scholarly journals Neural correlate of reduced respiratory chemosensitivity during chronic epilepsy

2022 ◽  
Author(s):  
Amol Bhandare ◽  
Nicholas Dale

While central autonomic cardiorespiratory dysfunction underlies sudden unexpected death in epilepsy (SUDEP), the specific neural mechanisms that lead to SUDEP remain to be determined. Here we took an advantage of single cell neuronal Ca2+ imaging and intrahippocampal kainic acid (KA)-induced chronic epilepsy in mice to investigate progressive changes in key cardiorespiratory brainstem circuits during chronic epilepsy. Following induction of status epilepticus (SE), we observed that the adaptive ventilatory responses to hypercapnia were reduced in mice with chronic epilepsy for 5 weeks post-SE. These changes were paralleled by reduced chemosensitivity of neurons in the retrotrapezoid nucleus (RTN), an important centre for respiratory chemosensitivity. Over the same period, chemosensory responses of the presympathetic RVLM neurons showed a slower decrease. Mice with chronic epilepsy were more sensitive to chemoconvulsants and exhibited a greatly reduced latency to seizure induction compared to naive mice. This enhanced sensitivity to seizures, which invade the RTN, puts the chemosensory circuits at further risk and increases the chances of terminal apnoea. Our findings establish a dysfunctional breathing phenotype with its RTN neuronal correlate in mice with chronic epilepsy and suggests a functional non-invasive biomarker test, based on respiratory chemosensitivity, to identify people with epilepsy at risk of SUDEP.

2021 ◽  
Vol 8 ◽  
Author(s):  
Enrice Huenerfauth ◽  
Jasmin Nessler ◽  
Johannes Erath ◽  
Andrea Tipold

Sudden unexpected death in human epileptic patients (SUDEP) is defined as death related to recurrent unprovoked seizures, death occurring unexpectedly, and suddenly in a patient with reasonable state of health, without an obvious medical cause of death, trauma, asphyxia, or intractable status epilepticus, and in post mortem examination no obvious reason for death can be found. “Probable SUDEP” (pSUDEP) is defined as SUDEP not confirmed pathologically. The adapted abbreviation for dogs is used in the following: “pSUDED” (probable sudden unexpected death in dogs with epilepsy). The aim of the present monocentric retrospective study using an online questionnaire was to evaluate the occurrence of pSUDED. Data of canine patients presented with seizures between 01/1998 and 05/2018 were retrospectively analyzed and classified according to their etiology (n = 1,503). Owners were contacted by telephone to participate in answering a validated questionnaire. A total of 509 owners were reached, and 373 owners completed the questionnaire. In addition to signalement (e.g., breed), special attention was paid to the frequency and presentation of seizures and seizures in the context of death. Fifty-one percent (191/373) of the dogs were dead at the endpoint of the study. A large proportion of the dogs was euthanized (149/191) because of seizure severity or health problems unrelated to seizures. Idiopathic epilepsy (IE) was diagnosed in 19/34 dogs which died unexpectedly. Of these seven animals had to be excluded for further investigation of pSUDED because of status epilepticus or aspiration pneumonia as a result of the seizures. In 12 dogs with IE the last seizure event occurred between 6 h and ~3 months before death. pSUDED was suspected in these dogs and an occurrence rate of 4.5–10% was calculated. pSUDED appears in a similar occurrence rate as human SUDEP and should be considered as a possible complication in epileptic dogs. The results of this study suggest that dogs with IE but especially those with brachycephalic syndrome and cluster seizures have an increased risk to die of pSUDED. Owners of dogs with seizures should be educated about the risk of sudden death in dogs with epilepsy.


Epilepsia ◽  
2005 ◽  
Vol 46 (7) ◽  
pp. 1021-1026 ◽  
Author(s):  
Heiko G. Niessen ◽  
Frank Angenstein ◽  
Stefan Vielhaber ◽  
Christian Frisch ◽  
Alexei Kudin ◽  
...  

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Abeer Alyami ◽  
Antonio Mirabile ◽  
Daniela Iacopino

Abstract Surface Enhanced Raman Scattering (SERS) has become an invaluable tool for the identification of colorants in artworks, due to its enhanced sensitivity and ability to quench fluorescence interference compared to Raman spectroscopy. However, the application of SERS to artwork analysis is still limited by its inherent invasiveness and the need for extraction procedures. In this work non-invasive transparent SERS probes were fabricated by self-assembly of Ag nanoparticles into glass and PDMS surfaces and used for identification of dye content in artistic drawings. SERS measurements were performed directly on the selected analytical surfaces by laser back illumination through the SERS probe. The non-invasiveness of fabricated probes was tested by optical microscopy. It was found that Ag nanoparticle/glass probes left no Ag nanoparticle residue after four consecutive depositions on sacrificial surfaces, whereas Ag nanoparticle/PDMS composites could be deposited and subsequently peeled off the analytical surfaces leaving no contamination traces. The high conformability, flexibility and transparency of Ag nanoparticle/PDMS composites enabled good adhesion to the surface of analyzed artistic drawings and therefore the generation of in situ SERS spectra from artistic drawings. The use of this method allowed identification of main dye components in real artworks comprising a red BIC ballpoint drawing and a Japanese woodblock print.


1988 ◽  
Vol 64 (6) ◽  
pp. 2659-2666 ◽  
Author(s):  
K. Axen ◽  
M. Bishop ◽  
F. Haas

First-breath ventilatory responses to graded elastic (delta E) and resistive (delta R) loads from 10 people with spinal muscular atrophy (SMA), 15 people with Duchenne muscular dystrophy (DMD), and 80 able-bodied people were compared. The SMA and DMD groups produced equal tidal volume, respiratory frequency, inspiratory duration (TI), expiratory duration, mean inspiratory airflow, and duty cycle responses to both delta E and delta R. Thus SMA (primarily a motoneuron disorder) and DMD (primarily a muscle disorder) have the same net effect on loaded breathing responses. The SMA and DMD groups failed to duplicate the normal group's short expirations during delta E, long inspirations during delta R, and thus, extended duty cycles during both delta E and delta R. The deficit in load compensation therefore was due to impaired regulation of respiratory timing (reflecting neural mechanisms) but not airflow defense (reflecting mechanical and neural mechanisms). One-fifth of the normal but none of the SMA or DMD subjects actively generated an "optimal" TI response (defined theoretically as TI greater than 160% control during large delta R and TI less than 75% control during large delta E). This lack of optimal responses, which is the same abnormality exhibited by quadriplegic people, suggests that SMA and DMD also impair human ability to discriminate between large delta R and delta E. These findings support the hypothesis that neuromuscular disorders can lead to disturbances in respiratory perception.


2021 ◽  
Author(s):  
Caroline B Ferreira ◽  
Talita M Silva ◽  
Phelipe E Silva ◽  
Catherine Czeisler ◽  
Jose J Otero ◽  
...  

Retrotrapezoid nucleus (RTN) neurons are involved in central chemoreception and respiratory control. Lineage tracing studies demonstrate RTN neurons to be derived from Phox2b and Atoh1 expressing progenitor cells in rhombere 4. Phox2b exon 3 mutations cause congenital central hypoventilation syndrome (CCHS), producing an impaired respiratory response to hypercapnia and hypoxia. Our goal was to investigate the extent to which a conditional mutation of Phox2b within Atoh1-derived cells might affect a) respiratory rhythm; b) ventilatory responses to hypercapnia and hypoxia and c) number of RTN-chemosensitive neurons. Here, we used a transgenic mouse line carrying a conditional Phox2bΔ8 mutation activated by cre-recombinase. We crossed them with Atoh1Cre mice. Ventilation was measured by whole body plethysmograph during neonate and adult life. In room air, experimental and control groups showed similar basal ventilation; however, Atoh1Cre/Phox2bΔ8 increased breath irregularity. The hypercapnia and hypoxia ventilatory responses were impaired in neonates. In contrast, adult mice recovered ventilatory response to hypercapnia, but not to hypoxia. Anatomically, we observed a reduction of the Phox2b+/TH- expressing neurons within the RTN region. Our data indicates that conditionally expression of Phox2b mutation by Atoh1 affect development of the RTN neurons and are essential for the activation of breathing under hypoxic and hypercapnia condition, providing new evidence for mechanisms related to CCHS neuropathology


2020 ◽  
Vol 33 (3) ◽  
pp. 375-383
Author(s):  
Bingwei Peng ◽  
Jialing Li ◽  
Xiaojing Li ◽  
Xiuying Wang ◽  
Haixia Zhu ◽  
...  

2012 ◽  
Vol 83 (Suppl 2) ◽  
pp. A38.1-A38
Author(s):  
AS Lacey ◽  
PEM Smith ◽  
MI Rees ◽  
RH Thomas

2011 ◽  
Vol 69 (5) ◽  
pp. 766-769 ◽  
Author(s):  
Vera C. Terra ◽  
Fulvio A. Scorza ◽  
Ricardo M. Arida ◽  
Regina M.F. Fernandes ◽  
Lauro Wichert-Ana ◽  
...  

Epilepsy is the main neurological condition in children and adolescents. Unfortunately patients with medical refractory epilepsy are more susceptible for clinical complications and death. We report a prospectively evaluated cohort of children followed for approximately 10 years. Fifty-three of 1012 patients died. Forty-two patients died due to epilepsy or its clinical complications and the main causes of death were pneumonia (in 16 cases), sepses (in 9 patients), status epilepticus (in 8 patients). In 11 patients cause of death was sudden unexpected death in epilepsy (SUDEP). Mental retardation was significantly more frequent in patients who did not die from SUDEP. SUDEP may be a significant condition associated with mortality in children and adolescents with epilepsy.


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