Pub Date : 2026-01-27DOI: 10.1016/j.bdcasr.2026.100128
Kenta Ochiai , Taku Omata , Jun-ichi Takanashi
Background
Primary exercise headache (PEH) occurs only during or shortly after strenuous physical exercise. Pediatric cases are under-recognized, and there is little practical guidance on its prevention.
Case presentation
A previously healthy, 14-year-old, female patient experienced exertion-only, holocranial, constricting headaches only while performing the 100-m, all-out sprints. The headache abated within 15 min with rest. A neurological examination and brain magnetic resonance imaging/magnetic resonance angiography were normal. Over-the-counter analgesics were ineffective, and ergotamine 1 mg provided modest benefit.
Intervention and outcomes
Pre-exercise indomethacin farnesil 25 mg administered 30–60 min before running led to a clear improvement. Increasing the dosage to 50 mg after two months achieved complete control over the symptom. By the 12-month follow-up, the patient had become capable of participating in athletic activities without any adverse events.
Conclusion
After excluding etiologies of secondary headaches, pre-exercise indomethacin farnesil therapy controlled the PEH well without any adverse effects, enabling the patient to resume her athletic activities. The present case provides practical details on the dosing, timing, and tolerability of indomethacin farnesil for PEH.
{"title":"Pre-exercise indomethacin farnesil for primary exercise headache in an adolescent: A case report","authors":"Kenta Ochiai , Taku Omata , Jun-ichi Takanashi","doi":"10.1016/j.bdcasr.2026.100128","DOIUrl":"10.1016/j.bdcasr.2026.100128","url":null,"abstract":"<div><h3>Background</h3><div>Primary exercise headache (PEH) occurs only during or shortly after strenuous physical exercise. Pediatric cases are under-recognized, and there is little practical guidance on its prevention.</div></div><div><h3>Case presentation</h3><div>A previously healthy, 14-year-old, female patient experienced exertion-only, holocranial, constricting headaches only while performing the 100-m, all-out sprints. The headache abated within 15 min with rest. A neurological examination and brain magnetic resonance imaging/magnetic resonance angiography were normal. Over-the-counter analgesics were ineffective, and ergotamine 1 mg provided modest benefit.</div></div><div><h3>Intervention and outcomes</h3><div>Pre-exercise indomethacin farnesil 25 mg administered 30–60 min before running led to a clear improvement. Increasing the dosage to 50 mg after two months achieved complete control over the symptom. By the 12-month follow-up, the patient had become capable of participating in athletic activities without any adverse events.</div></div><div><h3>Conclusion</h3><div>After excluding etiologies of secondary headaches, pre-exercise indomethacin farnesil therapy controlled the PEH well without any adverse effects, enabling the patient to resume her athletic activities. The present case provides practical details on the dosing, timing, and tolerability of indomethacin farnesil for PEH.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"4 1","pages":"Article 100128"},"PeriodicalIF":0.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We report the case of an infant with alobar holoprosencephaly with drug-resistant severe epilepsy. Due to a heavy seizure burden, frequent use of buccal midazolam was attempted, and the seizures and associated sleep disturbances were effectively controlled without major adverse events.
Case report
The patient was a female infant with alobar holoprosencephaly. At 60 days of age, she experienced clinical seizures with eye deviation, oral automatism, and clonic limb movements that rapidly worsened to frequent and prolonged seizures. Intravenous phenobarbital temporarily suppressed the seizures but caused prolonged sedation and feeding difficulty. Several oral anti-seizure medications were ineffective. We introduced the frequent, nightly repeated use of buccal midazolam for status epilepticus, leading to seizure-free intervals, better nutrition, and the establishment of sleep-wake cycles. No significant adverse effects were observed, including respiratory suppression.
Conclusion
Frequent use of buccal midazolam not only reduced the seizure burden but also improved sleep and nutrition related to seizures in a patient with holoprosencephaly.
{"title":"Daily use of buccal midazolam for refractory seizures in an infant with holoprosencephaly: A case report","authors":"Mizuki Nishida-Takagi, Hirokazu Kurahashi, Shingo Numoto, Yoshiteru Azuma, Akihisa Okumura","doi":"10.1016/j.bdcasr.2026.100127","DOIUrl":"10.1016/j.bdcasr.2026.100127","url":null,"abstract":"<div><h3>Introduction</h3><div>We report the case of an infant with alobar holoprosencephaly with drug-resistant severe epilepsy. Due to a heavy seizure burden, frequent use of buccal midazolam was attempted, and the seizures and associated sleep disturbances were effectively controlled without major adverse events.</div></div><div><h3>Case report</h3><div>The patient was a female infant with alobar holoprosencephaly. At 60 days of age, she experienced clinical seizures with eye deviation, oral automatism, and clonic limb movements that rapidly worsened to frequent and prolonged seizures. Intravenous phenobarbital temporarily suppressed the seizures but caused prolonged sedation and feeding difficulty. Several oral anti-seizure medications were ineffective. We introduced the frequent, nightly repeated use of buccal midazolam for status epilepticus, leading to seizure-free intervals, better nutrition, and the establishment of sleep-wake cycles. No significant adverse effects were observed, including respiratory suppression.</div></div><div><h3>Conclusion</h3><div>Frequent use of buccal midazolam not only reduced the seizure burden but also improved sleep and nutrition related to seizures in a patient with holoprosencephaly.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"4 1","pages":"Article 100127"},"PeriodicalIF":0.0,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guillain-Barré syndrome (GBS) and botulism primarily manifest as acute flaccid paralysis; thus, differentiating between these two conditions is challenging. However, reports describing this case in infants are rare. Herein, we report a rare case of infantile GBS with ptosis that was initially suspected to be infant botulism (IB).
Case presentation
An 11-month-old boy presented with intermittent exotropia and was unable to stand with support. The patient also experienced constipation, ptosis, flaccid paralysis of both lower limbs, and loss of deep tendon reflexes within several days of admission. Brain MRI and cerebrospinal fluid (CSF) examination on day 3 were normal. Given the presence of ptosis and constipation, in addition to generalized hypotonia, IB was suspected. However, the stool botulinum toxin test results were negative. Repetitive nerve stimulation performed during evoked electromyography showed no waxing, and nerve conduction studies revealed the absence of F-waves in the lower limbs. Repeat CSF analysis on day 13 revealed albuminocytological dissociation. Anti-GM1 and anti-GQ1b IgG antibodies were positive. Based on these findings and the clinical symptoms, a final diagnosis of GBS was made. Without any specific treatment, his muscle strength and tone gradually improved from day 7. He was discharged on day 20. Motor development remained normal, with independent walking achieved within 15 months of age.
Conclusion
This case highlights that infantile GBS may present with ptosis and mimic IB. Accurate diagnosis requires the synthesis of various clinical information, including the results of repeated CSF tests, neurophysiological studies, and analyses of toxins and anti-ganglioside antibodies.
{"title":"An infantile case of Guillain-Barré syndrome mimicking infant botulism exhibiting ptosis: A case report","authors":"Momoka Natsume, Takeshi Suzuki, Shotaro Ando, Toru Kato","doi":"10.1016/j.bdcasr.2026.100126","DOIUrl":"10.1016/j.bdcasr.2026.100126","url":null,"abstract":"<div><h3>Background</h3><div>Guillain-Barré syndrome (GBS) and botulism primarily manifest as acute flaccid paralysis; thus, differentiating between these two conditions is challenging. However, reports describing this case in infants are rare. Herein, we report a rare case of infantile GBS with ptosis that was initially suspected to be infant botulism (IB).</div></div><div><h3>Case presentation</h3><div>An 11-month-old boy presented with intermittent exotropia and was unable to stand with support. The patient also experienced constipation, ptosis, flaccid paralysis of both lower limbs, and loss of deep tendon reflexes within several days of admission. Brain MRI and cerebrospinal fluid (CSF) examination on day 3 were normal. Given the presence of ptosis and constipation, in addition to generalized hypotonia, IB was suspected. However, the stool botulinum toxin test results were negative. Repetitive nerve stimulation performed during evoked electromyography showed no waxing, and nerve conduction studies revealed the absence of F-waves in the lower limbs. Repeat CSF analysis on day 13 revealed albuminocytological dissociation. Anti-GM1 and anti-GQ1b IgG antibodies were positive. Based on these findings and the clinical symptoms, a final diagnosis of GBS was made. Without any specific treatment, his muscle strength and tone gradually improved from day 7. He was discharged on day 20. Motor development remained normal, with independent walking achieved within 15 months of age.</div></div><div><h3>Conclusion</h3><div>This case highlights that infantile GBS may present with ptosis and mimic IB. Accurate diagnosis requires the synthesis of various clinical information, including the results of repeated CSF tests, neurophysiological studies, and analyses of toxins and anti-ganglioside antibodies.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"4 1","pages":"Article 100126"},"PeriodicalIF":0.0,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pyridoxine-dependent epilepsy (PDE) is caused by biallelic disease-associated variants in the ALDH7A1 gene, leading to the accumulation of neurotoxic intermediates such as α-aminoadipic semialdehyde (α-AASA), despite adequate seizure control with pyridoxine. This accumulation is thought to contribute to intellectual and developmental impairments.
Case presentation
We report a case of PDE in a Japanese patient for whom a lysine-restricted diet involving a lysine- and tryptophan-free amino acid formula was introduced from early infancy. In this case, maternal pyridoxine treatment was also initiated prenatally. After birth, the patient was started on this formula together with oral arginine supplementation. The patient's serum α-AASA and pipecolic acid levels initially decreased following dietary intervention but gradually increased with age. Despite early diagnosis and treatment, the patient exhibited a significant delay in expressive language and a moderate delay in motor development, whereas other developmental domains remained within the normal to borderline range. Importantly, no clinical seizures have occurred since birth.
Conclusion
This is the first report of a Japanese patient with PDE who was treated with a lysine-restricted diet from infancy and whose clinical outcome was followed until 4 years of age. Although such dietary management may contribute to metabolic control, it requires sustained commitment and substantial effort from the family. Early diagnosis and timely initiation of treatment are critical for optimizing developmental outcomes. More case-based data and practical guidance on dietary adaptation are needed to improve long-term care strategies for PDE.
{"title":"Challenges and potential of an early lysine-restricted diet for pyridoxine-dependent epilepsy: A case report","authors":"Kaori Aiba , Tomoyuki Akiyama , Takao Togawa , Shinji Saitoh","doi":"10.1016/j.bdcasr.2026.100125","DOIUrl":"10.1016/j.bdcasr.2026.100125","url":null,"abstract":"<div><h3>Background</h3><div>Pyridoxine-dependent epilepsy (PDE) is caused by biallelic disease-associated variants in the <em>ALDH7A1</em> gene, leading to the accumulation of neurotoxic intermediates such as α-aminoadipic semialdehyde (α-AASA), despite adequate seizure control with pyridoxine. This accumulation is thought to contribute to intellectual and developmental impairments.</div></div><div><h3>Case presentation</h3><div>We report a case of PDE in a Japanese patient for whom a lysine-restricted diet involving a lysine- and tryptophan-free amino acid formula was introduced from early infancy. In this case, maternal pyridoxine treatment was also initiated prenatally. After birth, the patient was started on this formula together with oral arginine supplementation. The patient's serum α-AASA and pipecolic acid levels initially decreased following dietary intervention but gradually increased with age. Despite early diagnosis and treatment, the patient exhibited a significant delay in expressive language and a moderate delay in motor development, whereas other developmental domains remained within the normal to borderline range. Importantly, no clinical seizures have occurred since birth.</div></div><div><h3>Conclusion</h3><div>This is the first report of a Japanese patient with PDE who was treated with a lysine-restricted diet from infancy and whose clinical outcome was followed until 4 years of age. Although such dietary management may contribute to metabolic control, it requires sustained commitment and substantial effort from the family. Early diagnosis and timely initiation of treatment are critical for optimizing developmental outcomes. More case-based data and practical guidance on dietary adaptation are needed to improve long-term care strategies for PDE.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"4 1","pages":"Article 100125"},"PeriodicalIF":0.0,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-03DOI: 10.1016/j.bdcasr.2025.100123
Kumiko Ishiguro , Takayuki Kishi , Kentaro Sano , Minobu Shichiji , Takatoshi Sato , Keiko Ishigaki , Satoru Nagata
Background
Coronavirus disease 2019 (COVID-19) has been linked to the production of various autoantibodies and the development of autoimmune diseases. Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection may induce myositis, and several adult cases of dermatomyositis following COVID-19 have been reported. However, reports of juvenile dermatomyositis (JDM) following COVID-19 have been scarce.
Case presentation
We herein detail our experience with the management of two patients who developed JDM following COVID-19 infection. Patient 1 was a 4-year-old boy who developed muscle weakness following COVID-19 infection, which progressed to a rash, continuous fever, and muscle weakness severe enough to render him unable to stand or sit independently. He was subsequently diagnosed with JDM complicated by interstitial pneumonia and was treated with methylprednisolone, oral prednisolone, cyclosporine, and cyclophosphamide, which significantly ameliorated his symptoms within 3 months. Patient 2 was a 13-year-old girl who developed progressive muscle weakness following COVID-19 infection. Physical examination revealed proximal muscle weakness and joint contractures, whereas blood tests showed normal creatine kinase levels but slightly elevated aldolase levels. She was subsequently diagnosed with JDM and treated with methylprednisolone and cyclosporine, which significantly reduced her symptoms.
Discussion
These patients highlight the potential link between SARS-CoV-2 infection and the onset of JDM, with the proposed mechanisms including molecular mimicry, bystander activation, and excessive type I interferon production.
Conclusion
COVID-19 may act as a trigger for JDM onset, warranting awareness and further investigation into this association.
{"title":"New onset of juvenile dermatomyositis after COVID-19 infection in two patients: a case report","authors":"Kumiko Ishiguro , Takayuki Kishi , Kentaro Sano , Minobu Shichiji , Takatoshi Sato , Keiko Ishigaki , Satoru Nagata","doi":"10.1016/j.bdcasr.2025.100123","DOIUrl":"10.1016/j.bdcasr.2025.100123","url":null,"abstract":"<div><h3>Background</h3><div>Coronavirus disease 2019 (COVID-19) has been linked to the production of various autoantibodies and the development of autoimmune diseases. Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection may induce myositis, and several adult cases of dermatomyositis following COVID-19 have been reported. However, reports of juvenile dermatomyositis (JDM) following COVID-19 have been scarce.</div></div><div><h3>Case presentation</h3><div>We herein detail our experience with the management of two patients who developed JDM following COVID-19 infection. Patient 1 was a 4-year-old boy who developed muscle weakness following COVID-19 infection, which progressed to a rash, continuous fever, and muscle weakness severe enough to render him unable to stand or sit independently. He was subsequently diagnosed with JDM complicated by interstitial pneumonia and was treated with methylprednisolone, oral prednisolone, cyclosporine, and cyclophosphamide, which significantly ameliorated his symptoms within 3 months. Patient 2 was a 13-year-old girl who developed progressive muscle weakness following COVID-19 infection. Physical examination revealed proximal muscle weakness and joint contractures, whereas blood tests showed normal creatine kinase levels but slightly elevated aldolase levels. She was subsequently diagnosed with JDM and treated with methylprednisolone and cyclosporine, which significantly reduced her symptoms.</div></div><div><h3>Discussion</h3><div>These patients highlight the potential link between SARS-CoV-2 infection and the onset of JDM, with the proposed mechanisms including molecular mimicry, bystander activation, and excessive type I interferon production.</div></div><div><h3>Conclusion</h3><div>COVID-19 may act as a trigger for JDM onset, warranting awareness and further investigation into this association.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"4 1","pages":"Article 100123"},"PeriodicalIF":0.0,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Infliximab is a tumor necrosis factor alpha (TNFα) inhibitor used for treating rheumatic disorders, inflammatory bowel disease, and other conditions. Despite the recent increase in reports of central demyelinating lesions associated with the use of TNFα inhibitors, most cases have been observed in adults with gradual onset and only mild neurological sequelae. We report a pediatric case of fulminant demyelinating lesions associated with infliximab administration.
Case presentation
Our patient was an 8-year-old male diagnosed with ileocolonic Crohn's disease. Around 6 h after his second infliximab administration, he developed headache, eye pain, nausea, and loss of consciousness. He was subsequently intubated due to respiratory depression. Brain magnetic resonance imaging revealed a prominent mass effect in the pons with diffusion restriction extending from the brain stem to the cervical spinal cord, as well as scattered lesions in the deep gray matter and cerebral hemispheres with hemorrhage. The lesion distribution was similar to that of acute disseminated encephalomyelitis (ADEM). Furthermore, the rapid progression of symptoms and intracerebral bleeding were consistent with those observed in acute hemorrhagic leukoencephalitis, a severe variant of ADEM. Despite performing plasma exchange and steroid pulse therapy, the patient remained unconscious with quadriplegia and severe brainstem dysfunction and was maintained on tracheostomy-based ventilation.
Conclusion
Although extremely rare, central demyelinating lesions associated with TNFα inhibitors can develop among pediatric cases. Clinicians should therefore be aware of the possibility of a fulminant course in children.
{"title":"Fulminant central demyelinating lesions associated with infliximab treatment in a child with Crohn's disease: A case report","authors":"Azusa Ikeda , Megumi Tsuji , Yuta Fujii , Noriko Aida , Tomohide Goto","doi":"10.1016/j.bdcasr.2025.100124","DOIUrl":"10.1016/j.bdcasr.2025.100124","url":null,"abstract":"<div><h3>Background</h3><div>Infliximab is a tumor necrosis factor alpha (TNFα) inhibitor used for treating rheumatic disorders, inflammatory bowel disease, and other conditions. Despite the recent increase in reports of central demyelinating lesions associated with the use of TNFα inhibitors, most cases have been observed in adults with gradual onset and only mild neurological sequelae. We report a pediatric case of fulminant demyelinating lesions associated with infliximab administration.</div></div><div><h3>Case presentation</h3><div>Our patient was an 8-year-old male diagnosed with ileocolonic Crohn's disease. Around 6 h after his second infliximab administration, he developed headache, eye pain, nausea, and loss of consciousness. He was subsequently intubated due to respiratory depression. Brain magnetic resonance imaging revealed a prominent mass effect in the pons with diffusion restriction extending from the brain stem to the cervical spinal cord, as well as scattered lesions in the deep gray matter and cerebral hemispheres with hemorrhage. The lesion distribution was similar to that of acute disseminated encephalomyelitis (ADEM). Furthermore, the rapid progression of symptoms and intracerebral bleeding were consistent with those observed in acute hemorrhagic leukoencephalitis, a severe variant of ADEM. Despite performing plasma exchange and steroid pulse therapy, the patient remained unconscious with quadriplegia and severe brainstem dysfunction and was maintained on tracheostomy-based ventilation.</div></div><div><h3>Conclusion</h3><div>Although extremely rare, central demyelinating lesions associated with TNFα inhibitors can develop among pediatric cases. Clinicians should therefore be aware of the possibility of a fulminant course in children.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"4 1","pages":"Article 100124"},"PeriodicalIF":0.0,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biallelic loss-of-function variants in the nuclear export mediator factor (NEMF) gene are associated with a rare autosomal recessive neuropathy characterized by motor-predominant axonal polyneuropathy and variable intellectual disability. Since its first report in 2017, most cases have been described in individuals of Middle Eastern origin.
Case presentation
We describe a Japanese boy with infantile-onset chronic motor axonal polyneuropathy and mild intellectual delay. Muscle weakness gradually progressed from distal to proximal muscles. Intravenous immunoglobulin (IVIG) therapy resulted in only partial and temporary improvement. By age five, he became non-ambulatory and required intermittent ventilatory support. Whole-exome sequencing (WES) performed in 2016 failed to identify a genetic diagnosis. However, reanalysis of the same WES data in 2022 revealed two biallelic pathogenic splice-site variants in the NEMF gene—c.945+1delG (maternal) and c.2929-2A>G (paternal)—both predicted to cause aberrant splicing and premature translation termination. RNA analysis confirmed these findings. Public transcriptomic data from NEMF-knockdown cells revealed upregulation of immune-related gene sets, potentially explaining the transient response to IVIG.
Conclusion
This is the first reported case of NEMF-related neuropathy in East Asia. Our findings suggest that immune dysregulation may contribute to the disease mechanism in some cases. Furthermore, this case illustrates that in some rare diseases, reviewing previous next-generation sequencing (NGS) data that initially yielded no significant findings may lead to diagnostic success, thanks to the rapidly expanding body of knowledge on genotype–phenotype correlations. Periodic reinterpretation of genomic data can therefore be a valuable strategy in undiagnosed rare conditions.
{"title":"Axonal polyneuropathy and intellectual disability caused by biallelic NEMF variants identified by reviewing the previously acquired whole exome sequencing data: A case report","authors":"Konomi Shimoda , Shota Kato , Yuki Taniguchi , Yutaka Harita , Masashi Mizuguchi , Motohiro Kato","doi":"10.1016/j.bdcasr.2025.100122","DOIUrl":"10.1016/j.bdcasr.2025.100122","url":null,"abstract":"<div><h3>Background</h3><div>Biallelic loss-of-function variants in the nuclear export mediator factor (<em>NEMF</em>) gene are associated with a rare autosomal recessive neuropathy characterized by motor-predominant axonal polyneuropathy and variable intellectual disability. Since its first report in 2017, most cases have been described in individuals of Middle Eastern origin.</div></div><div><h3>Case presentation</h3><div>We describe a Japanese boy with infantile-onset chronic motor axonal polyneuropathy and mild intellectual delay. Muscle weakness gradually progressed from distal to proximal muscles. Intravenous immunoglobulin (IVIG) therapy resulted in only partial and temporary improvement. By age five, he became non-ambulatory and required intermittent ventilatory support. Whole-exome sequencing (WES) performed in 2016 failed to identify a genetic diagnosis. However, reanalysis of the same WES data in 2022 revealed two biallelic pathogenic splice-site variants in the <em>NEMF</em> gene—c.945+1delG (maternal) and c.2929-2A>G (paternal)—both predicted to cause aberrant splicing and premature translation termination. RNA analysis confirmed these findings. Public transcriptomic data from <em>NEMF</em>-knockdown cells revealed upregulation of immune-related gene sets, potentially explaining the transient response to IVIG.</div></div><div><h3>Conclusion</h3><div>This is the first reported case of <em>NEMF</em>-related neuropathy in East Asia. Our findings suggest that immune dysregulation may contribute to the disease mechanism in some cases. Furthermore, this case illustrates that in some rare diseases, reviewing previous next-generation sequencing (NGS) data that initially yielded no significant findings may lead to diagnostic success, thanks to the rapidly expanding body of knowledge on genotype–phenotype correlations. Periodic reinterpretation of genomic data can therefore be a valuable strategy in undiagnosed rare conditions.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"4 1","pages":"Article 100122"},"PeriodicalIF":0.0,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145840324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-12DOI: 10.1016/j.bdcasr.2025.100121
Ho-Eun Kang , Chung-Ming Chen , Rai-Hseng Hsu , Hsi Chang , Yi-Yu Su , Min-Lan Tsai
Background
Primary coenzyme Q10 (CoQ10) deficiency is a rare mitochondrial disorder caused by pathogenic variants in the COQ4 gene. Patients with neonatal onset biallelic COQ4 variants typically present with hypertrophic cardiomyopathy, encephalopathy, hypotonia, seizures, and lactic acidosis.
Case report
A female neonate born at 38 weeks and 5 days of gestation presented with frequent apneic episodes, early respiratory distress, and hypertrophic cardiomyopathy shortly after birth. Long-term video EEG monitoring revealed electroclinical findings including multifocal refractory seizures, electrographic seizures, involuntary movements, and episodic dystonia. Multiple anti-seizure medications were administered; however, the episodic dystonia persisted. At 22 days of age, the patient was diagnosed with primary CoQ10 deficiency, due to COQ4 mutations. Whole exome sequencing identified compound heterozygous mutations with a maternally inherited missense mutation, c.370G>A, p.(Gly124Ser), and a paternally inherited splicing mutation, c.402+1G>A. Following treatment with high-dose CoQ10, carnitine, and supportive care, the patient demonstrated improved feeding and spontaneous breathing, allowing discontinuation of ventilatory support. However, after transitioning to comfort care, the patient died of respiratory failure.
Conclusion
This case highlights the broad neurological phenotype associated with COQ4-related primary CoQ10 deficiency, presenting with a wide range of symptoms including apnea, multifocal refractory seizures, and notably, abnormal dystonic movements. Episodic dystonia is a rare manifestation, and to date, it has not been reported as a clinical sign in neonatal-onset COQ4-related disease. Long-term video EEG monitoring helps clarify the differentiation among apnea, dystonic movements, and seizures, facilitating precise treatment in conjunction with CoQ10 supplementation.
初级辅酶Q10 （CoQ10）缺乏症是由COQ4基因致病性变异引起的一种罕见的线粒体疾病。新生儿双等位基因COQ4变异的患者通常表现为肥厚性心肌病、脑病、低张力、癫痫发作和乳酸酸中毒。一例妊娠38周零5天出生的女性新生儿在出生后不久出现频繁的呼吸暂停发作、早期呼吸窘迫和肥厚性心肌病。长期视频脑电图监测显示的电临床表现包括多灶性难治性癫痫发作、电图癫痫发作、不自主运动和发作性肌张力障碍。给予多种抗癫痫药物；然而，发作性肌张力障碍持续存在。在22日龄时，由于COQ4突变，患者被诊断为原发性CoQ10缺乏症。全外显子组测序鉴定出复合杂合突变，包括母系遗传的错义突变c.370G> a, p.（Gly124Ser）和父系遗传的剪接突变c.402+1G> a。在给予大剂量辅酶q10、肉碱和支持治疗后，患者表现出改善的进食和自主呼吸，允许停止呼吸支持。然而，在过渡到舒适护理后，患者死于呼吸衰竭。结论：该病例突出了与辅酶q4相关的原发性辅酶q10缺乏症相关的广泛神经表型，表现为广泛的症状，包括呼吸暂停、多灶性难固性癫痫发作，尤其是异常张力障碍运动。阵发性肌张力障碍是一种罕见的表现，迄今为止，尚未报道其作为新生儿发病的辅酶q4相关疾病的临床体征。长期视频脑电图监测有助于明确呼吸暂停、肌张力障碍运动和癫痫发作之间的区别，促进与辅酶q10补充相结合的精确治疗。
{"title":"Electroclinical correlates of seizures and episodic dystonia in a neonate with primary coenzyme Q10 deficiency due to COQ4 mutations","authors":"Ho-Eun Kang , Chung-Ming Chen , Rai-Hseng Hsu , Hsi Chang , Yi-Yu Su , Min-Lan Tsai","doi":"10.1016/j.bdcasr.2025.100121","DOIUrl":"10.1016/j.bdcasr.2025.100121","url":null,"abstract":"<div><h3>Background</h3><div>Primary coenzyme Q10 (CoQ10) deficiency is a rare mitochondrial disorder caused by pathogenic variants in the <em>COQ4</em> gene. Patients with neonatal onset biallelic <em>COQ4</em> variants typically present with hypertrophic cardiomyopathy, encephalopathy, hypotonia, seizures, and lactic acidosis.</div></div><div><h3>Case report</h3><div>A female neonate born at 38 weeks and 5 days of gestation presented with frequent apneic episodes, early respiratory distress, and hypertrophic cardiomyopathy shortly after birth. Long-term video EEG monitoring revealed electroclinical findings including multifocal refractory seizures, electrographic seizures, involuntary movements, and episodic dystonia. Multiple anti-seizure medications were administered; however, the episodic dystonia persisted. At 22 days of age, the patient was diagnosed with primary CoQ10 deficiency, due to <em>COQ4</em> mutations. Whole exome sequencing identified compound heterozygous mutations with a maternally inherited missense mutation, c.370G>A, p.(Gly124Ser), and a paternally inherited splicing mutation, c.402+1G>A. Following treatment with high-dose CoQ10, carnitine, and supportive care, the patient demonstrated improved feeding and spontaneous breathing, allowing discontinuation of ventilatory support. However, after transitioning to comfort care, the patient died of respiratory failure.</div></div><div><h3>Conclusion</h3><div>This case highlights the broad neurological phenotype associated with <em>COQ4</em>-related primary CoQ10 deficiency, presenting with a wide range of symptoms including apnea, multifocal refractory seizures, and notably, abnormal dystonic movements. Episodic dystonia is a rare manifestation, and to date, it has not been reported as a clinical sign in neonatal-onset <em>COQ4</em>-related disease. Long-term video EEG monitoring helps clarify the differentiation among apnea, dystonic movements, and seizures, facilitating precise treatment in conjunction with CoQ10 supplementation.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"4 1","pages":"Article 100121"},"PeriodicalIF":0.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145748809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PAX2-related disorders, also known as renal coloboma syndrome, are typically characterized by renal and ocular abnormalities. Although PAX2 expression in the developing central nervous system has been reported, severe neurodevelopmental complications remain rare.
Case presentation
We report the case of a male infant referred at 17 months for evaluation of psychomotor developmental delay. He exhibited impaired social interaction, poor eye contact, limited verbal communication, irritability, and feeding difficulties. Renal ultrasonography revealed mild structural abnormalities, and ophthalmological evaluation showed optic nerve anomalies. Genetic analysis identified a novel heterozygous two-base-pair deletion in exon 2 of PAX2 (c.193_194del, p.Val65GlnfsTer36), inherited from his father, who had renal hypoplasia and subtle optic nerve findings. Over time, the patient developed persistent features of autism spectrum disorder and severe developmental delay, although renal function remained stable.
Conclusion
This case expands the phenotypic spectrum of PAX2-related disorders and suggests a potential link to severe neurodevelopmental involvement. Further research is needed to clarify the mechanisms underlying PAX2-associated neurodevelopmental phenotypes.
{"title":"Severe neurodevelopmental impairment in a child with PAX2-related renal Coloboma syndrome: A case report and literature review","authors":"Mai Kawamura , Takeshi Matsushige , Fumitaka Kohno , Yusuke Okada , Hikaru Kobayashi , Akinori Furusawa , Mayu Inohara , Madoka Hoshide , Setsuaki Kittaka , Naoya Morisada , Kandai Nozu , Shunji Hasegawa","doi":"10.1016/j.bdcasr.2025.100116","DOIUrl":"10.1016/j.bdcasr.2025.100116","url":null,"abstract":"<div><h3>Background</h3><div><em>PAX2</em>-related disorders, also known as renal coloboma syndrome, are typically characterized by renal and ocular abnormalities. Although <em>PAX2</em> expression in the developing central nervous system has been reported, severe neurodevelopmental complications remain rare.</div></div><div><h3>Case presentation</h3><div>We report the case of a male infant referred at 17 months for evaluation of psychomotor developmental delay. He exhibited impaired social interaction, poor eye contact, limited verbal communication, irritability, and feeding difficulties. Renal ultrasonography revealed mild structural abnormalities, and ophthalmological evaluation showed optic nerve anomalies. Genetic analysis identified a novel heterozygous two-base-pair deletion in exon 2 of <em>PAX2</em> (c.193_194del, p.Val65GlnfsTer36), inherited from his father, who had renal hypoplasia and subtle optic nerve findings. Over time, the patient developed persistent features of autism spectrum disorder and severe developmental delay, although renal function remained stable.</div></div><div><h3>Conclusion</h3><div>This case expands the phenotypic spectrum of <em>PAX2</em>-related disorders and suggests a potential link to severe neurodevelopmental involvement. Further research is needed to clarify the mechanisms underlying <em>PAX2</em>-associated neurodevelopmental phenotypes.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"4 1","pages":"Article 100116"},"PeriodicalIF":0.0,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145748549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) is a rare pediatric disorder often associated with neuroendocrine tumors (ROHHAD-NET). Recent studies have identified serum anti-ZSCAN1 antibodies in most patients, suggesting an autoimmune paraneoplastic neurological syndrome. Respiratory complications, particularly sleep-related hypoventilation, contribute to high mortality rates. Although immunomodulatory therapies have been attempted, their efficacy is limited.
Case presentation
A 2-year-old girl presented with rapid weight gain, hypothalamic dysfunction, autonomic abnormalities, and severe sleep-related hypoventilation. The patient developed intermittent strabismus, hyperphagia, and behavioral changes over 4 months. Imaging revealed a retroperitoneal paravertebral mass, which was pathologically diagnosed as ganglioneuroma. Laboratory findings revealed central hypothyroidism, growth hormone deficiency, hyperprolactinemia, and markedly elevated serum anti-ZSCAN1 antibody levels. Following admission, the patient experienced apnea, airway obstruction, excessive secretions, and wheezing during sleep, requiring mechanical ventilation. Immunotherapies, including plasma exchange, high-dose intravenous immunoglobulin, methylprednisolone pulse, rituximab, mycophenolate mofetil, and intrathecal methotrexate, improve appetite, behavior, and neuropsychiatric symptoms. Cerebrospinal fluid oligoclonal bands were negative, indicating partial immunological remission; however, sleep-related hypoventilation persisted. After discharge, the patient experienced sudden respiratory arrest during sleep and died despite resuscitation.
Conclusion
This case highlights that, ROHHAD-NET, autonomic dysfunction may cause complex sleep-related respiratory failure beyond simple obstructive or central hypoventilation. Elevated anti-ZSCAN1 antibody titers may be correlated with earlier disease onset and severity. Early recognition, aggressive immunomodulation, and consideration of ventilatory support are essential to prevent sudden deaths. Anti-ZSCAN1 antibodies may serve as useful biomarkers for the diagnosis and treatment of ROHHAD-NETs.
{"title":"Early-onset ROHHAD-NET syndrome with severe sleep-related respiratory distress: A case report","authors":"Yudai Hirakawa , Masanori Nishi , Naoya Higuchi , Hiroi Eguchi , Takuji Nakamura , Yuya Ito , Takaharu Yamada , Masafumi Sanefuji , Akari Nakamura-Utsunomiya , Muneaki Matsuo","doi":"10.1016/j.bdcasr.2025.100118","DOIUrl":"10.1016/j.bdcasr.2025.100118","url":null,"abstract":"<div><h3>Background</h3><div>Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) is a rare pediatric disorder often associated with neuroendocrine tumors (ROHHAD-NET). Recent studies have identified serum anti-ZSCAN1 antibodies in most patients, suggesting an autoimmune paraneoplastic neurological syndrome. Respiratory complications, particularly sleep-related hypoventilation, contribute to high mortality rates. Although immunomodulatory therapies have been attempted, their efficacy is limited.</div></div><div><h3>Case presentation</h3><div>A 2-year-old girl presented with rapid weight gain, hypothalamic dysfunction, autonomic abnormalities, and severe sleep-related hypoventilation. The patient developed intermittent strabismus, hyperphagia, and behavioral changes over 4 months. Imaging revealed a retroperitoneal paravertebral mass, which was pathologically diagnosed as ganglioneuroma. Laboratory findings revealed central hypothyroidism, growth hormone deficiency, hyperprolactinemia, and markedly elevated serum anti-ZSCAN1 antibody levels. Following admission, the patient experienced apnea, airway obstruction, excessive secretions, and wheezing during sleep, requiring mechanical ventilation. Immunotherapies, including plasma exchange, high-dose intravenous immunoglobulin, methylprednisolone pulse, rituximab, mycophenolate mofetil, and intrathecal methotrexate, improve appetite, behavior, and neuropsychiatric symptoms. Cerebrospinal fluid oligoclonal bands were negative, indicating partial immunological remission; however, sleep-related hypoventilation persisted. After discharge, the patient experienced sudden respiratory arrest during sleep and died despite resuscitation.</div></div><div><h3>Conclusion</h3><div>This case highlights that, ROHHAD-NET, autonomic dysfunction may cause complex sleep-related respiratory failure beyond simple obstructive or central hypoventilation. Elevated anti-ZSCAN1 antibody titers may be correlated with earlier disease onset and severity. Early recognition, aggressive immunomodulation, and consideration of ventilatory support are essential to prevent sudden deaths. Anti-ZSCAN1 antibodies may serve as useful biomarkers for the diagnosis and treatment of ROHHAD-NETs.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"4 1","pages":"Article 100118"},"PeriodicalIF":0.0,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145694285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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