Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) commonly presents with febrile seizure overlap and clusters of seizures several days later; however, information on the localization of seizure foci is scarce.
Case presentation
We present the case of a 6-year-old child who initially presented with seizures of the right upper and lower extremities as early seizures, but later, the focus of her seizure clusters shifted to the left upper extremity as late seizures. Arterial spin labeling (ASL) findings in the right cerebral hemisphere changed accordingly, but blood flow in the left frontal lobe was consistently enhanced, suggesting the presence of additional pathology.
Conclusion
This case expands our understanding of evolving seizure patterns in AESD and highlights the potential of ASL to elucidate its complex pathophysiology.
{"title":"AESD due to COVID-19 with shifting seizure focus laterality between early and late seizure, accompanied by characteristic blood flow signal changes on MRI","authors":"Kei Morota , Ryo Sugitate , Natsuki Yagi , Atsushi Matsui , Tomomi Ogata , Kazuhiro Muramatsu","doi":"10.1016/j.bdcasr.2024.100029","DOIUrl":"https://doi.org/10.1016/j.bdcasr.2024.100029","url":null,"abstract":"<div><h3>Background</h3><p>Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) commonly presents with febrile seizure overlap and clusters of seizures several days later; however, information on the localization of seizure foci is scarce.</p></div><div><h3>Case presentation</h3><p>We present the case of a 6-year-old child who initially presented with seizures of the right upper and lower extremities as early seizures, but later, the focus of her seizure clusters shifted to the left upper extremity as late seizures. Arterial spin labeling (ASL) findings in the right cerebral hemisphere changed accordingly, but blood flow in the left frontal lobe was consistently enhanced, suggesting the presence of additional pathology.</p></div><div><h3>Conclusion</h3><p>This case expands our understanding of evolving seizure patterns in AESD and highlights the potential of ASL to elucidate its complex pathophysiology.</p></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950221724000254/pdfft?md5=c801c4d9be98994ab828eac68b8070c0&pid=1-s2.0-S2950221724000254-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141487026","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 : 2024-06-26DOI: 10.1016/j.bdcasr.2024.100028
Joana Sa de Almeida , Joel Fluss , Méryle Laurent , Lina Quteineh , Christian Korff , Stéphanie Garcia-Tarodo
Introduction
SCN2A mutations have been associated with a wide phenotypic spectrum that includes, among others, developmental and epileptic encephalopathy (DEE), usually not associated with any brain structural counterpart.
Case description
We report the occurrence of a super-refractory status epilepticus (SRSE) in a 2-month-old infant, who presented at birth with refractory neonatal seizures attributed to an extensive bilateral polymicrogyria and cortical dysplasia. Upon his SRSE, he responded radically to the sodium-channel blocker phenytoin with complete seizure resolution and has remained seizure free during the 2-year follow-up period. A SCN2A pathogenic variant was found with predicted gain-of-function effect. Notably, brain MRI findings during the neonatal ictal phase showed signs of hypoxia with cytotoxic and vasogenic oedema, corresponding to the ictal localisation. These changes were not observed upon repetition of the brain MRI during the SRSE at 2 months of age, perhaps suggesting increased neonatal vulnerability to hypoxia in the presence of an SCN2A variant, that modifies over time.
Conclusion
Our case report highlights the importance of challenging our clinical management in the presence of refractory seizures attributed solely to a structural cause, with genetic testing providing a key insight for therapeutic management.
{"title":"SCN2A developmental and epileptic encephalopathy in an infant with bilateral polymicrogyria and opercular dysplasia","authors":"Joana Sa de Almeida , Joel Fluss , Méryle Laurent , Lina Quteineh , Christian Korff , Stéphanie Garcia-Tarodo","doi":"10.1016/j.bdcasr.2024.100028","DOIUrl":"https://doi.org/10.1016/j.bdcasr.2024.100028","url":null,"abstract":"<div><h3>Introduction</h3><p><em>SCN2A</em> mutations have been associated with a wide phenotypic spectrum that includes, among others, developmental and epileptic encephalopathy (DEE), usually not associated with any brain structural counterpart.</p></div><div><h3>Case description</h3><p>We report the occurrence of a super-refractory status epilepticus (SRSE) in a 2-month-old infant, who presented at birth with refractory neonatal seizures attributed to an extensive bilateral polymicrogyria and cortical dysplasia. Upon his SRSE, he responded radically to the sodium-channel blocker phenytoin with complete seizure resolution and has remained seizure free during the 2-year follow-up period. A <em>SCN2A</em> pathogenic variant was found with predicted gain-of-function effect. Notably, brain MRI findings during the neonatal ictal phase showed signs of hypoxia with cytotoxic and vasogenic oedema, corresponding to the ictal localisation. These changes were not observed upon repetition of the brain MRI during the SRSE at 2 months of age, perhaps suggesting increased neonatal vulnerability to hypoxia in the presence of an <em>SCN2A</em> variant, that modifies over time.</p></div><div><h3>Conclusion</h3><p>Our case report highlights the importance of challenging our clinical management in the presence of refractory seizures attributed solely to a structural cause, with genetic testing providing a key insight for therapeutic management.</p></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950221724000242/pdfft?md5=acd6b0f0752adfd6fc446be128364292&pid=1-s2.0-S2950221724000242-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141486917","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 : 2024-06-21DOI: 10.1016/j.bdcasr.2024.100027
Ken Nakano , Shingo Numoto , Akihisa Okumura , Kazuhiro Hirata , Sachie Kaneko , Yoichiro Oro
Background
Dextromethorphan (DXM) is a commonly used anti-tussive drug. DXM overdose can elicit neurobehavioral effects, such as hallucinations, stimulation, euphoria, and dissociation, and rarely cause seizures or coma.
Case report
A 14-year-old Japanese female was referred to the emergency department of our hospital in a coma following a seizure. She had no history of epilepsy or psychiatric diseases. Initially, the underlying causes of the coma and seizures were unclear. However, several used DXM packages were found in her school bag, and an overdose was suspected. The patient was diagnosed with DXM overdose. The neurobehavioral symptoms resolved without specific treatments. DXM concentrations in the blood and cerebrospinal fluid were 830 and 320 ng/mL, respectively.
Conclusion
The possibility of DXM overdose should be considered in patients admitted with seizures or comas of unknown cause.
{"title":"Seizure and coma with overdose dextromethorphan: A case report","authors":"Ken Nakano , Shingo Numoto , Akihisa Okumura , Kazuhiro Hirata , Sachie Kaneko , Yoichiro Oro","doi":"10.1016/j.bdcasr.2024.100027","DOIUrl":"https://doi.org/10.1016/j.bdcasr.2024.100027","url":null,"abstract":"<div><h3>Background</h3><p>Dextromethorphan (DXM) is a commonly used anti-tussive drug. DXM overdose can elicit neurobehavioral effects, such as hallucinations, stimulation, euphoria, and dissociation, and rarely cause seizures or coma.</p></div><div><h3>Case report</h3><p>A 14-year-old Japanese female was referred to the emergency department of our hospital in a coma following a seizure. She had no history of epilepsy or psychiatric diseases. Initially, the underlying causes of the coma and seizures were unclear. However, several used DXM packages were found in her school bag, and an overdose was suspected. The patient was diagnosed with DXM overdose. The neurobehavioral symptoms resolved without specific treatments. DXM concentrations in the blood and cerebrospinal fluid were 830 and 320 ng/mL, respectively.</p></div><div><h3>Conclusion</h3><p>The possibility of DXM overdose should be considered in patients admitted with seizures or comas of unknown cause.</p></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950221724000230/pdfft?md5=d2dced702be2380a3684a5efc01d3218&pid=1-s2.0-S2950221724000230-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141439165","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 : 2024-06-21DOI: 10.1016/j.bdcasr.2024.100026
Sarah Cellauro , Christian Korff , Maria Brunella Cipullo , Maria Isabel Vargas , Angelo Polito , Tiphaine Corbisier
Background
Spinal cord ischemia (SCI) is a rare but often devastating vascular disorder that may be caused by one of several etiologies and may be challenging to diagnose.
Case presentation
The patient exhibited alarming symptoms, including profound fatigue, altered consciousness, and hypercapnia, necessitating intubation. Notably, urinary retention was present, and initial investigations, including a normal brain computed tomography (CT) scan and lumbar puncture, failed to elucidate the underlying issue. Subsequent spinal magnetic resonance imaging (MRI) revealed a cervical spinal cord T2 hyperintensity, accompanied by signal restriction on diffusion-weighted sequences (DWI), leading to the diagnosis of SCI. Following this, the patient developed left hemiplegia. However, the clinical presentation exhibited a swift improvement, and complete resolution occurred within a week under the administration of intravenous steroids.
Discussion/conclusion
This case underscores the diagnostic challenge posed by SCI, particularly in the pediatric population. The swift response to intravenous steroids suggests a potential inflammatory component, implicating vasospasm or a minor spinal artery lesion. The suspected connection to prior microtrauma to the cervical spine during physical activity highlights the importance of considering vascular complications in the context of sports-related injuries. This report contributes to the understanding of SCI in children and emphasizes the need for heightened awareness among healthcare professionals when encountering similar clinical scenarios.
{"title":"Spinal cord ischemia revealed in the context of altered consciousness: A pediatric case report","authors":"Sarah Cellauro , Christian Korff , Maria Brunella Cipullo , Maria Isabel Vargas , Angelo Polito , Tiphaine Corbisier","doi":"10.1016/j.bdcasr.2024.100026","DOIUrl":"https://doi.org/10.1016/j.bdcasr.2024.100026","url":null,"abstract":"<div><h3>Background</h3><p>Spinal cord ischemia (SCI) is a rare but often devastating vascular disorder that may be caused by one of several etiologies and may be challenging to diagnose.</p></div><div><h3>Case presentation</h3><p>The patient exhibited alarming symptoms, including profound fatigue, altered consciousness, and hypercapnia, necessitating intubation. Notably, urinary retention was present, and initial investigations, including a normal brain computed tomography (CT) scan and lumbar puncture, failed to elucidate the underlying issue. Subsequent spinal magnetic resonance imaging (MRI) revealed a cervical spinal cord T2 hyperintensity, accompanied by signal restriction on diffusion-weighted sequences (DWI), leading to the diagnosis of SCI. Following this, the patient developed left hemiplegia. However, the clinical presentation exhibited a swift improvement, and complete resolution occurred within a week under the administration of intravenous steroids.</p></div><div><h3>Discussion/conclusion</h3><p>This case underscores the diagnostic challenge posed by SCI, particularly in the pediatric population. The swift response to intravenous steroids suggests a potential inflammatory component, implicating vasospasm or a minor spinal artery lesion. The suspected connection to prior microtrauma to the cervical spine during physical activity highlights the importance of considering vascular complications in the context of sports-related injuries. This report contributes to the understanding of SCI in children and emphasizes the need for heightened awareness among healthcare professionals when encountering similar clinical scenarios.</p></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950221724000229/pdfft?md5=b6b1044a0a5c3804f4451493534d9fce&pid=1-s2.0-S2950221724000229-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141439164","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 : 2024-06-20DOI: 10.1016/j.bdcasr.2024.100025
Takuya Hiraide , Wakako Yoshioka , Yusuke Ito , Rei Urushibata , Taiju Hayashi , Hidetoshi Ishigaki , Ichizo Nishino , Tokiko Fukuda
Background
RYR1 (ryanodine receptor 1), which functions as a calcium release channel in the sarcoplasmic reticulum and is associated with the susceptibility to malignant hyperthermia and several myopathies. Serum creatine kinase (CK) levels are important for the diagnosis of patients with neuromuscular diseases; however, CK levels can be elevated even in individuals without obvious clinical symptoms. Recently, RYR1 was reported as one of the genes responsible for asymptomatic or paucisymptomatic hyperCKemia.
Case presentation
Here, we report the case of a family with autosomal dominant hyperCKemia. The fraternal twin sisters complained of exertional myalgia after exercise, such as playing basketball, without evidence of muscle weakness or fatigue. Serum CK levels of the twin sister patients ranged from 642 U/L to 5620 U/L and from 411 U/L to 2609 U/L, respectively. The mother had hyperCKemia (523 U/L) without any neuromuscular symptoms. Muscle biopsy from one of the twin sisters showed no necrotic fibers, several regenerating fibers, and several fibers with internal nuclei. Exome sequencing of the same patient identified a novel, possibly pathogenic variant (NM_000540.3:c.682G>A, p.Glu228Lys) in RYR1. This variant was also detected by Sanger sequencing in another sister and mother with hyperCKemia.
Conclusions
Patients with possible pathogenic variants in RYR1 are at risk for malignant hyperthermia susceptibility and rhabdomyolysis. Genetic analyses, including RYR1 for cases with asymptomatic or paucisymptomatic hyperCKemia may be useful in identifying individuals at potential risk of malignant hyperthermia susceptibility and rhabdomyolysis.
{"title":"Familial hyperCKemia with exercise-induced myalgia associated with a novel missense variant in RYR1","authors":"Takuya Hiraide , Wakako Yoshioka , Yusuke Ito , Rei Urushibata , Taiju Hayashi , Hidetoshi Ishigaki , Ichizo Nishino , Tokiko Fukuda","doi":"10.1016/j.bdcasr.2024.100025","DOIUrl":"https://doi.org/10.1016/j.bdcasr.2024.100025","url":null,"abstract":"<div><h3>Background</h3><p><em>RYR1</em> (ryanodine receptor 1), which functions as a calcium release channel in the sarcoplasmic reticulum and is associated with the susceptibility to malignant hyperthermia and several myopathies. Serum creatine kinase (CK) levels are important for the diagnosis of patients with neuromuscular diseases; however, CK levels can be elevated even in individuals without obvious clinical symptoms. Recently, <em>RYR1</em> was reported as one of the genes responsible for asymptomatic or paucisymptomatic hyperCKemia.</p></div><div><h3>Case presentation</h3><p>Here, we report the case of a family with autosomal dominant hyperCKemia. The fraternal twin sisters complained of exertional myalgia after exercise, such as playing basketball, without evidence of muscle weakness or fatigue. Serum CK levels of the twin sister patients ranged from 642 U/L to 5620 U/L and from 411 U/L to 2609 U/L, respectively. The mother had hyperCKemia (523 U/L) without any neuromuscular symptoms. Muscle biopsy from one of the twin sisters showed no necrotic fibers, several regenerating fibers, and several fibers with internal nuclei. Exome sequencing of the same patient identified a novel, possibly pathogenic variant (NM_000540.3:c.682G>A, p.Glu228Lys) in <em>RYR1</em>. This variant was also detected by Sanger sequencing in another sister and mother with hyperCKemia.</p></div><div><h3>Conclusions</h3><p>Patients with possible pathogenic variants in <em>RYR1</em> are at risk for malignant hyperthermia susceptibility and rhabdomyolysis. Genetic analyses, including <em>RYR1</em> for cases with asymptomatic or paucisymptomatic hyperCKemia may be useful in identifying individuals at potential risk of malignant hyperthermia susceptibility and rhabdomyolysis.</p></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950221724000217/pdfft?md5=8c96035ab24b1d7f7975017d880a5cb8&pid=1-s2.0-S2950221724000217-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141434373","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}
Severe cases due to acute encephalopathy in patients with coronavirus disease 2019 (COVID-19) have been reported. Among acute encephalopathies, the cytokine storm type has a poor prognosis and no established treatment. Here, we describe two cases of COVID-19-related hemorrhagic shock and encephalopathy syndrome (HSES) with different outcomes.
Case presentation
Case 1 was a 2-year-11-month-old girl with no medical history. She developed a fever on the first day of the illness and was admitted to our pediatric intensive care unit (PICU) on day two due to status epilepticus. She had refractory shock from arrival, and was diagnosed with HSES. On day three, both pupils were dilated. A brain computed tomography (CT) scan showed diffuse cerebral edema. The electroencephalogram showed electrocerebral inactivity; brainstem reflexes were not observed. The patient died on day 13. Case 2 was a 6-year-old boy with a history of febrile seizures. He developed a fever on the first day of the illness and was admitted to our PICU on day three due to status epilepticus. A brain CT on admission showed cerebral edema. He developed hypotensive shock after admission, and was diagnosed with HSES. He received multidisciplinary treatment, and was extubated on day eight. The patient was diagnosed with HSES and received multidisciplinary treatment. The patient recovered and was extubated on day eight. He was discharged on day 17. Case 2 had a shorter duration of hypotension, temperature management at a lower temperature, and more aggressive anti-seizure medication use.
Conclusion
Circulatory stabilization is essential for hypothermia therapy and aggressive anti-seizure medication use, and important in terms of maintaining cerebral circulation. Therefore, early recovery from shock appeared to be the most crucial factor affecting the outcomes of both cases.
{"title":"Two cases of COVID-19-related hemorrhagic shock and encephalopathy syndrome with different outcomes","authors":"Keiichiro Toma , Kazunori Aoki , Hiroshi Kurosawa , Masahiro Nishiyama , Azusa Maruyama","doi":"10.1016/j.bdcasr.2024.100024","DOIUrl":"https://doi.org/10.1016/j.bdcasr.2024.100024","url":null,"abstract":"<div><h3>Background</h3><p>Severe cases due to acute encephalopathy in patients with coronavirus disease 2019 (COVID-19) have been reported. Among acute encephalopathies, the cytokine storm type has a poor prognosis and no established treatment. Here, we describe two cases of COVID-19-related hemorrhagic shock and encephalopathy syndrome (HSES) with different outcomes.</p></div><div><h3>Case presentation</h3><p>Case 1 was a 2-year-11-month-old girl with no medical history. She developed a fever on the first day of the illness and was admitted to our pediatric intensive care unit (PICU) on day two due to status epilepticus. She had refractory shock from arrival, and was diagnosed with HSES. On day three, both pupils were dilated. A brain computed tomography (CT) scan showed diffuse cerebral edema. The electroencephalogram showed electrocerebral inactivity; brainstem reflexes were not observed. The patient died on day 13. Case 2 was a 6-year-old boy with a history of febrile seizures. He developed a fever on the first day of the illness and was admitted to our PICU on day three due to status epilepticus. A brain CT on admission showed cerebral edema. He developed hypotensive shock after admission, and was diagnosed with HSES. He received multidisciplinary treatment, and was extubated on day eight. The patient was diagnosed with HSES and received multidisciplinary treatment. The patient recovered and was extubated on day eight. He was discharged on day 17. Case 2 had a shorter duration of hypotension, temperature management at a lower temperature, and more aggressive anti-seizure medication use.</p></div><div><h3>Conclusion</h3><p>Circulatory stabilization is essential for hypothermia therapy and aggressive anti-seizure medication use, and important in terms of maintaining cerebral circulation. Therefore, early recovery from shock appeared to be the most crucial factor affecting the outcomes of both cases.</p></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950221724000205/pdfft?md5=a922ff5de39808d41693d7f07094363d&pid=1-s2.0-S2950221724000205-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141324283","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}
Onasemnogene abeparvovec (OA) is an adeno-associated viral type 9 (AAV9) vector-based gene replacement therapy for infants with spinal muscular atrophy (SMA) if they are negative for anti-AAV9 antibodies. However, serious adverse events were reported after OA treatment.
Case presentation
A 2-month-old infant received a diagnosis of SMA type I because of progressive weakness and the result of genetic screening. The detectable anti-AAV9 antibody titers prompted us to start risdiplam immediately as the first-line treatment. OA was administered 7 months after birth when the titers declined to be negative. Fever and slightly elevated levels of transaminases were found one week after OA and improved spontaneously. Two months after OA, acute liver failure developed in association with respiratory syncytial virus infection. Intensive care with steroid therapy rescued this patient from life-threatening hepatopathy.
Discussion/conclusion
The anti-AAV9 antibody delayed OA in the early diagnosed case of SMA. The literature review found that all cases of liver failure occurred within the first 2 months of OA. Hepatopathy needs to be controlled in SMA cases with OA because of the potential factors to augment liver damage during infection.
背景Onasemnogene abeparvovec（OA）是一种基于腺相关病毒9型（AAV9）载体的基因替代疗法，适用于抗AAV9抗体阴性的脊髓性肌萎缩症（SMA）婴儿。病例介绍 一名 2 个月大的婴儿因进行性乏力和基因筛查结果被诊断为 SMA I 型。可检测到的抗 AAV9 抗体滴度促使我们立即开始利血平作为一线治疗。出生 7 个月后，当滴度下降至阴性时，我们开始使用 OA。OA 一周后发现发热和转氨酶水平轻微升高，并自行好转。OA 两个月后，由于呼吸道合胞病毒感染，出现了急性肝功能衰竭。讨论/结论抗 AAV9 抗体延迟了早期确诊 SMA 病例的 OA。文献综述发现，所有肝功能衰竭病例都发生在 OA 的最初 2 个月内。由于感染过程中存在加重肝损伤的潜在因素，因此需要对患有 OA 的 SMA 病例进行肝病控制。
{"title":"Acute liver failure worsened after respiratory syncytial virus infection in an infant with spinal muscular atrophy type I after receiving onasemnogene abeparvovec","authors":"Shohei Sakemi , Takako Fujita , Noriyuki Kaku , Shuichi Yatsuga , Kazutoshi Ito , Daiki Sasaoka , Hiromi Yamaguchi , Hitomi Hayashi , Takahito Inoue , Kanako Higashi , Yasunari Sakai , Shouichi Ohga , Shinichiro Nagamitsu","doi":"10.1016/j.bdcasr.2024.100022","DOIUrl":"https://doi.org/10.1016/j.bdcasr.2024.100022","url":null,"abstract":"<div><h3>Background</h3><p>Onasemnogene abeparvovec (OA) is an adeno-associated viral type 9 (AAV9) vector-based gene replacement therapy for infants with spinal muscular atrophy (SMA) if they are negative for anti-AAV9 antibodies. However, serious adverse events were reported after OA treatment.</p></div><div><h3>Case presentation</h3><p>A 2-month-old infant received a diagnosis of SMA type I because of progressive weakness and the result of genetic screening. The detectable anti-AAV9 antibody titers prompted us to start risdiplam immediately as the first-line treatment. OA was administered 7 months after birth when the titers declined to be negative. Fever and slightly elevated levels of transaminases were found one week after OA and improved spontaneously. Two months after OA, acute liver failure developed in association with respiratory syncytial virus infection. Intensive care with steroid therapy rescued this patient from life-threatening hepatopathy.</p></div><div><h3>Discussion/conclusion</h3><p>The anti-AAV9 antibody delayed OA in the early diagnosed case of SMA. The literature review found that all cases of liver failure occurred within the first 2 months of OA. Hepatopathy needs to be controlled in SMA cases with OA because of the potential factors to augment liver damage during infection.</p></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950221724000187/pdfft?md5=dafb38857909854437e404a8c24cb7f8&pid=1-s2.0-S2950221724000187-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141286065","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}
CDK13 (OMIM 603309), a cyclin-dependent kinase, phosphorylates RNA polymerase II and plays a role in various biological processes, including transcriptional regulation, alternative mRNA splicing, and axonal elongation. Patients with CDK13-related disorder present with facial abnormalities; hypotonia; congenital cardiac, renal, and skeletal abnormalities; and psychoneurological manifestations, including developmental delays, intellectual disabilities, and epilepsy.
Case presentation
We present the case of a 7-year-old female patient with CDK13-related disorder. The patient had peculiar facial features, such as microcephaly, hypertelorism, broad nasal root and alar, frontal hypertrichosis, small jaw and low auricle, and atrial septal defect. Additionally, she presented with hypotonia and developmental delays. Her developmental delay was remarkable with her age and her total developmental quotient on the Kyoto Scale of Psychological Development 2020 was 38 (postural-motor, 40; cognitive-adaptive, 41; and language-social, 34) at 7 years and 8 months of age. Her cognitive development was progressing slowly at her own pace, with support from social interactions, physiotherapy, and occupational therapy. Moreover, facial dysmorphism, developmental delays, and intellectual disabilities were highly frequent even among the 15 patients with the CDK13 c.2149G>A (p.Gly717Arg) variant through the literature review.
Conclusion
Patients with CDK13-related disorder typically exhibit facial dysmorphism, developmental delays, and intellectual disabilities, with the possibility of additional manifestations emerging in adulthood. This patient also presented the same manifestations as those of other patients with CDK13-related disorder. Clinical outcomes should be followed up for a long duration in this patient, as various clinical manifestations and problems may be expected.
{"title":"A pathogenic missense variant, c.2149G>A (p.Gly717Arg), in CDK13 in a female patient with CDK13-related disorder: A case report and literature review of 112 cases","authors":"Naoki Morooka , Jun Kido , Hiroe Ueno , Yohei Misumi , Keishin Sugawara , Shinichi Kameyama , Hiromi Fukuda , Takeshi Mizuguchi , Naomichi Matsumoto , Mitsuharu Ueda , Kimitoshi Nakamura","doi":"10.1016/j.bdcasr.2024.100023","DOIUrl":"https://doi.org/10.1016/j.bdcasr.2024.100023","url":null,"abstract":"<div><h3>Background</h3><p>CDK13 (OMIM 603309), a cyclin-dependent kinase, phosphorylates RNA polymerase II and plays a role in various biological processes, including transcriptional regulation, alternative mRNA splicing, and axonal elongation. Patients with <em>CDK13</em>-related disorder present with facial abnormalities; hypotonia; congenital cardiac, renal, and skeletal abnormalities; and psychoneurological manifestations, including developmental delays, intellectual disabilities, and epilepsy.</p></div><div><h3>Case presentation</h3><p>We present the case of a 7-year-old female patient with <em>CDK13</em>-related disorder. The patient had peculiar facial features, such as microcephaly, hypertelorism, broad nasal root and alar, frontal hypertrichosis, small jaw and low auricle, and atrial septal defect. Additionally, she presented with hypotonia and developmental delays. Her developmental delay was remarkable with her age and her total developmental quotient on the Kyoto Scale of Psychological Development 2020 was 38 (postural-motor, 40; cognitive-adaptive, 41; and language-social, 34) at 7 years and 8 months of age. Her cognitive development was progressing slowly at her own pace, with support from social interactions, physiotherapy, and occupational therapy. Moreover, facial dysmorphism, developmental delays, and intellectual disabilities were highly frequent even among the 15 patients with the <em>CDK13</em> c.2149G>A (p.Gly717Arg) variant through the literature review.</p></div><div><h3>Conclusion</h3><p>Patients with <em>CDK13</em>-related disorder typically exhibit facial dysmorphism, developmental delays, and intellectual disabilities, with the possibility of additional manifestations emerging in adulthood. This patient also presented the same manifestations as those of other patients with <em>CDK13</em>-related disorder. Clinical outcomes should be followed up for a long duration in this patient, as various clinical manifestations and problems may be expected.</p></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950221724000199/pdfft?md5=f83902fc7947eadd772be7a044d2e166&pid=1-s2.0-S2950221724000199-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141286066","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}
Pathogenic variants of ectodysplasin A (EDA) gene are responsible for the development of hypohidrotic ectodermal dysplasia (HED) and energy dysmetabolism. Patients with HED develop hyperthermia and dry skin owing to hypohidrosis. Influenza-associated encephalopathy (IAE) is characterized by developing impaired consciousness within a few days after influenza infection.
Case presentation
A 4-year-old boy with HED demonstrated IAE. He experienced frequent episodes of fever and exhibited typical HED features such as sparse hair, hypohidrosis, and dry skin. He was diagnosed with IAE at the age of 19 months and showed severe psychomotor impairment after this diagnosis.
Discussion
Cytokine storm, status epilepticus, and significant hyperthermia deriving from HED during influenza virus infection were determined to have contributed to the development of IAE resulting in defective energy metabolism and neuronal damage.
Conclusion
Cytokine storm and significant hyperthermia during the influenza virus infection might cause the development of IAE and enhance catabolism. Thermal control is essential for HED management. Therefore, controlling body temperature during the infectious viral state is essential.
{"title":"Hypohidrotic ectodermal dysplasia with influenza-associated encephalopathy: A case report","authors":"Takanobu Yoshida , Jun Kido , Mika Ogata , Tomoyuki Mizukami , Katsuki Hirai , Yohei Misumi , Toshiyuki Itai , Satoko Miyatake , Naomichi Matsumoto , Mitsuharu Ueda , Kimitoshi Nakamura","doi":"10.1016/j.bdcasr.2024.100018","DOIUrl":"https://doi.org/10.1016/j.bdcasr.2024.100018","url":null,"abstract":"<div><h3>Background</h3><p>Pathogenic variants of ectodysplasin A (<em>EDA</em>) gene are responsible for the development of hypohidrotic ectodermal dysplasia (HED) and energy dysmetabolism. Patients with HED develop hyperthermia and dry skin owing to hypohidrosis. Influenza-associated encephalopathy (IAE) is characterized by developing impaired consciousness within a few days after influenza infection.</p></div><div><h3>Case presentation</h3><p>A 4-year-old boy with HED demonstrated IAE. He experienced frequent episodes of fever and exhibited typical HED features such as sparse hair, hypohidrosis, and dry skin. He was diagnosed with IAE at the age of 19 months and showed severe psychomotor impairment after this diagnosis.</p></div><div><h3>Discussion</h3><p>Cytokine storm, status epilepticus, and significant hyperthermia deriving from HED during influenza virus infection were determined to have contributed to the development of IAE resulting in defective energy metabolism and neuronal damage.</p></div><div><h3>Conclusion</h3><p>Cytokine storm and significant hyperthermia during the influenza virus infection might cause the development of IAE and enhance catabolism. Thermal control is essential for HED management. Therefore, controlling body temperature during the infectious viral state is essential.</p></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S295022172400014X/pdfft?md5=cfc0494486e21284118c5ff06465c294&pid=1-s2.0-S295022172400014X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141239113","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 : 2024-05-25DOI: 10.1016/j.bdcasr.2024.100021
Beena Devanapalli , Rachel Sze Hui Wong , Natalie Lim , P Ian Andrews , Keshini Vijayan , Won-Tae Kim , Tiffany Wotton , Esther Tantsis , Enzo Ranieri , Adviye Ayper Tolun , Shanti Balasubramaniam
Background
Biotinidase (E.C. 3.5.1.12) is an enzyme which recycles biotin, a coenzyme of four carboxylases involved in fatty acid synthesis, amino acid catabolism and gluconeogenesis. Biotinidase deficiency (OMIM #253260) causes a reduction in free biotin leading to multiple carboxylase deficiency. In its severe form, children may have seizures, delayed development, respiratory issues, cutaneous manifestations, hearing and visual loss. The milder phenotype may manifest symptoms only when stressed, such as during infections.
Case presentation
We describe two infants who presented aged two and five months respectively, with generalised seizures, mild gross motor delay, elevated plasma and cerebrospinal fluid lactate levels. Moderate increases in propionylcarnitine and 3-hydroxyisovalerylcarnitine on plasma acylcarnitine profile suggested multiple carboxylase deficiency. Further testing confirmed biotinidase deficiency. Retrospective qualitative analysis of the newborn screening dried blood spot cards in both patients showed reduced biotinidase enzyme activity. Molecular analysis confirmed pathogenic homozygous variants in the BTD gene. They were commenced on oral biotin with no further seizures observed in either patient. Patient 1 also made significant developmental gains and achieved age-appropriate milestones by 12 months. At five years of age, he has receptive and expressive language delays.
Discussion/conclusion
Early identification and treatment of biotinidase deficiency can prevent lifelong complications and major disabilities, hence should be considered as an important differential of seizures and neurodevelopmental delay. Currently, biotinidase deficiency is not one of the conditions screened for in newborns in Australia, however with the evolving demographics due to robust immigration, the New South Wales Newborn Screening Program has reconsidered its inclusion in our screening program.
{"title":"Biotinidase deficiency: A treatable neurometabolic disorder","authors":"Beena Devanapalli , Rachel Sze Hui Wong , Natalie Lim , P Ian Andrews , Keshini Vijayan , Won-Tae Kim , Tiffany Wotton , Esther Tantsis , Enzo Ranieri , Adviye Ayper Tolun , Shanti Balasubramaniam","doi":"10.1016/j.bdcasr.2024.100021","DOIUrl":"https://doi.org/10.1016/j.bdcasr.2024.100021","url":null,"abstract":"<div><h3>Background</h3><p>Biotinidase (E.C. 3.5.1.12) is an enzyme which recycles biotin, a coenzyme of four carboxylases involved in fatty acid synthesis, amino acid catabolism and gluconeogenesis. Biotinidase deficiency (OMIM #253260) causes a reduction in free biotin leading to multiple carboxylase deficiency. In its severe form, children may have seizures, delayed development, respiratory issues, cutaneous manifestations, hearing and visual loss. The milder phenotype may manifest symptoms only when stressed, such as during infections.</p></div><div><h3>Case presentation</h3><p>We describe two infants who presented aged two and five months respectively, with generalised seizures, mild gross motor delay, elevated plasma and cerebrospinal fluid lactate levels. Moderate increases in propionylcarnitine and 3-hydroxyisovalerylcarnitine on plasma acylcarnitine profile suggested multiple carboxylase deficiency. Further testing confirmed biotinidase deficiency. Retrospective qualitative analysis of the newborn screening dried blood spot cards in both patients showed reduced biotinidase enzyme activity. Molecular analysis confirmed pathogenic homozygous variants in the <em>BTD</em> gene. They were commenced on oral biotin with no further seizures observed in either patient. Patient 1 also made significant developmental gains and achieved age-appropriate milestones by 12 months. At five years of age, he has receptive and expressive language delays.</p></div><div><h3>Discussion/conclusion</h3><p>Early identification and treatment of biotinidase deficiency can prevent lifelong complications and major disabilities, hence should be considered as an important differential of seizures and neurodevelopmental delay. Currently, biotinidase deficiency is not one of the conditions screened for in newborns in Australia, however with the evolving demographics due to robust immigration, the New South Wales Newborn Screening Program has reconsidered its inclusion in our screening program.</p></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950221724000175/pdfft?md5=58c224d89a5b4114572707b538317641&pid=1-s2.0-S2950221724000175-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141097290","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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