A Massachusetts teenager who participated in a social media challenge where users eat a spicy tortilla chip died from eating a large quantity of chile pepper extract and also had a congenital heart defect, according to autopsy results.
Harris Wolobah, from the city of Worcester, died on Sept. 1, 2023, after eating the chip manufactured by Paqui, a Texas-based subsidiary of the Hershey Co.
Wolobah died of cardiopulmonary arrest "in the setting of recent ingestion of food substance with high capsaicin concentration," according to the autopsy from the Chief Office of the Medical Examiner.
Capsaicin is the component that gives chile peppers their heat.
"Capsaicin consumption can also cause more serious health problems including chest pain, heart palpitations, and even heart attacks. Consumption of larger amounts of capsaicin can also cause repeated vomiting that can lead to life-threatening esophageal damage. Because of this, people should use caution when consuming foods or products that contain capsaicin," she wrote in an article about the Paqui challenge on the website Poison.org.
Paqui pulled the chips off of shelves shortly after Wolobah's death.
The autopsy also said that Harris had an enlarged heart and a congenital defect described as "myocardial bridging of the left anterior descending coronary artery."
Wolobah died after participating in the so-called "One Chip Challenge," a marketing campaign by Paqui. It involves eating a single spicy tortilla chip seasoned with Carolina Reaper and Naga Viper peppers, and then waiting as long as possible before eating or drinking anything else.
"Any time you're sort of testing the body to its maximum, bad things can happen," Bradford Holland, M.D., an otolaryngologist in Central Texas, previously told Fox News Digital.
After Wolobah's death, Paqui said its product clearly states it is not intended for children or anyone sensitive to spicy foods.
"While the Pacqui One Chip Challenge is intended for adults only, we have seen an increase in teen usage of the product," the company said at the time.
https://www.foxbusiness.com/fox-news-us/massachusetts-teen-died-eating-spicy-chip-social-media-challenge
Thursday, May 16, 2024
The genetic facets of Dravet syndrome: Recent insights
Mouhi HE, Abbassi M, Jalte M, Natiq A, Bouguenouch L, Chaouki S. The Genetic Facets of Dravet Syndrome: Recent Insights. Ann Child Neurol. 2024;32(2):67-82.
Abstract
Dravet syndrome (DS), previously known as severe myoclonic epilepsy of infancy, is a severe epileptic syndrome affecting children, with an incidence of 1/22,000 to 1/49,900 live births annually. Characterized by resistant and prolonged seizures, it often leads to intellectual impairment, with males being twice as susceptible as females. Its clinical features include recurrent seizures triggered by fever initially, but later occurring spontaneously, developmental delays, behavioral issues, and movement disorders. Sodium voltage-gated channel alpha subunit 1 (SCN1A) mutations, observed in about 90% of cases, are usually de novo, while mutations in other genes, such as protocadherin 19 (PCDH19), gamma-aminobutyric acid type A receptor subunit gamma 2 (GABRG2), and sodium voltage-gated channel alpha subunit 2 (SCN2A), can also contribute to the condition. Next-generation sequencing aids in identifying these genetic abnormalities. First-line treatments include anticonvulsant drugs such as valproate, clobazam, stiripentol, topiramate, and bromide. Second-line treatments for drug-resistant DS include stiripentol, fenfluramine, and cannabidiol. This literature review provides a comprehensive update on the genetic underpinnings of DS, highlighting SCN1A's predominant role and the emerging significance of other genes. Moreover, it emphasizes novel therapeutic approaches for drug-resistant forms, showcasing the efficacy of newer drugs such as stiripentol, fenfluramine, and cannabidiol. This synthesis contributes to our understanding of the genetic landscape of DS and informs clinicians about evolving treatment strategies for enhanced patient care.
Tuesday, May 14, 2024
Recovery potential in patients who died after withdrawal of life-sustaining treatment
Sanders WR, Barber JK, Temkin NR, Foreman B, Giacino JT, Williamson T, Edlow BL, Manley GT, Bodien YG. Recovery Potential in Patients Who Died After Withdrawal of Life-Sustaining Treatment: A TRACK-TBI Propensity Score Analysis. J Neurotrauma. 2024 May 13. doi: 10.1089/neu.2024.0014. Epub ahead of print. PMID: 38739032.
Abstract
Among patients with severe traumatic brain injury (TBI), there is high prognostic uncertainty but growing evidence that recovery of independence is possible. Nevertheless, families are often asked to make decisions about withdrawal of life-sustaining treatment (WLST) within days of injury. The range of potential outcomes for patients who died after WLST (WLST+) is unknown, posing a challenge for prognostic modeling and clinical counseling. We investigated the potential for survival and recovery of independence after acute TBI in patients who died after WLST. We used Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) data and propensity score matching to pair participants with WLST+ to those with a similar probability of WLST (based on demographic and clinical characteristics), but for whom life-sustaining treatment was not withdrawn (WLST-). To optimize matching, we divided the WLST- cohort into tiers (Tier 1 = 0-11%, Tier 2 = 11-27%, Tier 3 = 27-70% WLST propensity). We estimated the level of recovery that could be expected in WLST+ participants by evaluating 3-, 6-, and 12-month Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale outcomes in matched WLST- participants. Of 90 WLST+ participants (80% male, mean [standard deviation; SD] age = 59.2 [17.9] years, median [IQR] days to WLST = 5.4 [2.2, 11.7]), 80 could be matched to WLST- participants. Of 56 WLST- participants who were followed at 6 months, 31 (55%) died. Among survivors in the overall sample and survivors in Tiers 1 and 2, more than 30% recovered at least partial independence (GOSE ≥4). In Tier 3, recovery to GOSE ≥4 occurred at 12 months, but not 6 months, post-injury. These results suggest a substantial proportion of patients with TBI and WLST may have survived and achieved at least partial independence. However, death or severe disability is a common outcome when the probability of WLST is high. While further validation is needed, our findings support a more cautious clinical approach to WLST and more complete reporting on WLST in TBI studies.
__________________________________________________________________
It must be one of the hardest decisions people ever have to make: whether to let their loved one go, switching off their life support if signs suggest they won't recover from a traumatic brain injury that happened just days ago.
But recovery is unpredictable, so doctors don't really know which patients could possibly recover from severe head trauma if given more time, and who, if they were to live, would experience lasting brain damage and disability, compromising their quality of life.
It's a delicate balance of unthinkable probabilities that no one wants to consider.
Now a team of researchers have tried: William Sanders, a medical researcher at Massachusetts General Hospital in Boston, and colleagues compared the outcomes of 212 brain trauma patients, to try to understand the impossible – what might have happened to patients if life support was left on.
Their findings, from 18 trauma centers across the United States, suggest that some patients with brain injuries who died after life support was withdrawn may have survived and even recovered some level of independence six months after injury.
"Our findings support a more cautious approach to making early decisions on withdrawal of life support," says Yelena Bodien, a neurologist at Massachusetts General Hospital and senior author of the study.
Given the complexities, some guidelines recommend doctors refrain from making judgements about a patient's prognosis too early. Research has only faintly begun to understand different patterns of consciousness within comatose patients. No guidelines or algorithms exist to help clinicians identify which patients might make a meaningful recovery.
Yet families are often asked to make the call within 72 hours of someone sustaining a severe brain injury. Unless patients make a rapid recovery in the first few days, it's thought they are unlikely to survive or recover much at all.
The data Sanders and colleagues analyzed tentatively suggest otherwise.
From a cohort of 1,392 patients admitted to intensive care units with a traumatic brain injury, the researchers created a mathematical model to group patients based on their likelihood to have life support withdrawn, and their age, sex, health background, injury characteristics, and clinical features.
From there, Sanders and colleagues could match 80 people who died after their life support was turned off with 132 people who had a similar health trajectory up until and briefly after their brain injury, but didn't have life-sustaining treatment withdrawn.
This allowed the researchers to estimate the level of recovery that might have been possible at three, six, and 12 months for the 80 people who died soon after life support was withdrawn.
Of course, we'll never know what could have happened had the machines stayed on, but based on follow-up data of those in a similar, heart-wrenching position, we can glean some hazy insights.
The data revealed that 31 of the 56 brain trauma patients who stayed on life support died within six months; and 45 percent survived. Of the 25 patients who survived, more than 30 percent recovered enough in that same six-month period to have at least some independence in daily activities.
Just four patients recovered 'fully' to how they functioned before their injury.
While that's a remarkable outcome for a lucky few, the findings show that overall severe disability is common, although a lifetime in a vegetative state is unlikely and recovery to some degree is possible, even after a very serious injury.
"Traumatic brain injury is a chronic condition that requires long-term follow-ups to understand patient outcomes," Bodien says. "Delaying decisions regarding life support may be warranted to better identify patients whose condition may improve."
In this study, the researchers couldn't estimate potential outcomes for the oldest and most severely injured group, because no comparable patients were found among those whose life support stayed switched on.
Larger studies of more patients are needed to fill in the blanks and plot the recovery trajectories of these and other brain trauma patients.
The research has been published in the Journal of Neurotrauma.
https://www.sciencealert.com/study-more-patients-could-survive-brain-injuries-if-life-support-not-switched-off
Abstract
Among patients with severe traumatic brain injury (TBI), there is high prognostic uncertainty but growing evidence that recovery of independence is possible. Nevertheless, families are often asked to make decisions about withdrawal of life-sustaining treatment (WLST) within days of injury. The range of potential outcomes for patients who died after WLST (WLST+) is unknown, posing a challenge for prognostic modeling and clinical counseling. We investigated the potential for survival and recovery of independence after acute TBI in patients who died after WLST. We used Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) data and propensity score matching to pair participants with WLST+ to those with a similar probability of WLST (based on demographic and clinical characteristics), but for whom life-sustaining treatment was not withdrawn (WLST-). To optimize matching, we divided the WLST- cohort into tiers (Tier 1 = 0-11%, Tier 2 = 11-27%, Tier 3 = 27-70% WLST propensity). We estimated the level of recovery that could be expected in WLST+ participants by evaluating 3-, 6-, and 12-month Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale outcomes in matched WLST- participants. Of 90 WLST+ participants (80% male, mean [standard deviation; SD] age = 59.2 [17.9] years, median [IQR] days to WLST = 5.4 [2.2, 11.7]), 80 could be matched to WLST- participants. Of 56 WLST- participants who were followed at 6 months, 31 (55%) died. Among survivors in the overall sample and survivors in Tiers 1 and 2, more than 30% recovered at least partial independence (GOSE ≥4). In Tier 3, recovery to GOSE ≥4 occurred at 12 months, but not 6 months, post-injury. These results suggest a substantial proportion of patients with TBI and WLST may have survived and achieved at least partial independence. However, death or severe disability is a common outcome when the probability of WLST is high. While further validation is needed, our findings support a more cautious clinical approach to WLST and more complete reporting on WLST in TBI studies.
__________________________________________________________________
It must be one of the hardest decisions people ever have to make: whether to let their loved one go, switching off their life support if signs suggest they won't recover from a traumatic brain injury that happened just days ago.
But recovery is unpredictable, so doctors don't really know which patients could possibly recover from severe head trauma if given more time, and who, if they were to live, would experience lasting brain damage and disability, compromising their quality of life.
It's a delicate balance of unthinkable probabilities that no one wants to consider.
Now a team of researchers have tried: William Sanders, a medical researcher at Massachusetts General Hospital in Boston, and colleagues compared the outcomes of 212 brain trauma patients, to try to understand the impossible – what might have happened to patients if life support was left on.
Their findings, from 18 trauma centers across the United States, suggest that some patients with brain injuries who died after life support was withdrawn may have survived and even recovered some level of independence six months after injury.
"Our findings support a more cautious approach to making early decisions on withdrawal of life support," says Yelena Bodien, a neurologist at Massachusetts General Hospital and senior author of the study.
Given the complexities, some guidelines recommend doctors refrain from making judgements about a patient's prognosis too early. Research has only faintly begun to understand different patterns of consciousness within comatose patients. No guidelines or algorithms exist to help clinicians identify which patients might make a meaningful recovery.
Yet families are often asked to make the call within 72 hours of someone sustaining a severe brain injury. Unless patients make a rapid recovery in the first few days, it's thought they are unlikely to survive or recover much at all.
The data Sanders and colleagues analyzed tentatively suggest otherwise.
From a cohort of 1,392 patients admitted to intensive care units with a traumatic brain injury, the researchers created a mathematical model to group patients based on their likelihood to have life support withdrawn, and their age, sex, health background, injury characteristics, and clinical features.
From there, Sanders and colleagues could match 80 people who died after their life support was turned off with 132 people who had a similar health trajectory up until and briefly after their brain injury, but didn't have life-sustaining treatment withdrawn.
This allowed the researchers to estimate the level of recovery that might have been possible at three, six, and 12 months for the 80 people who died soon after life support was withdrawn.
Of course, we'll never know what could have happened had the machines stayed on, but based on follow-up data of those in a similar, heart-wrenching position, we can glean some hazy insights.
The data revealed that 31 of the 56 brain trauma patients who stayed on life support died within six months; and 45 percent survived. Of the 25 patients who survived, more than 30 percent recovered enough in that same six-month period to have at least some independence in daily activities.
Just four patients recovered 'fully' to how they functioned before their injury.
While that's a remarkable outcome for a lucky few, the findings show that overall severe disability is common, although a lifetime in a vegetative state is unlikely and recovery to some degree is possible, even after a very serious injury.
"Traumatic brain injury is a chronic condition that requires long-term follow-ups to understand patient outcomes," Bodien says. "Delaying decisions regarding life support may be warranted to better identify patients whose condition may improve."
In this study, the researchers couldn't estimate potential outcomes for the oldest and most severely injured group, because no comparable patients were found among those whose life support stayed switched on.
Larger studies of more patients are needed to fill in the blanks and plot the recovery trajectories of these and other brain trauma patients.
The research has been published in the Journal of Neurotrauma.
https://www.sciencealert.com/study-more-patients-could-survive-brain-injuries-if-life-support-not-switched-off
Monday, May 13, 2024
Alexander disease 2
Inspired by a patient
Paprocka J, Nowak M, Machnikowska-Sokołowska M, Rutkowska K, Płoski R. Leukodystrophy with Macrocephaly, Refractory Epilepsy, and Severe Hyponatremia-The Neonatal Type of Alexander Disease. Genes (Basel). 2024 Mar 11;15(3):350. doi: 10.3390/genes15030350. PMID: 38540409; PMCID: PMC10970303.
Abstract
Introduction: Alexander disease (AxD) is a rare neurodegenerative condition that represents the group of leukodystrophies. The disease is caused by GFAP mutation. Symptoms usually occur in the infantile age with macrocephaly, developmental deterioration, progressive quadriparesis, and seizures as the most characteristic features. In this case report, we provide a detailed clinical description of the neonatal type of AxD.
Method: Next-Generation Sequencing (NGS), including a panel of 49 genes related to Early Infantile Epileptic Encephalopathy (EIEE), was carried out, and then Whole Exome Sequencing (WES) was performed on the proband's DNA extracted from blood.
Case description: In the first weeks of life, the child presented with signs of increased intracranial pressure, which led to ventriculoperitoneal shunt implementation. Recurrent focal-onset motor seizures with secondary generalization occurred despite phenobarbital treatment. Therapy was modified with multiple anti-seizure medications. In MRI contrast-enhanced lesions in basal ganglia, midbrain and cortico-spinal tracts were observed. During the diagnostic process, GLUT-1 deficiency, lysosomal storage disorders, organic acidurias, and fatty acid oxidation defects were excluded. The NGS panel of EIEE revealed no abnormalities. In WES analysis, GFAP missense heterozygous variant NM_002055.5: c.1187C>T, p.(Thr396Ile) was detected, confirming the diagnosis of AxD.
Conclusion: AxD should be considered in the differential diagnosis in all neonates with progressive, intractable seizures accompanied by macrocephaly.
Joung J, Gallison K, Sollee JJ, Vigilante N, Cooper H, Liu GW, Ballester L, Faig W, Waldman AT. Acquisition and Loss of Developmental Milestones and Time to Disease-Related Outcomes in Cerebral Alexander Disease. J Child Neurol. 2023 Dec;38(13-14):672-678. doi: 10.1177/08830738231210040. Epub 2023 Nov 3. PMID: 37920915.
Abstract
Objective: To determine the ages at acquisition of developmental milestones, loss of motor function, and clinical symptoms in Alexander disease. Methods: Patients with confirmed cerebral Alexander disease were included. Data abstraction of developmental and disease-specific milestones was performed from medical records, physical exams, and questionnaires. Mixed effects logistic regression was used to determine if key clinical features were associated with milestone achievement, controlling for patient age. Results: 51 patients with cerebral/infantile Alexander disease were evaluated at a mean age of 10.96 years (range 2.29-31.08 years). Developmental milestones in Alexander disease were often achieved but delayed. Ambulation was achieved in 44 subjects (86%); 34 (67%) subjects walked independently (mean age 1.9 years, range 0.91-3.25 years) and an additional 10 (20%) subjects walked with assistance (mean age 3.9 years, range 1.8-8 years) but did not progress to independent ambulation. Developmental delay was the earliest and most prevalent symptom (N = 48 [94%], mean age 0.58 years), compared to an initial seizure (N = 41 [80%], mean age 2.80 years), and macrocephaly (N = 28 [55%], mean age 4.04 years), P < .0001 between these ages of onset. Loss of independent ambulation occurred in 11 of the 34 (32%) children who had acquired ambulation (range 3.41-15.10 years). Presence of seizures or macrocephaly did not predict the achievement or loss of ambulation. Conclusions: The clinical triad of developmental delay, seizures, and macrocephaly are not universally present in cerebral Alexander disease. Clinicians should have a high index of suspicion for Alexander disease in patients with mild delays and a first seizure.
Anis S, Fay-Karmon T, Lassman S, Shbat F, Lesman-Segev O, Mor N, Barel O, Dominissini D, Chorin O, Pras E, Greenbaum L, Hassin-Baer S. Adult-onset Alexander disease among patients of Jewish Syrian descent. Neurogenetics. 2023 Oct;24(4):303-310. doi: 10.1007/s10048-023-00732-w. Epub 2023 Sep 2. PMID: 37658208.
Abstract
Alexander disease (AxD) is a rare autosomal dominant leukodystrophy caused by heterozygous mutations in the glial fibrillary acid protein (GFAP) gene. The age of symptoms onset ranges from infancy to adulthood, with variable clinical and radiological manifestations. Adult-onset AxD manifests as a chronic and progressive condition, characterized by bulbar, motor, cerebellar, and other clinical signs and symptoms. Neuroradiological findings typically involve the brainstem and cervical spinal cord. Adult-onset AxD has been described in diverse populations but is rare in Israel. We present a series of patients diagnosed with adult-onset AxD from three families, all of Jewish Syrian descent. Five patients (4 females) were diagnosed with adult-onset AxD due to the heterozygous mutation c.219G > A, p.Met73Ile in GFAP. Age at symptoms onset ranged from 48 to 61 years. Clinical characteristics were typical and involved progressive bulbar and gait disturbance, followed by pyramidal and cerebellar impairment, dysautonomia, and cognitive decline. Imaging findings included medullary and cervical spinal atrophy and mostly infratentorial white matter hyperintensities. A newly recognized cluster of adult-onset AxD in Jews of Syrian origin is presented. This disorder should be considered in differential diagnosis in appropriate circumstances. Genetic counselling for family members is required in order to discuss options for future family planning.
Paprocka J, Nowak M, Machnikowska-Sokołowska M, Rutkowska K, Płoski R. Leukodystrophy with Macrocephaly, Refractory Epilepsy, and Severe Hyponatremia-The Neonatal Type of Alexander Disease. Genes (Basel). 2024 Mar 11;15(3):350. doi: 10.3390/genes15030350. PMID: 38540409; PMCID: PMC10970303.
Abstract
Introduction: Alexander disease (AxD) is a rare neurodegenerative condition that represents the group of leukodystrophies. The disease is caused by GFAP mutation. Symptoms usually occur in the infantile age with macrocephaly, developmental deterioration, progressive quadriparesis, and seizures as the most characteristic features. In this case report, we provide a detailed clinical description of the neonatal type of AxD.
Method: Next-Generation Sequencing (NGS), including a panel of 49 genes related to Early Infantile Epileptic Encephalopathy (EIEE), was carried out, and then Whole Exome Sequencing (WES) was performed on the proband's DNA extracted from blood.
Case description: In the first weeks of life, the child presented with signs of increased intracranial pressure, which led to ventriculoperitoneal shunt implementation. Recurrent focal-onset motor seizures with secondary generalization occurred despite phenobarbital treatment. Therapy was modified with multiple anti-seizure medications. In MRI contrast-enhanced lesions in basal ganglia, midbrain and cortico-spinal tracts were observed. During the diagnostic process, GLUT-1 deficiency, lysosomal storage disorders, organic acidurias, and fatty acid oxidation defects were excluded. The NGS panel of EIEE revealed no abnormalities. In WES analysis, GFAP missense heterozygous variant NM_002055.5: c.1187C>T, p.(Thr396Ile) was detected, confirming the diagnosis of AxD.
Conclusion: AxD should be considered in the differential diagnosis in all neonates with progressive, intractable seizures accompanied by macrocephaly.
Joung J, Gallison K, Sollee JJ, Vigilante N, Cooper H, Liu GW, Ballester L, Faig W, Waldman AT. Acquisition and Loss of Developmental Milestones and Time to Disease-Related Outcomes in Cerebral Alexander Disease. J Child Neurol. 2023 Dec;38(13-14):672-678. doi: 10.1177/08830738231210040. Epub 2023 Nov 3. PMID: 37920915.
Abstract
Objective: To determine the ages at acquisition of developmental milestones, loss of motor function, and clinical symptoms in Alexander disease. Methods: Patients with confirmed cerebral Alexander disease were included. Data abstraction of developmental and disease-specific milestones was performed from medical records, physical exams, and questionnaires. Mixed effects logistic regression was used to determine if key clinical features were associated with milestone achievement, controlling for patient age. Results: 51 patients with cerebral/infantile Alexander disease were evaluated at a mean age of 10.96 years (range 2.29-31.08 years). Developmental milestones in Alexander disease were often achieved but delayed. Ambulation was achieved in 44 subjects (86%); 34 (67%) subjects walked independently (mean age 1.9 years, range 0.91-3.25 years) and an additional 10 (20%) subjects walked with assistance (mean age 3.9 years, range 1.8-8 years) but did not progress to independent ambulation. Developmental delay was the earliest and most prevalent symptom (N = 48 [94%], mean age 0.58 years), compared to an initial seizure (N = 41 [80%], mean age 2.80 years), and macrocephaly (N = 28 [55%], mean age 4.04 years), P < .0001 between these ages of onset. Loss of independent ambulation occurred in 11 of the 34 (32%) children who had acquired ambulation (range 3.41-15.10 years). Presence of seizures or macrocephaly did not predict the achievement or loss of ambulation. Conclusions: The clinical triad of developmental delay, seizures, and macrocephaly are not universally present in cerebral Alexander disease. Clinicians should have a high index of suspicion for Alexander disease in patients with mild delays and a first seizure.
Anis S, Fay-Karmon T, Lassman S, Shbat F, Lesman-Segev O, Mor N, Barel O, Dominissini D, Chorin O, Pras E, Greenbaum L, Hassin-Baer S. Adult-onset Alexander disease among patients of Jewish Syrian descent. Neurogenetics. 2023 Oct;24(4):303-310. doi: 10.1007/s10048-023-00732-w. Epub 2023 Sep 2. PMID: 37658208.
Abstract
Alexander disease (AxD) is a rare autosomal dominant leukodystrophy caused by heterozygous mutations in the glial fibrillary acid protein (GFAP) gene. The age of symptoms onset ranges from infancy to adulthood, with variable clinical and radiological manifestations. Adult-onset AxD manifests as a chronic and progressive condition, characterized by bulbar, motor, cerebellar, and other clinical signs and symptoms. Neuroradiological findings typically involve the brainstem and cervical spinal cord. Adult-onset AxD has been described in diverse populations but is rare in Israel. We present a series of patients diagnosed with adult-onset AxD from three families, all of Jewish Syrian descent. Five patients (4 females) were diagnosed with adult-onset AxD due to the heterozygous mutation c.219G > A, p.Met73Ile in GFAP. Age at symptoms onset ranged from 48 to 61 years. Clinical characteristics were typical and involved progressive bulbar and gait disturbance, followed by pyramidal and cerebellar impairment, dysautonomia, and cognitive decline. Imaging findings included medullary and cervical spinal atrophy and mostly infratentorial white matter hyperintensities. A newly recognized cluster of adult-onset AxD in Jews of Syrian origin is presented. This disorder should be considered in differential diagnosis in appropriate circumstances. Genetic counselling for family members is required in order to discuss options for future family planning.
Friday, May 10, 2024
Pediatric palliative epilepsy surgery
M. Jeno, B. Zimmerman, S. Shandley, L. Wong-Kisiel, R. Singh, N. McNamara, E. Fedak Romanowski, Z. Grinspan, K. Eschbach, A. Alexander, P. McGoldrick, S. Wolf, S. Nangia, J. Bolton, J. Olaya, D.W. Shrey, S. Karia, C. Karakas, P. Tatachar, A.P. Ostendorf, S. Gedela, P. Javarayee, S. Reddy, C. Manuel, E. Gonzalez-Giraldo, J. Sullivan, J. Coryell, D. Depositario-Cabacar, J.S. Hauptman, D. Samanta, D. Armstrong, M.S. Perry, A. Marashly, M. Ciliberto. Pediatric palliative epilepsy surgery: a report from the Pediatric Epilepsy Research Consortium (PERC) Surgery Database. Pediatric Neurology (2024), doi: https://doi.org/10.1016/j.pediatrneurol.2024.04.028.
Introduction
Epilepsy is common, occurring in 0.5-1.5% of the pediatric US population, with drug-resistant epilepsy (DRE) occurring in nearly one-third of persons with epilepsy under 18 years of age. The International League Against Epilepsy (ILAE) defines DRE as “failure of adequate trials of two tolerated, appropriately chosen and used, antiepileptic drug schedules to achieve sustained seizure freedom”. After two anti-seizure medications (ASMs) have failed, the likelihood that an additional ASM will lead to seizure freedom is around 4-5%. These statistics have not changed despite increasing pharmaceutical options for the treatment of epilepsy over the last 20 years, highlighting the need for other treatment options for DRE. However, surgery continues to be an underutilized therapy, particularly when seizure freedom is not expected.
Definitive (or curative) surgical treatment for epilepsy is determined after identification of a seizure focus, followed by neurosurgical resection, disconnection, or ablation with the goal of achieving seizure freedom. Palliative epilepsy surgeries have a goal other than seizure freedom, including reduction of seizure severity, reduction in seizure frequency, or alleviation of a particular seizure type to improve quality of life. A palliative approach may be indicated when the epileptogenic zone cannot be fully resected due to failure of localization or lateralization, overlap with eloquent cortex, the presence of multiple epileptogenic zones, or the presence of generalized epilepsy. Corpus callosotomy, neuromodulation, and multiple subpial transections are procedures traditionally considered palliative procedures, though any surgical procedure can be considered a palliative treatment based on the preoperative goal of therapy including traditionally definitive procedures such as hemispherotomy, lobectomy, and lesionectomy.
Palliative epilepsy surgery can improve outcomes beyond what is captured with available surgical outcome measures, such as QOL in patients undergoing palliative hemispherotomy. Some palliative surgical procedures also have diagnostic utility that may lead to more definitive surgery later. For example, corpus callosotomy can help lateralize the seizure onset in frontal lobe epilepsies which can be difficult to lateralize on surface EEG. Responsive neurostimulation (RNS) allows long-term limited invasive EEG recording and can potentially lateralize or localize the most active seizure onset zone in suspected multifocal epilepsy leading to more definitive subsequent therapies.
Reducing seizures via epilepsy surgery, even without achieving seizure freedom, can help maximize neurodevelopmental potential and quality of life, as refractory seizures can lead to cognitive decline, impaired social outcomes, and higher risk of sudden unexplained death in epilepsy (SUDEP). This highlights the need to redefine surgical success as it relates to palliative procedures. In this paper, we evaluate the characteristics of children in the US offered palliative pediatric epilepsy surgery using a multicenter database to compare patient selection, evaluation, surgical treatment and outcomes of patients ultimately undergoing palliative epilepsy surgery.
Introduction
Epilepsy is common, occurring in 0.5-1.5% of the pediatric US population, with drug-resistant epilepsy (DRE) occurring in nearly one-third of persons with epilepsy under 18 years of age. The International League Against Epilepsy (ILAE) defines DRE as “failure of adequate trials of two tolerated, appropriately chosen and used, antiepileptic drug schedules to achieve sustained seizure freedom”. After two anti-seizure medications (ASMs) have failed, the likelihood that an additional ASM will lead to seizure freedom is around 4-5%. These statistics have not changed despite increasing pharmaceutical options for the treatment of epilepsy over the last 20 years, highlighting the need for other treatment options for DRE. However, surgery continues to be an underutilized therapy, particularly when seizure freedom is not expected.
Definitive (or curative) surgical treatment for epilepsy is determined after identification of a seizure focus, followed by neurosurgical resection, disconnection, or ablation with the goal of achieving seizure freedom. Palliative epilepsy surgeries have a goal other than seizure freedom, including reduction of seizure severity, reduction in seizure frequency, or alleviation of a particular seizure type to improve quality of life. A palliative approach may be indicated when the epileptogenic zone cannot be fully resected due to failure of localization or lateralization, overlap with eloquent cortex, the presence of multiple epileptogenic zones, or the presence of generalized epilepsy. Corpus callosotomy, neuromodulation, and multiple subpial transections are procedures traditionally considered palliative procedures, though any surgical procedure can be considered a palliative treatment based on the preoperative goal of therapy including traditionally definitive procedures such as hemispherotomy, lobectomy, and lesionectomy.
Palliative epilepsy surgery can improve outcomes beyond what is captured with available surgical outcome measures, such as QOL in patients undergoing palliative hemispherotomy. Some palliative surgical procedures also have diagnostic utility that may lead to more definitive surgery later. For example, corpus callosotomy can help lateralize the seizure onset in frontal lobe epilepsies which can be difficult to lateralize on surface EEG. Responsive neurostimulation (RNS) allows long-term limited invasive EEG recording and can potentially lateralize or localize the most active seizure onset zone in suspected multifocal epilepsy leading to more definitive subsequent therapies.
Reducing seizures via epilepsy surgery, even without achieving seizure freedom, can help maximize neurodevelopmental potential and quality of life, as refractory seizures can lead to cognitive decline, impaired social outcomes, and higher risk of sudden unexplained death in epilepsy (SUDEP). This highlights the need to redefine surgical success as it relates to palliative procedures. In this paper, we evaluate the characteristics of children in the US offered palliative pediatric epilepsy surgery using a multicenter database to compare patient selection, evaluation, surgical treatment and outcomes of patients ultimately undergoing palliative epilepsy surgery.
Epilepsy surgery in children with genetic etiologies
Coryell J, Singh R, Ostendorf AP, Eisner M, Alexander A, Eschbach K, Shrey DW, Olaya J, Ciliberto MA, Karakas C, Karia S, McNamara N, Romanowski EF, Kheder A, Pradeep J, Reddy SB, McCormack MJ, Bolton J, Wolf S, McGoldrick P, Hauptman JS, Samanta D, Tatachar P, Sullivan J, Auguste K, Gonzalez-Giraldo E, Marashly A, Depositario-Cabacar DF, Wong-Kisiel LC, Perry S. Epilepsy surgery in children with genetic etiologies: A prospective evaluation of current practices and outcomes. Seizure. 2023 Dec;113:6-12. doi: 10.1016/j.seizure.2023.10.011. Epub 2023 Oct 25. PMID: 38189708.
Abstract
Objective: This study assesses current practices and outcomes of epilepsy surgery in children with a genetic etiology. It explores the pre-surgical workup, types of surgeries, and post-surgical outcomes in a broad array of disorders.
Methods: Patients ≤18 years who completed epilepsy surgery and had a known genetic etiology prior to surgical intervention were extrapolated from the Pediatric Epilepsy Research Consortium (PERC) surgery database, across 18 US centers. Data were assessed univariably by neuroimaging and EEG results, genetic group (structural gene, other gene, chromosomal), and curative intent. Outcomes were based on a modified International League Against Epilepsy (ILAE) outcome score.
Results: Of 81 children with genetic epilepsy, 72 % had daily seizures when referred for surgery evaluation, which occurred a median of 2.2 years (IQR 0.3, 5.2) after developing drug resistance. Following surgery, 68 % of subjects had >50 % seizure reduction, with 33 % achieving seizure freedom [median follow-up 11 months (IQR 6, 17). Seizure freedom was most common in the monogenic structural group, but significant palliation was present across all groups. Presence of a single EEG focus was associated with a greater likelihood of seizure freedom (p=0.02).
Significance: There are meaningful seizure reductions following epilepsy surgery in the majority of children with a genetic etiology, even in the absence of a single structural lesion and across a broad spectrum of genetic causes. These findings highlight the need for expedited referral for epilepsy surgery and support of a broadened view of which children may benefit from epilepsy surgery, even when the intent is palliative.
Abstract
Objective: This study assesses current practices and outcomes of epilepsy surgery in children with a genetic etiology. It explores the pre-surgical workup, types of surgeries, and post-surgical outcomes in a broad array of disorders.
Methods: Patients ≤18 years who completed epilepsy surgery and had a known genetic etiology prior to surgical intervention were extrapolated from the Pediatric Epilepsy Research Consortium (PERC) surgery database, across 18 US centers. Data were assessed univariably by neuroimaging and EEG results, genetic group (structural gene, other gene, chromosomal), and curative intent. Outcomes were based on a modified International League Against Epilepsy (ILAE) outcome score.
Results: Of 81 children with genetic epilepsy, 72 % had daily seizures when referred for surgery evaluation, which occurred a median of 2.2 years (IQR 0.3, 5.2) after developing drug resistance. Following surgery, 68 % of subjects had >50 % seizure reduction, with 33 % achieving seizure freedom [median follow-up 11 months (IQR 6, 17). Seizure freedom was most common in the monogenic structural group, but significant palliation was present across all groups. Presence of a single EEG focus was associated with a greater likelihood of seizure freedom (p=0.02).
Significance: There are meaningful seizure reductions following epilepsy surgery in the majority of children with a genetic etiology, even in the absence of a single structural lesion and across a broad spectrum of genetic causes. These findings highlight the need for expedited referral for epilepsy surgery and support of a broadened view of which children may benefit from epilepsy surgery, even when the intent is palliative.
Wednesday, May 8, 2024
Acquired savant syndrome
In 2002, two men savagely attacked Jason Padgett outside a karaoke bar, leaving him with a severe concussion and post-traumatic stress disorder. But the incident also turned Padgett into a mathematical genius who sees the world through the lens of geometry.
Padgett, a furniture salesman from Tacoma, Washington, who had very little interest in academics, developed the ability to visualize complex mathematical objects and physics concepts intuitively. The injury, while devastating, seems to have unlocked part of his brain that makes everything in his world appear to have a mathematical structure.
"I see shapes and angles everywhere in real life" — from the geometry of a rainbow, to the fractals in water spiraling down a drain, Padgett told Live Science. "It's just really beautiful."
Padgett, who just published a memoir with Maureen Seaberg called "Struck by Genius" (Houghton Mifflin Harcourt, 2014), is one of a rare set of individuals with acquired savant syndrome, in which a normal person develops prodigious abilities after a severe injury or disease. Other people have developed remarkable musical or artistic abilities, but few people have acquired mathematical faculties like Padgett's.
Now, researchers have figured out which parts of the man's brain were rejiggered to allow for such savant skills, and the findings suggest such skills may lie dormant in all human brains.
'Struck by genius'
Before the injury, Padgett was a self-described jock and partyer. He hadn't progressed beyond than pre-algebra in his math studies. "I cheated on everything, and I never cracked a book," he said.
But all that would change the night of his attack. Padgett recalls being knocked out for a split second and seeing a bright flash of light. Two guys started beating him, kicking him in the head as he tried to fight back. Later that night, doctors diagnosed Padgett with a severe concussion and a bleeding kidney, and sent him home with pain medications, he said.
Soon after the attack, Padgett suffered from PTSD and debilitating social anxiety. But at the same time, he noticed that everything looked different. He describes his vision as "discrete picture frames with a line connecting them, but still at real speed." If you think of vision as the brain taking pictures all thes the frames without the smoothing. In addition, "everything has a pixilated look," he said.
"I see this image in my mind's eye, now in 3-D, every time imagine how my hand moves through space-time."
With Padgett's new vision came an astounding mathematical drawing ability. He started sketching circles made of overlapping triangles, which helped him understand the concept of pi, the ratio of a circle's circumference to its diameter. There's no such thing as a perfect circle, he said, which he knows because he can always see the edges of a polygon that approximates the circle.
Padgett dislikes the concept of infinity, because he sees every shape as a finite construction of smaller and smaller units that approach what physicists refer to as the Planck length, thought to be the shortest measurable length.
After his injury, Padgett was drawing complex geometric shapes, but he didn't have the formal training to understand the equations they represented. One day, a physicist spotted him making these drawings in a mall, and urged him to pursue mathematical training. Now Padgett is a sophomore in college and an aspiring number theorist.
Padgett's remarkable abilities garnered the interest of neuroscientists who wanted to understand how he developed them.
Beautiful mind
Berit Brogaard, a philosophy professor now at the University of Miami, in Coral Gables, Florida, and her colleagues scanned Padgett's brain with functional magnetic resonance imaging (fMRI) to understand how he acquired his savant skills and the synesthesia that allows him to perceive mathematical formulas as geometric figures. (Synesthesia is a phenomenon in which one sense bleeds into another.)
"Acquired savant syndrome is very rare," Brogaard said, adding that only 15 to 25 cases have ever been described in medical studies.
Functional magnetic resonance imaging measures changes in blood flow and oxygen use throughout the brain. During scans of Padgett, the researchers showed the man real and nonsense mathematical formulas meant to conjure images in his mind.
The resulting scans showed significant activity in the left hemisphere of Padgett's brain, where mathematical skills have been shown to reside. His brain lit up most strongly in the left parietal cortex, an area behind the crown of the head that is known to integrate information from different senses. There was also some activation in parts of his temporal lobe (involved in visual memory, sensory processing and emotion) and frontal lobe (involved in executive function, planning and attention).
But the fMRI only showed what areas were active in Padgett's brain. In order to show these particular areas were causing the man's synesthesia, Brogaard's team used transcranial magnetic stimulation (TMS), which involves zapping the brain with a magnetic pulse that activates or inhibits a specific region. When they zapped the parts of Padgett's parietal cortex that had shown the greatest activity in the fMRI scans, it made his synesthesia fade or disappear, according to a study published in August 2013 in the journal Neurocase.
Brogaard showed, in another study, that when neurons die, they release brain-signaling chemicals that can increase brain activity in surrounding areas. The increased activity usually fades over time, but sometimes it results in structural changes that can cause brain-activity modifications to persist, Brogaard told Live Science.
Scientists don't know whether the changes in Padgett's brain are permanent, but if he had structural changes, it's more likely his abilities are here to stay, Brogaard said.
The savant in everyone
So do abilities like Padgett's lie dormant in everyone, waiting to be uncovered? Or was there something unique about Padgett's brain to begin with?
Most likely, there is something dormant in everyone that Padgett tapped into, Brogaard said. "It would be quite a coincidence if he were to have that particular special brain and then have an injury," she said. "And he's not the only [acquired savant]."
In addition to head injuries, mental disease has also been known to reveal latent abilities. And Brogaard and others have done studies that suggest zapping the brains of normal people using TMS can temporarily bring out unusual mathematical and artistic skills.
It's always possible that having savant skills may come with trade-offs. In Padgett's case, he developed fairly severe post-traumatic stress disorder and obsessive-compulsive disorder, and he still finds it difficult to appear in public.
Yet Padgett wouldn't change his new abilities if he could. "It's so good, I can't even describe it," he said.
https://www.livescience.com/45349-brain-injury-turns-man-into-math-genius.html
See: https://www.youtube.com/watch?v=qX6ONPQGBfo
Padgett, a furniture salesman from Tacoma, Washington, who had very little interest in academics, developed the ability to visualize complex mathematical objects and physics concepts intuitively. The injury, while devastating, seems to have unlocked part of his brain that makes everything in his world appear to have a mathematical structure.
"I see shapes and angles everywhere in real life" — from the geometry of a rainbow, to the fractals in water spiraling down a drain, Padgett told Live Science. "It's just really beautiful."
Padgett, who just published a memoir with Maureen Seaberg called "Struck by Genius" (Houghton Mifflin Harcourt, 2014), is one of a rare set of individuals with acquired savant syndrome, in which a normal person develops prodigious abilities after a severe injury or disease. Other people have developed remarkable musical or artistic abilities, but few people have acquired mathematical faculties like Padgett's.
Now, researchers have figured out which parts of the man's brain were rejiggered to allow for such savant skills, and the findings suggest such skills may lie dormant in all human brains.
'Struck by genius'
Before the injury, Padgett was a self-described jock and partyer. He hadn't progressed beyond than pre-algebra in his math studies. "I cheated on everything, and I never cracked a book," he said.
But all that would change the night of his attack. Padgett recalls being knocked out for a split second and seeing a bright flash of light. Two guys started beating him, kicking him in the head as he tried to fight back. Later that night, doctors diagnosed Padgett with a severe concussion and a bleeding kidney, and sent him home with pain medications, he said.
Soon after the attack, Padgett suffered from PTSD and debilitating social anxiety. But at the same time, he noticed that everything looked different. He describes his vision as "discrete picture frames with a line connecting them, but still at real speed." If you think of vision as the brain taking pictures all thes the frames without the smoothing. In addition, "everything has a pixilated look," he said.
"I see this image in my mind's eye, now in 3-D, every time imagine how my hand moves through space-time."
With Padgett's new vision came an astounding mathematical drawing ability. He started sketching circles made of overlapping triangles, which helped him understand the concept of pi, the ratio of a circle's circumference to its diameter. There's no such thing as a perfect circle, he said, which he knows because he can always see the edges of a polygon that approximates the circle.
Padgett dislikes the concept of infinity, because he sees every shape as a finite construction of smaller and smaller units that approach what physicists refer to as the Planck length, thought to be the shortest measurable length.
After his injury, Padgett was drawing complex geometric shapes, but he didn't have the formal training to understand the equations they represented. One day, a physicist spotted him making these drawings in a mall, and urged him to pursue mathematical training. Now Padgett is a sophomore in college and an aspiring number theorist.
Padgett's remarkable abilities garnered the interest of neuroscientists who wanted to understand how he developed them.
Beautiful mind
Berit Brogaard, a philosophy professor now at the University of Miami, in Coral Gables, Florida, and her colleagues scanned Padgett's brain with functional magnetic resonance imaging (fMRI) to understand how he acquired his savant skills and the synesthesia that allows him to perceive mathematical formulas as geometric figures. (Synesthesia is a phenomenon in which one sense bleeds into another.)
"Acquired savant syndrome is very rare," Brogaard said, adding that only 15 to 25 cases have ever been described in medical studies.
Functional magnetic resonance imaging measures changes in blood flow and oxygen use throughout the brain. During scans of Padgett, the researchers showed the man real and nonsense mathematical formulas meant to conjure images in his mind.
The resulting scans showed significant activity in the left hemisphere of Padgett's brain, where mathematical skills have been shown to reside. His brain lit up most strongly in the left parietal cortex, an area behind the crown of the head that is known to integrate information from different senses. There was also some activation in parts of his temporal lobe (involved in visual memory, sensory processing and emotion) and frontal lobe (involved in executive function, planning and attention).
But the fMRI only showed what areas were active in Padgett's brain. In order to show these particular areas were causing the man's synesthesia, Brogaard's team used transcranial magnetic stimulation (TMS), which involves zapping the brain with a magnetic pulse that activates or inhibits a specific region. When they zapped the parts of Padgett's parietal cortex that had shown the greatest activity in the fMRI scans, it made his synesthesia fade or disappear, according to a study published in August 2013 in the journal Neurocase.
Brogaard showed, in another study, that when neurons die, they release brain-signaling chemicals that can increase brain activity in surrounding areas. The increased activity usually fades over time, but sometimes it results in structural changes that can cause brain-activity modifications to persist, Brogaard told Live Science.
Scientists don't know whether the changes in Padgett's brain are permanent, but if he had structural changes, it's more likely his abilities are here to stay, Brogaard said.
The savant in everyone
So do abilities like Padgett's lie dormant in everyone, waiting to be uncovered? Or was there something unique about Padgett's brain to begin with?
Most likely, there is something dormant in everyone that Padgett tapped into, Brogaard said. "It would be quite a coincidence if he were to have that particular special brain and then have an injury," she said. "And he's not the only [acquired savant]."
In addition to head injuries, mental disease has also been known to reveal latent abilities. And Brogaard and others have done studies that suggest zapping the brains of normal people using TMS can temporarily bring out unusual mathematical and artistic skills.
It's always possible that having savant skills may come with trade-offs. In Padgett's case, he developed fairly severe post-traumatic stress disorder and obsessive-compulsive disorder, and he still finds it difficult to appear in public.
Yet Padgett wouldn't change his new abilities if he could. "It's so good, I can't even describe it," he said.
https://www.livescience.com/45349-brain-injury-turns-man-into-math-genius.html
See: https://www.youtube.com/watch?v=qX6ONPQGBfo
https://www.youtube.com/watch?v=GDU7lEmiiD8
See: Treffert DA, Treffert DA. The Sudden Savant: A New Form of Extraordinary Abilities. WMJ. 2021 Apr;120(1):69-73. PMID: 33974770.
Abstract
Introduction: Savant Syndrome previously has been characterized as either congenital or acquired. This report describes sudden savant syndrome in which neurotypical persons have the sudden emergence of savant skills without underlying disability or brain injury and without prior interest or ability in the newly emerged skill areas.
Case presentation: Eleven cases are described in which savant abilities suddenly and unexpectedly surfaced in neurotypical persons with no special prior interest or ability in the new skills, accompanied by an obsessive interest with and compulsive need to display the new abilities. All participants completed an online survey to record their demographics and skill characteristics.
Discussion: The acquired savant, and now the sudden savant, raise questions about the dormant potential for such buried skills in everyone. The challenge is to be able to tap such latent abilities without head injury or other precipitating events.
Conclusion: This paper documents 11 cases of sudden savant syndrome, which is a new and additional form of savant abilities surfacing in neurotypical persons without developmental disabilities (such as autism) or head or other brain injury (acquired savant syndrome). It opens new paths of inquiry for exploration of extraordinary abilities perhaps within everyone.
See: Treffert DA, Treffert DA. The Sudden Savant: A New Form of Extraordinary Abilities. WMJ. 2021 Apr;120(1):69-73. PMID: 33974770.
Abstract
Introduction: Savant Syndrome previously has been characterized as either congenital or acquired. This report describes sudden savant syndrome in which neurotypical persons have the sudden emergence of savant skills without underlying disability or brain injury and without prior interest or ability in the newly emerged skill areas.
Case presentation: Eleven cases are described in which savant abilities suddenly and unexpectedly surfaced in neurotypical persons with no special prior interest or ability in the new skills, accompanied by an obsessive interest with and compulsive need to display the new abilities. All participants completed an online survey to record their demographics and skill characteristics.
Discussion: The acquired savant, and now the sudden savant, raise questions about the dormant potential for such buried skills in everyone. The challenge is to be able to tap such latent abilities without head injury or other precipitating events.
Conclusion: This paper documents 11 cases of sudden savant syndrome, which is a new and additional form of savant abilities surfacing in neurotypical persons without developmental disabilities (such as autism) or head or other brain injury (acquired savant syndrome). It opens new paths of inquiry for exploration of extraordinary abilities perhaps within everyone.
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