Brain and Development Case Reports最新文献

{"title":"Two cases of COVID-19-related hemorrhagic shock and encephalopathy syndrome with different outcomes","authors":"Keiichiro Toma ,&nbsp;Kazunori Aoki ,&nbsp;Hiroshi Kurosawa ,&nbsp;Masahiro Nishiyama ,&nbsp;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":"2 3","pages":"Article 100024"},"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}

{"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 ,&nbsp;Takako Fujita ,&nbsp;Noriyuki Kaku ,&nbsp;Shuichi Yatsuga ,&nbsp;Kazutoshi Ito ,&nbsp;Daiki Sasaoka ,&nbsp;Hiromi Yamaguchi ,&nbsp;Hitomi Hayashi ,&nbsp;Takahito Inoue ,&nbsp;Kanako Higashi ,&nbsp;Yasunari Sakai ,&nbsp;Shouichi Ohga ,&nbsp;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":"2 3","pages":"Article 100022"},"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}

{"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 ,&nbsp;Jun Kido ,&nbsp;Hiroe Ueno ,&nbsp;Yohei Misumi ,&nbsp;Keishin Sugawara ,&nbsp;Shinichi Kameyama ,&nbsp;Hiromi Fukuda ,&nbsp;Takeshi Mizuguchi ,&nbsp;Naomichi Matsumoto ,&nbsp;Mitsuharu Ueda ,&nbsp;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&gt;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":"2 3","pages":"Article 100023"},"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}

{"title":"Hypohidrotic ectodermal dysplasia with influenza-associated encephalopathy: A case report","authors":"Takanobu Yoshida ,&nbsp;Jun Kido ,&nbsp;Mika Ogata ,&nbsp;Tomoyuki Mizukami ,&nbsp;Katsuki Hirai ,&nbsp;Yohei Misumi ,&nbsp;Toshiyuki Itai ,&nbsp;Satoko Miyatake ,&nbsp;Naomichi Matsumoto ,&nbsp;Mitsuharu Ueda ,&nbsp;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":"2 2","pages":"Article 100018"},"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}

{"title":"Biotinidase deficiency: A treatable neurometabolic disorder","authors":"Beena Devanapalli ,&nbsp;Rachel Sze Hui Wong ,&nbsp;Natalie Lim ,&nbsp;P Ian Andrews ,&nbsp;Keshini Vijayan ,&nbsp;Won-Tae Kim ,&nbsp;Tiffany Wotton ,&nbsp;Esther Tantsis ,&nbsp;Enzo Ranieri ,&nbsp;Adviye Ayper Tolun ,&nbsp;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":"2 2","pages":"Article 100021"},"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}

{"title":"Cerebrospinal fluid leakage after COVID-19: A pediatric case","authors":"Rika Tobiume ,&nbsp;Yukihiko Konishi ,&nbsp;Kosuke Koyano ,&nbsp;Shinji Nakamura ,&nbsp;Sae Nishisho ,&nbsp;Takayuki Wakabayashi ,&nbsp;Noriko Fuke ,&nbsp;Ami Mizuo ,&nbsp;Takuma Iwaki ,&nbsp;Takashi Kusaka","doi":"10.1016/j.bdcasr.2024.100019","DOIUrl":"https://doi.org/10.1016/j.bdcasr.2024.100019","url":null,"abstract":"<div><h3>Background</h3><p>Various neurological and psychiatric symptoms have emerged after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the virus that causes coronavirus disease 2019 (COVID-19). These symptoms include exercise intolerance such as muscle weakness, fatigue, and pain as well as cognitive and mood disorders (brain fog). Further, frequent autonomic disorders such as hypotension and hypothermia have been recognized in adults and children, many of whom have been diagnosed with orthostatic dysregulation (OD). Some children with OD have developed cerebrospinal fluid leakage (CFL).</p></div><div><h3>Case Presentation</h3><p>Herein, we describe the case of a boy aged 9 years and 9 months who presented with orthostatic headaches, dizziness, and nausea. He was diagnosed with CFL after SARS-CoV-2 infection when a spinal MRI revealed an incomplete floating dural sac sign in the thoracic and lumbar spine. An epidural saline injection was administered, and he was discharged after his symptoms improved.</p></div><div><h3>Discussion/Conclusion</h3><p>The causes of CFL include trauma due to accidents or sports, or are idiopathic due to unknown causes. However, the onset of CFL might involve COVID-19. Understanding the relationship between COVID-19 and CFL onset may lead to better treatment outcomes for children with apparent symptoms of OD, such as orthostatic headaches, dizziness, and nausea, after contracting COVID-19.</p></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"2 2","pages":"Article 100019"},"PeriodicalIF":0.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950221724000151/pdfft?md5=58c98bd702d075ba176b424a8dab2400&pid=1-s2.0-S2950221724000151-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077927","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}

{"title":"Dramatic benzodiazepine receptor downregulation observed in holoprosencephaly with drug-resistant epilepsy","authors":"Kousuke Nakamura ,&nbsp;Sayaka Ishii ,&nbsp;Kei Tamaru ,&nbsp;Takeshi Inukai ,&nbsp;Masao Aihara ,&nbsp;Yoshimi Kaga","doi":"10.1016/j.bdcasr.2024.100020","DOIUrl":"https://doi.org/10.1016/j.bdcasr.2024.100020","url":null,"abstract":"<div><h3>Background</h3><p>Holoprosencephaly (HPE), a central nervous system malformation caused by a defect in the separation of cerebral hemispheres during development, is associated with drug-resistant epilepsy. Animal studies on HPE have suggested its association with dysplasia of the inhibitory interneurons in the cerebral cortex; however, this association has not been reported in patients with HPE. In this study, we presented cases of three children with HPE who were examined for the distribution of benzodiazepine receptors, which are receptors of the inhibitory system, using ¹²³I-iomazenil single-photon emission computed tomography (SPECT).</p></div><div><h3>Case presentation</h3><p>All three children had drug-resistant epilepsy with frequent daily seizures. ^99mTc ethyl cysteinate dimer (ECD) SPECT and ¹²³I-iomazenil SPECT were performed to evaluate the epileptogenicity. ^99mTc ECD SPECT showed generalized only cerebral hypoperfusion, and ¹²³I-iomazenil SPECT showed widespread benzodiazepine receptor depression in the cerebrum, thalamus, and brainstem. Although, benzodiazepines, including clonazepam, clobazam, and lorazepam have limited effects on epileptic seizures, the addition of levetiracetam led to the reduction in seizure frequency in all three patients.</p></div><div><h3>Conclusion</h3><p>The SPECT findings in children with HPE suggested a defect in the development of GABAergic-benzodiazepinergic inhibitory neurons, especially in the thalamus and brainstem. Therefore, it is inferred that conventional antiepileptic drugs that potentiate the mechanisms of inhibitory neurons are less effective. Agents, with alternative mechanisms of action may be useful for the treatment of refractory epilepsy.</p></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"2 2","pages":"Article 100020"},"PeriodicalIF":0.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950221724000163/pdfft?md5=5a3443e732e6a17a1c88ae76703d0f91&pid=1-s2.0-S2950221724000163-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141072943","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}

{"title":"Progress in cardiorespiratory fitness and motor coordination skills in children with attention-deficit/hyperactivity disorder with easy fatigue and physical inactivity due to the side effects of guanfacine extended-release","authors":"Ken Kikuchi ,&nbsp;Midori Hayashi ,&nbsp;Manami Honda","doi":"10.1016/j.bdcasr.2024.100017","DOIUrl":"https://doi.org/10.1016/j.bdcasr.2024.100017","url":null,"abstract":"<div><h3>Introduction</h3><p>Guanfacine extended-release (GXR), a medication administered to treat attention-deficit/hyperactivity disorder (ADHD), demonstrates side effects, including hypotension, bradycardia, sedation, and somnolence. Children with ADHD with easy fatigue and physical inactivity caused by these side effects have been reported in clinical practice. ADHD medications improve motor function in the short term. Herein, we report the progress in cardiorespiratory fitness (CRF) and motor function of children with ADHD with easy fatigue and physical inactivity after GXR treatment.</p></div><div><h3>Case presentation</h3><p>A 7-year-old patient with ADHD began to demonstrate marked fatigue and physical inactivity after taking GXR. His treatment was then combined with physical therapy which was continued once a month for approximately one year and included a treadmill exercise test (10-minute walk with a multistep load protocol of 3.0–8.0 km/h) and instruction in motor coordination skills, including home exercises. The GXR dose was increased approximately every 9–10 months, considering the weight and increasing problems at home. Motor coordination skills improved immediately after the increased GXR dose, and the CRF progressed well as the effect of medication subsided.</p></div><div><h3>Discussion/Conclusion</h3><p>Fatigue and physical inactivity should be considered in exercise therapy in combination with GXR administration. Thus, combined exercise therapy and medication that considers CRF and skill acquisition status may be effective for children with ADHD.</p></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"2 2","pages":"Article 100017"},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950221724000138/pdfft?md5=eaad3f139612902633ffee0008507ab5&pid=1-s2.0-S2950221724000138-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140816744","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}

{"title":"ATP1A3 potentially causes hereditary spastic paraplegia: A case report of a patient presenting with lower limb spasticity and intellectual disability","authors":"Satomi Okano ,&nbsp;Yoshio Makita ,&nbsp;Yuki Ueda ,&nbsp;Akie Miyamoto ,&nbsp;Hajime Tanaka ,&nbsp;Kumiko Yanagi ,&nbsp;Tadashi Kaname","doi":"10.1016/j.bdcasr.2024.100016","DOIUrl":"https://doi.org/10.1016/j.bdcasr.2024.100016","url":null,"abstract":"<div><h3>Background</h3><p>Sodium/potassium (Na⁺/K⁺) ATPase is a heteromeric protein complex responsible for maintaining the Na⁺/K⁺ electrochemical gradient across the neuronal plasma membrane. The α₃ isoform of the Na⁺/K⁺ ATPase, encoded by <em>ATP1A3</em>, acts as a rescue pump and is predominantly present in the neurons of the central nervous system. The <em>de novo</em> variants of <em>ATP1A3</em> cause several distinct neurological syndromes.</p></div><div><h3>Case</h3><p>We presented the case of a boy with no family history of neurological diseases who was harboring a <em>de novo</em> pathogenic variation, NM_152296:c.974G &gt; T, p.Gly325Val, in <em>ATP1A3</em>. He presented with a rare spastic paraplegia of the lower extremities, autism spectrum disorder, and intellectual disability.</p></div><div><h3>Discussion and conclusion</h3><p>Previous studies have demonstrated the <em>ATP1A3</em> variant p.Gly325 to be pathogenic for dystonia, face dysmorphia, encephalopathy, brain magnetic resonance imaging abnormalities, and no hemiplegia. A recent study has revealed, for the first time, the development of spastic paraplegia as a manifestation of the <em>de novo ATP1A3</em> p.Pro775Leu pathogenic variant. In this case report, we concluded that another <em>de novo</em> pathogenic variation in <em>ATP1A3</em>, p.Gly325Val, manifests as spastic paraplegia and intellectual disability in the index patient. These results suggest that <em>ATP1A3</em> is a novel causative gene of hereditary spastic paraplegia.</p></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"2 2","pages":"Article 100016"},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950221724000126/pdfft?md5=37966604029c10c2d51110aa000d5840&pid=1-s2.0-S2950221724000126-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140632529","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}

{"title":"A case of SCN8A-related developmental epileptic encephalopathy diagnosed by clinical speculation driven targeted DNA sequencing and remission of epilepsy by sodium channel blockers combination therapy","authors":"Yoshitaka Mitsui ,&nbsp;Hitoshi Sato ,&nbsp;Sumihito Togi ,&nbsp;Hiroki Ura ,&nbsp;Yo Niida","doi":"10.1016/j.bdcasr.2024.100015","DOIUrl":"https://doi.org/10.1016/j.bdcasr.2024.100015","url":null,"abstract":"<div><h3>Background</h3><p><em>SCN8A</em>-related epilepsy and/or neurodevelopmental disorders encompass a very broad spectrum of phenotypes. The most severe form, <em>SCN8A</em> developmental and epileptic encephalopathy (DEE), develops intractable epilepsy from early infancy and can lead to sudden death. Early diagnosis and therapeutic intervention are essential, but diagnosis is based on genetic testing and definitive diagnosis is often delayed.</p></div><div><h3>Case report</h3><p>A 4-month-old girl presented with intractable epilepsy. Most antiepileptic drugs were ineffective, but high doses of phenytoin suppressed seizures, so a sodium channelopathy was suspected and targeted DNA sequencing was performed, which revealed a pathogenic missense variant Val1315Met in the <em>SCN8A</em> gene. Based on the diagnosis, combination therapy with sodium channel blockers (SCBs) was initiated and the seizures resolved.</p></div><div><h3>Conclusion</h3><p>We experienced SCN8A-DEE, which led to early diagnosis based on clinical course and improved prognosis. It is noteworthy that even when the effect of a single SCB is insufficient, as in this case, combination therapy can lead to seizure free in <em>SCN8A</em>-DEE.</p></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"2 2","pages":"Article 100015"},"PeriodicalIF":0.0,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950221724000114/pdfft?md5=c2b03afa5c9c502e8a31a1152be803d9&pid=1-s2.0-S2950221724000114-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140546103","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}