Severe and progressive neuronal loss in myelomeningocele begins before 16 weeks of pregnancy
Authors: Jelena Martinovic
Selima Ben Miled
Ferechte Encha-Razavi
Syril James
Julie Bruneau
Aude Tessier
Yoann Saillour
Jean-Paul Duong Van Huyen
Brigitte Leroy
Yves Ville
Julien Stirnemann
Amel Sekour
Frédéric Causeret
Maryse Bonnière-Darcy
Laurence Loeuillet
Tania Attie-Bitach
Homa Adle-Biassette
Julia Tantau
Houria Salhi
Bettina Bessières
Journal: American Journal of Obstetrics and Gynecology (2020)
Discipline: CLINICAL MEDICINE
Keywords: autopsies; fetal surgery; motor function; motor neurons loss; myelomeningocele

Abstract:  Background: Despite undisputable benefits, midtrimester prenatal surgery is not a cure for myelomeningocele (MMC): residual intracranial and motor deficits leading to lifelong handicap question the timing of prenatal surgery. Indeed, the timing and intensity of intrauterine spinal cord injury remains ill defined. Objective: We aimed to describe the natural history of neuronal loss in MMC in utero based on postmortem pathology. Study design: Pathology findings were analyzed in 186 cases of myelomeningocele with lesion level between S1 and T1. Using a case-control, cross-sectional design, we investigated the timewise progression and topographic extension of neuronal loss between 13 and 39 weeks. Motor neurons were counted on histology at several spinal levels in 54 isolated MMC meeting quality criteria for cell counting. These were expressed as observed-to-expected ratios, after matching for gestational age and spinal level with 41 controls. Results: Chiari II malformation increased from 30.7% to 91.6% after 16 weeks. The exposed spinal cord displayed early, severe, and progressive neuronal loss: the observed-to-expected count dropped from 17% to ≤2% after 16 weeks. Neuronal loss extended beyond the lesion to the upper levels: in cases &lt;16 weeks, the observed-to-expected motor neuron count was 60% in the adjacent spinal cord, decreasing at a rate of 16% per week. Progressive loss was also found in the upper thoracic cord, but in much smaller proportions. The observed-over-expected ratio of motor neurons was not correlated with the level of myelomeningocele. Conclusions: Significant neuronal loss is present ≤16 weeks in the exposed cord and progressively extends cranially. Earlier prenatal repair (&lt;16 weeks) could prevent Chiari II malformation in 69.3% of cases, rescue the 17% remaining motor neurons in the exposed cord, and prevent the extension to the upper spinal cord. 

Retracted: No

PubPeer comments:
 https: twitter.com C_Althaus status 1258376414644011008?s=19 https: twitter.com C_Althaus status 1257296547781509120?s=19 https: twitter.com richardneher status 1257288261288054787?s=19 https: twitter.com negatingspirit status 1258372854363668481?s=19 https: twitter.com degerman_per status 1260901824116203524?s=19 , 
 Compared to the April 9 report of the authors based on 500 study participants there are some discrepancies to the current version describing 919 individuals - the percentage of PCR+ individuals was previously given as 2% but is now reported to be 3.6% (Fig 1C). Either the initial figure was wrong or the additional 419 individuals must have had a much higher prevalence - the preliminary case fatality CFR was 0.37% based on 7 individuals. An analysis of the public obituaries in Gangelt makes it likely that there are 11 instead of 7 cases, see the more detailed break down at http: www.wjst.de blog sciencesurf 2020 05 the-gangelt-study 3 as well as some caveats of my own analysis - So not only the base number but also the extrapolation of infected persons in Germany is questionable , 
 There are several major problems with this paper. 1. Why did the authors anticipate that SARS-CoV-2 was the agent that infected people. Why did they not test the people for influenza, that was going around that time in that region? 2. The first hint for SARS-CoV-2 stemmed from a couple living in that area. On 25 February 2020 they were tested positive in the University Clinic Du00fcsseldorf (source: German Wikipedia). Somebody (who?) speculated that this couple could have inocuated people from Heinsberg during a carnival event ( Kappensitzung ). However, that event took place already on 16 February 2020. This track is imaginable only when assuming an extremely long incubation period. However, for other respiratory viruses such as influenza the incubation period has been estimated being between 1 and 4 days. 3. Moreover, this would necessitate the assumption that the couple was able to spread the virus although being asymptomatic for several days after the event. Certainly, in the beginning of an infection some people may neclect or disregard the beginning infection. But in this case several days? 4. Why does the paper provide no details on that couple? And their relation to the carnival event ( Kappensitzung )? All in all: Does the paper really focus on corona and not on influenza as far as the diseased are concerned? ,