Tuesday, August 30, 2022

Long-term outcome of epilepsy and cortical malformations due to abnormal migration and postmigrational development

Laura LicchettaLuca VignatelliFrancesco ToniAndrea TegliaLaura Maria Beatrice BelottiLorenzo FerriVeronica MenghiBarbara MostacciLidia Di VitoFrancesca BisulliPaolo Tinuper.  Long-term Outcome of Epilepsy and Cortical Malformations Due to Abnormal Migration and Postmigrational Development. A Cohort Study. 


Primary amebic meningoencephalitis 6

A child likely died from a rare infection caused by a brain-eating amoeba after swimming in an eastern Nebraska river, health officials said, making it the second such probable death in the Midwest this summer and raising the question of whether climate change is playing a role.

The Douglas County Department of Health based in Omaha, Nebraska, reported Wednesday that doctors believe the child died of primary amebic meningoencephalitis, a usually fatal infection caused by the naegleria fowleri amoeba. Health officials believe the child came into contact with the amoeba on Sunday while swimming in the Elkhorn River just west of Omaha.

Officials have not released the child's identity.

Last month, a Missouri resident died of the same infection likely caused by the amoeba at Lake of Three Fires in southwestern Iowa. Iowa officials closed the lake's beach as a precaution for nearly three weeks.

People are usually infected when water containing the amoeba enters the body through the nose while swimming or diving into lakes and rivers. Other sources have been documented, including tainted tap water in a Houston-area city in 2020. Symptoms include fever, headache, nausea or vomiting, progressing to a stiff neck, loss of balance, hallucinations and seizures.

The Centers for Disease Control and Prevention says naegleria fowleri infections are rare — there are about three cases in the United States every year — but that those infections are overwhelmingly fatal.

There were 154 cases reported between 1962 and 2021 in the U.S., with only four survivors, according to the CDC. Of those, 71 cases were reported between 2000 and 2021. Texas and Florida recorded the most infections with 39 and 37 cases respectively, and the amoeba is typically found in southern states because it thrives in waters that are warmer than 86 degrees Fahrenheit (30 Celsius).

But infections have migrated north in recent years, including two cases in Minnesota since 2010, Douglas County Health Director Dr. Lindsey Huse noted during a news conference Thursday.

“Our regions are becoming warmer,” she said. “As things warm up, the water warms up and water levels drop because of drought, you see that this organism is a lot happier and more typically grows in those situations.”

According to the National Water Information System, the surface water temperature near where the child was swimming was between 86 and 92 degrees.

Jacob Lorenzo-Morales, a researcher at the Universidad de La Laguna in the Canary Islands who has studied naegleria fowleri, said Thursday that an increase in infections since 2000 can be blamed on two factors: better knowledge and diagnosis of the disease, and the rising temperature in bodies of water providing “a perfect environment” for the amoeba to thrive.

Researcher Sutherland Maciver, who has studied the amoeba at the Centre for Discovery Brain Sciences at Edinburgh Medical School in Scotland, says not all infections are reported and that the 430 cases that have ever been reported worldwide are almost certainly an undercount. And, he said, scientists cannot say with certainty that the Nebraska case is directly attributable to climate change.

The two researchers co-authored a paper titled “Is Naegleria fowleri an Emerging Parasite?” that examined factors behind the increase in reported cases.

Health officials recommend that freshwater swimmers plug their noses, avoid putting their heads underwater and avoid activities such as water skiing and tubing, which could force water into the nose, eyes or mouth. You cannot be infected by drinking contaminated water.


Prospective concussion test

The start of football season brings the return of that important topic: Concussions.

There's a new test that was approved by the FDA in December that could change the game, and its creator is from Minneapolis.

The test uses a camera to track each eye, as the patient watches a 220-second video, which is moving in a square motion around a screen.

Dr. Uzma Samadani has been working on the EyeBOX for 10 years. It's the first approved minimally-invasive concussion diagnostic, doing what no other test can.

"He can follow my finger, but I'm not going to be able to detect really subtle differences between the right eye and the left eye just by looking at him," Samadani said.  

When Jon Johnston came in (see https://jonjohnston.com/my-heart-attack-and-tbi-survivor-story/), his scans showed nothing wrong. But this test, showed his eyes moving out of sync and independent of each other, proved otherwise.

"When a normal person watches the video, their eyes are moving together in the horizontal plane, whereas his eyes are not," said Samadani.

"This takes some of the uncertainty out of it, and that's a huge factor I think," said Johnston.

Theoretically, this test could be used on a football sideline now, conducted by a medical professional. But a consumer-friendly version might change in-game concussion protocols in a big way. A phone version of the test is in the works and could be available sooner than later.

"Probably one or two years," said Samadani.


SCN4A variant associated with a severe congenital myasthenic syndrome/myopathy phenotype

Berghold VM, Koko M, Berutti R and Plecko B (2022) Case report: Novel SCN4A variant associated with a severe congenital myasthenic syndrome/myopathy phenotype. Front. Pediatr. 10:944784. doi: 10.3389/fped.2022.944784

We present a now 18-year-old female patient with a severe congenital myopathy phenotype, originally diagnosed as mitochondrial myopathy, however later revealed to constitute a SCN4A-related myopathy based on genetic testing. After birth, floppiness, bradycardia and respiratory insufficiency ensued, and moderately reduced mitochondrial complex I activity was found in muscle tissue (tested at 3 weeks and 3 years of age, respectively). She was treated with riboflavin, carnitine, creatine and a ketogenic diet. At the age of 13 years, whole exome sequencing challenged the initial diagnosis by identifying two (compound heterozygous) SCN4A variants affecting the highly conserved voltage sensor and pore regions of the voltage-gated sodium channel NaV1.4: a known pathogenic loss of function (LOF) variant [c.4360C>T; p.(Arg1454Trp)] and a novel variant of uncertain significance [c.3615C>G; p.(Asn1205Lys)]. For this novel variant, a LOF effect was predicted by in silico, clinical and functional evidence from paralog human sodium channels, and the variant was accordingly classified as likely pathogenic. The patient's phenotype is in line with the few published cases of autosomal recessive SCN4A-related myopathy. There was limited benefit from treatment with salbutamol and acetazolamide, while pyridostigmine caused side effects at a minor dose. This report highlights the importance of genetic testing in severe myopathies particularly in regard to treatment options and the value of paralog information in evaluating ion channel variations.

Monday, August 29, 2022

Use of whole-genome sequencing for mitochondrial disease diagnosis

Ryan L. Davis, Kishore R. Kumar, Clare Puttick, Christina Liang, Kate E. Ahmad, Fabienne Edema-Hildebrand, Jin-Sung Park, Andre E. Minoche, Velimir Gayevskiy, Amali C. Mallawaarachchi, John Christodoulou, Deborah Schofield, Marcel E. Dinger, Mark J. Cowley, Carolyn M. Sue.  Use of Whole-Genome Sequencing for Mitochondrial Disease Diagnosis. Neurology Aug 2022, 99 (7) e730-e742; DOI: 10.1212/WNL.0000000000200745


Background and Objectives Mitochondrial diseases (MDs) are the commonest group of heritable metabolic disorders. Phenotypic diversity can make molecular diagnosis challenging, and causative genetic variants may reside in either mitochondrial or nuclear DNA. A single comprehensive genetic diagnostic test would be highly useful and transform the field. We applied whole-genome sequencing (WGS) to evaluate the variant detection rate and diagnostic capacity of this technology with a view to simplifying and improving the MD diagnostic pathway.

Methods Adult patients presenting to a specialist MD clinic in Sydney, Australia, were recruited to the study if they satisfied clinical MD (Nijmegen) criteria. WGS was performed on blood DNA, followed by clinical genetic analysis for known pathogenic MD-associated variants and MD mimics.

Results Of the 242 consecutive patients recruited, 62 participants had “definite,” 108 had “probable,” and 72 had “possible” MD classification by the Nijmegen criteria. Disease-causing variants were identified for 130 participants, regardless of the location of the causative genetic variants, giving an overall diagnostic rate of 53.7% (130 of 242). Identification of causative genetic variants informed precise treatment, restored reproductive confidence, and optimized clinical management of MD.

Discussion Comprehensive bigenomic sequencing accurately detects causative genetic variants in affected MD patients, simplifying diagnosis, enabling early treatment, and informing the risk of genetic transmission.


Thursday, August 25, 2022

Premature declaration of death

A 3-year-old girl woke up during her funeral before being officially declared dead after doctors mistakenly presumed her dead the first time. 

The family of Camila Roxana Martinez Mendoza is accusing the Salinas de Hidalgo Basic Community Hospital of negligence after reportedly declaring the toddler dead too soon. 

The young girl was experiencing stomach pains, vomiting and fever when her mother, Mary Jane Mendoza, took her to see a pediatrician in the family’s hometown of Villa de Ramos on Aug. 17, El Universal newspaper reported. 

The doctor escalated the issue and recommended that the child be taken to the hospital in the central Mexican state of San Luis Potosí to be treated for dehydration. 

Doctors at Salinas de Hidalgo Basic Community Hospital placed a cold towel over her little body to lower her body temperature and placed a pulse oximeter on one of her fingers to keep track of her oxygen levels.


Camila was released from the hospital with a prescription for paracetamol — which treats pain and fever — but continued to deteriorate as the day continued. She was seen by another doctor who instructed her mother to feed her fruits and water and prescribed a different medication. 

Despite the medications and advice from medical experts, the toddler continued vomiting. Her worried parents took her to see another doctor, who suggested she be rushed to the emergency room. 

Camila was readmitted to Salinas between 9 and 10 p.m., and doctors worked to help the young girl. 

“They wanted to give her (intravenous therapy). They took a long time to put oxygen on her,” her mother said. “They didn’t put it on her because they couldn’t find her little veins; finally, a nurse managed it.” 

After about 10 minutes, the IV was removed from the little girl, who was then taken away to rest. “She still was hugging me, they took her away and told me, ‘You have to let her rest in peace.'” the grieving mother remembered. 

Bizarrely, Mendoza was then kept from her ailing daughter in a separate, locked room. She was able to get out but still could not get into the room where her daughter was being kept. Camila was later declared dead from dehydration. 

The next day, a funeral viewing was held for friends and family to mourn the beloved toddler when Mendoza noticed the glass window of the coffin fogging up. 

Other funeral attendees told the distraught mother that she must be hallucinating and dissuaded her from opening the coffin. However, Camila’s paternal grandmother reportedly rushed to take a closer look when she noticed Camila’s eyes moving and shockingly discovered she had a pulse. 

Camila was rushed by ambulance back to the Salinas hospital, where doctors unsuccessfully attempted to revive her and declared her dead again — this time from cerebral edema (brain swelling). 

“That was really where my baby was done. We are devastated because my girl was a very happy person, she got along with everyone, she didn’t single anyone out,” Mendoza said. “We have many people on the ranch who support us because she was cherished.” 

The family was planning to send Camila to her first day of kindergarten this week. 


See: https://childnervoussystem.blogspot.com/2018/05/premature-organ-donation.html