Thursday, August 31, 2023

Clinical spectrum and treatment outcomes of patients with developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep

Tchah N, Yang D, Kim HD, Lee JS, Kim SH, Kang HC. Clinical Spectrum and Treatment Outcomes of Patients with Developmental and/or Epileptic Encephalopathy with Spike-and-Wave Activation in Sleep. Ann Child Neurol. 2022;30(4):189-196.


Developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep (D/EE-SWAS) is a spectrum of conditions characterized by various phenotypes of cognitive, linguistic, and behavioral regression associated with spike-and-wave activation in sleep. We aimed to investigate the phenotypic spectrum and treatment outcomes of pediatric patients with D/EE-SWAS.

We retrospectively analyzed the medical records of pediatric patients diagnosed with D/EE-SWAS and treated at Severance Children’s Hospital from 2006 to 2022. We extracted information from their medical records on electroencephalography before and after treatment, types of treatment, seizure frequency, and developmental profiles. The primary outcome was reduction of the spike-wave index on electroencephalography after treatment.

Twenty-one patients with a median age of 5.3 years (interquartile range, 4.1 to 6.6) at diagnosis were included. Ten patients had delayed development. The patients received various anti-seizure medications. Fourteen received long-term, high-dose steroid therapy, 10 were placed on a ketogenic diet, four received intravenous steroid pulse therapy, and one each was treated with intravenous immunoglobulin and cannabidiol. The most effective treatments were steroid therapy and a ketogenic diet, which were also effective in reducing seizures and improving cognition. Side effects during treatment were transient and treatable.

We described the clinical spectrum of pediatric patients with D/EE-SWAS. Steroid therapy and a ketogenic diet can be considered effective therapeutic options for patients with D/EE SWAS.

Wednesday, August 23, 2023

Iron and tic disorders

Inspired by a patient

Avrahami M, Barzilay R, HarGil M, Weizman A, Watemberg N. Serum Ferritin Levels Are Lower in Children With Tic Disorders Compared with Children Without Tics: A Cross-Sectional Study. J Child Adolesc Psychopharmacol. 2017 Mar;27(2):192-195. doi: 10.1089/cap.2016.0069. Epub 2016 Aug 22. PMID: 27548271.


Objectives: Alteration in peripheral iron indices has been reported in a number of movement disorders, particularly Parkinson's disease. We hypothesized that iron stores may be diminished in children at an early stage of tic disorder.

Methods: Using data retrieved from electronic medical records, we compared serum ferritin levels, an indicator of body iron store balance, in drug-naive children diagnosed for the first time with tic disorder (study group; N = 47, 32 boys/15 girls, aged 8.66 ± 3.17 years) compared to age- and sex-matched children with headaches (comparison group, n = 100, 62 boys/38 girls, aged 9.51 ± 3.15 years) treated in the same pediatric neurological clinic.

Results: Mean serum ferritin levels were significantly lower (-32%, p = 0.01) in the tic disorder group compared to the headache group. No significant differences were detected in circulatory hemoglobin, iron, transferrin, and platelet count between the two groups.

Conclusion: Our findings suggest that body iron stores may be reduced in children with recent-onset tic disorder.

Ghosh D, Burkman E. Relationship of serum ferritin level and tic severity in children with Tourette syndrome. Childs Nerv Syst. 2017 Aug;33(8):1373-1378. doi: 10.1007/s00381-017-3424-z. Epub 2017 May 3. PMID: 28470381.


Purpose: Tics can be considered hyperkinetic movements akin to restless leg syndrome (RLS). Drawing the analogy of iron deficiency as an etiology of RLS, it is conceivable that iron deficiency may underlie or worsen tics in Tourette syndrome (TS). The purpose of this study was to evaluate the relationship between serum ferritin levels and tic severity, as well as consequent impact on life, in children with TS.

Methods: Children <18 years, diagnosed with TS during 2009-2015, were reviewed. Only those with serum ferritin testing were included. The following data were collected: tic severity, impact on life, medication, comorbidities, blood count, and serum ferritin at diagnosis and follow-up.

Results: In fifty-seven patients, M:F = 2:1, serum ferritin was 48.0 ± 33.28 ng/mL, tic severity score 2.3 ± 0.80, impact on life score 2.2 ± 0.93, and composite score 4.57 ± 1.6. Serum ferritin was not influenced by comorbid obsessive compulsive disorder (OCD), attention deficit hyperactive disorder (ADHD), or anxiety (P > 0.16). Thirty-eight percent with low serum ferritin (≤50 ng/mL) (n = 37) had severe tics (>5 composite score), compared with 25% in normal ferritin group (n = 20). Over 6-12 months, tic severity score improved in both iron treated groups, deficient (2.70 to 1.90) and sufficient (2.40 to 1.95), whereas tics worsened or remained the same when not treated with iron.

Conclusions: Our data suggest iron deficiency may be associated with more severe tics with higher impact on TS children, independent of the presence of OCD, ADHD, or anxiety. Iron supplementation showed a trend towards improvement of tic severity upon follow-up. We suggest a double-blind, placebo-controlled prospective study to reach a definite conclusion.

Kanaan AS, Yu D, Metere R, Schäfer A, Schlumm T, Bilgic B, Anwander A, Mathews CA, Scharf JM, Müller-Vahl K, Möller HE. Convergent imaging-transcriptomic evidence for disturbed iron homeostasis in Gilles de la Tourette syndrome. Neurobiol Dis. 2023 Aug 2;185:106252. doi: 10.1016/j.nbd.2023.106252. Epub ahead of print. PMID: 37536382.


Gilles de la Tourette syndrome (GTS) is a neuropsychiatric movement disorder with reported abnormalities in various neurotransmitter systems. Considering the integral role of iron in neurotransmitter synthesis and transport, it is hypothesized that iron exhibits a role in GTS pathophysiology. As a surrogate measure of brain iron, quantitative susceptibility mapping (QSM) was performed in 28 patients with GTS and 26 matched controls. Significant susceptibility reductions in the patients, consistent with reduced local iron content, were obtained in subcortical regions known to be implicated in GTS. Regression analysis revealed a significant negative association of tic scores and striatal susceptibility. To interrogate genetic mechanisms that may drive these reductions, spatially specific relationships between susceptibility and gene-expression patterns from the Allen Human Brain Atlas were assessed. Correlations in the striatum were enriched for excitatory, inhibitory, and modulatory neurochemical signaling mechanisms in the motor regions, mitochondrial processes driving ATP production and iron‑sulfur cluster biogenesis in the executive subdivision, and phosphorylation-related mechanisms affecting receptor expression and long-term potentiation in the limbic subdivision. This link between susceptibility reductions and normative transcriptional profiles suggests that disruptions in iron regulatory mechanisms are involved in GTS pathophysiology and may lead to pervasive abnormalities in mechanisms regulated by iron-containing enzymes.

Tang CY, Wen F. Serum ferritin levels in children with attention deficit hyperactivity disorder and tic disorder. World J Clin Cases. 2022 Aug 6;10(22):7749-7759. doi: 10.12998/wjcc.v10.i22.7749. PMID: 36158507; PMCID: PMC9372851.


Background: Iron plays an important role in neurodevelopmental functions in the brain. Serum ferritin levels are different in children with attention deficit hyperactivity disorder and tic disorder than in healthy children.

Aim: To explore the current status of iron deficiency in children with neurodevelopmental disorders and its sex and age effects.

Methods: A total of 1565 children with attention deficit hyperactivity disorder (ADHD), 1694 children with tic disorder (TD), 93 children with ASD and 1997 healthy control children were included between January 1, 2020, and December 31, 2021 at Beijing Children's Hospital. We describe the differences in age levels and ferritin levels between different disease groups and their sex differences. The differences between the sexes in each disease were analyzed using the t test. The incidence rate of low serum ferritin was used to describe the differences between different diseases and different age groups. A chi-square test was used to analyze the difference in the incidence of low serum ferritin between the disease group and the control group. Analysis of variance was used for comparisons between subgroups, and regression analysis was used for confounding factor control.

Results: A total of 1565 ADHD patients aged 5-12 years were included in this study, and the average serum ferritin levels of male and female children were 36.82 ± 20.64 μg/L and 35.64 ± 18.56 μg/L, respectively. A total of 1694 TD patients aged 5-12 years were included in this study, and the average serum ferritin levels of male and female children were 35.72 ± 20.15 μg/L and 34.54 ± 22.12 μg/L, respectively. As age increased, the incidence of low serum ferritin in ADHD and TD first decreased and then increased, and 10 years old was the turning point of rising levels. The incidence of ADHD with low serum ferritin was 8.37%, the incidence of TD with low serum ferritin was 11.04%, and the incidence of the healthy control group with low serum ferritin was 8.61%, among which male children with TD accounted for 9.25% and female children with TD accounted for 11.62%. There was a significant difference among the three groups (P < 0.05). In addition, there were 93 children with ASD with an average serum ferritin level of 30.99 ± 18.11 μg/L and a serum ferritin incidence of 15.05%.

Conclusion: In conclusion, low serum ferritin is not a risk factor for ADHD or TD. The incidence of low serum ferritin levels in children with ADHD and TD between 5 and 12 years old decreases first and then increases with age.

Chen MH, Su TP, Chen YS, Hsu JW, Huang KL, Chang WH, Chen TJ, Bai YM. Association between psychiatric disorders and iron deficiency anemia among children and adolescents: a nationwide population-based study. BMC Psychiatry. 2013 Jun 4;13:161. doi: 10.1186/1471-244X-13-161. PMID: 23735056; PMCID: PMC3680022.


Background: A great deal of evidence has shown that iron is an important component in cognitive, sensorimotor, and social-emotional development and functioning, because the development of central nervous system processes is highly dependent on iron-containing enzymes and proteins. Deficiency of iron in early life may increase the risk of psychiatric morbidity.

Methods: Utilizing the National Health Insurance Database from 1996 to 2008, children and adolescents with a diagnosis of IDA were identified and compared with age and gender-matched controls (1:4) in an investigation of the increased risk of psychiatric disorders.

Results: A total of 2957 patients with IDA, with an increased risk of unipolar depressive disorder (OR = 2.34, 95% CI = 1.58 ~ 3.46), bipolar disorder (OR = 5.78, 95% CI = 2.23 ~ 15.05), anxiety disorder (OR = 2.17, 95% CI = 1.49 ~ 3.16), autism spectrum disorder (OR = 3.08, 95% CI = 1.79 ~ 5.28), attention deficit hyperactivity disorder (OR = 1.67, 95% CI = 1.29 ~ 2.17), tic disorder (OR = 1.70, 95% CI = 1.03 ~ 2.78), developmental delay (OR = 2.45, 95% CI = 2.00 ~ 3.00), and mental retardation (OR = 2.70, 95% CI = 2.00 ~ 3.65), were identified. A gender effect was noted, in that only female patients with IDA had an increased OR of bipolar disorder (OR = 5.56, 95% CI = 1.98 ~ 15.70) and tic disorder (OR = 2.95, 95% CI = 1.27 ~ 6.86).

Conclusion: Iron deficiency increased the risk of psychiatric disorders, including mood disorders, autism spectrum disorder, attention deficit hyperactivity disorder, and developmental disorders. Further study is required to clarify the mechanism in the association between IDA and psychiatric disorder.

Efficiency of brivaracetam in a tertiary referral epilepsy center.

Steinhoff BJ, Bacher M, Bucurenciu I, Hillenbrand B, Intravooth T, Kornmeier R, Kurth C, Stockinger J, Staack AM. Real-life experience with brivaracetam in 101 patients with difficult-to-treat epilepsy-A monocenter survey. Seizure. 2017 May;48:11-14. doi: 10.1016/j.seizure.2017.03.010. Epub 2017 Mar 18. PMID: 28364655.


Purpose: To assess the efficiency of brivaracetam under real-world conditions in a tertiary referral epilepsy center.

Methods: We consecutively collected patients treated at our center with brivaracetam (BRV). After a minimum observation period of six months we retrospectively analyzed the efficiency of BRV.

Results: Data of 101 patients (mean age 42 years, range 18-81 years, 54 females,) were analyzed. The median number of antiepileptic drugs (AEDs) used prior to BRV was 10 (range 2-18). The initial dose of BRV was at least 50mg per day, the mean maintenance dose at cut-off was 168.6mg (median 200mg, range 50-400mg). Efficacy data were assessed for the last three months or at the time of the last observation carried forward if BRV had been discontinued prematurely. Responder rate was 27.8% (n=28) with 7% seizure-free patients. Adverse events (AEs) occurred in 37 patients (37%). Most frequent AEs were dizziness (16%) and somnolence (11%). Psychiatric adverse events comprised irritability, aggression, depression and psychosis in single cases. Retention rate after six months was 51.5%. Main reason for discontinuation was a lack of efficacy. In 43 cases LEV and BRV were switched. The switch was performed abruptly without complications. In 26 cases (60%) BRV was discontinued and re-switched to LEV within weeks, mainly due to a lack of better efficacy. After the switch from LEV to BRV we even saw an aggravation both of seizure frequency and severity in 5 cases. Retention rate in patients who had not been on LEV was 57%.

Conclusion: In our hands BRV appeared to be well tolerated and easy to handle. The retention rate was influenced by patients who were switched from LEV and re-switched because BRV was not more efficient. Switching from and re-switching to LEV was easy.

Wednesday, August 16, 2023

1p36 deletion syndrome

Inspired by a patient

Jacquin C, Landais E, Poirsier C, Afenjar A, Akhavi A, Bednarek N, Bénech C, Bonnard A, Bosquet D, Burglen L, Callier P, Chantot-Bastaraud S, Coubes C, Coutton C, Delobel B, Descharmes M, Dupont JM, Gatinois V, Gruchy N, Guterman S, Heddar A, Herissant L, Heron D, Isidor B, Jaeger P, Jouret G, Keren B, Kuentz P, Le Caignec C, Levy J, Lopez N, Manssens Z, Martin-Coignard D, Marey I, Mignot C, Missirian C, Pebrel-Richard C, Pinson L, Puechberty J, Redon S, Sanlaville D, Spodenkiewicz M, Tabet AC, Verloes A, Vieville G, Yardin C, Vialard F, Doco-Fenzy M. 1p36 deletion syndrome: Review and mapping with further characterization of the phenotype, a new cohort of 86 patients. Am J Med Genet A. 2023 Feb;191(2):445-458. doi: 10.1002/ajmg.a.63041. Epub 2022 Nov 11. PMID: 36369750; PMCID: PMC10100125.


Chromosome 1p36 deletion syndrome (1p36DS) is one of the most common terminal deletion syndromes (incidence between 1/5000 and 1/10,000 live births in the American population), due to a heterozygous deletion of part of the short arm of chromosome 1. The 1p36DS is characterized by typical craniofacial features, developmental delay/intellectual disability, hypotonia, epilepsy, cardiomyopathy/congenital heart defect, brain abnormalities, hearing loss, eyes/vision problem, and short stature. The aim of our study was to (1) evaluate the incidence of the 1p36DS in the French population compared to 22q11.2 deletion syndrome and trisomy 21; (2) review the postnatal phenotype related to microarray data, compared to previously publish prenatal data. Thanks to a collaboration with the ACLF (Association des Cytogénéticiens de Langue Française), we have collected data of 86 patients constituting, to the best of our knowledge, the second-largest cohort of 1p36DS patients in the literature. We estimated an average of at least 10 cases per year in France. 1p36DS seems to be much less frequent than 22q11.2 deletion syndrome and trisomy 21. Patients presented mainly dysmorphism, microcephaly, developmental delay/intellectual disability, hypotonia, epilepsy, brain malformations, behavioral disorders, cardiomyopathy, or cardiovascular malformations and, pre and/or postnatal growth retardation. Cardiac abnormalities, brain malformations, and epilepsy were more frequent in distal deletions, whereas microcephaly was more common in proximal deletions. Mapping and genotype-phenotype correlation allowed us to identify four critical regions responsible for intellectual disability. This study highlights some phenotypic variability, according to the deletion position, and helps to refine the phenotype of 1p36DS, allowing improved management and follow-up of patients.

Greco M, Ferrara P, Farello G, Striano P, Verrotti A. Electroclinical features of epilepsy associated with 1p36 deletion syndrome: A review. Epilepsy Res. 2018 Jan;139:92-101. doi: 10.1016/j.eplepsyres.2017.11.016. Epub 2017 Dec 2. PMID: 29212048.


1p36 terminal deletion is a recently recognized syndrome with multiple congenital anomalies and intellectual disability. It occurs approximately in 1 out of 5000 to 10,000 live births and is the most common subtelomeric microdeletion observed in human. Medical problems commonly caused by terminal deletions of 1p36 include developmental delay, intellectual disability, seizures, vision problems, hearing loss, short stature, brain anomalies, congenital heart defects, cardiomyopathy, renal anomalies and distinctive facial features. Although the syndrome is considered clinically recognizable, there is significant phenotypic variation among affected individuals. Genotype-phenotype correlation in this syndrome is complicated, because of the similar clinical evidence seen in patients with different deletion sizes. We review 34 scientific articles from 1996 to 2016 that described 315 patients with 1p36 delection syndrome. The aim of this review is to find a correlation between size of the 1p36-deleted segments and the neurological clinical phenotypes with the analysis of electro-clinical patterns associated with chromosomal aberrations, that is a major tool in the identification of epilepsy susceptibility genes. Our finding suggest that developmental delay and early epilepsy are frequent findings in 1p36 deletion syndrome that can contribute to a poor clinical outcome for this reason this syndrome should be searched for in patients presenting with infantile spasms associated with a hypsarrhythmic EEG, particulary if they are combined with dismorphic features, severe hypotonia and developmental delay.

Carter LB, Battaglia A, Cherry A, Manning MA, Ruzhnikov MR, Bird LM, Dowsett L, Graham JM Jr, Alkuraya FS, Hashem M, Dinulos MB, Vallee S, Adam MP, Glass I, Beck AE, Stevens CA, Zackai E, McDougall C, Keena B, Peron A, Vignoli A, Seaver LH, Slavin TP, Hudgins L. Perinatal distress in 1p36 deletion syndrome can mimic hypoxic ischemic encephalopathy. Am J Med Genet A. 2019 Aug;179(8):1543-1546. doi: 10.1002/ajmg.a.61266. Epub 2019 Jun 17. PMID: 31207089; PMCID: PMC7254578.


1p36 deletion syndrome is a well-described condition with a recognizable phenotype, including cognitive impairment, seizures, and structural brain anomalies such as periventricular leukomalacia (PVL). In a large series of these individuals by Battaglia et al., "birth history was notable in 50% of the cases for varying degrees of perinatal distress." Given the potential for perinatal distress, seizures and PVL, we questioned if this disorder has clinical overlap with hypoxic ischemic encephalopathy (HIE). We reviewed the medical records of 69 individuals with 1p36 deletion to clarify the perinatal phenotype of this disorder and determine if there is evidence of perinatal distress and/or hypoxic injury. Our data provides evidence that these babies have signs of perinatal distress. The majority (59% term; 75% preterm) needed resuscitation and approximately 18% had cardiac arrest. Most had abnormal brain imaging (84% term; 73% preterm) with abnormal white matter findings in over half of patients. PVL or suggestion of "hypoxic insult" was present in 18% of term and 45% of preterm patients. In conclusion, individuals with 1p36 deletion have evidence of perinatal distress, white matter changes, and seizures, which can mimic HIE but are likely related to their underlying chromosome disorder.

Rocha CF, Vasques RB, Santos SR, Paiva CL. Mini-Review: Monosomy 1p36 syndrome: reviewing the correlation between deletion sizes and phenotypes. Genet Mol Res. 2016 Feb 22;15(1). doi: 10.4238/gmr.15017942. PMID: 26910004.


The major clinical features of monosomy 1p36 deletion are developmental delay and hypotonia associated with short stature and craniofacial dysmorphisms. The objective of this study was to review the cases of 1p36 deletion that was reported between 1999 and 2014, in order to identify a possible correlation between the size of the 1p36-deleted segment and the clinical phenotype of the disease. Scientific articles published in the (National Center for Biotechnology Information; NCBI and Scientific Electronic Library Online ( databases were searched using key word combinations, such as "1p36 deletion", "monosomy 1p36 deletion", and "1p36 deletion syndrome". Articles in English or Spanish reporting the correlation between deletion sizes and the respective clinical phenotypes were retrieved, while letters, reviews, guidelines, and studies with mouse models were excluded. Among the 746 retrieved articles, only 17 (12 case reports and 5 series of cases), comprising 29 patients (9 males and 20 females, aged 0 months (neonate) to 22 years) bearing the 1p36 deletions and whose clinical phenotypes were described, met the inclusion criteria. The genotype-phenotype correlation in monosomy 1p36 is a challenge because of the variability in the size of the deleted segment, as well as in the clinical manifestations of similar size deletions. Therefore, the severity of the clinical features was not always associated with the deletion size, possibly because of the other influences, such as stochastic factors, epigenetic events, or reduced penetration of the deleted genes.

Shimada S, Shimojima K, Okamoto N, Sangu N, Hirasawa K, Matsuo M, Ikeuchi M, Shimakawa S, Shimizu K, Mizuno S, Kubota M, Adachi M, Saito Y, Tomiwa K, Haginoya K, Numabe H, Kako Y, Hayashi A, Sakamoto H, Hiraki Y, Minami K, Takemoto K, Watanabe K, Miura K, Chiyonobu T, Kumada T, Imai K, Maegaki Y, Nagata S, Kosaki K, Izumi T, Nagai T, Yamamoto T. Microarray analysis of 50 patients reveals the critical chromosomal regions responsible for 1p36 deletion syndrome-related complications. Brain Dev. 2015 May;37(5):515-26. doi: 10.1016/j.braindev.2014.08.002. Epub 2014 Aug 27. PMID: 25172301.


Objective: Monosomy 1p36 syndrome is the most commonly observed subtelomeric deletion syndrome. Patients with this syndrome typically have common clinical features, such as intellectual disability, epilepsy, and characteristic craniofacial features.

Method: In cooperation with academic societies, we analyzed the genomic copy number aberrations using chromosomal microarray testing. Finally, the genotype-phenotype correlation among them was examined.

Results: We obtained clinical information of 86 patients who had been diagnosed with chromosomal deletions in the 1p36 region. Among them, blood samples were obtained from 50 patients (15 males and 35 females). The precise deletion regions were successfully genotyped. There were variable deletion patterns: pure terminal deletions in 38 patients (76%), including three cases of mosaicism; unbalanced translocations in seven (14%); and interstitial deletions in five (10%). Craniofacial/skeletal features, neurodevelopmental impairments, and cardiac anomalies were commonly observed in patients, with correlation to deletion sizes.

Conclusion: The genotype-phenotype correlation analysis narrowed the region responsible for distinctive craniofacial features and intellectual disability into 1.8-2.1 and 1.8-2.2 Mb region, respectively. Patients with deletions larger than 6.2 Mb showed no ambulation, indicating that severe neurodevelopmental prognosis may be modified by haploinsufficiencies of KCNAB2 and CHD5, located at 6.2 Mb away from the telomere. Although the genotype-phenotype correlation for the cardiac abnormalities is unclear, PRDM16, PRKCZ, and RERE may be related to this complication. Our study also revealed that female patients who acquired ambulatory ability were likely to be at risk for obesity.

Monday, August 14, 2023

Delayed response to pyridoxine in pyridoxine-dependent epilepsy

Olivier Fortin, Kelsey Christoffel, Youssef Kousa, Ilana Miller, Eyby Leon, Kelsey Donoho, Sarah B. Mulkey, Tayyba Anwar. Pearls & Oy-sters: Delayed Response to Pyridoxine in Pyridoxine-Dependent Epilepsy. Neurology Aug 2023, 10.1212/WNL.0000000000207829; DOI: 10.1212/WNL.0000000000207829


Inborn errors of metabolism are a diverse group of genetic disorders including many that cause neonatal-onset epilepsy such as pyridoxine-dependent epilepsy (PDE). PDE occurs secondary to biallelic pathogenic variants in ALDH7A1 and can present with refractory neonatal seizures and status epilepticus. Neonatal seizures and encephalopathy are modifiable with pyridoxine (vitamin B6) supplementation. However, the clinical response to pyridoxine supplementation can be delayed. We present the case of a full-term neonate with PDE in which seizure cessation was seen a few hours after intravenous pyridoxine load, but the improvement in EEG background and level of clinical encephalopathy occurred five days later. We share this case to provide an example in which clinical improvement in PDE was gradual and required continuation of treatment for several days illustrating the necessity of continuing vitamin B6 supplementation in suspected cases until confirmatory genetic testing is obtained or an alternate cause is found.

Peer victimization and suicidality associated with higher headache frequency

Christelle Nilles, Jeanne VA Williams, Scott Patten, Tamara Pringsheim, Serena L. Orr. Association Between Peer Victimization, Gender Diversity, Mental Health, and Recurrent Headaches in Adolescents: A Canadian Population-Based Study. Neurology Aug 2023, 10.1212/WNL.0000000000207738; DOI: 10.1212/WNL.0000000000207738


Background and objectives: It is unknown whether bullying and gender diversity are associated with increased headache frequency in adolescents. Our study aimed to assess the association between peer victimization, gender diversity, and frequent recurrent headaches in adolescents, while controlling for age, sex, socioeconomic status, and potential confounders (mood and anxiety disorders, suicidality).

Methods: This was a cross-sectional observational study of adolescents aged 12-17 using data from a Canadian population-based health survey. Headache frequency was dichotomized into ‘≤once/week’ or ‘>once/week’ (i.e. frequent recurrent headaches). Logistic regression was used to quantify the association between frequent peer victimization (overt or relational), gender diversity (female sex at birth+male gender, male sex at birth+female gender, or gender diverse), mood/anxiety disorder, suicidality, and the odds of frequent recurrent headaches. The fully adjusted multivariable logistic regression model included all exposures and was controlled for age, sex, and socioeconomic status. Bootstrap replicate weighting was used to account for survey design effects.

Results: There were an estimated 2,268,840 eligible participants (weighted sample size) (mean age=14.4y, 48.8% females, 0.5% gender diverse) and 11.2% reported frequent recurrent headaches. Frequent recurrent headaches were associated with older age (OR=1.26 per year of age, 95%CI=1.20-1.31), female sex (OR=2.89, 95%CI=2.47-3.37), and being gender diverse (OR=3.30, 95%CI=1.64-6.63, adjusted for age/sex). Youth with frequent headaches had higher odds of experiencing both overt and relational bullying compared to peers (OR=2.69, 95%CI=2.31-3.14, and OR=3.03, 95%CI=2.58-3.54, adjusted for age/sex). In the fully adjusted model, frequent headaches were no longer associated with gender diversity (OR=1.53, 95%CI=0.63-3.69), but were still associated with frequent overt and relational peer victimization (OR=1.82, 95%CI=1.41-2.34, and OR=1.54, 95%CI=1.17-2.03, respectively), suicidality (OR=1.83, 95%CI=1.44-2.32), and having a mood or anxiety disorder (OR=1.50, 95%CI=1.01-2.21, and OR=1.74, 95%CI=1.24-2.45, respectively). In a model adjusted for age, sex, and mood/anxiety disorders, the risk of suicidality increased incrementally with headache frequency.

Discussion: Peer victimization and suicidality may be associated with higher headache frequency in adolescents with headaches, independently of mood and anxiety symptoms. Gender diverse adolescents may have a higher risk of experiencing frequent headaches as compared to cisgender peers, and this may be explained by associated psychosocial factors (anxiety, depression, suicidality, peer victimization).

Adolescents who have been bullied or who have considered or attempted suicide may be more likely to experience frequent headaches than their peers who have not experienced bullying or suicidality, according to study results published online ahead of print in Neurology.

“Headaches are a common problem for teenagers, but our study looked beyond the biological factors to also consider the psychological and social factors that are associated with headaches,” said study author Serena L. Orr, MD, MSc, of the University of Calgary in Canada. “Our findings suggest that bullying and attempting or considering suicide may be linked to frequent headaches in teenagers, independent of mood and anxiety disorders.”

More than 2.2 million Canadian adolescents, ages 12 through 17, were included in the observational study. Participants answered question about their headache frequency, mental health, peer victimization, and suicidality.

Some 11% of adolescents reported having frequent, recurring headaches, defined as one or more headaches per week. Meanwhile, 25% of participants reported being victims of frequent overt bullying, which spanned physical and verbal aggression as well as virtual threats, and 17% reported being victims of frequent relational bullying, such as exclusion, rumors, and having harmful information about them posted online. According to the study, 17% of participants reported considering or attempting suicide.

Analysis indicated that adolescents with frequent headaches were nearly 3 times more likely to have experienced bullying compared with their peers. Teens who had been bullied or had suicidal thoughts or attempts were nearly twice as likely to have frequent headaches. Teens with mood disorders were 50% more likely, and teens with anxiety disorders were 74% more likely, to have frequent headaches compared with peers.

A third of teens with frequent headaches had suicidal thoughts or attempts compared with 14% of teens without frequent headaches.

An association between gender diversity and frequent headaches dissolved after researchers adjusted for factors including being bullied or having a diagnosed mood or anxiety disorder.

“Though gender diverse teens appear to have a higher risk of frequent, recurring headaches, this association disappears after controlling for bullying, anxiety, depression, and suicidal tendencies, suggesting that perhaps gender diversity is not, in and of itself, related to frequent headaches, but that the psychosocial factors associated with it may explain this link,” said Dr Orr. “This is important information because these factors are preventable and treatable, and as such, must be examined further.”

Friday, August 11, 2023

Foreign accent syndrome 4

Broderick A, Labriola MK, Shore N, et al. Foreign accent syndrome as a heralding manifestation of transformation to small cell neuroendocrine prostate cancer. BMJ Case Reports CP 2023;16:e251655.


A man in his 50s with metastatic hormone-sensitive prostate cancer, receiving androgen deprivation therapy and abiraterone acetate/prednisone, presented with an uncontrollable ‘Irish brogue’ accent despite no Irish background, consistent with foreign accent syndrome (FAS). He had no neurological examination abnormalities, psychiatric history or MRI of the brain abnormalities at symptom onset. Imaging revealed progression of his prostate cancer, despite undetectable prostate-specific antigen levels. Biopsy confirmed transformation to small cell neuroendocrine prostate cancer (NEPC). Despite chemotherapy, his NEPC progressed resulting in multifocal brain metastases and a likely paraneoplastic ascending paralysis leading to his death. We report FAS as the presenting manifestation of transformation to small cell NEPC, a previously undescribed phenomenon. His presentation was most consistent with an underlying paraneoplastic neurological disorder (PND), despite a negative serum paraneoplastic panel. This report enhances the minimal existing literature on FAS and PNDs associated with transformed NEPC.

Key Takeaways

Recently, a man suddenly woke up with an Irish accent after being diagnosed with cancer.

Foreign accent syndrome is a rare disorder that can be caused by tumors, brain injury, and other conditions.

A full medical care team will usually be needed to help a patient with foreign accent syndrome.

Imagine suddenly speaking with an accent that sounds like you were born and raised in, say, Italy or Jamaica. That’s what happens to patients with foreign accent syndrome (FAS), a rare condition that researchers are striving to better understand.

In a recent report of FAS published in BMJ Case Reports, researchers out of Duke University in Durham, North Carolina, and Carolina Urologic Research Center in South Carolina shared the story of a man in his 50s who developed the syndrome after a cancer diagnosis.

The individual in the case report was diagnosed with metastatic hormone-sensitive prostate cancer. Twenty months after his diagnosis, he developed “an uncontrollable ‘Irish brogue’ accent despite no Irish background,” according to the report’s authors. The man had never been to Ireland and had never spoken with an Irish accent prior to this point.

“He had no neurological examination abnormalities, psychiatric history, or MRI of the brain abnormalities at symptom onset,” the report stated.

What is foreign accent syndrome?

Foreign accent syndrome is real, although it’s rare. According to the Callier Center for Communication Disorders at the University of Texas at Dallas, FAS (which has also been referred to as pseudo-FAS and dysprosody) is a speech disorder that causes a sudden change to a person’s speaking speech patterns.

The onset of FAS can be sudden or gradual. “In [the case of the man in the report], it developed over days but worsened. It can be very quick,” Andrew J. Armstrong, MD, MSc, and Medical Oncologist at Duke Cancer Center, tells

The first case of FAS was reported in 1907. Since, there have been around 112 known cases, with FAS affecting people in multiple countries and in multiple ways. The accents in FAS are all over the spectrum, with people whose American accents became Caribbean or whose Japanese accents became Chinese.

FAS patients’ accents are perceived as “foreign,” largely due to changes in the “timing, intonation, and tongue placement” of the speaker. For example, some FAS patients may put stress on different syllables, while others have trouble pronouncing consonants clearly.

So when people with FAS speak in a French or Irish accent, for example, it’s not really French or Irish. “Although it is called foreign accent syndrome, the accents heard are not true accents of any specific language. Instead, they tend to sound like a mix of different accents or dialects,” says Nick Bach, PsyD.

The causes of FAS

“Stroke, trauma, brain tumors, and psychiatric conditions [are the main causes] of FAS,” says Armstrong. Cases of FAS have also been reported in psychiatry, in cases of mania, bipolar disorder, and schizophrenia, among other conditions. The researchers believe that paraneoplastic neurological disorder (PND)—effects caused by systemic malignancies that impact the nervous system—was ultimately the cause of FAS in the case report's individual. “The term PND is reserved for those disorders that are caused by an autoimmune response directed against antigens common to the tumor and nerve cells,” according to the Journal of Neurology, Neurosurgery & Psychiatry. According to the report, the patient’s biopsy revealed small-cell neuroendocrine prostate cancer (NEPC), which progressed despite treatment and led to multifocal brain metastases and paraneoplastic ascending paralysis.

The report suggests that this was the first case of FAS found in a patient with prostate cancer but the third case in a patient with malignancy.

“We have no other clear explanation other than a paraneoplastic syndrome given the timing, persistence of symptoms, lack of psychiatric conditions or metastases or lesions in the brain at the time of onset,” says Armstrong. “We provide this report in case future patients may be identified and hopefully a specific antibody may be identified to better explain why this happened.”

Treating FAS and supporting patients

Diagnosis of FAS will require testing your patient’s language skills and recording their speech patterns, as well as EEG, MRI, PT, CT, or PET scans. Treating the underlying issue—whether that be a neurological disorder or a tumor, for example—is the recommended form of treatment, Armstrong says. Treating FAS takes a village, and would ideally include a speech-language pathologist, a neurologist, a radiologist, a neuropsychologist, and a psychologist. Some cases of FAS have resolved without intervention, while others evolve or remain, according to ASHAWire.

While medical treatment is key, treating the psychological impact of FAS is also necessary, as developing a new accent can cause a loss of identity.Reader TMP. ‘I’ve lost my identity’: on the mysteries of foreign accent syndrome. The MIT Press Reader. Some patients say they’ve also faced discrimination when speaking in public or being accused of faking their accents.

Psychologists play a part in the care team

“When a patient has developed FAS, psychologists can help treat them in a number of ways,” Bach says.

“This may involve helping them to develop new communication strategies or to understand and accept the changes to their speech. Additionally, psychologists can also provide support and guidance to patients as they navigate challenges such as social isolation or discrimination."

“By working with a psychologist, patients with FAS can receive the specialized care and support they need to manage their condition.”

Bach advises MDs who may work with a FAS patient to have compassion. “I believe that it is essential for medical professionals to be able to understand the unique challenges that patients with FAS face,” Bach says.

“I think that developing a supportive relationship with patients is key in helping them manage their condition.”

Thursday, August 10, 2023

Occult brain tumor

Our dear friend, Liza Burke, desperately needs our help. Liza, a senior at UGA, was enjoying her last spring break in Cabo San Lucas with a big group of friends. She woke Friday morning feeling great. At breakfast, she complained of a headache and went back to the room to rest. A few hours later, her friends called the doctor because they couldn't wake her. She was immediately rushed to the hospital where she was diagnosed with Arteriovenous malformation (AVM) which cause her brain to hemorrhage. She is currently on life-support. Her family and doctors are working hard to give her the best medical treatment possible. They have agreed that she needs to return to the U.S. immediately to receive expert care from experienced doctors. So many people have reached out wanting to help which is a testament to how many people Liza has touched. She is genuine, dynamic, playful and fierce. She has so much left to give to the world. Please continue to pray for her full recovery. All donations will help fund her life-flight transport from Mexico to Jacksonville. Thank you for loving our sweet Liza...

Liza suffered a brain hemorrhage while on Spring Break with friends in Mexico on Friday, March 10. She spent 3 nights in a small, private hospital in Cabo San Lucas, where her life was saved. Your contributions enabled her family to cover hospital costs for her care in Cabo San Lucas and her air ambulance travel to Jacksonville, Florida where she will receive the best medical care possible. Our strong girl is fighting, and we are slowly seeing signs of improvement as she can squeeze her mom’s hand, move her limbs slightly, and nod or shake her head in response to questions. We are still unsure of what lies ahead as there remain so many unknowns. Liza's care team is doing all they can to work towards the next steps...

A lot has changed since our last update. A very talented team of doctors have been working hard on our sweet Liza to get a firm diagnosis. We know now that is not AVM, but a brain tumor located near her brain stem. We had a successful biopsy yesterday and the pathology team is working to determine exactly what we are dealing with.

From Laura (mom)

10:30am update. It's Friday, the last day for action before the hospital goes dormant for 2 days. Dormant like this tumor likely was for many years before it became aggressive in a very short time. Thankfully, our optimistic Dr. Trifiletti (radiologist) is pushing her radiation mask through for today-even if they need to make it while she is still on the ventilator. We won't have a full pathology report for a week but he intends to start radiation on Monday as soon as the mask is ready. She'll get 30 sessions daily M-F over the next 5-6 weeks. There are potential side effects but well worth the risk given the rapid growth. Currently Liza is breathing on her own but until she responds to our commands (toe wiggle, hand squeeze) the doctors are reluctant to remove the vent. Please pray for her responsiveness and her fighting spirit. She's the leader in this fight but we are her warriors marching into battle with her...

Our strong Liza began radiation treatments yesterday, which will continue daily over the next six weeks. Her incredible medical team, including the wonderful Dr. Q, confirms that she is battling an aggressive brain tumor. Results from the brain biopsy, expected later this week, will allow them to further determine more specifics and adjust her treatment plan as needed. The family has decided to re-open the GoFundMe as costs associated with her care far exceed any medical coverage. We are extraordinarily grateful for your support and continued prayers for Liza’s recovery. As her mom, Laura, said, “Liza’s the leader in this fight but we are her warriors marching into battle with her.”...

"It is with both relief and belief that I share Liza’s passing at around 2:20 last night. Liza has now been reunited with her sister and they are making up for lost time!

Celebrations of Liza’s big energy are in the planning stages: one in Athens and another at a later date in her hometown of Asheville...

The family and friends of Liza thank you for your continued support of Liza through your thoughts, prayers and donations. At this time, we are closing the donations and ask that you consider donating to the Liza and Edie Burke Foundation. Please see details below.

Eliza (Liza) Grace Burke arrived right on schedule on July 10, 2001 and wasted no time living life to the fullest. She cherished her siblings, Jack and Edie. As her older sister’s abilities declined from the effects of MPS1, Liza proudly assumed the role of little “big sister” until Edie’s death when Liza was only six. Liza was the youngest of ten children born in her neighborhood in one calendar year and, although she was the smallest, she was the fiercest and the undisputed leader of the pack. She was open to wonder and magic, and was frequently found resting with her head on the family sofa and her feet in the air. She was steadfast in her love for family and friends (offering encouragement or a tiny shoulder to cry on), much like her abundant respect and care for animals (fostering and socializing limitless kittens) as well as the planet (recycle and stop wasting the AC, people!).

Liza lived large, like every day could be her last. She was not only at ease in nature, she was intrepid—whether watching sunsets from a mountain top tent, swimming solo across any body of water, or surfing in Central America. As Liza matured, she accomplished more in 21 years than many people do in a lifetime. She spoke two languages, played guitar, traveled the world, went skydiving, hiked across a glacier, joyfully sang and danced — always without fear of judgement. When she decided to go to the University of Georgia, she did so because others told her they LOVED it, not because of where its education might take her. It was the experience that mattered to Liza. She had an innate way of bringing people together, making everyone feel loved, and sharing her contagious laugh with those she met.

Astronomers have determined that the brightest, hottest, and most active stars have the shortest lifespans. Liza is like one of those brightest stars. In her short time here, she gave off an extraordinary amount of light, energy, and love. Her life serves a reminder to go through life unapologetically, take chances, speak and act boldly, cherish the little things, laugh often, and to stay present.

Following a six-week battle with a previously-undiagnosed brain tumor, Liza transitioned into the next realm peacefully while being cared for by friends and family. Heaven is undoubtedly rejoicing at her arrival. But she will be missed by so many in her hometown of Asheville, NC, and home-away-from-home, Athens, GA. Her survivors look forward to the day that Liza guides them from this lifetime into their next big adventure. They include her mother Laura McKeithen (Bryan Mickler); father Tom Burke; brother Jack Burke; and grandparents Loy McKeithen (Susan); Kitty McKeithen and Dennis Burke along with countless aunts, uncles, cousins, and friends across the globe.


A college student fell unconscious on Spring Break: Her story sheds light on a rare brain disorder

Wednesday, August 9, 2023

Neurofibromatosis--mother and child

A Pennsylvania mother and her one-year-old son share an unusual bond. They are both living with the same rare genetic disease.

Lindsey Marson, 28, and her son, Bryson, were both born with Neurofibromatosis Type 1 (NF), "a genetic disorder that causes tumors to form throughout the body," according to Johns Hopkins Medicine.

The specific type of NF that Marson and her son have "is one of the most common inherited disorders and affects about one in every 3,000 people," the health care organization continued.

Even though the stay-at-home-mom and her baby have the same genetic disease, they are each impacted in different ways.

When Lindsey Marson was born, one of the hospital's nurses noticed several "light brown, flat patches" on her body — and indicated that this could be sign of NF, Marson told Fox News Digital.

As she continued to grow, her right leg started to curve into an "S" shape, called congenital pseudarthrosis of the tibia, another indicator of NF, she said. 

By the age of two, Marson was clinically diagnosed with NF Type 1.

Marson said that as a child, she had to have her leg lengthened and strengthened through an external fixation device, which ensures bones remain in an "optimal position during the healing process," according to the National Library of Medicine.

"I literally had 10 rods drilled through my bones. They came out through my skin, surrounded by a halo, and I had to turn pins each night that would separate the broken bone inside my leg," Marson said. 

"So that way new bone could grow, and my legs could catch up."

In spite of facing health challenges during her growing-up years, Marson was able to attend high school and even go on to beauty school before working at a hair salon for almost two years.

Being a hairdresser meant continuous standing. And even though Marson wears a brace full time, she found that long hours of sustained movement on her legs began to cause a great deal of pain, she said.

Marson left her salon and moved into a human resources position, which she said she loved because she calls herself a "people person."

"I wanted to change the dynamic of HR to employees or associates, because HR is always scary, and I never wanted to be the scary HR lady," Marson said.

"I wanted to be the one where people were like, ‘I can go to her for anything.'"

During her time in HR, Marson became pregnant with Bryson. Before that, she was doing research on genetic tests in the hope that he would not inherit the disease, she said.

"With NF, you have a 50% chance of passing along [the condition] to your child," Marson added.

Bryson was her "surprise blessing," as she likes to put it.

Marson said she chose to forgo any NF testing for her baby while she was pregnant, because she was planning on having the baby no matter the outcome.

One thing she learned along the way: NF presents itself differently for almost every person — even if people have the same type.

When Bryson was born, his eye was swollen and doctors at the time believed it was from birth trauma following her Caesarian section, Marson stated.

Shortly after giving birth, Marson took one-month-old Bryson to see an ophthalmologist, where he had an MRI.

"The MRI showed that he had a large plexiform tumor behind his eye, in his face and in part of his brain," Marson said.

By the time Bryson was three months old, the large tumor had grown — so he was taken to Children's Hospital of Philadelphia (CHOP) to start chemo.

He was put on MEK chemotherapy, an oral form of chemo that can administered at home.

While the chemo stabilized the tumor, side effects left Bryson with a severe rash — so Marson and Bryson's oncologist decided to stop administering the chemo, Marson said.

Surgery could not remove Bryson's tumor in its entirety because his particular tumor is "like a spider web throughout his face, his brain [and] his eye," Marson explained.

The tumor in Bryson's eye began compromising his vision, so a portion of the tumor was removed by his ophthalmologist.

Marson is now over a year old, but the tumors in his face and brain have only continued to grow, Marson said after her son had another MRI in May.

Marson and her son went through genetic testing, and it lined up perfectly. 

They "have the exact same variant," she stated — but they have completely different symptoms.

"I saw that NF could be severe, but I totally thought, 'I didn't have it severe, so Bryson is not going to have it severe,'" she added.

While seeing her son struggle with NF has been difficult, Marson said her own diagnosis of the same genetic disease has made it slightly easier because she has a level of understanding her own parents did not have when she was growing up.

"We are definitely closer because of this. I mean, he is my little baby."

"It was still really scary, and I still felt extremely guilty," Marson said.

She added, "It was still hard, but it wasn't as hard because I knew all the terminology and I knew what to expect."

Marson believes the best thing a parent can do for a child is be an advocate — and find moments of positivity.

She started a Facebook page to educate others on the condition, hoping to bring awareness to NF and help others know how to recognize it in a child.

"We are definitely closer because of this. I mean, he is my little baby," Marson said of herself and her son.

"I feel like we have a stronger bond because of it and I know what he is going through, and I will be there for him 100% of the time," she said. 

This year, the Children's Tumor Foundation featured Marson and Bryson in a photo series with other parents and their children who are fighting NF together.

Tuesday, August 8, 2023

The study and use of psychedelics in cluster headache

Headache Horizons: The Study and Use of Psychedelics in Cluster Headache

Psychedelics have a history of use in headache disorders and evidence exists for their therapeutic benefit in cluster headache.

Risako A. Shirane, MD, MSc; Christopher H. Gottschalk, MD, FAHS; and Emmanuelle A.D. Schindler, MD, PhD, FAHS

Cluster headache (CH) is a rare primary headache disorder characterized by paroxysmal attacks of unilateral severe orbital or periorbital pain. Also known as suicide headache, CH is said to be the most intensely painful condition known to humankind. CH affects up to 0.1% of the population, with a significant male predominance. CH refers to the disorder; cluster attacks, to the paroxysms of head pain. People with episodic CH have pain attacks during cluster periods or cycles, which last from weeks to months. People with chronic CH have attacks year-round without a remission period (an extended attack-free period) for longer than 3 months. Cluster attacks occur up to 8 times per day, each lasting for 15 to 180 minutes. Because of its severity and propensity to occur overnight, CH has deleterious effects on sleep, as well as quality of life overall.

Abortive treatment in CH involves the inhalation of high-flow oxygen or use of parenteral triptan medication. The newest abortive therapy is noninvasive vagus nerve stimulation (gammaCore; electroCore, Rockaway, NJ). Preventive treatment, which suppresses attacks during cycles or in chronic CH, has included such medications as verapamil and lithium. The noninvasive vagus nerve stimulation device also can be used in preventive treatment, as can galcanezumab (Emgality; Eli Lilly, Indianapolis, IN), a monoclonal antibody against calcitonin gene-related peptide, for treatment of episodic CH. Transitional treatments in CH are short-term interventions that serve to suppress attack frequency or intensity, shorten cluster cycles, or induce temporary remission in chronic CH. Such treatments include pulse regimens with corticosteroid or dihydroergotamine, or anesthetic nerve blockade of occipital nerves or the sphenopalatine ganglion.

Whereas treatment options in CH have increased in recent years, their use often is limited by poor accessibility, low tolerability, or medical contraindications. Therefore, there is an ongoing need to identify other treatment options for CH. Emerging data suggest that psychedelic drugs possess therapeutic potential and do so in a novel way. In this brief narrative review, we explore the history of psychedelics in headache medicine and the existing evidence on their therapeutic benefits for CH.

Definition of a Psychedelic

In this review, we discuss classic psychedelics, which are a group of 5-hydoxytryptamine (5-HT) 2A receptor agonists that produce acute alterations in sensation, perception, mood, and consciousness. The most well-known classic psychedelics include psilocybin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), and mescaline. Reports of therapeutic benefits of psychedelic drugs exist for several neuropsychiatric disorders, including depression, obsessive-compulsive disorder, and substance use disorders, as well as chronic pain disorders. Unlike conventional medications, psychedelics show long-lasting (ie, months) therapeutic effects after limited dosing (ie, 1 to 3 doses) based on existing clinical reports. However, because of their acute intoxicating effects and associated regulatory concerns, psychedelics are not available for routine clinical use.

Drugs such as ketamine and 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) also produce acute psychedelic-like effects; however, they are not classic psychedelics, because of their distinct pharmacology. Although ketamine has been suggested to have abortive effects in CH,4 the effects do not appear to be long-lasting after limited dosing, as occurs with the classic psychedelics. MDMA does not appear to have beneficial effects in CH. One survey study suggested that MDMA extended the duration of a CH attack.

History of Psychedelics in Headache Medicine

Albert Hofmann, a Swiss chemist, created LSD in 1938 while seeking to identify a bronchoconstrictive and vasoconstrictive medicine. He first discovered the psychedelic effects of LSD in 1943 and later isolated psilocybin from Psilocybe mushrooms. Psychedelics were first investigated as treatments for headache disorders more than 60 years ago. Several medications routinely used in headache management share chemical or pharmacologic properties with psychedelic drugs. For example, triptans, dihydroergotamine (DHE), and methylsergide are all serotonergic compounds that share an indolamine structure with psilocybin, LSD, and DMT.

Scientific inquiry into the effects of psychedelics on CH remains limited, but a global community of people with CH has led the research initiative by sharing their experiences. The first documentation of disease self-management with a psychedelic was reported by an individual with episodic CH in the late 1990s, who posted on a CH website message board ( about therapeutic effects after ingestion of LSD (which was taken for recreational purposes). Despite initial resistance, reports of success using LSD and psilocybin mushrooms in CH spread among the CH community. Now, scientists are studying these patient-informed treatment regimens; controlled studies on the safety and therapeutic effects of psychedelics are starting to emerge.

Descriptive Studies

What appears to set psychedelics apart from other headache medicines is their reported ability to produce lasting therapeutic effects after small, limited doses (1 to 3). This is in stark contrast with conventional medications that are dosed daily (sometimes lifelong), and take weeks or months for the desired effects, and maximal effects, to occur. Although psychedelics have also been reported to abort CH attacks,7,8 given the short duration and high frequency of attacks in the disorder, this method of treatment is not practical.

Several descriptive studies have supported the ability of psychedelics to induce and prolong remission periods with limited administration of low doses and subhallucinogenic doses7-11. A small survey of people with CH in 2006 showed that 88% and 52% of respondents found LSD and psilocybin to be effective preventive agents, respectively. A more recent online survey of nearly 500 people with CH showed that psilocybin, LSD, and lysergic acid amide (LSA; a psychedelic found in morning glory seeds) were significantly more effective than verapamil and prednisone in preventing CH attacks. A review of CH survey studies identified consistency among reports of psilocybin and LSD preventive effectiveness. Psilocybin is the most commonly tried psychedelic in these surveys11 and individuals reported dosing from every few weeks to twice annually. Low and subpsychedelic doses of LSD and psilocybin are reported to be used, and in a case series, a nonhallucinogenic congener of LSD, 2-bromo-LSD (BOL-148), was also shown to break a CH cycle, reduce attack frequency and intensity, and induce remission.

Clinical Trials

Some small controlled clinical trials have evaluated the safety and efficacy of psilocybin. Studies of LSD in CH are ongoing or in preparation. The first randomized controlled study of psilocybin in CH13 used a patient-informed, low-dose pulse regimen and demonstrated safety of psilocybin with no unexpected or serious adverse events. The weekly attack frequency was moderately reduced in the experimental group in the first 3 weeks, and this was particularly notable among individuals with chronic CH. The change in attack frequency was not statistically significant (P=.251), likely because of the small sample size. The researchers also observed separation of therapeutic and acute psychotropic effects. An extension phase of this study has completed and will begin to inform on the safety and efficacy of repeating the psilocybin pulse regimen (Psilocybin for the Treatment of Cluster Headache, NCT02981173). A study with an open-label design, EPOCH (Prophylactic Effects of Psilocybin on Chronic Cluster Headache, NCT04280055), investigating the effects of the same low-dose psilocybin pulse in chronic CH showed that the treatment was safe, was well-tolerated, and reduced attack frequency by 30% (P=.008) (Table 2).

The small number of participants in each study limits reliability and generalizability of the findings. Even with ongoing work, differences in dosing regimens and outcomes among studies will limit the consolidation of findings. Larger, more representative trials are required, although there are unique logistic and methodologic challenges associated with both CH and psychedelic trials, including recruitment difficulty because of rarity of the disease, timing of drug administration in episodic cases, and controlling for comorbidities and polypharmacy.

Whereas the acute psychedelic effects are believed to be relevant in the therapeutic use of psychedelics in psychiatric disease, research of psilocybin in CH and migraine has demonstrated that the transitional therapeutic effects are independent of the psychedelic effects.13,15 This along with reports of the use of low and subpsychedelic doses by people with CH7,8 and the therapeutic effects of the nonpsychedelic compound BOL-148 in CH12 urge the consideration of an alternate mechanism of action. Researchers in the open-label EPOCH study performed functional MRI before and after psilocybin administration and found involvement of hypothalamic–diencephalic functional connectivity in treatment response.14 The relationship of treatment response to circadian and sleep systems is also being investigated in the Psilocybin for the Treatment of Cluster Headache clinical trial.


Psychedelics have emerged as a potential therapeutic drug class for CH. Their beneficial effects have been reported for decades, although the existing data from clinical trials are far from conclusive and must be interpreted with caution. Continued research on psychedelics is warranted, particularly as psychedelics may also offer a means to understand the pathogenesis of CH.

Monday, August 7, 2023

Water toxicity

An Indiana mom of two collapsed and died from water toxicity after drinking too much water in a short period of time, her family says.

Ashley Summers, 35, was near Monticello at Lake Freeman with her husband and two daughters over July 4th weekend when she was hospitalized with brain swelling, Ashley’s brother, Devon Miller, told WRTV.

"Someone said she drank four bottles of water in 20 minutes," Miller said. "I mean, an average water bottle is like 16 ounces, so that was 64 ounces that she drank in a span of 20 minutes. That’s half a gallon. That’s what you’re supposed to drink in a whole day."

The Mayo Clinic says that the daily fluid intake for women should be about 92 ounces, with 20% of daily fluids usually coming from foods.

Summers had said she was feeling dehydrated, lightheaded and had a headache, noting that she felt like she could not drink enough water, her family told the outlet.

The mom of two passed out in a garage and was rushed to a hospital.

Summers, however, never regained consciousness, and doctors said she died of water toxicity, according to the family.

"It was a shock to all of us," Miller said. "When they first started talking about water toxicity. It was like, ‘this is a thing?’"

Hyponatremia, also known as water toxicity, occurs when the concentration of sodium in your blood is abnormally low, according to the Mayo Clinic.

"When this happens, your body's water levels rise, and your cells begin to swell," the clinic says. "This swelling can cause many health problems, from mild to life-threatening."

To prevent hyponatremia, the clinic advises drinking water in moderation and to consider drinking sports beverages that contain electrolytes during endurance activities.

Summers was an organ donor and donated her heart, liver, lungs, kidneys and some of her long bone tissue to help save five other lives, her family said.

Rangan GK, Dorani N, Zhang MM, Abu-Zarour L, Lau HC, Munt A, Chandra AN, Saravanabavan S, Rangan A, Zhang JQJ, Howell M, Wong AT. Clinical characteristics and outcomes of hyponatraemia associated with oral water intake in adults: a systematic review. BMJ Open. 2021 Dec 9;11(12):e046539. doi: 10.1136/bmjopen-2020-046539. PMID: 34887267; PMCID: PMC8663108.


Introduction: Excessive water intake is rarely associated with life-threatening hyponatraemia. The aim of this study was to determine the clinical characteristics and outcomes of hyponatraemia associated with excess water intake.

Methods: This review was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All studies (case reports, observational or interventional studies) reporting excess water intake and hyponatraemia in adults (1946-2019) were included.

Results: A total of 2970 articles were identified and 177 were included (88.7% case reports), consisting of 590 patients. The mean age was 46±16 years (95% CI 44 to 48 years), 47% female, 52% had a chronic psychiatric disorder and 31% had no underlying condition. The median volume of water consumed and serum sodium at presentation was 8 L/day (95% CI 8.9 to 12.2 L/day) and 118 mmol/L (95% CI 116 to 118 mmol/L), respectively. The motivator for increased water consumption was psychogenic polydipsia (55%); iatrogenic (13%); exercise (12%); habitual/dipsogenic polydipsia (7%) and other reasons (13%). The clinical features on presentation were severe in 53% (seizures, coma); moderate in 35% (confusion, vomiting, agitation) and mild in 5% (dizziness, lethargy, cognitive deficit) and not reported in 5% of studies. Treatment was supportive in 41% of studies (fluid restriction, treatment of the underlying cause, emergency care), and isotonic and hypertonic saline was used in 18% and 28% of cases, respectively. Treatment-related complications included osmotic demyelination (3%) and rhabdomyolysis (7%), and death occurred in 13% of cases.

Conclusion: Water intoxication is associated with significant morbidity and mortality and requires daily intake to substantially exceed population-based recommendations. The limitations of this analysis are the low quality and high risk of bias of the included studies.

Bafarat AY, Labban SA, Alhatmi N, Aly H, Bashah DM, Alshaiki F. Hyponatremia-Induced Seizure in a Patient With Psychogenic Polydipsia: A Case Report. Cureus. 2023 Apr 17;15(4):e37710. doi: 10.7759/cureus.37710. PMID: 37206512; PMCID: PMC10191386.


Psychogenic polydipsia is a rare condition characterized by overconsumption of water. It can lead to water intoxication, which is potentially a life-threatening situation. Moreover, it usually occurs in patients with mental disorders, mainly schizophrenia. This report discusses a successful treatment of a 16-year-old male with psychogenic polydipsia and delusional disorder presenting to the emergency room with a hyponatremia-induced seizure. After stabilizing the patient, he was referred to a psychologist, and behavioral therapy was conducted. Post-discharge follow-ups revealed that behavioral therapy and the use of self-monitoring technique were effective in controlling the patient's condition. His water intake was reduced from 15 liters per day to three liters per day. This case highlights the importance of psychological assessment for patients with features suggestive of psychogenic polydipsia. It also highlights the need for immediate admission and prompt treatment for such patients as it is a high-risk condition.

Sunday, August 6, 2023

COACH syndrome

Inspired by a colleague's patient

Sambharia M, Freese ME, Donato F, Bathla G, Abukhiran IMM, Dantuma MI, Mansilla MA, Thomas CP. Suspected Autosomal Recessive Polycystic Kidney Disease but Cerebellar Vermis Hypoplasia, Oligophrenia Ataxia, Coloboma, and Hepatic Fibrosis (COACH) Syndrome in Retrospect, A Delayed Diagnosis Aided by Genotyping and Reverse Phenotyping: A Case Report and A Review of the Literature. Nephron. 2023 Jan 6:1-9. doi: 10.1159/000527991. Epub ahead of print. PMID: 36617405.


The clinical features of cerebellar vermis hypoplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis (COACH) characterize the rare autosomal recessive multisystem disorder called COACH syndrome. COACH syndrome belongs to the spectrum of Joubert syndrome and related disorders (JSRDs) and liver involvement distinguishes COACH syndrome from the rest of the JSRD spectrum. Developmental delay and oculomotor apraxia occur early but with time, these can improve and may not be readily apparent or no longer need active medical management. Congenital hepatic fibrosis and renal disease, on the other hand, may develop late, and the temporal incongruity in organ system involvement may delay the recognition of COACH syndrome. We present a case of a young adult presenting late to a Renal Genetics Clinic for evaluation of renal cystic disease with congenital hepatic fibrosis, clinically suspected to have autosomal recessive polycystic kidney disease. Following genetic testing, a reevaluation of his medical records from infancy, together with reverse phenotyping and genetic phasing, led to a diagnosis of COACH syndrome.

George A, Cogliati T, Brooks BP. Genetics of syndromic ocular coloboma: CHARGE and COACH syndromes. Exp Eye Res. 2020 Apr;193:107940. doi: 10.1016/j.exer.2020.107940. Epub 2020 Feb 4. PMID: 32032630; PMCID: PMC7310839.


Optic fissure closure defects result in uveal coloboma, a potentially blinding condition affecting between 0.5 and 2.6 per 10,000 births that may cause up to 10% of childhood blindness. Uveal coloboma is on a phenotypic continuum with microphthalmia (small eye) and anophthalmia (primordial/no ocular tissue), the so-called MAC spectrum. This review gives a brief overview of the developmental biology behind coloboma and its clinical presentation/spectrum. Special attention will be given to two prominent, syndromic forms of coloboma, namely, CHARGE (Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, and Ear anomalies/deafness) and COACH (Cerebellar vermis hypoplasia, Oligophrenia, Ataxia, Coloboma, and Hepatic fibrosis) syndromes. Approaches employed to identify genes involved in optic fissure closure in animal models and recent advances in live imaging of zebrafish eye development are also discussed.

Sanjeev RK, Kapoor S, Goyal M, Kapur R, Gleeson JG. Molar Tooth Sign with Deranged Liver Function Tests: An Indian Case with COACH Syndrome. Case Rep Pediatr. 2015;2015:385910. doi: 10.1155/2015/385910. Epub 2015 May 17. PMID: 26075130; PMCID: PMC4449927.


We report the first genetically proven case of COACH syndrome from the Indian subcontinent in a 6-year-old girl who presented with typical features of Joubert syndrome along with hepatic involvement. Mutation analysis revealed compound heterozygous missense mutation in the known gene TMEM67 (also called MKS3).

Brancati F, Iannicelli M, Travaglini L, Mazzotta A, Bertini E, Boltshauser E, D'Arrigo S, Emma F, Fazzi E, Gallizzi R, Gentile M, Loncarevic D, Mejaski-Bosnjak V, Pantaleoni C, Rigoli L, Salpietro CD, Signorini S, Stringini GR, Verloes A, Zabloka D, Dallapiccola B, Gleeson JG, Valente EM; International JSRD Study Group. MKS3/TMEM67 mutations are a major cause of COACH Syndrome, a Joubert Syndrome related disorder with liver involvement. Hum Mutat. 2009 Feb;30(2):E432-42. doi: 10.1002/humu.20924. PMID: 19058225; PMCID: PMC2635428.


The acronym COACH defines an autosomal recessive condition of Cerebellar vermis hypo/aplasia, Oligophrenia, congenital Ataxia, Coloboma and Hepatic fibrosis. Patients present the "molar tooth sign", a midbrain-hindbrain malformation pathognomonic for Joubert Syndrome (JS) and Related Disorders (JSRDs). The main feature of COACH is congenital hepatic fibrosis (CHF), resulting from malformation of the embryonic ductal plate. CHF is invariably found also in Meckel syndrome (MS), a lethal ciliopathy already found to be allelic with JSRDs at the CEP290 and RPGRIP1L genes. Recently, mutations in the MKS3 gene (approved symbol TMEM67), causative of about 7% MS cases, have been detected in few Meckel-like and pure JS patients. Analysis of MKS3 in 14 COACH families identified mutations in 8 (57%). Features such as colobomas and nephronophthisis were found only in a subset of mutated cases. These data confirm COACH as a distinct JSRD subgroup with core features of JS plus CHF, which major gene is MKS3, and further strengthen gene-phenotype correlates in JSRDs.

Thursday, August 3, 2023

Primary amebic meningoencephalitis 7

A high school senior from Georgia has died after becoming infected with what the state’s Department of Health says is a rare "brain-eating amoeba." 

The 17-year-old, named in media reports as Megan Ebenroth, passed away on July 22. 

"I’m still in shock," her mother, identified by the Atlanta Journal-Constitution as Christina Ebenroth, said to the newspaper. "But I can’t keep silent about her. She was extraordinary." 

The newspaper reports that Ebenroth, a straight-A student who had aspirations to go to the University of Georgia, went swimming in a lake with friends near her home in McDuffie County in early July before treatment for a migraine turned into an emergency room visit, hospitalization and intubation. 

"They were so caring, I had the best doctors and nurses. I don’t blame anyone," Christina Ebenroth told the Journal-Constitution. "This was an act of God. Right now, I’ve got to figure out why." 

The Georgia Department of Health, citing medical privacy law, told Fox News Digital on Thursday that it was not releasing the name of the individual after issuing a press release warning the public about the passing of a state resident from a "Naegleria fowleri infection, a rare infection which destroys brain tissue, causing brain swelling and usually death." 

"Naegleria fowleri is an amoeba (single-celled living organism) that lives in soil and warm, freshwater lakes, rivers, ponds, and hot springs," the department said. "Naegleria fowleri is not found in salt water, such as the ocean, and it is not found in properly treated drinking water and swimming pools." 

"Naegleria fowleri is commonly called the ‘brain-eating amoeba’ because it can cause a brain infection, primary amebic meningoencephalitis (PAM), when water containing the amoeba goes up the nose. It cannot infect people if swallowed and is not spread from person to person," added a press release from the agency. "Only about three people in the United States get infected each year, but these infections are usually fatal." 

The department said symptoms of such an infection usually start around day five, beginning with "severe headache, fever, nausea and vomiting and progress to stiff neck, seizures, and coma that can lead to death." 

It concluded by saying that "[t]hough the risk of infection is low, recreational water users should always assume there is a risk when they enter warm fresh water" and that there have been five other cases of Naegleria fowleri reported in Georgia since 1962. 

Ebenroth’s cause of death was ruled as a brain infection, WBJF reports. 

She was the president of her school’s Beta Club and vice president of its Spanish Club, in addition to being a member of her high school’s tennis team, according to the Atlanta Journal-Constitution. 

"We are deeply saddened by the death of THS Senior Megan Ebenroth on Saturday, July 22," Thomson High School said on its Facebook page, adding that "a time of prayer and balloon release" would be held in her memory.

Wednesday, August 2, 2023

Breakthrough ADHD treatment with random noise stimulation and cognitive training

Ornella, DK., Noam, M., Shachar, H. et al. Transcranial random noise stimulation combined with cognitive training for treating ADHD: a randomized, sham-controlled clinical trial. Transl Psychiatry 13, 271 (2023).


Non-invasive brain stimulation has been suggested as a potential treatment for improving symptomology and cognitive deficits in Attention-Deficit/Hyperactivity Disorder (ADHD), the most common childhood neurodevelopmental disorder. Here, we examined whether a novel form of stimulation, high-frequency transcranial random noise stimulation (tRNS), applied with cognitive training (CT), may impact symptoms and neural oscillations in children with ADHD. We conducted a randomized, double-blind, sham-controlled trial in 23 unmedicated children with ADHD, who received either tRNS over the right inferior frontal gyrus (rIFG) and left dorsolateral prefrontal cortex (lDLPFC) or sham stimulation for 2 weeks, combined with CT. tRNS + CT yielded significant clinical improvements (reduced parent-reported ADHD rating-scale scores) following treatment, compared to the control intervention. These improvements did not change significantly at a 3-week follow-up. Moreover, resting state (RS)-EEG periodic beta bandwidth of the extracted peaks was reduced in the experimental compared to control group immediately following treatment, with further reduction at follow-up. A lower aperiodic exponent, which reflects a higher cortical excitation/inhibition (E/I) balance and has been related to cognitive improvement, was seen in the experimental compared to control group. This replicates previous tRNS findings in adults without ADHD but was significant only when using a directional hypothesis. The experimental group further exhibited longer sleep onset latencies and more wake-up times following treatment compared to the control group. No significant group differences were seen in executive functions, nor in reported adverse events. We conclude that tRNS + CT has a lasting clinical effect on ADHD symptoms and on beta activity. These results provide a preliminary direction towards a novel intervention in pediatric ADHD.

Dakwar-Kawar O, Berger I, Barzilay S, Grossman ES, Cohen Kadosh R, Nahum M. Examining the Effect of Transcranial Electrical Stimulation and Cognitive Training on Processing Speed in Pediatric Attention Deficit Hyperactivity Disorder: A Pilot Study. Front Hum Neurosci. 2022 Jul 27;16:791478. doi: 10.3389/fnhum.2022.791478. PMID: 35966992; PMCID: PMC9363890.


Objective: Processing Speed (PS), the ability to perceive and react fast to stimuli in the environment, has been shown to be impaired in children with attention deficit hyperactivity disorder (ADHD). However, it is unclear whether PS can be improved following targeted treatments for ADHD. Here we examined potential changes in PS following application of transcranial electric stimulation (tES) combined with cognitive training (CT) in children with ADHD. Specifically, we examined changes in PS in the presence of different conditions of mental fatigue.

Methods: We used a randomized double-blind active-controlled crossover study of 19 unmedicated children with ADHD. Participants received either anodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (dlPFC) or transcranial random noise stimulation (tRNS), while completing CT, and the administration order was counterbalanced. PS was assessed before and after treatment using the MOXO-CPT, which measures PS in the presence of various conditions of mental fatigue and cognitive load.

Results: tRNS combined with CT yielded larger improvements in PS compared to tDCS combined with CT, mainly under condition of increased mental fatigue. Further improvements in PS were also seen in a 1-week follow up testing.

Conclusion: This study provides initial support for the efficacy of tRNS combined with CT in improving PS in the presence of mental fatigue in pediatric ADHD.

A breakthrough in treating attention-deficit/hyperactivity disorder could “significantly improve” the lives of children with the condition, experts said.

A new study found that brain stimulation combined with cognitive training can improve symptoms of ADHD.

“ADHD is one of the most common neurodevelopmental disorders affecting children across the world,” Ornella Dakwar-Kawar, a post-doctoral researcher at the Hebrew University of Jerusalem, said in a press release.

“Treating the condition with medication improves a child’s attention span and overall mood, however … there can be side effects including headache and a loss of appetite,” Dakwar-Kawar added.

“There is, therefore, a pressing need for developing and testing novel, non-pharmacological interventions for ADHD.”

ADHD symptoms include trouble paying attention, overactivity, and impulsive behaviors, according to the Centers for Disease Control and Prevention.

The CDC estimates that 6 million children in the US ages 3 to 17 have been diagnosed with ADHD.

The condition is usually treated with a combination of behavior therapy and medication.

Researchers at the University of Surrey and the Hebrew University conducted a clinical trial with 23 children ages 6 to 12 who were unmedicated.

The researchers administered a non-invasive brain stimulation with a mild electrical current running through two electrodes.

Cognitive treatment included problem-solving and reading comprehension.

After two weeks, 55% of the children showed significant clinical improvements in their ADHD symptoms, as reported by their parents, in comparison to 17% of children in the control group who received placebo brain stimulation.

The improvements were maintained at three weeks post-trial, with 64% reporting positive effects from the treatment compared to 33% in the control group.

After two weeks, 55% of the children showed significant clinical improvements in their ADHD symptoms, as reported by their parents, in comparison to 17% of children in the control group who received placebo brain stimulation.

The improvements were maintained at three weeks post-trial, with 64% reporting positive effects from the treatment compared to 33% in the control group.

The study, published in the journal Translational Psychiatry, also found that participants had changes in their brain electrical activity patterns, even three weeks after treatment.

“I believe that the scientific community is duty-bound to investigate and develop ever more effective and longer-lasting treatments for ADHD,” said Roi Cohen Kadosh, co-lead of the study and professor of cognitive neuroscience at the University of Surrey.

“The findings we demonstrate in our study suggest that a combination of transcranial direct current stimulation (tRNS), which is shown to be safe with minimal side effects, has the potential to transform the lives of children and their families,” Kadosh added.

“The results from this proof-of-concept study, together with previous results we received using tRNS, increase our confidence that in the future non-invasive brain stimulation may be able to provide an alternative to medication as a treatment pathway for children,” Kadosh continued.

“However, our important test will be the results from a multi-center clinical trial with a larger sample that we will start soon.”

Scientists noted that further research and trials would need to be done to make brain stimulation a practical therapy for children with ADHD.

“This is an important first step in offering new therapeutic options for ADHD. Future studies, with larger and more varied samples, should help establish this as a viable therapy for ADHD, and help us understand the underlying mechanisms of the disorder,” said Dr. Mor Nahum, co-lead of the study and head of the Computerized Neurotherapy Lab at the Hebrew University.

“If the results will be replicated in future larger studies we will be able to offer a novel, promising non-invasive, and safe treatment to large number of children and their families not only in the field of ADHD but in other neurodevelopmental disorders,” said professor Itai Berger, co-lead of the study.

Sperm donation

A sperm donor fathered at least 15 children — without telling parents he's a carrier of a genetic disease causing low IQ and developmental delays

A UK sperm donor has fathered at least 15 kids without fully disclosing he's a carrier of fragile X, court documents say.

The condition can lead to low IQ and developmental and behavioral problems, especially in boys.

The man has been denied contact with some of his kids, and his name is public to protect future parents.

A UK sperm donor who says he's fathered 15 children did not explain to at least some of the mothers he has fragile X syndrome, an incurable genetic disease causing developmental delays and intellectual disability, according to court documents.

The 37-year-old man, James MacDougall, advertised himself as a private sperm donor to lesbian couples on Facebook. His condition would likely bar him from donating through a regulated bank.

Now, MacDougall's application to a family court in Derby, UK, to spend time with some of his children — despite his original agreements of no contact — have been denied. The judge, Justice Nathalie Lieven, said giving MacDougall parental responsibility for his children would cause them harm.

She said that although their original agreement does refer to fragile X syndrome, MacDougall failed to explain it to them and ensure they understood what it meant. MacDougall "took advantage of these young women's vulnerability and their strong desire to have children," Lieven said in the verdict.

The judge also made MacDougall's name public so that future prospective parents will know his history if they Google him. "The usual approach of anonymity in the family courts should not be used as a way for parents to behave in an unacceptable manner and then hide behind the cloak of anonymity," Lieven said.
The case involved three moms in their 20s

The case involved three partnered moms in their early 20s, one with two children fathered by MacDougall and two who each had one child with MacDougall's sperm. MacDougall wanted some parental rights for these children, though he seemed content to let the other women who've used his sperm stipulate the terms of their relationship, the court documents state.

The mom of two, called SW, told the court her 3-year-old child fathered by MacDougall is nonverbal and "has challenging behavior," court documents say. The documents illustrate a complicated relationship between the woman and MacDougall, who spent some time with the son and lived with the family during the initial COVID-19 lockdown.

But in June 2020, SW, who has learning difficulties of her own, asked MacDougall to leave, citing inappropriate behavior like making sexual advances and showering with the baby. Soon he was arrested after attacking her, though MacDougall said SW's bruises were likely the result of "playfighting" between her and her new partner. He said SW had used him for money.

The second mom, identified as EG, told the court she did not read the agreement including MacDougall's condition properly.

As for the third mom, KE, MacDougall had already been granted legal access to his biological son, who considered MacDougall his dad. But the toddler had recently suffered "nonaccidental bruises" under his care, court documents state, and the case is adjourned while social services investigates.

MacDougall's parents told the Daily Mail their son is a "victim." They adopted him as an abused baby, they said, and he lives on disability money while volunteering.

"He is kind-hearted and would do anything for anybody, but he is gullible," the mom said. "He just wanted to help those people, help those women in a gay relationship fulfill their dreams and become parents."

Fragile X syndrome can cause life-long impairments

Fragile X syndrome is the most common known cause of intellectual disability, according to the CDC, with about 1 in 7,000 males and 1 in 11,000 females diagnosed.

It tends to be more severe in boys and men: Boys with it have an average IQ under 55, while the average score in the general population is 100. By the time they're adults, 76% of women with the condition can read books with new words or ideas, compared to just 19% of men, the CDC reports.

The condition can cause learning disabilities and cognitive impairment, and kids with it may also have mental health conditions like attention deficit disorder, anxiety, and hyperactivity. About a third of fragile X patients meet criteria of autism spectrum disorder, according to the National Library of Medicine. Some are prone to seizures.

The condition can also lead to distinct physical features, like a long, narrow face, large ears, low muscle tone, and flat feet, according to the Cleveland Clinic. It's not life-threatening, and can be managed with medications and therapy.

Private sperm donation isn't uncommon

Being a carrier of fragile X makes it difficult if not impossible to donate to a sperm bank. At one California clinic, less than 1% of applicants make the cut after providing all their medical records and undergoing testing, US News previously reported.

Advertising sperm through social media means fewer stipulations for the donor, many of whom say they do it to help people build families. MacDougall told the court he originally became a donor to help a friend.

Private sperm donation also means far fewer costs for parents-to-be. One woman, Kayla Ellis, previously told Insider's Julia Naftulin how she and her wife conceived twice with one sperm donor for less than $300 (none of which went to the donor). In contrast, going to a bank for two children with the same biological father can cost about $10,000, the New York Times reported.

Ellis now helps educate others on sperm donation through TikTok. She required potential donors to give STD test results, undergo background checks, and sign a notarized contract for the agreement.

Still, there are legal risks — like the chance that a donor may want custody or a mom may want child support — as well as medical ones, as MacDougall's case shows. Home insemination, the typical mode of conception in these cases, can come with risks too, like cramping and infection.

A Maryland woman who was conceived via sperm donation recently took a DNA test and discovered that she has 65 brothers and sisters all over North America.

Brenna Siperko, a 20-year-old who was raised Ellicott City, Maryland, had known for most of her life that she was a sperm donor baby, but only recently found out how many siblings she has through her biological father’s donation.

In January 2022, Siperko took a 23andMe DNA test and found out that she had 13 siblings. Once she discovered them, they connected her to even more individuals who were conceived with the same father.

So far the young woman has discovered she has 65 half-siblings.

She told USA Today she had expected a least a few undiscovered members of her family, saying, "I had always thought I probably have siblings somewhere, or at least a couple since I come from a donor. I took my test and found out from 23andMe."

The discovery of dozens of blood relatives was "exciting" for Siperko, who grew up in an only-child household for much of her life with her mom and her stepdad. Eventually her parents had a son, but that was the extent of her family until she took the DNA test as a young woman.

She has gotten to know several of her newfound half-siblings, finding out that they not only share a biological father, but that many of them are around the same age and share similar interests.

She stated, "I found people my age. It was really exciting because I found people with common interests who I could become close to. They're really easy to talk to."

Siperko described her new family network, which she now engages in a family group chat, as a built-in support group. She told the outlet that whenever she has an issue or is excited to share something, she will text the group and they will give her feedback.

The young woman revealed that she has met at least six half-siblings who live in Maryland, noting that there are more of them in her home state than anywhere else in the country.

Among them is 27-year-old Fabiana, who lives in Baltimore. Siperko said that she and her other siblings look up to Fabiana as a wise older sister who they go to for advice.

"She’s kind of like the mom of the group, I suppose. She gives the best advice," Siperko claimed.

Her other sperm donor siblings are spread out throughout North America, with some living in Canada, Texas, New York, Florida, Michigan, New Jersey and California.

She also remarked that she sees plenty of physical resemblances among her and her newfound siblings.

Siperko stated, "A lot of our eyes are the same. It's like darker, more almond-shaped eyes … If you just put side-by-side pictures, you could definitely see the resemblance, kind of in the face shape, the eyebrows, sometimes the nose."

The young woman added, "It's weird to see myself in other people who I haven't known my whole life."

Though Siperko has been excited to meet her family, there has been controversy surrounding sperm donors and the massive families that can come from their donations.

Donor Sibling Registry co-founder and director Wendy Kramer, who helped connect Shiperko with 38 of her half siblings, mentioned the lack of regulations for donating sperm. Specifically, she claimed that clinic involved in the practice do not have "accurate record-keeping on the children born."

She told USA Today that it's irresponsible for this industry to create so many of these half-sibling families without keeping medical records of each member. Additionally, Kramer argued that clinics need to put a limit on how many children can be had from each donor.

The donor advocate stated, "It's just about a profit for selling sperm with no thought whatsoever given to the human beings they're helping to create."

Kramer also spoke from her own experience having a child via sperm donation, stating, "I used California Cryobank and my son has … half-siblings coast to coast, up and down, even in Puerto Rico. You never know where your half siblings can be."

Fox News Digital reached out to a major sperm bank for response to some of Kramer’s criticisms and is waiting for a response.