Many patients with lissencephaly present with infantile epileptic spasms syndrome (IESS) or West syndrome and require adrenocorticotrophic hormone (ACTH) treatment. The difference of adverse events of ACTH treatment between lissencephaly and other disorders is unknown.
Case presentation
We report the case of an infant with lissencephaly and IESS followed by severe hypertension with cardiac hypertrophy after ACTH treatment, requiring continuous administration of antihypertensive drugs. The infant was delivered at 39 weeks of gestation with a birth weight of 2484 g and was admitted to the neonatal intensive care unit for transient tachypnea. Brain MRI showed posterior predominant agyria compatible to classical lissencephaly grade 2. He harbored a novel de novo variant of PAFAH1B1 or LIS1 gene, c.485G>A, p. (Gly162Asp). At the age of 5 months, he developed epileptic spasms with hypsarrhythmia on electroencephalogram, leading to the diagnosis of IESS. ACTH and vitamin B6 treatments were effective for seizures and hypsarrhythmia. However, the patient had hypertension (138/100 mmHg) and cardiac hypertrophy and required continuous administration of nicardipine intravenously(0.6–1.0 μg/kg/min).
Conclusion
Patients with lissencephaly might be susceptible to severe cardiac adverse events with ACTH treatment.
背景：许多无脑畸形患者存在婴儿癫痫性痉挛综合征（IESS）或West综合征，需要促肾上腺皮质激素（ACTH）治疗。无脑畸形与其他疾病ACTH治疗不良事件的差异尚不清楚。我们报告了一例婴儿无脑畸形和IESS，在ACTH治疗后出现严重高血压并心脏肥厚，需要持续服用降压药。该婴儿在妊娠39周时出生，出生体重为2484 g，因短暂性呼吸急促住进新生儿重症监护病房。脑MRI显示后显性失稳符合典型无脑畸形2级。他携带了一种新的PAFAH1B1或LIS1基因的新变体，c.485G> a, p. （Gly162Asp）。5个月大时，脑电图显示癫痫性痉挛伴心律失常，诊断为IESS。ACTH和维生素B6治疗对癫痫发作和心律失常有效。然而，患者有高血压（138/100 mmHg）和心脏肥厚，需要持续静脉给予尼卡地平（0.6-1.0 μg/kg/min）。结论无脑畸形患者经ACTH治疗后易发生严重的心脏不良事件。
{"title":"Hypertension due to ACTH treatment for lissencephaly with a novel PAFAH1B1 variant","authors":"Natsumi Ida , Yoshifusa Abe , Ryo Karato , Madoka Shirai , Kaori Kamijo , Mariko Takase , Takeshi Shimizu , Rei Ebata , Takeshi Mikawa , Mitsuhiro Kato","doi":"10.1016/j.bdcasr.2025.100065","DOIUrl":"10.1016/j.bdcasr.2025.100065","url":null,"abstract":"<div><h3>Background</h3><div>Many patients with lissencephaly present with infantile epileptic spasms syndrome (IESS) or West syndrome and require adrenocorticotrophic hormone (ACTH) treatment. The difference of adverse events of ACTH treatment between lissencephaly and other disorders is unknown.</div></div><div><h3>Case presentation</h3><div>We report the case of an infant with lissencephaly and IESS followed by severe hypertension with cardiac hypertrophy after ACTH treatment, requiring continuous administration of antihypertensive drugs. The infant was delivered at 39 weeks of gestation with a birth weight of 2484 g and was admitted to the neonatal intensive care unit for transient tachypnea. Brain MRI showed posterior predominant agyria compatible to classical lissencephaly grade 2. He harbored a novel <em>de novo</em> variant of <em>PAFAH1B1</em> or <em>LIS1</em> gene, c.485G>A, p. (Gly162Asp). At the age of 5 months, he developed epileptic spasms with hypsarrhythmia on electroencephalogram, leading to the diagnosis of IESS. ACTH and vitamin B6 treatments were effective for seizures and hypsarrhythmia. However, the patient had hypertension (138/100 mmHg) and cardiac hypertrophy and required continuous administration of nicardipine intravenously(0.6–1.0 μg/kg/min).</div></div><div><h3>Conclusion</h3><div>Patients with lissencephaly might be susceptible to severe cardiac adverse events with ACTH treatment.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"3 1","pages":"Article 100065"},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hemorrhagic shock and encephalopathy syndrome (HSES) is a severe, rare condition with poor prognosis primarily affecting infants and young children. Symptoms include fever, shock, encephalopathy, watery diarrhea, bleeding tendency, and hepatic and renal dysfunction; however, the etiology of HSES remains unknown. We present the case of an infant who developed HSES after initial cytomegalovirus (CMV) infection, suggesting the pathogenesis of hemophagocytic lymphohistiocytosis (HLH).
Case presentation
A 56-day-old male infant was admitted to the intensive care unit due to circulatory failure and convulsive seizures. Suspecting septic shock, the infant was initially treated with catecholamines, continuous midazolam for sedation, and antibiotics. Although the seizures had temporarily ceased after admission, the patient experienced recurrent convulsive seizures on day 2 and was administered multiple antiepileptic drugs. Despite these treatments, the patient developed refractory status epilepticus, necessitating thiamylal anesthetic therapy. The initial blood, urine, and cerebrospinal fluid cultures were negative. The patient met the criteria for HSES (encephalopathy, shock, disseminated intravascular coagulopathy, watery diarrhea, cytopenia, acidemia, hepatic and renal dysfunction, and negative blood and cerebrospinal fluid cultures). Furthermore, the patient fulfilled the criteria for HLH (fever, cytopenia, hypertriglyceridemia, hypofibrinogenemia, and elevated ferritin and soluble interleukin-2 receptor levels), with prior CMV infection implicated as a potential trigger.
Conclusion
We encountered an infant who developed HSES with HLH secondary to a CMV infection. This study provides new insights into the pathogenesis of HSES involving the HLH pathology.
{"title":"Hemorrhagic shock and encephalopathy syndrome with hemophagocytic lymphohistiocytosis pathology caused by cytomegalovirus infection","authors":"Shinji Harada , Masahiro Nishiyama , Mao Mizuta , Masaki Shimizu , Azusa Maruyama , Hiroshi Kurosawa , Yasuo Nakagishi","doi":"10.1016/j.bdcasr.2025.100062","DOIUrl":"10.1016/j.bdcasr.2025.100062","url":null,"abstract":"<div><h3>Background</h3><div>Hemorrhagic shock and encephalopathy syndrome (HSES) is a severe, rare condition with poor prognosis primarily affecting infants and young children. Symptoms include fever, shock, encephalopathy, watery diarrhea, bleeding tendency, and hepatic and renal dysfunction; however, the etiology of HSES remains unknown. We present the case of an infant who developed HSES after initial cytomegalovirus (CMV) infection, suggesting the pathogenesis of hemophagocytic lymphohistiocytosis (HLH).</div></div><div><h3>Case presentation</h3><div>A 56-day-old male infant was admitted to the intensive care unit due to circulatory failure and convulsive seizures. Suspecting septic shock, the infant was initially treated with catecholamines, continuous midazolam for sedation, and antibiotics. Although the seizures had temporarily ceased after admission, the patient experienced recurrent convulsive seizures on day 2 and was administered multiple antiepileptic drugs. Despite these treatments, the patient developed refractory status epilepticus, necessitating thiamylal anesthetic therapy. The initial blood, urine, and cerebrospinal fluid cultures were negative. The patient met the criteria for HSES (encephalopathy, shock, disseminated intravascular coagulopathy, watery diarrhea, cytopenia, acidemia, hepatic and renal dysfunction, and negative blood and cerebrospinal fluid cultures). Furthermore, the patient fulfilled the criteria for HLH (fever, cytopenia, hypertriglyceridemia, hypofibrinogenemia, and elevated ferritin and soluble interleukin-2 receptor levels), with prior CMV infection implicated as a potential trigger.</div></div><div><h3>Conclusion</h3><div>We encountered an infant who developed HSES with HLH secondary to a CMV infection. This study provides new insights into the pathogenesis of HSES involving the HLH pathology.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"3 1","pages":"Article 100062"},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143149213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Familial hemiplegic migraine (FHM) is a subtype of migraine with three identified causative genes: CACNA1A, ATP1A2, and SCN1A. However, diagnosis and treatment of FHM are challenging because of the wide phenotypic variation. We describe a family with genetically diagnosed CACNA1A-related FHM1 in which the proband presented with acute encephalopathy-like symptoms.
Case presentation
The proband was a 10-year-old girl admitted to our hospital with headache, paresthesia, frequent vomiting, and impaired consciousness. Blood test results and brain imaging were unremarkable, but she had persistent impaired consciousness. Electroencephalography indicated cerebral dysfunction. Consequently, she was treated with intravenous methylprednisolone pulse therapy and intravenous immune globulin for suspected acute encephalopathy. After treatment, her level of consciousness gradually improved, but headache persisted. Detailed interviews revealed that several maternal relatives had similar symptoms; the proband's younger sister subsequently developed headaches and paralysis. Given these findings, we conducted genetic counseling and familial genetic analysis with informed consent, which led to the diagnosis of CACNA1A-related FHM1. The proband started acetazolamide therapy, which successfully prevented the recurrence of attacks. This genetic information was also beneficial for managing the mother's and sister's conditions.
Conclusion
In the proband, FHM attacks were severe and occurred at a young age, making genetic diagnosis particularly important. Genetic diagnosis was useful in understanding the symptoms and guiding management for the patient as well as affected family members.
{"title":"CACNA1A-related familial hemiplegic migraine presenting with prolonged impaired consciousness","authors":"Mami Akamatsu , Gen Furukawa , Masayuki Hirai , Midori Yamada , Ayami Yoshikane , Naoko Ishihara , Hiroki Kurahashi , Tetsushi Yoshikawa","doi":"10.1016/j.bdcasr.2025.100063","DOIUrl":"10.1016/j.bdcasr.2025.100063","url":null,"abstract":"<div><h3>Background</h3><div>Familial hemiplegic migraine (FHM) is a subtype of migraine with three identified causative genes: <em>CACNA1A</em>, <em>ATP1A2</em>, and <em>SCN1A</em>. However, diagnosis and treatment of FHM are challenging because of the wide phenotypic variation. We describe a family with genetically diagnosed <em>CACNA1A</em>-related FHM1 in which the proband presented with acute encephalopathy-like symptoms.</div></div><div><h3>Case presentation</h3><div>The proband was a 10-year-old girl admitted to our hospital with headache, paresthesia, frequent vomiting, and impaired consciousness. Blood test results and brain imaging were unremarkable, but she had persistent impaired consciousness. Electroencephalography indicated cerebral dysfunction. Consequently, she was treated with intravenous methylprednisolone pulse therapy and intravenous immune globulin for suspected acute encephalopathy. After treatment, her level of consciousness gradually improved, but headache persisted. Detailed interviews revealed that several maternal relatives had similar symptoms; the proband's younger sister subsequently developed headaches and paralysis. Given these findings, we conducted genetic counseling and familial genetic analysis with informed consent, which led to the diagnosis of <em>CACNA1A</em>-related FHM1. The proband started acetazolamide therapy, which successfully prevented the recurrence of attacks. This genetic information was also beneficial for managing the mother's and sister's conditions.</div></div><div><h3>Conclusion</h3><div>In the proband, FHM attacks were severe and occurred at a young age, making genetic diagnosis particularly important. Genetic diagnosis was useful in understanding the symptoms and guiding management for the patient as well as affected family members.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"3 1","pages":"Article 100063"},"PeriodicalIF":0.0,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Children with severe motor and intellectual disabilities (SMID) experience numerous serious physical health problems and comorbidities. Children with SMID require long-term care from a multidisciplinary team, including rehabilitation. Acute pancreatitis is a life-threating comorbidity in children with SMID. Risk factors for acute pancreatitis in patients with SMID include the absence of voluntary movement, requirement of respiratory devices, panhypopituitarism, thermoregulatory dysfunction, oral administration of valproic acid, gallstones, and low serum albumin levels.
Case presentation
We encountered two children with SMID who had been followed at our facility and hospital for an extended period. Both patients were at high risk for developing pancreatitis, particularly after undergoing ventilator support following tracheostomy and the introduction of gastrostomy feeding. In both cases, the diagnosis was triggered by changes in vital signs, such as an increase in heart rate, and confirmed by imaging findings consistent with acute pancreatitis. Both patients faced challenges with enteral nutrition after developing pancreatitis, as attempts to restart it led to relapse of pancreatitis. Ultimately, both patients experienced severe outcomes.
Conclusion
Efforts to prevent pancreatitis onset are crucial. When changes in a child's physical condition are suspected, especially in children with SMID who have risk factors, pancreatitis should be considered in the differential diagnosis. Regular blood tests should include serum amylase levels. Once pancreatitis is diagnosed, treatment should closely follow established guidelines. Additionally, all staff involved in the care of children with SMID should be aware of the prevalence of acute pancreatitis in this population.
{"title":"Examination of two cases with severe motor and intellectual disabilities who died due to acute pancreatitis and review of the literature","authors":"Shungo Fujiki , Emiko Kobayashi , Kuniko Tokoro , Sotaro Yuzawa , Eiji Matsukuma , Atsushi Imamura , Hideo Kaneko","doi":"10.1016/j.bdcasr.2024.100061","DOIUrl":"10.1016/j.bdcasr.2024.100061","url":null,"abstract":"<div><h3>Background</h3><div>Children with severe motor and intellectual disabilities (SMID) experience numerous serious physical health problems and comorbidities. Children with SMID require long-term care from a multidisciplinary team, including rehabilitation. Acute pancreatitis is a life-threating comorbidity in children with SMID. Risk factors for acute pancreatitis in patients with SMID include the absence of voluntary movement, requirement of respiratory devices, panhypopituitarism, thermoregulatory dysfunction, oral administration of valproic acid, gallstones, and low serum albumin levels.</div></div><div><h3>Case presentation</h3><div>We encountered two children with SMID who had been followed at our facility and hospital for an extended period. Both patients were at high risk for developing pancreatitis, particularly after undergoing ventilator support following tracheostomy and the introduction of gastrostomy feeding. In both cases, the diagnosis was triggered by changes in vital signs, such as an increase in heart rate, and confirmed by imaging findings consistent with acute pancreatitis. Both patients faced challenges with enteral nutrition after developing pancreatitis, as attempts to restart it led to relapse of pancreatitis. Ultimately, both patients experienced severe outcomes.</div></div><div><h3>Conclusion</h3><div>Efforts to prevent pancreatitis onset are crucial. When changes in a child's physical condition are suspected, especially in children with SMID who have risk factors, pancreatitis should be considered in the differential diagnosis. Regular blood tests should include serum amylase levels. Once pancreatitis is diagnosed, treatment should closely follow established guidelines. Additionally, all staff involved in the care of children with SMID should be aware of the prevalence of acute pancreatitis in this population.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"3 1","pages":"Article 100061"},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143149212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
KCNT1 variants are associated with drug-resistant epilepsy, including epilepsy in infancy with migrating focal seizures, and may be associated with aortopulmonary collateral arteries (APCAs). Deaths due to hemoptysis caused by disrupted APCAs have also been reported.
Case report
The patient had seizures since 1 month of age. Interictal EEG reveals a suppression-burst pattern. At 3 months of age, echocardiography revealed abnormal blood flow originating in the aorta and a dilated left side of the heart, and contrast-enhanced CT showed numerous APCAs. A targeted sequence analysis revealed a variant of KCNT1 (NM_020822.3:c.1130G>C p.Cys377Ser) at 8 months of age. His seizures were refractory and occurred frequently daily, and he had severe psychomotor retardation. Coil embolization for APCAs was performed four times since 4 months of age, and he had never experienced hemoptysis.
Discussion/Conclusion
The complications of drug-resistant epilepsy and APCAs should be considered in cases of KCNT1 variants. APCAs can be challenging to diagnose in the early postnatal period, and regular cardiovascular evaluations are necessary. Early embolization of APCAs prior to pulmonary hemorrhage onset may effectively prevent pulmonary hemorrhage and mitigate heart failure.
背景：kcnt1变异与耐药癫痫相关，包括婴儿期伴有迁移局灶性癫痫的癫痫，并可能与主动脉-肺侧支动脉（APCAs）相关。由于APCAs中断而导致的咯血死亡也有报道。病例报告：患者自1个月大起癫痫发作。间期脑电图显示抑制-爆发模式。3个月大时，超声心动图显示主动脉血流异常，左侧心脏扩张，增强CT显示大量apca。靶序列分析显示，KCNT1 （NM_020822.3: C . 1130g >C . p.Cys377Ser）在8月龄时出现变异。他的癫痫发作是难治性的，每天频繁发生，他有严重的精神运动迟缓。自4个月大以来，进行了4次APCAs线圈栓塞，从未发生过咯血。讨论/结论KCNT1变异应考虑耐药癫痫和apca的并发症。apca在产后早期诊断可能具有挑战性，定期进行心血管评估是必要的。肺出血前早期栓塞apca可有效预防肺出血，减轻心力衰竭。
{"title":"A boy with drug-resistant epilepsy and aortopulmonary collateral arteries arising from a KCNT1 variant","authors":"Kentaro Okada , Takaaki Sawada , Shiro Ozasa , Keiko Nomura , Natsumi Fujiyama , Shoichiro Kusunoki , Kotaro Anan , Fumiya Miyamura , Osamu Matsuo , Yuta Inoue , Naomi Tsuchida , Naomichi Matsumoto , Kimitoshi Nakamura","doi":"10.1016/j.bdcasr.2024.100060","DOIUrl":"10.1016/j.bdcasr.2024.100060","url":null,"abstract":"<div><h3>Background</h3><div><em>KCNT1</em> variants are associated with drug-resistant epilepsy, including epilepsy in infancy with migrating focal seizures, and may be associated with aortopulmonary collateral arteries (APCAs). Deaths due to hemoptysis caused by disrupted APCAs have also been reported.</div></div><div><h3>Case report</h3><div>The patient had seizures since 1 month of age. Interictal EEG reveals a suppression-burst pattern. At 3 months of age, echocardiography revealed abnormal blood flow originating in the aorta and a dilated left side of the heart, and contrast-enhanced CT showed numerous APCAs. A targeted sequence analysis revealed a variant of <em>KCNT1</em> (NM_020822.3:c.1130G>C p.Cys377Ser) at 8 months of age. His seizures were refractory and occurred frequently daily, and he had severe psychomotor retardation. Coil embolization for APCAs was performed four times since 4 months of age, and he had never experienced hemoptysis.</div></div><div><h3>Discussion/Conclusion</h3><div>The complications of drug-resistant epilepsy and APCAs should be considered in cases of <em>KCNT1</em> variants. APCAs can be challenging to diagnose in the early postnatal period, and regular cardiovascular evaluations are necessary. Early embolization of APCAs prior to pulmonary hemorrhage onset may effectively prevent pulmonary hemorrhage and mitigate heart failure.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"3 1","pages":"Article 100060"},"PeriodicalIF":0.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-08DOI: 10.1016/j.bdcasr.2024.100058
Greta Senkeviciute , Evelina Dagyte , Vytautas Sliuzas , Skaiste Peciuliene , Birute Burnyte
Introduction
Mosaicism is a phenomenon when a single fertilized egg develops into an embryo comprising two or more cell clones, each with a unique genotype. Mosaic trisomy 12 is a rare condition with a very variable phenotype. Confirmation of the diagnosis is difficult due to the different ratios and distribution of mosaic cells, various affected tissues, false-negative results and presence of extraembryonic mosaicism.
Case presentation
In this study, we report a patient with developmental delay, brain anomalies (mega cisterna magna, hypoplastic corpus callosum and hypophyseal fossa), chorioretinal pigmentary dysplasia, congenital heart disease, bilateral cryptorchidism, hydronephrosis, and dysmorphic features associated to a trisomy 12 mosaicism.
Discussion
The manifestation of trisomy 12 mosaicism is multisystemic, and the most frequent finding is dysmorphic features. Other common findings are developmental delay, congenital heart disease, gastrointestinal system malformations, skeletal anomalies, and hypotonia. Fluorescence in situ hybridization analysis, array comparative genomic hybridisation or single nucleotide polymorphism array are being proposed as first-tier methods for diagnosing mosaic trisomy 12.
Conclusion
This study expands the phenotypic spectrum associated with this rare condition. Detailed investigation allows individualized care of patients with trisomy 12 mosaicism.
{"title":"Mosaic trisomy 12 – A case of a rare phenotypic association and literature review","authors":"Greta Senkeviciute , Evelina Dagyte , Vytautas Sliuzas , Skaiste Peciuliene , Birute Burnyte","doi":"10.1016/j.bdcasr.2024.100058","DOIUrl":"10.1016/j.bdcasr.2024.100058","url":null,"abstract":"<div><h3>Introduction</h3><div>Mosaicism is a phenomenon when a single fertilized egg develops into an embryo comprising two or more cell clones, each with a unique genotype. Mosaic trisomy 12 is a rare condition with a very variable phenotype. Confirmation of the diagnosis is difficult due to the different ratios and distribution of mosaic cells, various affected tissues, false-negative results and presence of extraembryonic mosaicism.</div></div><div><h3>Case presentation</h3><div>In this study, we report a patient with developmental delay, brain anomalies (mega cisterna magna, hypoplastic corpus callosum and hypophyseal fossa), chorioretinal pigmentary dysplasia, congenital heart disease, bilateral cryptorchidism, hydronephrosis, and dysmorphic features associated to a trisomy 12 mosaicism.</div></div><div><h3>Discussion</h3><div>The manifestation of trisomy 12 mosaicism is multisystemic, and the most frequent finding is dysmorphic features. Other common findings are developmental delay, congenital heart disease, gastrointestinal system malformations, skeletal anomalies, and hypotonia. Fluorescence in situ hybridization analysis, array comparative genomic hybridisation or single nucleotide polymorphism array are being proposed as first-tier methods for diagnosing mosaic trisomy 12.</div></div><div><h3>Conclusion</h3><div>This study expands the phenotypic spectrum associated with this rare condition. Detailed investigation allows individualized care of patients with trisomy 12 mosaicism.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"3 1","pages":"Article 100058"},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143149209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-06DOI: 10.1016/j.bdcasr.2024.100059
Teona Shatirishvili , Zura Katsitadze , Yi Shiau Ng , Ashwin Achuthaprasad , Charlotte L. Alston , Emma L. Blakey , Douglass M. Turnbull , Kakha Bregvadze , Tinatin Tkemaladze , Nana Nino Tatishvili
Background
MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is a multisystem disorder with diverse clinical presentations. Approximately 80 % of MELAS cases are linked to the m.3243A>G pathogenic variant in the MT-TL1. Pathogenic variants in other mtDNA genes, including MT-ND1, can also cause MELAS. We report a case of MELAS in a 16-year-old boy with a novel m.3764C>G variant in the MT-ND1.
Case presentation
A 9 years old male patient developed bilateral sensorineural hearing loss followed by a generalized tonic-clonic seizure. At 15, he exhibited progressive fatigue, muscle weakness, and stroke-like episodes. MRI revealed stroke-like lesions in the brain. Over two years, he experienced multiple hospital admissions for severe symptoms including right-sided hemiparesis, hemianopia, seizures, and encephalopathy. Despite treatment, his condition deteriorated, leading to multi-organ failure and death at 16. Molecular genetic analysis identified a heteroplasmic m.3764C>G variant in MT-ND1.
Discussion/Conclusion
Presented case highlights the novel m.3764C>G variant in MT-ND1 associated with MELAS, emphasizing the variant's pathogenicity based on its absence in human mitochondrial databases, de novo occurrence, and predicted severe impact on ND1 protein function. The patient's rapidly progressive disease course contrasts with typical MELAS trajectories, underscoring the variant's severity. This report expands the clinical and mutational spectrum of MELAS and underscores the need for further research into MT-ND1 related MELAS.
{"title":"Novel m.3764C>G variant in MT-ND1 linked to severe MELAS syndrome: A case report","authors":"Teona Shatirishvili , Zura Katsitadze , Yi Shiau Ng , Ashwin Achuthaprasad , Charlotte L. Alston , Emma L. Blakey , Douglass M. Turnbull , Kakha Bregvadze , Tinatin Tkemaladze , Nana Nino Tatishvili","doi":"10.1016/j.bdcasr.2024.100059","DOIUrl":"10.1016/j.bdcasr.2024.100059","url":null,"abstract":"<div><h3>Background</h3><div>MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is a multisystem disorder with diverse clinical presentations. Approximately 80 % of MELAS cases are linked to the m.3243A>G pathogenic variant in the <em>MT-TL1</em>. Pathogenic variants in other mtDNA genes, including <em>MT-ND1</em>, can also cause MELAS. We report a case of MELAS in a 16-year-old boy with a novel m.3764C>G variant in the <em>MT-ND1</em>.</div></div><div><h3>Case presentation</h3><div>A 9 years old male patient developed bilateral sensorineural hearing loss followed by a generalized tonic-clonic seizure. At 15, he exhibited progressive fatigue, muscle weakness, and stroke-like episodes. MRI revealed stroke-like lesions in the brain. Over two years, he experienced multiple hospital admissions for severe symptoms including right-sided hemiparesis, hemianopia, seizures, and encephalopathy. Despite treatment, his condition deteriorated, leading to multi-organ failure and death at 16. Molecular genetic analysis identified a heteroplasmic m.3764C>G variant in <em>MT-ND1</em>.</div></div><div><h3>Discussion/Conclusion</h3><div>Presented case highlights the novel m.3764C>G variant in <em>MT-ND1</em> associated with MELAS, emphasizing the variant's pathogenicity based on its absence in human mitochondrial databases, <em>de novo</em> occurrence, and predicted severe impact on ND1 protein function. The patient's rapidly progressive disease course contrasts with typical MELAS trajectories, underscoring the variant's severity. This report expands the clinical and mutational spectrum of MELAS and underscores the need for further research into <em>MT-ND1</em> related MELAS.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"3 1","pages":"Article 100059"},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143149210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Focal cortical dysplasia (FCD) type II is a group of malformation of cortical development (MCD) which is the result of abnormal proliferation in the brain. Nowadays, FCD II is classified as mTORopathies caused by mutations leading to abnormal hyperactivation of the mTOR pathway. It locates in the same subcategory as hemimegalencephaly (HME) and tuberous sclerosis complex (TSC).
Case presentation
We describe a child with refractory focal status epilepticus and brain MRI features of FCD type II, who did not respond to the usual anti-seizure medications (ASMs) but showed a dramatic response after initiation of vigabatrin. Vigabatrin is an anti-seizure medication with a high response rate for the treatment of infantile spasms and refractory focal epilepsy in TSC.
Conclusion
We concluded that vigabatrin could be a promising precision therapy for refractory epilepsy of FCD type II, which has the same pathologic and molecular abnormalities as TSC.
{"title":"Vigabatrin efficacy in focal cortical dysplasia type II with refractory focal status epilepticus, suspected role of mTOR inhibition","authors":"Safoura Kowkabi , Zahra Rezaei , Reza Kaboodkhani , Parvin Ghaemmaghami , Mohammad Kaboodkhani","doi":"10.1016/j.bdcasr.2024.100055","DOIUrl":"10.1016/j.bdcasr.2024.100055","url":null,"abstract":"<div><h3>Background</h3><div>Focal cortical dysplasia (FCD) type II is a group of malformation of cortical development (MCD) which is the result of abnormal proliferation in the brain. Nowadays, FCD II is classified as mTORopathies caused by mutations leading to abnormal hyperactivation of the mTOR pathway. It locates in the same subcategory as hemimegalencephaly (HME) and tuberous sclerosis complex (TSC).</div></div><div><h3>Case presentation</h3><div>We describe a child with refractory focal status epilepticus and brain MRI features of FCD type II, who did not respond to the usual anti-seizure medications (ASMs) but showed a dramatic response after initiation of vigabatrin. Vigabatrin is an anti-seizure medication with a high response rate for the treatment of infantile spasms and refractory focal epilepsy in TSC.</div></div><div><h3>Conclusion</h3><div>We concluded that vigabatrin could be a promising precision therapy for refractory epilepsy of FCD type II, which has the same pathologic and molecular abnormalities as TSC.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"3 1","pages":"Article 100055"},"PeriodicalIF":0.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143149208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Glial fibrillary acidic protein astrocytopathy (GFAP-A) is an autoimmune central nervous system disease associated with auto-antibodies against GFAP, an intermediate filament protein in astrocytes. GFAP-A typically presents as middle-age-onset subacute meningoencephalitis or meningoencephalomyelitis; however, we present a childhood-onset case of meningomyelitis with persistent fever and malaise.
Case presentation
A fourteen-year-old girl presented with persistent high-grade fever, head and body aches, nausea, neck rigidity, weakness in the extremities, and dysuria. An initial diagnosis of aseptic meningitis was made based on increased cells and proteins in her spinal fluid; however, fever and malaise persisted, and no pathogenic antigens or antibodies could be detected. Subsequently, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) showed extensive longitudinal FDG accumulation along the spinal cord. Ophthalmological examination revealed papilledema. Magnetic resonance imaging of the brain and spine revealed no abnormalities. Based on a suspicion of autoimmune meningomyelitis, we started immunotherapy on day 27. Intravenous methylprednisolone, followed by prednisolone administration relieved the fever and accompanying symptoms that had persisted for a month. A definitive diagnosis of GFAP-A was confirmed by detecting cerebrospinal fluid GFAP-immunoglobulin G in a cell-based assay. Prednisolone was tapered off, with no relapse or significant sequelae.
Discussion/conclusion
In children with persistent fever and neurological symptoms, autoimmune central nervous system disorders such as GFAP-A should be considered in the differential diagnosis; further, if infectious pathogens are excluded, immunotherapy should be initiated early. The clinical presentation of GFAP-A is diverse, including cases with no symptoms of encephalopathy. FDG-PET findings in the spinal cord can be a valuable diagnostic aid.
{"title":"Childhood autoimmune glial fibrillary acidic protein astrocytopathy with spinal cord FDG accumulation on 18F-FDG-PET imaging","authors":"Tatsunori Itabashi , Yuki Ueda , Akio Kimura , Takayoshi Shimohata , Tomonobu Sato","doi":"10.1016/j.bdcasr.2024.100056","DOIUrl":"10.1016/j.bdcasr.2024.100056","url":null,"abstract":"<div><h3>Background</h3><div>Glial fibrillary acidic protein astrocytopathy (GFAP-A) is an autoimmune central nervous system disease associated with auto-antibodies against GFAP, an intermediate filament protein in astrocytes. GFAP-A typically presents as middle-age-onset subacute meningoencephalitis or meningoencephalomyelitis; however, we present a childhood-onset case of meningomyelitis with persistent fever and malaise.</div></div><div><h3>Case presentation</h3><div>A fourteen-year-old girl presented with persistent high-grade fever, head and body aches, nausea, neck rigidity, weakness in the extremities, and dysuria. An initial diagnosis of aseptic meningitis was made based on increased cells and proteins in her spinal fluid; however, fever and malaise persisted, and no pathogenic antigens or antibodies could be detected. Subsequently, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) showed extensive longitudinal FDG accumulation along the spinal cord. Ophthalmological examination revealed papilledema. Magnetic resonance imaging of the brain and spine revealed no abnormalities. Based on a suspicion of autoimmune meningomyelitis, we started immunotherapy on day 27. Intravenous methylprednisolone, followed by prednisolone administration relieved the fever and accompanying symptoms that had persisted for a month. A definitive diagnosis of GFAP-A was confirmed by detecting cerebrospinal fluid GFAP-immunoglobulin G in a cell-based assay. Prednisolone was tapered off, with no relapse or significant sequelae.</div></div><div><h3>Discussion/conclusion</h3><div>In children with persistent fever and neurological symptoms, autoimmune central nervous system disorders such as GFAP-A should be considered in the differential diagnosis; further, if infectious pathogens are excluded, immunotherapy should be initiated early. The clinical presentation of GFAP-A is diverse, including cases with no symptoms of encephalopathy. FDG-PET findings in the spinal cord can be a valuable diagnostic aid.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"3 1","pages":"Article 100056"},"PeriodicalIF":0.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hybrid Assistive Limb (HAL) is a movement support robot that assists the walking function of patients with diseases causing muscle weakness in the lower limbs.
Intrathecal baclofen (ITB) therapy exerts positive effects on muscle tone in children with severe spasticity who have difficulty walking.
The present case report describes a child with spastic paraplegia who underwent intensive robotic rehabilitation with HAL and combined ITB therapy.
Case
A 14-year-old boy with spastic paraplegia from Pelizaeus-Merzbacher disease was undergoing treatment with oral muscle relaxants and botulinum toxin A. However, the medications were ineffective and his spasticity was progressing. A baclofen infusion pump was implanted with the catheter tip at the T10 level and ITB therapy was started. A regimen of 12.5 μg/day dose of baclofen was administered and his spasticity of limbs and trunk were attenuated. Walking practice using HAL was performed under spasticity relief by ITB therapy and gait function and patterns, excluding endurance, were improved. The attenuation of spasticity by ITB therapy made “Lying, Rolling and Sitting” easier for the patient, but may have affected “Standing”, which was supported using spasticity, and also affected the Caregiver Assistance Scale of the Mobility domain of the Pediatric Evaluation of Disability Inventory (PEDI). While, the amount of assistance required for the Activities of Daily Living (ADLs) related to self-care and the overall caregiver burden both decreased.
Conclusion
This is the first case report to demonstrate the efficacy and safety of combined ITB therapy and HAL rehabilitation in an ambulatory pediatric patient.
{"title":"Efficacy of combined treatment with a wearable cyborg hybrid assistive limb and intrathecal baclofen therapy in a pediatric patient with spastic paraplegia","authors":"Tomoyuki Masuda , Ryota Nishikawa , Takenori Natsume , Masahisa Komatsu , Motomu Maruyama , Sayaka Sato , Saki Otao , Masaru Nasuno , Shihoko Takeuchi , Maki Shirai , Mitsuo Motobayashi , Yuka Misawa , Yosuke Miyairi , Yuji Inaba","doi":"10.1016/j.bdcasr.2024.100053","DOIUrl":"10.1016/j.bdcasr.2024.100053","url":null,"abstract":"<div><h3>Background</h3><div>Hybrid Assistive Limb (HAL) is a movement support robot that assists the walking function of patients with diseases causing muscle weakness in the lower limbs.</div><div>Intrathecal baclofen (ITB) therapy exerts positive effects on muscle tone in children with severe spasticity who have difficulty walking.</div><div>The present case report describes a child with spastic paraplegia who underwent intensive robotic rehabilitation with HAL and combined ITB therapy.</div></div><div><h3>Case</h3><div>A 14-year-old boy with spastic paraplegia from Pelizaeus-Merzbacher disease was undergoing treatment with oral muscle relaxants and botulinum toxin A. However, the medications were ineffective and his spasticity was progressing. A baclofen infusion pump was implanted with the catheter tip at the T10 level and ITB therapy was started. A regimen of 12.5 μg/day dose of baclofen was administered and his spasticity of limbs and trunk were attenuated. Walking practice using HAL was performed under spasticity relief by ITB therapy and gait function and patterns, excluding endurance, were improved. The attenuation of spasticity by ITB therapy made “Lying, Rolling and Sitting” easier for the patient, but may have affected “Standing”, which was supported using spasticity, and also affected the Caregiver Assistance Scale of the Mobility domain of the Pediatric Evaluation of Disability Inventory (PEDI). While, the amount of assistance required for the Activities of Daily Living (ADLs) related to self-care and the overall caregiver burden both decreased.</div></div><div><h3>Conclusion</h3><div>This is the first case report to demonstrate the efficacy and safety of combined ITB therapy and HAL rehabilitation in an ambulatory pediatric patient.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"2 4","pages":"Article 100053"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142744319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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