Fetal surgery in the context of myelomeningocele: repercussions and prognosis

Background: Myelomeningocele (MMC) is a congenital malformation of neural tube closure. The clinical picture comprises sensory and motor deficits at the point of spinal cord injury and below, in addition to ventriculomegaly, which requires ventriculo-peritoneal drains (DVP). Exposure of nervous tissue to amniotic fluid and trauma to the uterine wall, generates secondary damage. Intrauterine correction is the gold standard for MMC and aims to reduce organic and functional sequelae, improving the patient’s neurological prognosis. Objectives: The objective of this work is to identify the impact of fetal surgery against MMC. Methods: An integrative literature review was carried out based on articles selected from the Google Scholar and Scientific Eletronic Library Online databases. Results: The benefits of intrauterine neurosurgery outweigh the harm, based on maternal complications. Such maternal risks are: oligohydramnios, spontaneous rupture of the membrane, uterine dehiscence, premature birth, infections, blood transfusion, acute lung edema and contraindication for vaginal delivery due to uterine scarring. For the child, all the studies analyzed showed the same gains, extremely significant when compared to postnatal surgery: better cognitive development, greater probability of walking without using orthoses, less need for DVP. The gains from the fetal surgery technique go beyond the postnatal intervention. Conclusions: Therefore, the importance of early intrauterine treatment, in a properly equipped place and by qualified professionals, is reiterated, offering comprehensive care to pregnant women, preventing potential impasses and aiming at a better prognosis and quality of life for the child.

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The voltage-gated proton channel Hv1 contributes to neuronal injury and motor deficits in a mouse model of spinal cord injury

10.21203/rs.3.rs-59578/v2 ◽

2020 ◽

Author(s):

Madhuvika Murugan ◽

Jiaying Zheng ◽

Gongxiong Wu ◽

Rochelle Mogilevsky ◽

Xin Zheng ◽

...

Keyword(s):

Oxidative Stress ◽

Spinal Cord ◽

Macrophage Activation ◽

Neuronal Loss ◽

Motor Recovery ◽

Proton Channel ◽

Motor Deficits ◽

Voltage Gated ◽

Secondary Damage ◽

Cord Injury

Abstract Traumatic injury to the spinal cord initiates a series of pathological cellular processes that exacerbate tissue damage at and beyond the original site of injury. This secondary damage includes oxidative stress and inflammatory cascades that can lead to further neuronal loss and motor deficits. Microglial activation is an essential component of these secondary signaling cascades. The voltage-gated proton channel, Hv1, functionally expressed in microglia has been implicated in microglia polarization and oxidative stress in ischemic stroke. Here, we investigate whether Hv1 mediates microglial/macrophage activation and aggravates secondary damage following spinal cord injury (SCI). Following contusion SCI, wild-type (WT) mice showed significant tissue damage, white matter damage and impaired motor recovery. However, mice lacking Hv1 (Hv1-/-) showed significant white matter sparing and improved motor recovery. The improved motor recovery in Hv1-/- mice was associated with decreased interleukin-1β, reactive oxygen/ nitrogen species production and reduced neuronal loss. Further, deficiency of Hv1 directly influenced microglia activation as noted by decrease in microglia numbers, soma size and reduced outward rectifier K+ current density in Hv1-/- mice compared to WT mice at 7 d following SCI. Our results therefore implicate that Hv1 may be a promising potential therapeutic target to alleviate secondary damage following SCI caused by microglia/macrophage activation.

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The voltage-gated proton channel Hv1 contributes to neuronal injury and motor deficits in a mouse model of spinal cord injury

10.21203/rs.3.rs-59578/v1 ◽

2020 ◽

Author(s):

Madhuvika Murugan ◽

Jiaying Zheng ◽

Gongxiong Wu ◽

Rochelle Mogilevsky ◽

Xin Zheng ◽

...

Keyword(s):

Oxidative Stress ◽

Spinal Cord ◽

Macrophage Activation ◽

Neuronal Loss ◽

Motor Recovery ◽

Proton Channel ◽

Motor Deficits ◽

Voltage Gated ◽

Secondary Damage ◽

Cord Injury

Abstract Traumatic injury to the spinal cord initiates a series of pathological cellular processes that exacerbate tissue damage at and beyond the original site of injury. This secondary damage includes oxidative stress and inflammatory cascades that can lead to further neuronal loss and motor deficits. Microglial activation is an essential component of these secondary signaling cascades. The voltage-gated proton channel, Hv1, functionally expressed in microglia has been implicated in microglia polarization and oxidative stress in ischemic stroke. Here, we investigate whether Hv1 mediates microglial/macrophage activation and aggravates secondary damage following spinal cord injury (SCI). Following contusion SCI, wild-type (WT) mice showed significant tissue damage, white matter damage and impaired motor recovery. However, mice lacking Hv1 (Hv1-/-) showed significant white matter sparing and improved motor recovery. The improved motor recovery in Hv1-/- mice was associated with decreased interleukin-1β, reactive oxygen/ nitrogen species production and reduced neuronal loss. Further, deficiency of Hv1 directly influenced microglia activation as noted by decrease in microglia numbers, soma size and reduced outward rectifier K+ current density in Hv1-/- mice compared to WT mice at 7d following SCI. Our results therefore implicate that Hv1 may be a promising potential therapeutic target to alleviate secondary damage following SCI caused by microglia/macrophage activation.

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The voltage-gated proton channel Hv1 contributes to neuronal injury and motor deficits in a mouse model of spinal cord injury

Molecular Brain ◽

10.1186/s13041-020-00682-6 ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Madhuvika Murugan ◽

Jiaying Zheng ◽

Gongxiong Wu ◽

Rochelle Mogilevsky ◽

Xin Zheng ◽

...

Keyword(s):

Oxidative Stress ◽

Spinal Cord ◽

Macrophage Activation ◽

Neuronal Loss ◽

Motor Recovery ◽

Proton Channel ◽

Motor Deficits ◽

Voltage Gated ◽

Secondary Damage ◽

Cord Injury

Abstract Traumatic injury to the spinal cord initiates a series of pathological cellular processes that exacerbate tissue damage at and beyond the original site of injury. This secondary damage includes oxidative stress and inflammatory cascades that can lead to further neuronal loss and motor deficits. Microglial activation is an essential component of these secondary signaling cascades. The voltage-gated proton channel, Hv1, functionally expressed in microglia has been implicated in microglia polarization and oxidative stress in ischemic stroke. Here, we investigate whether Hv1 mediates microglial/macrophage activation and aggravates secondary damage following spinal cord injury (SCI). Following contusion SCI, wild-type (WT) mice showed significant tissue damage, white matter damage and impaired motor recovery. However, mice lacking Hv1 (Hv1−/−) showed significant white matter sparing and improved motor recovery. The improved motor recovery in Hv1−/− mice was associated with decreased interleukin-1β, reactive oxygen/ nitrogen species production and reduced neuronal loss. Further, deficiency of Hv1 directly influenced microglia activation as noted by decrease in microglia numbers, soma size and reduced outward rectifier K+ current density in Hv1−/− mice compared to WT mice at 7 d following SCI. Our results therefore implicate that Hv1 may be a promising potential therapeutic target to alleviate secondary damage following SCI caused by microglia/macrophage activation.

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Neurosurgeons’ opinions on the prenatal management of myelomeningocele

Neurosurgical FOCUS ◽

10.3171/2019.7.focus19362 ◽

2019 ◽

Vol 47 (4) ◽

pp. E10 ◽

Cited By ~ 1

Author(s):

Pravesh S. Gadjradj ◽

Jochem K. H. Spoor ◽

Alex J. Eggink ◽

René Wijnen ◽

Jena L. Miller ◽

...

Keyword(s):

Online Survey ◽

Tertiary Care ◽

Surgical Techniques ◽

Fetal Surgery ◽

Pediatric Neurosurgery ◽

Standard Of Care ◽

Maternal Complications ◽

Training Models ◽

Fetal Repair ◽

Maternal Risks

OBJECTIVEImprovements in imaging and surgical technological innovations have led to the increasing implementation of fetal surgical techniques. Open fetal surgery has demonstrated more favorable clinical outcomes in children born with open myelomeningocele (MMC) than those following postnatal repair. However, primarily because of maternal risks but also because of fetal risks, fetal surgery for MMC remains controversial. Here, the authors evaluated the contemporary management of MMC in the hope of identifying barriers and facilitators for neurosurgeons in providing fetal surgery for MMC.METHODSAn online survey was emailed to members of the Congress of Neurological Surgeons (CNS) and the International Society for Pediatric Neurosurgery (ISPN) in March 2019. The survey focused on 1) characteristics of the respondents, 2) the practice of counseling on and managing prenatally diagnosed MMC, and 3) barriers, facilitators, and expectations of fetal surgery for MMC. Reminders were sent to improve the response rate.RESULTSA total of 446 respondents filled out the survey, most (59.2%) of whom specialized in pediatric neurosurgery. The respondents repaired an average of 9.6 MMC defects per year, regardless of technique. Regardless of the departments in which respondents were employed, 91.0% provided postnatal repair of MMC, 13.0% open fetal repair, and 4.9% fetoscopic repair. According to the surgeons, the most important objections to performing open fetal surgery were a lack of cases available to become proficient in the technique (33.8%), the risk of maternal complications (23.6%), and concern for fetal complications (15.2%). The most important facilitators according to advocates of prenatal closure are a decreased rate of shunt dependency (37.8%), a decreased rate of hindbrain herniation (27.0%), and an improved rate of motor function (18.9%). Of the respondents, only 16.9% agreed that open fetal surgery should be the standard of care.CONCLUSIONSThe survey results showed diversity in the management of patients with MMC. In addition, significant diversity remains regarding fetal surgery for MMC closure. Despite the apparent benefits of open fetal surgery in selected pregnancies, only a minority of centers and providers offer this technique. As a more technically demanding technique that requires multidisciplinary effort with less well-established long-term outcomes, fetoscopic surgery may face similar limited implementation, although the surgery may pose fewer maternal risks than open fetal surgery. Centralization of prenatal treatment to tertiary care referral centers, as well as the use of sophisticated training models, may help to augment the most commonly cited objection to the implementation of prenatal closure, which is the overall limited caseload.

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Review for "Novel circular RNA 2960 contributes to secondary damage of spinal cord injury by sponging miRNA ‐124"

10.1002/cne.25030/v1/review1 ◽

2020 ◽

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Secondary Damage ◽

Cord Injury

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Alteraciones sistémicas y metabólicas producidas por lesión medular

Latin american journal of clinical sciences and medical technology ◽

10.34141/ljcs6429407 ◽

2019 ◽

Vol 1 (1) ◽

pp. 59-75

Author(s):

Gabriel Guízar Sahagún

Keyword(s):

Spinal Cord ◽

Daily Living ◽

Autonomic Function ◽

Clinical Presentation ◽

Scientific Literature ◽

International Standards ◽

Therapeutic Approaches ◽

Cord Injury ◽

Life Threatening ◽

The Impact

Besides the well-known loss of motor and sensory capabilities, people with spinal cord injury (SCI) experience a broad range of systemic and metabolic abnormalities including, among others, dysfunction of cardiovascular, respiratory, gastrointestinal, urinary, and endocrine systems. These alterations are a significant challenge for patients with SCI because such disorders severely interfere with their daily living and can be potentially life-threatening. Most of these disorders are associated with impairment of regulation of the autonomic nervous system, arising from disruption of connections between higher brain centers and the spinal cord caudal to the injured zone. Thus, the higher and more complete the lesion, the greater the autonomic dysfunction and the severity of complications.This article summarizes the medical scientific literature on key systemic and metabolic alterations derived of SCI. It provides information primarily focused on the pathophysiology and clinical presentation of these disorders, as well as some guides to prevent and alleviate such complications. Due to the impact of these alterations, this topic must be a priority and diffuse to those involved with the care of people with SCI, including the patient himself/herself. We consider that any collaborative effort should be supported, like the development of international standards, to evaluate autonomic function after SCI, as well as the development of novel therapeutic approaches.

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