and acquired models of SRS and discuss the methodology used to monitor and detect SRS in mice and rats.

Improving control effects of absence seizures using single-pulse alternately resetting stimulation (SARS) of corticothalamic circuit

Presently,we develop a simplified corticothalamic(SCT)model and propose a single-pulse alternately resetting stimulation(SARS)with sequentially applying anodic(A,“+”)or cathodic(C,“−”)phase pulses to the thalamic reticular(RE)nuclei,thalamus-cortex(TC)relay nuclei,and cortical excitatory(EX)neurons,respectively.Abatement effects of ACC-SARS of RE,TC,and EX for the 2 Hz-4 Hz spike and wave discharges(SWD)of absence seizures are then concerned.The m∶n on-off ACC-SARS protocol is shown to effectively reduce the SWD with the least current consumption.In particular,when its frequency is out of the 2 Hz-4 Hz SWD dominant rhythm,the desired seizure abatements can be obtained,which can be further improved by our proposed directional steering(DS)stimulation.The dynamical explanations for the SARS induced seizure abatements are lastly given by calculating the averaged mean firing rate(AMFR)of neurons and triggering averaged mean firing rates(TAMFRs)of 2 Hz-4 Hz SWD.

The efficacy and tolerability of lamotrigine adjunctive/monotherapy in patients with partial seizures refractory to poly-AEDs

Objective： This study was designed as an open-label trial to assess the effects of changing the antiepileptic drugs （AEDs） regimen to lamotrigine （LTG） as adjunctive/monotherapy in patients with partial seizures who were dissatisfied with their drug regimen because of intractable seizures. Methods： The patients were recruited from mulficenters using the following criteria： age≥ 18 years; at least 3 seizures per month during the last 16 weeks; previous use of at least 3 AEDs. The study involved a baseline phase and 2 experimental phases： LTG was first added to the regimen, and then patients could gradually change to LTG monotherapy if their seizures were reduced by at least 50 percent/month. Tolerability, the primary end point, was assessed using the Liverpool Adverse Experience Profile （LAEP）. Secondary end points included quality of life, as measured with the Quality of Life in Epilepsy-31 inventory. Reductions in seizures from baseline throughout each phase were also analyzed. Results： One hundred and fourteen patients aged between 18 and 52 years （age 27.8___ 13.2 years; 71 men and 43 women） were enrolled. After adding LTG, 105 patients （92.11%） Completed adjunctive therapy. Upon completion of the adjunctive phase, mean improvement from baseline was 2.6 points on the LAEP （p=0.037）. The overall score on the QOLIE-31 improved by 8.49 points from baseline （p=0.023）. At the end of the trial, 26 （22.81%） of patients completed LTG monotherapy, and 65 patients （57.02%） experienced at least 50% reduction in seizure frequency compared to baseline, The mean improvement from baseline was 5.1 points on the LAEP （p=0.0059）, and the overall score on the QOLIE-31 score improved by 12,72 points from baseline（p=0,0071）. Twenty-two （19.30%） patients reported adverse effects and 9 patients discontinued participation in the trial because of adverse effects. Conclusion： For patients with partial seizures who were dissatisfied with their AED regimen because of intractable seizures, adding LTG to the drug regimen was well tolerated and effective in improving the quality of life and controlling seizures. Furthermore, switching to LTG monotherapy was associated with further improvement.

Pneumonia and seizures due to hypereosinophilic syndrome—organ damage and eosinophilia without synchronisation:A case report

BACKGROUND Hypereosinophilic syndrome(HES)is a condition characterized by increased eosinophil proliferation in the bone marrow,as well as tissue eosinophilia,often causing organ damage.The cause of the disease is unknown.Initial symptoms include fatigue,cough,shortness of breath,myalgia,angioedema,fever,and pneumonia.In addition to the respiratory symptoms,damage to the central nervous system can lead to severe seizures.Here,we report a case with pneumonia and complex partial seizures secondary to HES.CASE SUMMARY A 94-year-old woman was admitted to our hospital for heart failure and bloody stools.After admission,she also showed symptoms of pneumonia.Non-contrast computed tomography of the chest showed pleural effusion and infiltrative shadows.Lower gastrointestinal endoscopy showed multiple ulcers in the sigmoid colon.Blood analyses showed marked eosinophilia(eosinophils 1760/mm3,total leukocytes 6850/mm3).Initial treatment with furosemide 20 mg/d and prednisolone 25 mg/d relieved these symptoms.However,the patient subsequently experienced localised epileptic seizures characterized by bilateral eyelid twitching and eyes rolling upwards,without generalized convulsions,and respiratory arrest occurred.Electroencephalography showed spikes and waves.Non-contrast magnetic resonance imaging of the brain showed extensive periventricular hyperintensity.With administration of levetiracetam 1000 mg/d the epileptic seizures disappeared.However,the patient’s consciousness remained impaired,and her pneumonia worsened again.Two weeks later,she died of pneumonia.CONCLUSION HES symptoms are variable and atypical,and the level and timing of eosinophilia and organ damage are often discordant.

Response of levetiracetam in neonatal seizures

AIM: To review the clinical response to levetiracetam(LEV) in neonatal seizure management in intensive care unit.METHODS: Medical records of neonates who received LEV from January 2009 to August 2014 were reviewed. Their demographic data, clinical characteristics, etiology, seizures, electroencephalograms, response to treatment and outcome were noted. Literature review of use of LEV in neonates were also performed via Pub Med and EMBASE with keywords- "neonates", "seizures", "epilepsy" and "LEV" up to Sep 2014 and retrieved the publications. The response rate to LEV was compared.RESULTS: Twelve neonates were identified during the study period. All patients received phenobarbitone loading prior to consideration of LEV. Seven(58%) and nine(75%) achieved seizure freedom 24 h and 72 h after LEV was added, both clinically and electrographically. No serious adverse effects were associated with LEV use. From the literature, there are total 144 neonates reported to have used LEV. The overall results suggested that LEV could control up to 90% of neonatal seizures.CONCLUSION: LEV was found to be relatively safe and efficacious in treating neonatal seizures, but might not work well in the most severe hypoxic ischemic encephalopathy.

Elevated NKCC1 transporter expression facilitates early post-traumatic brain injury seizures

As a leading cause for morbidity and mortality in young adults,traumatic brain injury（TBI）,along with the poorly understood TBI-related seizures inducing their predispositions,pose a major health and socioeconomic problem in the world（Huang,2013）.

An insulinoma with clinical and electroencephalographic features resembling complex partial seizures

We described a female patient with insulinoma who experienced recurrent episodes of automatism,confusion and convulsion.Furthermore,her electroencephalography(EEG)findings resembled the pattern in complex partial seizures with secondary generalization.The interictal EEG showed spikes and sharp waves,as well as focal slowing over the left temporal lobe,and the ictal EEG revealed generalized spikes and sharp waves associated with diffused slowing.She was initially misdiagnosed as pharmacoresistant epilepsy.After the insulinoma was found and surgically removed,her EEG turned normal and she was sei- zure-free during the 4-year follow-up.This report highlights the need for careful reassessment of all seizures refractory to medi- cation,even for the patients associated with epileptiform discharges on EEG.

ACTA2 mutation is responsible for multisystemic smooth muscle dysfunction syndrome with seizures:A case report and review of literature

BACKGROUND ACTA2 gene is a specific gene that encodes actinα2.Multisystem smooth muscle dysfunction syndrome(MSMDS)is a multisystem disease characterized by aortic and cerebrovascular lesions caused by ACTA2 gene mutations.There have been many reports of cardiac,pulmonary and cerebrovascular lesions caused by MSMDS;however,few studies have focused on seizures caused by MSMDS.CASE SUMMARY Our patient was a girl aged 7 years and 8 mo with recurrent cough,asthma and seizures for 7 years.She was diagnosed with severe pneumonia,congenital heart disease,cardiac insufficiency,and malnutrition in the local hospital.Cardiac ultrasonography revealed congenital heart disease,patent ductus arteriosus(with a diameter of 0.68 cm),left coronary arteriectasis,patent oval foramen(0.12 cm),tricuspid and pulmonary regurgitation,and pulmonary hypertension.Cerebral magnetic resonance imaging and magnetic resonance angiography indicated stiffness in the brain vessels,together with multiple aberrant signaling shadows in bilateral paraventricular regions.A heterozygous mutation(c.536G>A)was identified in the ACTA2 gene,resulting in generation of p.R179H.Finally,the girl was diagnosed with MSMDS combined with epilepsy.The patient had 4 episodes of seizures before treatment,and no onset of seizure was reported after oral administration of sodium valproate for 1 year.CONCLUSION MSMDS has a variety of clinical manifestations and unique cranial imaging features.Cerebrovascular injury and white matter injury may lead to seizures.Gene detection can confirm the diagnosis and prevent missed diagnosis or misdiagnosis.