Thursday, June 29, 2023

The prevalence of parent-reported autism spectrum disorder among US children

Kogan MD, Vladutiu CJ, Schieve LA, Ghandour RM, Blumberg SJ, Zablotsky B, Perrin JM, Shattuck P, Kuhlthau KA, Harwood RL, Lu MC. The Prevalence of Parent-Reported Autism Spectrum Disorder Among US Children. Pediatrics. 2018 Dec;142(6):e20174161. doi: 10.1542/peds.2017-4161. PMID: 30478241; PMCID: PMC6317762.


Objectives: To estimate the national prevalence of parent-reported autism spectrum disorder (ASD) diagnosis among US children aged 3 to 17 years as well as their treatment and health care experiences using the 2016 National Survey of Children's Health (NSCH).

Methods: The 2016 NSCH is a nationally representative survey of 50 212 children focused on the health and well-being of children aged 0 to 17 years. The NSCH collected parent-reported information on whether children ever received an ASD diagnosis by a care provider, current ASD status, health care use, access and challenges, and methods of treatment. We calculated weighted prevalence estimates of ASD, compared health care experiences of children with ASD to other children, and examined factors associated with increased likelihood of medication and behavioral treatment.

Results: Parents of an estimated 1.5 million US children aged 3 to 17 years (2.50%) reported that their child had ever received an ASD diagnosis and currently had the condition. Children with parent-reported ASD diagnosis were more likely to have greater health care needs and difficulties accessing health care than children with other emotional or behavioral disorders (attention-deficit/hyperactivity disorder, anxiety, behavioral or conduct problems, depression, developmental delay, Down syndrome, intellectual disability, learning disability, Tourette syndrome) and children without these conditions. Of children with current ASD, 27% were taking medication for ASD-related symptoms, whereas 64% received behavioral treatments in the last 12 months, with variations by sociodemographic characteristics and co-occurring conditions.

Conclusions: The estimated prevalence of US children with a parent-reported ASD diagnosis is now 1 in 40, with rates of ASD-specific treatment usage varying by children's sociodemographic and co-occurring conditions.

SUDEP counseling: Where do we stand?

Whitney R, Jones KC, Sharma S, RamachandranNair R. SUDEP counseling: Where do we stand? Epilepsia. 2023 Jun;64(6):1424-1431. doi: 10.1111/epi.17617. Epub 2023 Apr 21. PMID: 37039574.


Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related death in children and adults living with epilepsy. Several recent clinical practice guidelines have recommended that all individuals living with epilepsy and their caregivers be informed about SUDEP as a part of routine epilepsy counseling. Furthermore, several studies over the last two decades have explored the state of SUDEP counseling. Patients with epilepsy and their families want to be informed about the risk of SUDEP at or near the time of diagnosis, and preferably in person. Despite guideline recommendations, many pediatric and adult neurologists do not routinely inform individuals with epilepsy and their families about SUDEP. Some neurologists discuss SUDEP with only a subset of patients with epilepsy, such as those with risk factors like frequent generalized or focal to bilateral tonic-clonic seizures, nocturnal seizures, noncompliance, or medically refractory epilepsy. Proponents of routine SUDEP counseling argue that patients with epilepsy and their families have a "right to know" and that counseling may positively impact epilepsy self-management (i.e., behavioral modification and risk reduction). Some neurologists still believe that SUDEP counseling may cause unnecessary stress and anxiety for patients and their families (although this is erroneous) and that they also have a "right not to know." This narrative review explores the current gaps in SUDEP counseling, patients' and caregivers' perspectives of SUDEP counseling, and SUDEP prevention.

Euthanasia for autism!

Netherlands programs have euthanized otherwise healthy individuals with autism and intellectual handicaps in recent years, researchers have found. 

Five individuals under the age of 30, who cited autism as a factor in their decision to seek legal euthanasia, are among the cases reviewed by specialists at the U.K.'s Kingston University. 

"Factors directly associated with intellectual disability and/or ASD were the sole cause of suffering described in 21% of cases and a major contributing factor in a further 42% of cases," Kingston University's report on the issue found. 

The study noted that in many cases, doctors determined there was "no prospect of improvement" for intellectually challenged individuals because there is no treatment for their handicap.

"Reasons for the EAS [euthanasia and physician-assisted suicide] request included social isolation and loneliness (77%), lack of resilience or coping strategies (56%), lack of flexibility (rigid thinking or difficulty adapting to change) (44%) and oversensitivity to stimuli (26%). In one-third of cases, physicians noted there was ‘no prospect of improvement’ as ASD and intellectual disability are not treatable," the study reads.

Palliative care specialist Irene Tuffrey-Wijne — one of the lead authors of the Kingston University report — found Dutch doctors were legally killing patients who sought their own euthanasia because their intellectual disability or mental condition prevented them from leading a normal life, according to The Associated Press.

One record includes the case of a Dutch woman in her 30s with autism and borderline personality disorder. Doctors determined her afflictions prevented her from maintaining relationships and made forming connections with others "too difficult."

"There’s no doubt in my mind these people were suffering," Tuffrey-Wijne said. "But is society really OK with sending this message, that there’s no other way to help them, and it’s just better to be dead?"

Dutch psychologist Dr. Bram Sizoo expressed horror at the trend of autistic youths seeking assisted suicide and euthanasia's expanding acceptance.

"Some of them are almost excited at the prospect of death," Sizoo said. "They think this will be the end of their problems and the end of their family’s problems."

The Royal Dutch Medical Association has left the decision of who qualifies for assisted suicide up to medical professionals with few hard guidelines or rules.

Normal outcome with prenatal intervention for riboflavin transporter defect

Elks N, Wilmshurst JM, Raga SV. Normal Outcome With Prenatal Intervention for Riboflavin Transporter Defect. Pediatr Neurol. 2023 Jul;144:16-18. doi: 10.1016/j.pediatrneurol.2023.04.004. Epub 2023 Apr 7. PMID: 37116404.


Background: Riboflavin transporter deficiency is a rare but severe neurometabolic disorder.

Methods: We report two siblings with pathogenic variants in SLC52A3 gene, resulting in riboflavin transporter 3 deficiency.

Results: The first sibling was diagnosed at age 11 months with severe respiratory compromise and regression of developmental milestones. His symptoms significantly improved with riboflavin supplementation therapy. The younger sibling was diagnosed by antenatal genetic analysis; riboflavin supplementation was initiated in utero and continued from birth. Now at age two years, he remains clinically asymptomatic despite genetic confirmation of riboflavin transporter deficiency.

Conclusions: Antenatal riboflavin supplementation is a safe and effective treatment for the prevention of symptomatic manifestations of riboflavin transporter deficiency.

Tuesday, June 27, 2023

Association of MTOR mutations with developmental brain disorders

Inspired by a patient. See:

Mirzaa GM, Campbell CD, Solovieff N, et al. Association of MTOR Mutations With Developmental Brain Disorders, Including Megalencephaly, Focal Cortical Dysplasia, and Pigmentary Mosaicism. JAMA Neurol. 2016;73(7):836–845. doi:10.1001/jamaneurol.2016.036


Importance Focal cortical dysplasia (FCD), hemimegalencephaly, and megalencephaly constitute a spectrum of malformations of cortical development with shared neuropathologic features. These disorders are associated with significant childhood morbidity and mortality.

Objective To identify the underlying molecular cause of FCD, hemimegalencephaly, and diffuse megalencephaly.

Design, Setting, and Participants Patients with FCD, hemimegalencephaly, or megalencephaly (mean age, 11.7 years; range, 2-32 years) were recruited from Pediatric Hospital A. Meyer, the University of Hong Kong, and Seattle Children’s Research Institute from June 2012 to June 2014. Whole-exome sequencing (WES) was performed on 8 children with FCD or hemimegalencephaly using standard-depth (50-60X) sequencing in peripheral samples (blood, saliva, or skin) from the affected child and their parents and deep (150-180X) sequencing in affected brain tissue. Targeted sequencing and WES were used to screen 93 children with molecularly unexplained diffuse or focal brain overgrowth. Histopathologic and functional assays of phosphatidylinositol 3-kinase–AKT (serine/threonine kinase)–mammalian target of rapamycin (mTOR) pathway activity in resected brain tissue and cultured neurons were performed to validate mutations.

Main Outcomes and Measures Whole-exome sequencing and targeted sequencing identified variants associated with this spectrum of developmental brain disorders.

Results Low-level mosaic mutations of MTOR were identified in brain tissue in 4 children with FCD type 2a with alternative allele fractions ranging from 0.012 to 0.086. Intermediate-level mosaic mutation of MTOR (p.Thr1977Ile) was also identified in 3 unrelated children with diffuse megalencephaly and pigmentary mosaicism in skin. Finally, a constitutional de novo mutation of MTOR (p.Glu1799Lys) was identified in 3 unrelated children with diffuse megalencephaly and intellectual disability. Molecular and functional analysis in 2 children with FCD2a from whom multiple affected brain tissue samples were available revealed a mutation gradient with an epicenter in the most epileptogenic area. When expressed in cultured neurons, all MTOR mutations identified here drive constitutive activation of mTOR complex 1 and enlarged neuronal size.

Conclusions and Relevance In this study, mutations of MTOR were associated with a spectrum of brain overgrowth phenotypes extending from FCD type 2a to diffuse megalencephaly, distinguished by different mutations and levels of mosaicism. These mutations may be sufficient to cause cellular hypertrophy in cultured neurons and may provide a demonstration of the pattern of mosaicism in brain and substantiate the link between mosaic mutations of MTOR and pigmentary mosaicism in skin.

Mirzaa GM, Campbell CD, Solovieff N, Goold C, Jansen LA, Menon S, Timms AE, Conti V, Biag JD, Adams C, Boyle EA, Collins S, Ishak G, Poliachik S, Girisha KM, Yeung KS, Chung BHY, Rahikkala E, Gunter SA, McDaniel SS, Macmurdo CF, Bernstein JA, Martin B, Leary R, Mahan S, Liu S, Weaver M, Doerschner M, Jhangiani S, Muzny DM, Boerwinkle E, Gibbs RA, Lupski JR, Shendure J, Saneto RP, Novotny EJ, Wilson CJ, Sellers WR, Morrissey M, Hevner RF, Ojemann JG, Guerrini R, Murphy LO, Winckler W, Dobyns WB. Association of MTOR Mutations With Developmental Brain Disorders, Including Megalencephaly, Focal Cortical Dysplasia, and Pigmentary Mosaicism. JAMA Neurol. 2016 Jul 1;73(7):836-845. doi: 10.1001/jamaneurol.2016.0363. PMID: 27159400; PMCID: PMC4979321.


Importance: Focal cortical dysplasia (FCD), hemimegalencephaly, and megalencephaly constitute a spectrum of malformations of cortical development with shared neuropathologic features. These disorders are associated with significant childhood morbidity and mortality.

Objective: To identify the underlying molecular cause of FCD, hemimegalencephaly, and diffuse megalencephaly.

Design, setting, and participants: Patients with FCD, hemimegalencephaly, or megalencephaly (mean age, 11.7 years; range, 2-32 years) were recruited from Pediatric Hospital A. Meyer, the University of Hong Kong, and Seattle Children's Research Institute from June 2012 to June 2014. Whole-exome sequencing (WES) was performed on 8 children with FCD or hemimegalencephaly using standard-depth (50-60X) sequencing in peripheral samples (blood, saliva, or skin) from the affected child and their parents and deep (150-180X) sequencing in affected brain tissue. Targeted sequencing and WES were used to screen 93 children with molecularly unexplained diffuse or focal brain overgrowth. Histopathologic and functional assays of phosphatidylinositol 3-kinase-AKT (serine/threonine kinase)-mammalian target of rapamycin (mTOR) pathway activity in resected brain tissue and cultured neurons were performed to validate mutations.

Main outcomes and measures: Whole-exome sequencing and targeted sequencing identified variants associated with this spectrum of developmental brain disorders.

Results: Low-level mosaic mutations of MTOR were identified in brain tissue in 4 children with FCD type 2a with alternative allele fractions ranging from 0.012 to 0.086. Intermediate-level mosaic mutation of MTOR (p.Thr1977Ile) was also identified in 3 unrelated children with diffuse megalencephaly and pigmentary mosaicism in skin. Finally, a constitutional de novo mutation of MTOR (p.Glu1799Lys) was identified in 3 unrelated children with diffuse megalencephaly and intellectual disability. Molecular and functional analysis in 2 children with FCD2a from whom multiple affected brain tissue samples were available revealed a mutation gradient with an epicenter in the most epileptogenic area. When expressed in cultured neurons, all MTOR mutations identified here drive constitutive activation of mTOR complex 1 and enlarged neuronal size.

Conclusions and relevance: In this study, mutations of MTOR were associated with a spectrum of brain overgrowth phenotypes extending from FCD type 2a to diffuse megalencephaly, distinguished by different mutations and levels of mosaicism. These mutations may be sufficient to cause cellular hypertrophy in cultured neurons and may provide a demonstration of the pattern of mosaicism in brain and substantiate the link between mosaic mutations of MTOR and pigmentary mosaicism in skin.

Yield of neurodiagnostic testing in children presenting to a pediatric emergency department with altered mental status

Camila Ospina Jimenez, Lalitha Sivaswamy, Giovanni Castellucci, Birce Taskin, Ahmad Farooqi, 
Nirupama Kannikeswaran. Yield of Neurodiagnostic Testing in Children Presenting to a Pediatric Emergency Department With Altered Mental Status. Pediatric Neurology. In press.


Background: Emergency department (ED) visits for altered mental status (AMS) in children are common. Neuroimaging is often performed to ascertain etiology, but its utility has not been well studied. Our objective is to describe the yield of neuroimaging studies in children who present to an ED with AMS. Methods: We performed a retrospective chart review of children 0-18 years of age, presenting to our PED between 2018 and 2021 with AMS. We abstracted patient demographics, physical examination, neuroimaging and EEG results, and final diagnosis. Neuroimaging and EEG studies were classified as normal or abnormal. Abnormal studies were categorized as clinically important and contributory: abnormalities that were clinically important and contributed to the etiology, clinically important but noncontributory: abnormalities that were clinically significant but did not explain the etiology, and incidental: abnormalities that were not clinically significant. Results: We analyzed 371 patients. The most common etiology of AMS was toxicologic (188, 51%) with neurologic causes (n = 50, 13.5%) accounting for a minority. Neuroimaging was performed in one-half (169, 45.5%) and abnormalities were noted in 44 (26%) studies. Abnormalities were clinically important and contributed to the etiologic diagnosis of AMS in 15/169 (8.9%), clinically important and noncontributory in 18/169 (10.7%), and incidental in 11/169 (6.5%). EEG was performed in 65 patients (17.5%), of which 17 (26%) were abnormal with only one being clinically important and contributory. Conclusions: Though neuroimaging was performed in approximately one half of the cohort, it was contributory in a minority. Similarly, diagnostic utility of EEG in children with AMS was low.

Monday, June 26, 2023

TANGO2 mutations 2

Dines JN, Golden-Grant K, LaCroix A, Muir AM, Cintrón DL, McWalter K, Cho MT, Sun A, Merritt JL, Thies J, Niyazov D, Burton B, Kim K, Fleming L, Westman R, Karachunski P, Dalton J, Basinger A, Ficicioglu C, Helbig I, Pendziwiat M, Muhle H, Helbig KL, Caliebe A, Santer R, Becker K, Suchy S, Douglas G, Millan F, Begtrup A, Monaghan KG, Mefford HC. TANGO2: expanding the clinical phenotype and spectrum of pathogenic variants. Genet Med. 2019 Mar;21(3):601-607. doi: 10.1038/s41436-018-0137-y. Epub 2018 Sep 24. Erratum in: Genet Med. 2018 Oct 15;: PMID: 30245509; PMCID: PMC6752277.


Purpose: TANGO2-related disorders were first described in 2016 and prior to this publication, only 15 individuals with TANGO2-related disorder were described in the literature. Primary features include metabolic crisis with rhabdomyolysis, encephalopathy, intellectual disability, seizures, and cardiac arrhythmias. We assess whether genotype and phenotype of TANGO2-related disorder has expanded since the initial discovery and determine the efficacy of exome sequencing (ES) as a diagnostic tool for detecting variants.

Methods: We present a series of 14 individuals from 11 unrelated families with complex medical and developmental histories, in whom ES or microarray identified compound heterozygous or homozygous variants in TANGO2.

Results: The initial presentation of patients with TANGO2-related disorders can be variable, including primarily neurological presentations. We expand the phenotype and genotype for TANGO2, highlighting the variability of the disorder.

Conclusion: TANGO2-related disorders can have a more diverse clinical presentation than previously anticipated. We illustrate the utility of routine ES data reanalysis whereby discovery of novel disease genes can lead to a diagnosis in previously unsolved cases and the need for additional copy-number variation analysis when ES is performed.

Sunday, June 25, 2023

De novo ATP1A3 variants cause polymicrogyria

Inspired by a patient

Miyatake S, Kato M, Kumamoto T,  Hirose T, Koshimizu E, Matsui T, Takeuchi H, Doi H, Hamada K, Nakashima M, Sasaki K, Yamashita A, Takata A, Hamanaka K, Satoh M, Miyama T, Sonoda Y, Sasazuki M, Torisu H, Hara T, Sakai Y, Noguchi Y, Miura M, Nishimura Y, Nakamura K, Asai H, Hinokuma N, Miya F, Tsunoda T, Togawa M, Ikeda Y, Kimura N, Amemiya K, Horino A, Fukuoka M, Ikeda H, Merhav G, Ekhilevitch N, Miura M, Mizuguchi T, Miyake N, Suzuki A, Ohga S, Saitsu H, Takahashi H, Tanaka F, Ogata K, Ohtaka-Maruyama C, Matsumoto N. De novo ATP1A3 variants cause polymicrogyria. Sci Adv. 2021 Mar 24;7(13):eabd2368. doi: 10.1126/sciadv.abd2368. PMID: 33762331; PMCID: PMC7990330.


Polymicrogyria is a common malformation of cortical development whose etiology remains elusive. We conducted whole-exome sequencing for 124 patients with polymicrogyria and identified de novo ATP1A3 variants in eight patients. Mutated ATP1A3 causes functional brain diseases, including alternating hemiplegia of childhood (AHC), rapid-onset dystonia parkinsonism (RDP), and cerebellar ataxia, areflexia, pes cavus, optic nerve atrophy, and sensorineural deafness (CAPOS). However, our patients showed no clinical features of AHC, RDP, or CAPOS and had a completely different phenotype: a severe form of polymicrogyria with epilepsy and developmental delay. Detected variants had different locations in ATP1A3 and different functional properties compared with AHC-, RDP-, or CAPOS-associated variants. In the developing cerebral cortex of mice, radial neuronal migration was impaired in neurons overexpressing the ATP1A3 variant of the most severe patients, suggesting that this variant is involved in cortical malformation pathogenesis. We propose a previously unidentified category of polymicrogyria associated with ATP1A3 abnormalities.

Monday, June 19, 2023

Premature declaration of death 2

An Ecuadorian woman who surprised guests at her wake by knocking on her coffin earlier this month died Friday after a week of intensive care.

Doctors declared 76-year-old Bella Montoya, a retired nurse, dead after she suffered a possible stroke and cardiopulmonary arrest. Ecuador’s health ministry said Montoya did not respond to resuscitation efforts.

Her family had previously gathered for a wake at a funeral home on June 9, just hours after Montoya was declared dead by doctors the first time. But everything came to a stop when they heard a sound coming from inside the coffin.

Montoya’s son, Gilberto Barbera, told the Associated Press the sound gave everyone a "fright." He also said his mother’s condition remained dire, and she was returned to the hospital immediately.

On Saturday morning, Barbera told the publication that doctors at the hospital where she was rushed after the wake confirmed Montoya died Friday evening.

According to the health ministry, Montoya died from an ischemic stroke.

The ministry added that she remained under "permanent surveillance" but did not give any more information about the investigation surrounding the case.

Barbera also said he did not receive an explanation as to what occurred, warning that things "are not going to stay like this."

He said Montoya’s sister filed a formal complaint about the incident and is looking to find out who the doctor was who declared her dead.

Montoya’s remains were sent back to the same funeral home where she previously regained consciousness, and her son said she will be buried at a public cemetery.

Wednesday, June 14, 2023

Seizures and daily headaches for the past month

What suddenly caused a state of altered consciousness in a 6-year-old child who had been having seizures and daily headaches for the past month? That's what physicians in India had to determine, as Vimal Kumar Paliwal, DM, of Sanjay Gandhi Postgraduate Institute of Medical Sciences in Lucknow, and co-authors recounted in JAMA Neurology.

At presentation, the child's caregivers explained that the child had started having a mild to moderate occipital headache every day starting about 1 month ago, which they described as pulsating in nature. Sometimes, when the headache became severe, it was accompanied by vomiting and sensitivity to light and sound.

The previous day, the boy had passed out for several hours after having four to five episodes of generalized tonic-clonic seizures. He had come to on his own over the course of the day, they said.

He had not had a fever, lost weight, or had limb weakness, changes in vision, or any signs of stroke. His birth and childhood development had been unremarkable.

On physical examination, clinicians noted that the patient's heart rate was regular at 80 beats per minute, and all peripheral pulses were palpable without any radio-femoral delay. Blood pressure was 170/110 mm Hg, with "less than 10 mm Hg difference of systolic and diastolic blood pressure in other limbs," the authors noted.

Clinicians performed an abdominal examination and noted abdominal bruit. An abdominal ultrasound showed that the patient had a small asymmetrical right kidney and an enlarged left kidney; likewise, renal Doppler findings suggested stenosis of the right renal artery.

Fundus examination revealed papilledema with changes suggestive of hypertensive retinopathy. The child was not oriented to place and time, they said.

Examination of the patient's cranial nerves, and motor, sensory, and autonomic system revealed nothing unusual. Meningeal signs were absent, and there was no evidence of neurocutaneous markers. An MRI of the patient's brain showed bilateral white matter hyperintensity that was especially pronounced on both sides of the parieto-occipital region.

Findings of a CT angiogram of the patient's abdomen included short segment and short circumferential thickening of the descending aorta with right renal artery narrowing, the team noted. A follow-up MRI of the brain showed that the white matter hyperintensities were significantly reduced.

Clinicians considered several conditions that might have caused the patient's symptoms, including atherosclerosis, Moyamoya disease with renovascular hypertension, and fibromuscular dysplasia, before settling on Takayasu arteritis.

They explained why they ruled out the differential diagnoses. Renovascular hypertension is often caused by atherosclerosis in adults, and by fibromuscular dysplasia in children, Paliwal and colleagues noted. This patient did not have any evidence of the characteristic atheroma at the bifurcation of the renal artery and abdominal aorta. The team ruled out possible atherosclerosis based on CT findings of atheroma at origin of the renal artery, and narrowing of the whole length of the right renal artery.

They determined that the patient did not have fibromuscular dysplasia, which "is a nonatherosclerotic, noninflammatory vascular disease that mainly affects coronary and renal arteries." Fibromuscular dysplasiaopens in a new tab or window generally involves the middle and distal two-thirds of the main renal artery, spares ostia, and rarely involves the aorta, they added; thus, the diagnosis was ruled out in this case.

Regarding the third diagnosis considered, "Moyamoya disease is a nonatherosclerotic cerebrovascular disease that presents with supraclinoid stenosis of internal carotid arteries and produces extensive collaterals," Paliwal and co-authors wrote.

The disease tends to present quite differently in children than it does in adults, they noted. For instance, pediatric presentation of Moyamoya diseaseopens in a new tab or window tends to involve cerebral ischemic events, as opposed to cerebral ischemia or intracerebral hemorrhage generally seen in adults. Children are also much less likely to present with renovascular hypertension, which has been observed in 5% to 8% of affected children versus 28.8% of adults, the authors said. In addition, Moyamoya disease affects only a third of the main renal artery, the ostia is spared, and the aorta only rarely involved.

In this patient, stenosis of the entire renal artery from its origin including the ostia, and thickening of the aorta wall, all suggested Takayasu arteritis as the correct diagnosis. This chronic granulomatous vasculitis "affects the tunica media of medium/large arteries and produces narrowing, stenosis, and aneurysmal dilatation of aorta and its branches," they wrote.

Takayasu arteritis "presents with an early systemic phase characterized by malaise, myalgia, weight loss, and fever, and the late vaso-occlusive phase that manifests with stroke, syncope, limb claudication, pulselessness, hypertension, and vascular bruit," Paliwal and team wrote.

Early systemic signs and symptoms tend to be missed in children, who are significantly more likely to have headache, cardiomyopathy, kidney failure, and elevated systolic blood pressure compared with adults.

The condition is also associated with elevations in biomarkers of inflammation, including C-reactive protein, erythrocyte sedimentation rate, fibrinogen, β-2-microglobulin, haptoglobin, and orosomucoid, although these are not diagnostic of Takayasu arteritis.

Evidence of hypertension, pulse deficit, or claudication; discrepancies in blood pressure in limbs and bruits; and abnormal findings on angiograms all support a Takayasu arteritis diagnosis.

Updated diagnostic criteria require "angiographic abnormality of the aorta or its main branches, coronaries, or pulmonary arteries not because of fibromuscular dysplasia or similar causes," the authors noted.

Similar conditions to rule out in diagnosing Takayasu arteritis include giant-cell arteritis with large vessel involvement in adults; medium-sized vasculitis with cross-symptomatology, such as Kawasaki disease with coronary involvement; polyarteritis nodosa that involves the mesentery and kidney; and lupus.

Takayasu arteritis can be managed by reduction of high blood pressure, treatment with oral corticosteroids, use of immunosuppressant medications to control disease activity, aspirin, and specific treatment for vaso-occlusive disease.

In this case, treatment with amlodipine and an ACE inhibitor relieved the child's headache and controlled his hypertension. The team prescribed oral corticosteroids but did not recommend kidney angioplasty, since a diethylenetriamine pentaacetic acid scan had revealed evidence of impaired right kidney function.

Posterior reversible encephalopathy syndrome rarely affects children, Paliwal and colleagues noted. It is most likely to occur in patients with acute lymphocytic leukemia who are starting chemotherapy, or less often, during hematopoietic stem cell transplantation.

However, "Takayasu arteritis frequently presents with hypertension in children, which makes it an ideal setting for the development of posterior reversible encephalopathy syndrome," they concluded.

Chavan A, Paliwal VK, Singh V. Posterior Reversible Encephalopathy Syndrome in a Child With Renovascular Hypertension. JAMA Neurol. Published online June 05, 2023. doi:10.1001/jamaneurol.2023.1501

Thursday, June 8, 2023

Social media checking behaviors in early adolescence and changes in the brain’s sensitivity to social rewards and punishments

Maza MT, Fox KA, Kwon SJ, Flannery JE, Lindquist KA, Prinstein MJ, Telzer EH. Association of Habitual Checking Behaviors on Social Media With Longitudinal Functional Brain Development. JAMA Pediatr. 2023 Feb 1;177(2):160-167. doi: 10.1001/jamapediatrics.2022.4924. Erratum in: JAMA Pediatr. 2023 Feb 13;: PMID: 36595277; PMCID: PMC9857400.

Key Points

Question Is adolescents’ frequency of checking behaviors on 3 social media platforms (Facebook, Instagram, Snapchat) associated with longitudinal changes in functional brain development across adolescence.

Findings In this cohort study of 169 sixth- and seventh-grade students, participants who engaged in habitual checking behaviors showed a distinct neurodevelopmental trajectory within regions of the brain comprising the affective salience, motivational, and cognitive control networks in response to anticipating social rewards and punishments compared with those who engaged in nonhabitual checking behaviors.

Meaning These results suggest that habitual checking of social media in early adolescence may be longitudinally associated with changes in neural sensitivity to anticipation of social rewards and punishments, which could have implications for psychological adjustment.


Importance Social media platforms provide adolescents with unprecedented opportunities for social interactions during a critical developmental period when the brain is especially sensitive to social feedback.

Objective To explore how adolescents’ frequency of checking behaviors on social media platforms is associated with longitudinal changes in functional brain development across adolescence.

Design, Setting, and Participants A 3-year longitudinal cohort study of functional magnetic resonance imaging (fMRI) among sixth- and seventh-grade students recruited from 3 public middle schools in rural North Carolina.

Exposures At wave 1, participants reported the frequency at which they checked Facebook, Instagram, and Snapchat.

Main Outcome or Measure Neural responses to the Social Incentive Delay task when anticipating receiving social feedback, measured annually using fMRI for 3 years. Participants saw a cue that indicated whether the social feedback (adolescent faces with emotional expressions) would be a reward, punishment, or neutral; after a delay, a target appeared and students responded by pressing a button as quickly as possible; a display of social feedback depended on trial type and reaction time.

Results Of 178 participants recruited at age 12 years, 169 participants (mean [SD] age, 12.89 [0.58] years; range, 11.93-14.52 years; 91 [53.8%] female; 38 [22.5%] Black, 60 [35.5%] Latinx, 50 [29.6%] White, 15 [8.9%] multiracial) met the inclusion criteria. Participants with habitual social media checking behaviors showed lower neural sensitivity to social anticipation at age 12 years compared with those with nonhabitual checking behaviors in the left amygdala, posterior insula (PI), and ventral striatum (VS; β, −0.22; 95% CI, −0.33 to −0.11), right amygdala (β, −0.19; 95% CI, −0.30 to −0.08), right anterior insula (AI; β, −0.23; 95% CI, −0.37 to −0.09), and left dorsolateral prefrontal cortex (DLPFC; β, −0.29; 95% CI, −0.44 to −0.14). Among those with habitual checking behaviors, there were longitudinal increases in the left amygdala/PI/VS (β, 0.11; 95% CI, 0.04 to 0.18), right amygdala (β, 0.09; 95% CI, 0.02 to 0.16), right AI (β, 0.15; 95% CI, 0.02 to 0.20), and left DLPFC (β, 0.19; 95% CI, 0.05 to 0.25) during social anticipation, whereas among those with nonhabitual checking behaviors, longitudinal decreases were seen in the left amygdala/PI/VS (β, −0.12; 95% CI, −0.19 to −0.06), right amygdala (β, −0.10; 95% CI, −0.17 to −0.03), right AI (β, −0.13; 95% CI, −0.22 to −0.04), and left DLPFC (β, −0.10, 95% CI, −0.22 to −0.03).

Conclusions and Relevance The results of this cohort study suggest that social media checking behaviors in early adolescence may be associated with changes in the brain’s sensitivity to social rewards and punishments. Further research examining long-term associations between social media use, adolescent neural development, and psychological adjustment is needed to understand the effects of a ubiquitous influence on development for today’s adolescents.


Using MRI brain scans, researchers at the University of North Carolina found that teens who frequently checked social media were more likely to see increased activation in the regions of the brain that regulate reward centers and those that may play a role in regulating decision-making around social situations...

The results showed that students who used social media more frequently had increased activation in parts of their brain, possibly making them more prone to peer feedback and hypersensitivity and possibly leading to changes in impulse control and regulation, according to ABC News chief medical correspondent Dr. Jennifer Ashton.

Although MRIs can measure changes in the brain, it's often not clear if those changes are temporary or permanent, nor is it clear whether those changes impact a person's overall well-being.

But Ashton, who was not a researcher on the study, said the study raises questions about whether changes in the brain can impact both short and long-term behavior...

The study does have limitations, including relying on self-reported accounts of social media use, which can be unreliable. It also did not include TikTok, one of the most popular social media apps among teens.

There are though known negative impacts of social media and screen time on young people's health.

"It's the same thing that we see with increased screen use in teens," Ashton said. "Anyone using a screen a lot, even on social media, obviously can have associated increased rates of obesity, irregular or dysregulated sleep, something that we know is very important, particularly in this age group, an increased risk of depression, and an overall decrease in [physical] activity."...

Ashton said parents should also encourage digital literacy in their kids, noting, "This isn't going away. We want to be able to use it and use it safely."

Assisted suicide becomes 3rd leading cause of death in Quebec

Canada looks set to face another record-shattering year of euthanasia deaths in 2023 after a reported 35 percent rise to some 13,500 state-sponsored suicides in 2022, an analysis of official data shows.

Regional health chiefs won’t release their formal tally for some weeks, but data from Ontario, Alberta, Quebec, and Nova Scotia already show steep rises in euthanasia deaths last year right across Justin Trudeau’s Canada, the Daily Mail reports. The data claim was shared with the outlet.

Based on already available state-level figures, the Euthanasia Prevention Coalition assessed MAID (Medical Assistance in Dying) cases rose from just over 10,000 in 2021 to around 13,500 in the next year, a 34 percent increase nationwide.

That number is forecast to rise again before this year is out with euthanasia already the 3rd leading cause of death in Quebec — seven percent of all deaths.

Canada legalized assisted suicide in 2016.

Euthanasia was initially limited to patients over the age of 18 suffering from a terminal illness — but, as critics predicted, the standards have been relentlessly loosened with every passing year.

Canada is one of only seven countries that allows medical professionals to administer lethal drugs to patients, rather than providing suicide formulations and requiring the patient to inject themselves. It is the only country that allows nurse practitioners to kill their patients.

Anti-euthanasia activists point to the “heavy promotion” of assisted suicide and the relative ease of access for the steep rise.

Daniel Zekveld, an analyst with ARPA Canada, a Christian advocacy group, said the country had created “one of the most permissive euthanasia regimes in the world” where deaths “steadily rise.”

“Safeguards continue to be relaxed and euthanasia is increasingly offered as an easy solution to suffering,” Zekveld told

“Instead of normalizing euthanasia and accepting the deaths of thousands of Canadians, Canada needs to promote suicide prevention and life-affirming care for all.”

Alberta, Ontario, and Quebec are among Canada’s most populous provinces and all recorded big increases in adults with a serious illness, disease, or disability opting for euthanasia last year.

Quebec alone saw a 51 percent uptick in MAiD deaths from 2,427 in financial year 2021 to 3,663 in 2022.

That means some seven percent of all deaths in Quebec are state-sanctioned, making it the third top cause of death in the province after cancer and heart disease.

Vancouver Archbishop J. Michael Miller said in 2022 Canada’s assisted suicide laws are “morally depraved.”

“In six years, Canada has gone from totally banning euthanasia to one of the most permissive euthanasia regimes in the world — and even more access could be coming, including allowing ‘mature minors’ to request it,” Miller said.

Montreal Rabbi Berel Bell agreed.

“From our viewpoint, every life has equal value … but when a life should end is not something that should be left up to human beings,” Bell said.

“Our Creator knows how and when to end lives, and He does it every day. And if a person that is alive, whatever the reason why they need to be alive is something beyond human comprehension,” Bell added.

Euthanasia is currently legal in only seven countries—including Belgium, Canada, Colombia, Luxembourg, the Netherlands, and Spain—as well as a few states in Australia.

Wednesday, June 7, 2023

Elevated levels of atypical handedness in autism

Markou P, Ahtam B, Papadatou-Pastou M. Elevated Levels of Atypical Handedness in Autism: Meta-Analyses. Neuropsychol Rev. 2017 Sep;27(3):258-283. doi: 10.1007/s11065-017-9354-4. Epub 2017 Jul 23. PMID: 28735387.


An elevated prevalence of atypical handedness (left-, mixed-, or non-right-handedness) has been repeatedly reported in individuals with Autism Spectrum Disorder (ASD) compared to typically developing individuals. However, the exact magnitude of this difference as well as the presence of possible moderating factors remains unknown. Here, we present three sets of meta-analyses of studies that assessed the handedness prevalence among individuals with ASD, totaling 1199 individuals (n = 723 individuals with ASD and n = 476 typically developing individuals). Meta-analysis set 1 found that individuals with ASD are 3.48, 2.49, and 2.34 times more likely to be non-right-handed, left-handed, and mixed-handed compared to typically developing individuals, respectively. Meta-analysis set 2 found a 45.4%, 18.3%, and 36.1% prevalence of non-right-handedness, left-handedness, and mixed-handedness, respectively, amongst individuals with ASD. The classification of handedness, the instrument used to measure handedness, and the main purpose of the study were found to moderate the findings of meta-analysis set 2. Meta-analysis set 3 revealed a trend towards weaker handedness for individuals with ASD. The elevated levels of atypical handedness in individuals with ASD could be attributed to atypicalities in cerebral structure and lateralization for language in individuals with ASD.

Diffusion-weighted magnetic resonance imaging demonstrates white matter alterations in watershed regions in children with moyamoya without stroke or silent infarct

Banu Ahtam, Marina Solti, Justin M. Doo, Henry A. Feldman, Rutvi Vyas, Fan Zhang, Lauren J. O'Donnell, Yogesh Rathi, Edward R. Smith, Darren Orbach, Alfred P. See, P. Ellen Grant, Laura L. Lehman. Diffusion-Weighted Magnetic Resonance Imaging Demonstrates White Matter Alterations in Watershed Regions in Children With Moyamoya Without Stroke or Silent Infarct. Pediatric Neurology. Published: March 15, 2023 DOI:



Moyamoya is a disease with progressive cerebral arterial stenosis leading to stroke and silent infarct. Diffusion-weighted magnetic resonance imaging (dMRI) studies show that adults with moyamoya have significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) compared with controls, which raises concern for unrecognized white matter injury. Children with moyamoya have significantly lower FA and higher MD in their white matter compared with controls. However, it is unknown which white matter tracts are affected in children with moyamoya.


We present a cohort of 15 children with moyamoya with 24 affected hemispheres without stroke or silent infarct compared with 25 controls. We analyzed dMRI data using unscented Kalman filter tractography and extracted major white matter pathways with a fiber clustering method. We compared the FA, MD, AD, and RD in each segmented white matter tract and combined white matter tracts found within the watershed region using analysis of variance.


Age and sex were not significantly different between children with moyamoya and controls. Specific white matter tracts affected included inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, thalamofrontal, uncinate fasciculus, and arcuate fasciculus. Combined watershed region white matter tracts in children with moyamoya had significantly lower FA (−7.7% ± 3.2%, P = 0.02) and higher MD (4.8% ± 1.9%, P = 0.01) and RD (8.7% ± 2.8%, P = 0.002).


Lower FA with higher MD and RD is concerning for unrecognized white matter injury. Affected tracts were located in watershed regions suggesting that the findings may be due to chronic hypoperfusion. These findings support the concern that children with moyamoya without overt stroke or silent infarction are sustaining ongoing injury to their white matter microstructure and provide practitioners with a noninvasive method of more accurately assessing disease burden in children with moyamoya.

Tuesday, June 6, 2023

Migraine in children and adolescents

Initial imaging studies usually are not appropriate for evaluation of primary headaches in children. Imaging should be performed only in children with red flags in their history, such as early morning headache with vomiting, worsening headache symptoms, worsening of headache when supine, pain with Valsalva maneuver, rapid onset, mental status changes, or abnormal findings on physical examination. When neuroimaging is indicated, MRI is preferred over CT, because of exposure to ionizing radiation from the latter...

Periodic Syndromes Related to Migraine

Migraines in childhood may not always present as headache. There are several episodic syndromes in children that are believed to be “migraine variants” but remain underdiagnosed because of inadequate recognition of these disorders. They occur at a younger age and may be migraine precursors in the developing brain. Periodic syndromes typically vary with age at presentation and can occur as early as infancy. These migraine equivalents have similar characteristics despite their heterogenous presentation, including periodic nature, hereditary component, family history of migraine, evolution of the clinical picture to classic types of migraine, and no prominent headache in the symptomatology.

Benign paroxysmal torticollis (BPT) is the rarest of the 4 periodic syndromes and the earliest in onset, occurring in the first 2 years of life.9 BPT is characterized by spontaneous, recurrent head tilting in infants and toddlers. Episodes typically last for a few days at a time and resolve by 3 years of age. Accompanying symptoms can include vomiting, irritability, vertigo, ataxia, and pallor. It is important to distinguish BPT from the more common typical torticollis of infancy and Sandifer syndrome.

Toddlers and school-age children may present with paroxysmal vertigo, cyclic vomiting, and abdominal migraine. Benign paroxysmal vertigo (BPV) is an event characterized by vertigo, nystagmus, and vomiting that can last minutes to hours with spontaneous resolution. BPV presents abruptly, with or without accompanying pallor or fearfulness. Onset is typically early, between 2 and 5 years of age. Treatment includes rest, reassurance, and hydration. Differential diagnosis includes vestibular dysfunction following an ear infection or postinfectious inflammation of the vestibular nerve. These episodes also may elicit concern for posterior fossa lesion, focal onset seizure, or postictal behavior.

Cyclic vomiting syndrome (CVS) comprises recurrent attacks of vomiting and nausea, lasting from 1 hour to 5 days, that are associated with pallor and lethargy. There is complete symptom resolution between attacks. The average age at onset is 5 years. Children often are able to identify triggers, such as foods, stress, or illness. Lifestyle measures such as adequate sleep and hydration are recommended for episode prevention. When making a CVS diagnosis, it is important to rule out an underlying gastrointestinal, metabolic, or mitochondrial disorder.

Abdominal migraine represents 4% to 15% of pediatric gastroenterology cases, is more common in those with a migraine family history, and rarely persists into adulthood. Pain is dull, midline or periumbilical, and moderate to severe in intensity, lasting 2 to 72 hours if not treated. Headache is not a prominent feature; vasomotor symptoms, such as nausea, vomiting, pallor, and anorexia, are common. Up to 70% of children with abdominal migraine will develop more traditional migraine later in life, typically at 9 to 10 years of age.

Adolescents may present with acute confusional migraines, characterized by agitation and pronounced memory disturbance. Symptoms can last up to 8 hours. Headache is not an important symptom and usually is not recognized during the acute attack. Headaches precede, accompany, or follow the acute confusional state in about 80% of patients. Neurologic examination reveals no focal signs during the attack and is obligatorily normal afterward. Attacks are usually relieved by sleep. Acute confusional migraines can be triggered by mild head trauma, leading to a false diagnosis of cerebral concussion. Metabolic and toxic encephalopathies, endocrine disturbances, infection, posterior fossa tumors, nonconvulsive status epilepticus, and stroke can present like acute confusional migraines. Therefore, although the diagnosis of acute confusional migraines is clinical, it is often a diagnosis of exclusion...


When patients are hesitant to use pharmaceuticals for migraine prevention, there is evidence that nutraceuticals such as riboflavin or magnesium can be alternatives. One randomized controlled trial evaluated 98 adolescents with migraine treatment with riboflavin 400 mg vs placebo for 12 weeks and found improvement in headache frequency, duration, and disability scores. Another study compared the response to ibuprofen or acetaminophen taken acutely for migraine over an 18-month period in children and adolescents on 400 mg magnesium daily versus controls who were not on magnesium. Pretreatment with magnesium reduced pain intensity acutely when combined with acetaminophen or ibuprofen (P<.01) and resulted in reduced migraine frequency.

A nutraceutical also may improve the results of migraine prevention medications. Two different studies showed that supplementation with vitamin D increased the efficacy of both amitriptyline and topiramate in migraine prevention. Nutraceuticals such as riboflavin, magnesium, and coenzyme Q10 have low-risk profiles and may represent suitable first-line treatments, especially for patients who prefer not to take prescription medication.

Pharmaceuticals for Prevention

Pharmaceuticals for prevention of pediatric migraine include topiramate, propranolol, and amitriptyline. Topiramate is the only FDA-approved medication for migraine prevention in those aged 12 to 17 years. Per the current pediatric migraine prevention guidelines from the American Academy of Neurology and American Headache Society, individuals taking topiramate at a dose of 100 mg/day or 2 to 3 mg/kg/d are more likely than those taking placebo to have a reduction in the frequency of migraine or headaches. Per the same guidelines, children with migraine receiving propranolol at a dose of 20 to 40 mg 3 times a day may be more likely than those receiving placebo to have at least a 50% reduction in headache attacks. Amitriptyline was found to decrease frequency of headache days and migraine-related disability, but only when combined with cognitive-behavioral therapy.

The CHAMP study (Childhood and Adolescent Migraine Prevention) aimed to identify an optimal first-line migraine preventative treatment for people aged 8 to 17 years. The study concluded that amitriptyline and topiramate did not work better than placebo and had more adverse effects. These study results, however, may not be applicable to the population of children and adolescents excluded from the study, namely those who have continuous headache, medication overuse, or a high degree of migraine-related disability.

Achieving clinically meaningful improvement should be the standard for assessing the efficacy of a given treatment. Involvement of patients and their parents in determining what meaningful improvement means to them can improve understanding and adherence. Comorbidities should help guide the treatment. Individuals with mood disorder may benefit from a trial of amitriptyline. Obese patients may benefit from a trial of topiramate, which is an appetite suppressor...


Available evidence24 supports the use of a combined pharmacotherapy and behavioral approach for migraine prevention in children and adolescents. Psychologic treatments, such as cognitive-behavioral therapy, should be considered, either as first-line treatment or in combination with pharmaceutical-based therapies. Psychologic treatments delivered in a face-to-face format are effective in reducing pain and disability in children and adolescents with headache, with therapeutic gains maintained across time.

OnabotulinumA toxin

Although onabotulinumA toxin did not gain FDA approval for migraine treatment in those under age 18 after failing to show greater efficacy than placebo, a later crossover trial of onabotulinumA toxin for treatment of youth with chronic migraine showed that, compared with a placebo, children and adolescents who received a trial of onabotulinumA toxin injections administered in 3-month intervals and 6-week follow-up visits demonstrated a statistically significant decrease in migraine frequency and intensity.


A recent open-label study25 examined the safety, tolerability, and efficacy of a remote electrical neuromodulation device for treatment of acute migraine attacks among adolescents with migraine. Results showed that 71% of the participants experienced pain relief and 35% achieved pain freedom within 2 hours of symptom onset. Sustained pain relief was demonstrated among 90% of the participants at 24 hours. These preliminary data resulted in FDA clearance of the neuromodulation device for use among adolescents for acute treatment of migraine.
On the Horizon

For children and adolescents who have failed other treatments, monoclonal antibodies that target the calcitonin gene-related peptide may be an option. Calcitonin gene-related peptide is an amino acid peptide found in sensory fibers in the central nervous system that is involved in processing and pain modulation and has been implicated in the pathophysiology of migraine. In adults, antagonism of this pathway has been associated with diminished headache days and medication usage.

Anti–calcitonin gene-related peptide monoclonal antibodies are not currently FDA-approved for the treatment of migraines in people younger than 18.18 Several randomized controlled trials in children and adolescents with episodic and chronic migraine are underway.  A special interest group of the American Headache Society for use of anti–calcitonin gene-related peptide monoclonal antibodies in children24 recommends these medications for postpubertal adolescents experiencing frequent migraines with moderate or severe migraine-related disability. Individuals should have had adequate trials of established migraine preventive therapies, and previous options should have been expanded beyond prescription preventive medications to include, but not require, cognitive-behavioral therapy, as well as treatments with fewer side effects, such as neuromodulation devices and supplements.

Given the need to weigh potential benefits of therapy with unknown risks, an initial 2-month trial at the lowest available dose is recommended. If there is no improvement, a higher dose may be tried for another 2 months. If there is still no improvement, or if medication is not tolerated, it should be stopped.


Migraines present differently in young people than they do in adults, and children and adolescents require a different approach than their adult counterparts in all aspects of the clinic visit, from taking a history to providing treatment options. Episodic syndromes are migraine variants that may benefit from migraine treatment even if they do not present with a headache. The health care provider must understand the role of therapies such as cognitive-behavioral therapy in helping young patients manage headache pain, and to consider these therapies not only as adjunctive treatment but also as first-line treatment for the management of migraines in children and adolescents.

The ketogenic diet program at Texas Children’s Hospital

Treating Intractable Epilepsy with Diet: The Ketogenic Diet Program at Texas Children’s Hospital

Texas Children's Hospital

June 01, 2023

A robust ketogenic diet program is an essential tool for any epilepsy treatment center. For the past five years, the Epilepsy Center at Texas Children’s Hospital, known for its groundbreaking advances in epilepsy surgery, has heavily invested in its ketogenic diet program. Gloria Diaz-Medina, MD, pediatric neurologist, and Akshat Katyayan, MD, pediatric neurologist are co-directors of the Ketogenic Diet Program at Texas Children’s and have recently added Maureen Handoko, MD, PhD, pediatric neurologist, as their third dedicated ketogenic diet physician.

“If you look at many of the top programs in the country, they are either really good surgical programs or they are really good medical or keto programs,” said Dr. Katyayan. “We have struck the right balance wherein we are a well-known surgical program and also a very large ketogenic program.”

Traditional medical ketosis

While low-carbohydrate high-fat diets have been highly publicized for weight loss in recent years, a medical ketosis program requires strict adherence and monitoring and is typically only used for recalcitrant epilepsy when 2 or more medications have failed to have a significant effect.

“The reduction of glucose in the body plus production of ketone bodies have been shown to be neuroprotective to the brain and control seizures,” said Dr. Diaz-Medina.

Though the specific metabolic pathway, or likely pathways, by which the diet works are unknown, the formula for generating ketone bodies is well understood: for every 5 grams of food a patient eats, 4 grams must be fat and 1 gram must be protein and/or carbohydrate. If this ratio is strictly adhered to, the body will produce the desired ketone bodies. Blood monitoring for beta-hydroxybutyrate — a type of ketone body — in the clinic and urine dipsticks for ketones at home are both used to ensure that the patient has achieved the desired state of ketosis.

Initiating a ketogenic diet in children

Significant efforts are made by the physicians and dietitians at the Ketogenic Diet Program at Texas Children’s to educate caregivers and patients about the diet before it begins.

“The traditional ketogenic diet is a strict diet. It requires hospital admission during the initiation because it carries a higher risk for complications, such as low blood sugar and acid-base imbalance,” said Dr. Handoko.

During this time, the patient’s diet is gradually transitioned over the course of 4-5 days to the 4:1 ratio of fats to protein and carbohydrates. Labs are checked frequently, and the family receives further education about implementing the diet at home.

“Once they are stable in the hospital, their blood glucose has been stable and the acid in the blood has been stable, in general, they stay stable after discharge,” said Dr. Diaz-Medina.

Alternatives to a traditional ketogenic diet

Some patients are unable to adhere to the rigor required in a traditional ketogenic diet or do not tolerate it metabolically.

“For a formula-fed patient, the ease of transition to the ketogenic diet formula improves compliance,” said Dr. Handoko. For this reason, infants and G-tube fed patients are typically placed on the traditional ketogenic diet.

“If older patients have more restrictive eating habits, then they are more likely to go on an outpatient diet like a Modified Atkins or a low glycemic diet,” said Dr. Katyayan.

Older children can still benefit from a degree of carbohydrate restriction guided by the experts at a ketogenic diet program. These diets can be initiated in the clinic, as they do not have a significant risk of low blood sugars or acid-base imbalances. Likewise, ketone bodies are not measured as routinely. The patient’s seizure frequency is followed closely instead.

“There is research that seems to indicate that the success rates of modified Atkins and low glycemic index diets may be comparable to the traditional ketogenic diet, but still, multiple decades of research is available on a traditional ketogenic diet, and so generally if we can do the traditional ketogenic diet, that’s always the preference,” said Dr. Katyayan.

Evaluating the effectiveness of ketogenesis and low glycemic diets

Regardless of which diet patients start, they will continue to see the providers at the Ketogenic Diet Program for evaluation.

“We usually tell them, ‘Please give us 3-6 months to see if the diet will be effective.’ For us, that means that there has been more than 50% seizure reduction from their baseline. If that has been achieved, then we keep them on the diet for at least 2 years,” said Dr. Diaz-Medina.

Many patients at 2 years will opt to stay on the diet if it is effective. There is no limit to how long a child can stay in ketosis if their monitoring labs remain stable. Even if the diet is going well, some patients will decide to wean off the diet. If the seizures return during this process, which occurs over several weeks, the patient returns to the fat, protein, and carbohydrate ratio they were at before the increased incidence of seizures. Many patients, however, tolerate the gradual return to carbohydrates.

“At the 2-year mark, if we decide to wean off, 80% of those patients will retain the benefit from the diet even though it has been stopped,” said Dr. Diaz-Medina.

Referrals to the Texas Children's Ketogenic Diet Program originate from Texas Children’s Epilepsy Center. Refer a patient to Texas Children's Epilepsy Center through their online portal or by calling 832-TCH-CARE (832-824-2273).

Monday, June 5, 2023

Medical gaslighting

 Patients who don’t feel heard by a health care professional are finding a voice on social media — with the hashtag #medicalgaslighting now garnering more than 226 million views on TikTok.

"Medical gaslighting" is a term used to describe the situation in which patients — often young individuals, women and minorities — feel their symptoms are inappropriately dismissed or labeled as psychological when they go to see a doctor.

The term "gaslighting" originates from a 1938 play about a diabolical husband who plots to drive his wife insane through treacherous mind games.

In 1944, MGM released the psychological thriller "Gaslight," starring acclaimed actress Ingrid Bergman, who won an Oscar for her convincing portrayal of an abused wife.

She discovers that her husband was planning to institutionalize her so that he could collect on her inheritance by driving her insane — in part by dimming the gaslights in the home while tricking her to believe it was in her imagination.

"When it comes to our personal health, we should all feel confident and empowered to be our own advocates," Sylvia Kang, CEO and founder of health care company Mira in San Ramon, California, told Fox News Digital.

Mira helps women conceive with a home fertility tracker that provides personalized insights into menstrual cycles to maximize the chances of getting pregnant.

Some 65% of American women felt that their doctor dismissed, ignored or minimized the severity of their medical concerns.

Approximately 65% of American women felt that their doctor "dismissed, ignored or minimized the severity of their medical concerns," according to a recent nationwide survey commissioned by Mira.

The survey also found that female millennials felt especially impacted, with 72% feeling ignored or dismissed by doctors, per a press release on Mira's website. 

Medical gaslighting is not new

In 1977, the U.S. Food and Drug Administration (FDA) recommended that reproductive-age women be excluded from early clinical drug trials. 

There was a concern that the studies could potentially harm the fetuses of pregnant women and that hormonal changes during pregnancy would complicate the study’s results, according to the National Institutes of Health (NIH).

During this time, few females worked in medicine or research — and many women thought their needs were not a priority in scientific research, per the Office of Research on Women’s Health.

The policy also recommended excluding single women, those who used contraception and those whose husbands had a vasectomy, per the NIH.

"Medical gaslighting by health care providers can have a devastating impact on women," Shawana S. Moore, a board-certified women’s health nurse practitioner who specializes in women's health in Atlanta, Georgia, told Fox News Digital.

Research shows there’s still a gender gap in how providers are evaluating women compared to men.

"These experiences can erode trust in medical professionals, create feelings of self-doubt and lead to delays in receiving proper care."

A 1993 law now mandates that medical research funded by the NIH include women and minorities — but 30 years later, research shows there’s still a gender gap in how providers are evaluating women compared to men.

A 2019 Danish study found that, with the exception of osteoporosis, women were on average diagnosed four years later for over 700 diseases.

"Experiencing medical gaslighting throughout my fertility journey was deeply disheartening, especially as a woman with hormonal imbalance and a higher BMI [body mass index] who sought to be well-informed and actively participate in my own care," Kristy P., 33, a member of the Mira community who lives in Orlando, Florida, told Fox News Digital. 

She said she felt "disregarded and frustrated" when her providers immediately pushed for invasive procedures such as in vitro fertilization (IVF) — solely based on her weight — rather than considering alternative treatment options based on her individual circumstances.

One example of how some providers may not consider differences in symptoms between genders has to do with chest pain.

Subtle chest pain symptoms

The classic symptoms of a heart attack are uncomfortable chest pain or chest pressure — sometimes described as a squeezing sensation that radiates to one or both arms — which lasts for more than a few minutes, according to the American Heart Association.

Many people assume heart disease is only a men’s health issue, but it is actually the No. 1 killer of American women.

"But women may experience other symptoms that are typically less associated with heart attack, such as shortness of breath, nausea/vomiting and back or jaw pain," the association noted on its website.

Some women who experience a heart attack may complain of pressure in the upper back that is described as a "squeezing" sensation or a feeling that a rope is being tied around them, the association added on its website.

Many people assume heart disease is only a men’s health issue, yet it’s actually the No. 1 killer of American women. 

However, only slightly more than half of women in the U.S. are aware of this, according to the Centers for Disease Control and Prevention (CDC).

More women die from the condition compared to all types of cancer combined, per the American Heart Association.

‘A powerful reminder’

Some experts suggest bringing a loved one along to an appointment to avoid feeling discounted by health professionals.

"Women have the power to speak up and challenge dismissive attitudes in health care to receive the care they deserve," Moore said. 

Doctors spend years in medical school in the U.S. to master why a patient is coming to see them — what medical professionals refer to as the "chief complaint."

"Women have the power to speak up and challenge dismissive attitudes in health care to receive the care they deserve."

By simply talking to and examining patients, doctors can make the proper diagnosis without performing any further testing in 80% of cases, according to multiple studies.

Many doctors work hard to follow this practice — but some patients feel a subset can do better.

"My story serves as a powerful reminder that weight should not be a barrier to compassionate and personalized care," said the Orlando woman. 

Kang of Mira in California is recommending that women become their own health advocates.

"As women are diagnosed an average of four years later than men, there is no shame in asserting yourself by asking plenty of questions, expressing any concerns and seeking second opinions when your gut tells you something is off," she said.

Intranasal ketamine for refractory chronic migraine

Yuan H, Natekar A, Park J, Lauritsen CG, Viscusi ER, Marmura MJ. Real-world study of intranasal ketamine for use in patients with refractory chronic migraine: a retrospective analysis. Reg Anesth Pain Med. 2023 May 30:rapm-2022-104223. doi: 10.1136/rapm-2022-104223. Epub ahead of print. PMID: 37253638.


Introduction: Subanesthetic ketamine infusion has been used for managing refractory headache in inpatient or outpatient infusion settings. Intranasal ketamine may be an alternative option for outpatient care.

Methods: A retrospective study was conducted at a single tertiary headache center to assess the clinical effectiveness and tolerability of intranasal ketamine in patients with refractory chronic migraine. Candidates who received intranasal ketamine between January 2019 and February 2020 were screened through an electronic medical record query. Manual chart reviews and structured telephone interviews were conducted on obtaining informed consent.

Results: Of 242 subjects screened, 169 (79.9% women) of median (IQR) age 44 (22) years were interviewed. They reported a median (IQR) of 30 (9) monthly headache days and tried 4 (1) classes of preventive medications. Overall, they used 6 (6) sprays per day, with a median (IQR) of spray use of 10 (11) days per month. Intranasal ketamine was reported as 'very effective' in 49.1% and the quality of life was considered 'much better' in 35.5%. At the time of the interview, 65.1% remained current intranasal ketamine users and 74.0% reported at least one adverse event.

Conclusion: In this descriptive study, intranasal ketamine served as an acute treatment for refractory chronic migraine by reducing headache intensity and improving quality of life with relatively tolerable adverse events. Most patients found intranasal ketamine effective and continued to use it despite these adverse events. Given the potential for overuse, it should be reserved for those clearly in need of more effective rescue treatment with appropriate safety precautions. Well-designed prospective placebo-controlled trials are necessary to demonstrate the efficacy and safety of intranasal ketamine in patients with migraine.

Nearly half of patients with refractory chronic migraine interviewed about their use of intranasal ketamine considered the treatment “very effective,” and more than two-thirds said it improved their quality of life. Researchers reported their single-center study results in the journal Regional Anesthesia & Pain Medicine.

“Clinicians should only consider the use of a potentially addictive medication such as ketamine for significantly disabled patients with migraine…,” wrote corresponding author Michael J. Marmura, MD, Thomas Jefferson University Department of Neurology, Philadelphia, Pennsylvania, and study coauthors. “At Jefferson, we have more than 20 years of experience in ketamine infusion for chronic pain and headache and have written guidelines on ketamine use. Understanding the potential risk for outpatient intranasal ketamine use, we have established several strategies/safeguards to ensure patient safety.”

The retrospective study included 169 patients with refractory chronic migraine who received intranasal ketamine at the Jefferson Headache Center between January 2019 and February 2020. Patients in the study experienced a median 30 headache days a month and had tried 4 classes of preventive medications.

“While effective treatment options are limited, as-needed intranasal ketamine seemed to have mitigated acute headache pain intensity and reduced other acute medication use,” researchers reported.

Overall, patients used 6 sprays of intranasal ketamine daily on a median 10 days a month. Some 49.1% of participants deemed the treatment “very effective,” and 39.6% found it “somewhat effective.” Intranasal ketamine led to a “much better” quality of life in 35.5% of patients and “somewhat better” quality of life in 42.6% of patients.

When interviewed for the study, 65.1% of the patients were still using intranasal ketamine. Nearly 75% reported at least one adverse event. Fatigue and double vision/blurred vision were the most common, followed by cognitive adverse events such as confusion/dissociation, vivid dreams, or hallucination.

“These adverse events were usually short-lasting,” researchers wrote, “and patients continued using intranasal ketamine with caution afterwards.”

While further studies are needed to confirm the findings, “this retrospective study suggests that intranasal ketamine may offer a pain-relieving effect with limited morbidity for refractory chronic migraine in the outpatient setting,” the authors advised.