Prenatal sirolimus treatment for rhabdomyomas In tuberous sclerosis

Daniel Ebrahimi-Fakhari MD, Gabrielle Stires FNP, Eunice Hahn MD, Darcy Krueger MD, PhD, David Neal Franz MD. Prenatal Sirolimus Treatment For Rhabdomyomas In Tuberous Sclerosis.  Pediatric Neurology, in press.

Abstract

Background

In tuberous sclerosis most cardiac rhabdomyomas regress spontaneously. In some cases, the tumors can cause life-threatening hemodynamic comprise requiring subsequent surgical resection. The mTOR inhibitors everolimus and sirolimus have shown to be effective treatments for multiple conditions. There are four cases reporting off-label treatment with transplacental sirolimus in tuberous sclerosis for fetal rhabdomyomas. The optimal dosing regimen is unknown. 

Methods

Retrospective chart review of all patients treated prenatally with sirolimus for rhabdomyomas. All fetuses had a clinical and molecular diagnosis of tuberous sclerosis (2012 Consensus Diagnostic Criteria, including a positive genetic test). Clinical history, mTOR inhibitor dosing and levels, outcome and adverse events were reviewed after initiation of sirolimus treatment. 

Results

Three fetuses were treated with maternal sirolimus. Dosing regimens and subsequent trough levels differed from 1 mg/day to 6 mg/day and <1.0 ng/mL to 12.2 ng/mL. Cardiac rhabdomyomas gradually shrunk in all patients. Growth restriction was noted in one patient. No severe adverse events occurred during the treatment period. 

Conclusions

Maternal sirolimus appears to be a safe treatment option in prenatally detected rhabdomyomas with possible need for intervention. Follow-up visits with fetal ultrasound, echocardiography and laboratory work should be performed weekly during the treatment period. The optimal dosing and trough level timepoints remain unclear. Based on our results we recommend a sirolimus starting dose of at least 2 mg/m 2 /day, preferably 3-3.5mg/m 2 /day to achieve a target trough level of 10-12 ng/mL.

Two-year-old cognitive outcomes in children of pregnant women with epilepsy

Meador KJ, Cohen MJ, Loring DW, May RC, Brown C, Robalino CP, Matthews AG, Kalayjian LA, Gerard EE, Gedzelman ER, Penovich PE, Cavitt J, Hwang S, Sam M, Pack AM, French J, Tsai JJ, Pennell PB; Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs Investigator Group. Two-Year-Old Cognitive Outcomes in Children of Pregnant Women With Epilepsy in the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs Study. JAMA Neurol. 2021 Aug 1;78(8):927-936. doi: 10.1001/jamaneurol.2021.1583. PMID: 34096986; PMCID: PMC8185630.

Abstract

Importance: The neurodevelopmental risks of fetal exposure are uncertain for many antiseizure medications (ASMs).

Objective: To compare children at 2 years of age who were born to women with epilepsy (WWE) vs healthy women and assess the association of maximum ASM exposure in the third trimester and subsequent cognitive abilities among children of WWE.

Design, setting, and participants: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational, multicenter investigation of pregnancy outcomes that enrolled women from December 19, 2012, to January 13, 2016, at 20 US epilepsy centers. Children are followed up from birth to 6 years of age, with assessment at 2 years of age for this study. Of 1123 pregnant women assessed, 456 were enrolled; 426 did not meet criteria, and 241 chose not to participate. Data were analyzed from February 20 to December 4, 2020.

Main outcomes and measures: Language domain score according to the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), which incorporates 5 domain scores (language, motor, cognitive, social-emotional, and general adaptive), and association between BSID-III language domain and ASM blood levels in the third trimester in children of WWE. Analyses were adjusted for multiple potential confounding factors, and measures of ASM exposure were assessed.

Results: The BSID-III assessments were analyzed in 292 children of WWE (median age, 2.1 [range, 1.9-2.5] years; 155 female [53.1%] and 137 male [46.9%]) and 90 children of healthy women (median age, 2.1 [range, 2.0-2.4] years; 43 female [47.8%] and 47 male [52.2%]). No differences were found between groups on the primary outcome of language domain (-0.5; 95% CI, -4.1 to 3.2). None of the other 4 BSID-III domains differed between children of WWE vs healthy women. Most WWE were taking lamotrigine and/or levetiracetam. Exposure to ASMs in children of WWE showed no association with the language domain. However, secondary analyses revealed that higher maximum observed ASM levels in the third trimester were associated with lower BSID-III scores for the motor domain (-5.6; 95% CI, -10.7 to -0.5), and higher maximum ASM doses in the third trimester were associated with lower scores in the general adaptive domain (-1.4; 95% CI, -2.8 to -0.05).

Conclusions and relevance: Outcomes of children at 2 years of age did not differ between children of WWE taking ASMs and children of healthy women.

Courtesy of: https://www.mdlinx.com/journal-summary/two-year-old-cognitive-outcomes-in-children-of-pregnant-women-with-epilepsy-in-the-maternal-outcomes/1b1TvE0B3weAykWbhMdzI2

 

 

Outcomes of children and adolescents 1 year after being seen in a multidisciplinary psychogenic nonepileptic seizures clinic

Fredwall M, Terry D, Enciso L, Burch MM, Trott K, Albert DVF. Outcomes of children and adolescents 1 year after being seen in a multidisciplinary psychogenic nonepileptic seizures clinic. Epilepsia. 2021 Aug 2. doi: 10.1111/epi.17031. Epub ahead of print. PMID: 34339046.

Abstract

Objective: Psychogenic nonepileptic seizures (PNES) are paroxysmal events that may involve altered subjective experience and change in motor activity with a psychological cause. The aim of this work is to describe a population of pediatric patients with PNES and identify factors predictive of 12-month outcomes. 

Methods: We conducted a prospective observational study of children and adolescents referred to the multidisciplinary Nationwide Children's Hospital PNES clinic between November 2017 and July 2019. Information was collected from patients during clinic visits and semistructured follow-up phone calls. Descriptive statistics and Fisher exact test were used for analysis. 

Results: Of the 139 consecutive patients referred to the PNES clinic, 104 were seen in clinic and 63 answered 12-month follow-up calls. Patients with comorbid epilepsy had increased rates of participation at 12-month follow-up (p = .04). Complete remission was achieved by 32% (20/63) of patients at 12 months. Combined PNES remission and improvement was 89% (56/63) at 12 months. Patients and families who were linked with counseling at 1 month were more likely to achieve remission at 12 months (p = .005). Less than half (44%, 28/63) of patients reached at 12 months had their events documented on video-electroencephalogram (EEG) at diagnosis; however, those who did were not more likely to be accepting of the diagnosis at 12 months (p = 1.0), be linked with counseling at 12 months (p = .59), or be event-free at 12 months (p = .79). 

Significance: Remission occurred in one third of patients by 12 months; however, improvement in events was seen in 89%. Connection to counseling by 1 month was associated with increased remission rates at 12 months. Capturing events on video-EEG was not associated with increased acceptance or event freedom at 12 months. Diagnosis should be followed by strong encouragement to connect with counseling quickly to achieve a goal of increasing 12-month PNES remission rates.

Courtesy of: https://www.mdlinx.com/journal-summary/outcomes-of-children-and-adolescents-1-year-after-being-seen-in-a-multidisciplinary-psychogenic/6ChWH7Oofre7HhYwhbfQZp

Separation of craniopagus twins in Israel

For the first time in Israel, twins conjoined at the head were separated successfully. 

The operation, conducted by Soroka Medical Center in the southern city of Be’er Sheba, was a huge success. Doctors expect the girls, who were born last year in August, will live completely normal lives. 

“They are breathing and eating on their own,” Eldad Silberstein, head of the hospital’s plastic surgery department, told Israel’s Channel 12 news. 

“This was a rare and complex surgery that has been conducted only 20 times worldwide and now, for the first time, in Israel,” said Mickey Gideon, Soroka’s chief pediatric neurosurgeon. 

The 12-hour procedure, with the assistance of dozens of experts from Israel and abroad, involved cranial reconstruction and scalp grafts. 

Dr. Isaac Lazar, director of the Pediatric Intensive Care Unit at Soroka, described to Times of Israel the moment on Sunday when the girls looked at each other for the first time and the “unbelievable joy” felt by the parents. 

“When the nurses brought the babies together, newly separated, they looked at each other, made noises, and gently touched each other — it was beautiful,” Lazar told Times of Israel in an interview. “You could see the communication between them, and it was just so special.” 

“Any wrong decision could have been the difference between life and death,” Lazar said. “It was so delicate, as the surgery was performed between major blood vessels in the babies’ heads. We all knew that any bleed could have catastrophic consequences.” 

The operation was “complicated beyond anything one could imagine,” he added. “The babies were connected by the back of their heads in an area where there was no skin and no skull. We had to take action to make them grow more skin.” 

“Because the babies couldn’t move their heads for the first 12 months of their lives, there’s a physical handicap, but with the right rehabilitation for their physical and cognitive development, we expect them to catch up with their milestones,” the doctor explained. 

“One of the reasons for doing this now, as early as possible, is to allow normal development, and our hope is that this is now very likely.”

https://unitedwithisrael.org/a-first-in-israel-doctors-separate-twins-conjoined-at-the-head-operation-a-success/?

Alta Fixsler

Every life is precious, no matter what one’s circumstances!

Little Alta Fixsler was born eight weeks prematurely in Royal Manchester Children’s Hospital.  A traumatic birth deprived Alta of oxygen for twenty-five long minutes causing severe brain injury and no expectation for her to live more than a day.  But with HaShem’s help coupled with the loving embrace of her parents and Modern Medicine’s gift of the ventilator, this beloved Jewish daughter survived her first harrowing days of life.  Despite Alta’s strides in weaning off ventilation and transitioning to a lower level of respiratory support or that plans were being formulated to bring her home, someone at the hospital made a series of unilateral decisions that resulted in Alta having to go back on ventilation.   After that it was only a matter of time before pressure began to mount on her parents to withdraw life support under the guise of concern for her pain and no promise of recovery or a normal life.  When Alta’s parents refused to consent, Manchester University Foundation Trust (NHS) went to Court against them and were granted guardianship and the right to withdraw her life support, r”l.

In conjunction with efforts being made on Alta’s behalf, Crown Heights Women for the Safety and Integrity of Israel and its many members around the world have sent the below appeal to British Prime Minister Boris Johnson.

BS”D

To the Rt Hon Prime Minister Boris Johnson,

We were duly impressed with the United Kingdom’s humanitarian commitment pledged by yourself and fellow parliamentarians on August 18th to rescue tens of thousands of Afghanis from certain persecution and death as the Taliban take over in the wake of the US withdrawal from Afghanistan.

At the same time, however, we cannot understand why the same kind of compassion and political will has not been shown towards Alta Fixsler.

Across the globe people of goodwill from all walks of life and religions are praying for this special little girl to be given a chance.

The Lubavitcher Rebbe, the greatest lover of humanity in our time, repeatedly emphasized that acts of goodness and kindness bring light and peace to the entire world.

And so, Mr. Prime Minister, we plead with you to immediately intercede on Alta’s behalf to find a way she can leave the UK either to the US or to her home country in the State of Israel.

As we’ve no doubt you are already familiar with the particulars of Alta’s birth and her medical issues as well as the High Court’s decision, we only ask that you to consider the following three key points.

To be clear, we respect the strict separation of powers that make up the UK government and are not asking you to override in any way the Court’s ruling.

Alta and the Fixslers are Israeli citizens.

Mr. Prime Minister, Alta and her parents are Israeli citizens.  Avraham Fixsler is also an American citizen and Mrs. Fixsler additionally holds Hungarian citizenship.  The Fixslers always intended to return to their home country and have made no application for British citizenship. 

As such there can be no justification for expropriating the Fixsler’s parental rights – who are neither British citizens nor have they committed any crime on UK soil – or Alta’s right to live, simply because she sadly suffered brain injuries at birth.

Palliative care is a horribly painful way to end life.

Benign sounding terms like palliative and hospice care disguise the true ordeal a person endures when life support is taken away.

Here is what happens when ventilation is withdrawn:  First there is a physically painful struggle by the patient to breathe accompanied by panic, fear, and agitation – especially when the fight to live is deliberately being suppressed.   Saliva and secretions begin pooling in the lungs and the sounds of death rattle in the chest.

In order to “calm and comfort” the patient during this “merciful” form of legalized murder, a powerful mix of opiates, barbiturates or analgesics must be given to keep the person sedated until he or she succumbs and dies.

As much as an adult in this state might be able to reconcile their final moments – if this has been a deliberate decision to do so [and one we do not agree with] – for anyone else, especially a child, this can only be terrifying!

How can this possibly be in Alta’s best interests?!

Yet NHS has taken it even one step further.  The Court’s ruling gave room for Alta to pass away in the comfort of her parents’ home in Manchester surrounded by her loving family.

Instead, NHS unilaterally decided that Alta may only die in a hospice or in the hospital which they themselves concede is a cold, windowless environment.

Surely Mr. Prime Minister you realize the above scenarios are far more “painful” and distressing than anything that might occur during a responsible transport with appropriate pain control.

Alta does not have to die

No doubt Mr. Prime Minister you are aware that medical facilities in Israel are ready to admit Alta as a patient under their care.  Surely, there is room to reevaluate this option.

But if not, we beg you to find a way Alta can be transferred to the US where Senator Charles Shumer has procured a visa for Alta to enter the country for care and where there is widespread bi-partisan support in Congress endorsing her move.

A highly qualified medical transport is already in place to transfer Alta at absolutely no cost to NHS or the UK.

Mr. Prime Minister, Rosh HaShana, the Jewish New Year, is fast approaching.  This is the birthday of Mankind when Adam and Eve were created and judged.   The fate of Alta should be emblematic of Humanity’s appreciation for the preciousness of every life, no matter what one’s circumstances.

https://blogs.timesofisrael.com/every-life-is-precious-no-matter-what-ones-circumstances/ 

See: https://childnervoussystem.blogspot.com/2021/06/intervention-to-prevent-health.
https://childnervoussystem.blogspot.com/2021/08/another-sanction-of-murder-by-the.html

https://childnervoussystem.blogspot.com/2021/08/intervention-to-prevent-health.html

Primary amebic meningoencephalitis 5

A California boy who was on life support after he contracted a brain-eating amoeba likely while swimming in a lake has died, his family recently told news outlets. David Pruitt, 7, had been flown to UC Davis Medical Center on July 30, according to the family’s fundraising page. 

About a week later, the boy died. His aunt, Crystal Hayley, said he was diagnosed with primary amebic meningoencephalitis (PAM), a rare, devastating infection of the brain. The Associated Press reported that earlier this month, health officials in Tehama County said that a child under 10 was likely infected in a Tehama County lake, but did not reveal exactly where or the child’s age. 

According to the Tehama County Health Services Agency, there have only been 10 PAM cases reported in California since 1971. 

PAM is caused by Naegleria fowleri, also known as a brain-eating amoeba, which is found in warm freshwater and soil. It usually infects people when contaminated water enters the body through the nose, and travels to the brain where it causes PAM. Usually, most PAM cases are fatal, according to the Centers for Disease Control and Prevention (CDC).

It was not clear exactly when David had gone swimming, as symptoms of PAM typically begin one to nine days after. Death typically occurs between one and 18 days after symptoms begin. The CDC notes that PAM is difficult to detect due to rapid progression of illness.  

https://www.foxnews.com/health/california-boy-brain-eating-amoeba-death