Relation between coffee consumption and risk of seizure-related respiratory dysfunction in patients with drug-resistant focal epilepsy.

OBJECTIVE: Caffeine is an antagonist of the adenosine pathway, which is involved in regulation of breathing. Extracellular concentrations of adenosine are increased in the immediate aftermath of a seizure. Seizure-related overstimulation of adenosine receptors might promote peri-ictal apnea. However, the relation between caffeine consumption and risk of seizure-related respiratory dysfunction in patients with drug-resistant focal epilepsy remains unknown. METHODS: We performed a cross-sectional analysis of data collected in patients included in the SAVE study in Lyon's epilepsy monitoring unit at the Adult Epilepsy Department of the Lyon University Hospital between February 2016 and October 2018. The video-electroencephalographic recordings of 156 patients with drug-resistant focal epilepsy included in the study were reviewed to identify those with ≥1 focal seizure (FS), valid pulse oximetry (SpO2 ) measurement, and information about usual coffee consumption. This latter was collected at inclusion using a standardized self-questionnaire and further classified into four groups: none, rare (≤3 cups/week), moderate (4 cups/week to 3 cups/day), and high (≥4 cups/day). Peri-ictal hypoxemia (PIH) was defined as SpO2 < 90% for at least 5 s occurring during the ictal period, the post-ictal period, or both. RESULTS: Ninety patients fulfilled inclusion criteria, and 323 seizures were analyzed. Both the level of usual coffee consumption (p = .033) and the level of antiepileptic drug withdrawal (p = .004) were independent risk factors for occurrence of PIH. In comparison with FS in patients with no coffee consumption, risk of PIH was four times lower in FS in patients with moderate consumption (odds ratio [OR] = .25, 95% confidence interval [CI] = .07-.91, p = .036) and six times lower in FS in patients with high coffee consumption (OR = .16, 95% CI = .04-.66, p = .011). However, when PIH occurred, its duration was longer in patients with moderate or high consumption than in those with no coffee consumption (p = .042). SIGNIFICANCE: Coffee consumption may be a protective factor for seizure-related respiratory dysfunction, with a dose-dependent effect.

Restoration of breathing after opioid overdose and spinal cord injury using temporal interference stimulation.

Respiratory insufficiency is a leading cause of death due to drug overdose or neuromuscular disease. We hypothesized that a stimulation paradigm using temporal interference (TI) could restore breathing in such conditions. Following opioid overdose in rats, two high frequency (5000 Hz and 5001 Hz), low amplitude waveforms delivered via intramuscular wires in the neck immediately activated the diaphragm and restored ventilation in phase with waveform offset (1 Hz or 60 breaths/min). Following cervical spinal cord injury (SCI), TI stimulation via dorsally placed epidural electrodes uni- or bilaterally activated the diaphragm depending on current and electrode position. In silico modeling indicated that an interferential signal in the ventral spinal cord predicted the evoked response (left versus right diaphragm) and current-ratio-based steering. We conclude that TI stimulation can activate spinal motor neurons after SCI and prevent fatal apnea during drug overdose by restoring ventilation with minimally invasive electrodes.

Breath-Holding Spells in Pediatrics: A Narrative Review of the Current Evidence.

BACKGROUND: Breath-holding spells are common, frightening, but fortunately benign events. Familiarity with this condition is important so that an accurate diagnosis can be made. OBJECTIVE: To familiarize physicians with the clinical manifestations, diagnosis, evaluation, and management of children with breath-holding spells. METHODS: A PubMed search was completed in Clinical Queries using the key term "breath-holding spells". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article. RESULTS: Breath-holding spells affect 0.1 to 4.6% of otherwise healthy young children. The onset is usually between 6 and 18 months of age. The etiopathogenesis is likely multifactorial and includes autonomic nervous system dysregulation, vagally-mediated cardiac inhibition, delayed myelination of the brain stem, and iron deficiency anemia. Breath-holding spells may be cyanotic or pallid. The former are usually precipitated by anger or frustration while the latter are more often precipitated by pain or fear. In the cyanotic type, the child usually emits a short, loud cry, which leads to a sudden involuntary holding of the breath in forced expiration. The child becomes cyanosed, rigid or limp, followed by a transient loss of consciousness, and a long-awaited inspiration and resolution of the spell. In the pallid type, crying may be minimal or "silent". The apneic period in the pallid type is briefer than that in the cyanotic type prior to the loss of consciousness and posture. The episode in the pallid type then proceeds in the same manner as a cyanotic spell except that the child in the pallid type develops pallor rather than cyanosis. In both types, the entire episode lasts approximately 10 to 60 seconds. The spells usually disappear spontaneously by 5 years of age. CONCLUSION: Although breath-holding spells are benign, they can be quite distressing to the parents. Confident reassurance and frank explanation are the cornerstones of treatment. Underlying cause, if present, should be treated. Interventions beyond iron supplementation may be considered for children with severe and frequent breath-holding spells which have a strong impact on the lifestyle of both the child and family.

Clinical Outcomes Associated with a Failed Infant Car Seat Challenge.

OBJECTIVE: To assess comorbid conditions and clinical outcomes among late preterm and low birth weight term infants (<2.5 kg) who failed the Infant Car Seat Challenge (ICSC) on the Mother-Baby Unit. STUDY DESIGN: This was a retrospective chart review of consecutive infants who failed ICSC on the Mother-Baby Unit and were subsequently admitted to the neonatal intensive care unit at Prentice Women's Hospital between January 1, 2009, and December 31, 2015. Regression models were used to estimate risk differences (RDs) with 95% CIs for factors related to length of stay. RESULTS: A total of 148 infants were studied (43% male; 37% delivered via cesarean). ICSC failure in the Mother-Baby Unit was due to desaturation, bradycardia, and tachypnea in 59%, 37%, and 4% of infants, respectively. During monitoring on the neonatal intensive care unit, 39% of infants experienced apnea (48% in preterm vs 17% in term infants) in the supine position, 19% received phototherapy, and 2% and 6.8% received nasogastric and thermoregulatory support, respectively. Univariate predictors of increased duration of stay (days) were younger gestational age, apnea, nasogastric support, intravenous fluids, and antibiotics (all P < .05). In multivariable analysis adjusted for gestational age and discharge weight, only apnea (RD, 4.87; 95% CI, 2.99-6.74; P < .001), administration of antibiotics (RD, 3.25; 95% CI, 0.29-6.21; P < .032), and intravenous fluid support (RD, 4.87; 95% CI, 0.076-9.66; P < .047) remained independent predictors of a longer duration of stay. CONCLUSION: Infants who failed ICSC were at risk for comorbid conditions that prolonged hospital stay beyond the neonatal intensive care unit observation period. Almost one-half of late preterm infants who failed ICSC had apnea events in the supine position.

[A 14-day-old boy with jaundice and apnoea]. / 14 dager gammel gutt med gulsott og apnéanfall.

We describe an infant who was readmitted from home at 14 days of age with jaundice and a history of apnoea and episodes of retrocollis/opisthotonos. He had been only mildly jaundiced on discharge from the maternity clinic at 2 days of age. The total serum bilirubin (TSB) on admission was 542 µmol/L, and the infant was treated intensively with triple phototherapy and exchange transfusion. In contrast to what is recommended in Norwegian national guidelines for management of neonatal jaundice, the parents had apparently neither received oral nor written information about jaundice and its follow-up at the time of discharge from maternity. They therefore contacted their child healthcare centre when they had questions about jaundice, though the national guidelines specifically state that follow-up for neonatal jaundice during the first 2 weeks of life is the responsibility of the birth hospital. Inappropriate advice resulted in delayed referral, and the child has been diagnosed with chronic kernicterus, probably the first such case in Norway since national guidelines were formalised in 2006. Genetic work-up disclosed compound heterozygosity for Crigler-Najjar syndrome type I, to the best of our knowledge the first instance of this disorder ever to have been diagnosed in Norway. The incidence of kernicterus is Norway is much lower than in other industrialised countries. This is most likely due to national guidelines for management of neonatal jaundice, which place the responsibility for management and follow-up of jaundice with the birth hospital during the crucial first 2 weeks of life. This case report reminds us that tragedies may occur when guidelines are disregarded.

Apparent life-threatening events in infants and homeopathy: an alternative explanation.

BACKGROUND: A recent report showed increased frequency of apparent life-threatening events (ALTEs) in infants treated with the homeopathic medication GaliCol-Baby (GCB). The premise was that the ALTEs resulted from toxic effects of the drug's components. We examine an alternative explanation. METHOD: The toxicological literature was searched for known reactions to the various GCB components, noting doses and reported symptoms. Dosage quantities and severity of reaction to the GCB were ranked independently by two groups of physicians, and a dose-response curve was generated. Reported toxic doses and symptoms were compared with those of the GCB series. The homeopathic literature was searched as well to determine the propensity of the GCB components to cause ALTE symptoms, when given in homeopathic doses to healthy volunteers (proving). RESULTS: Doses ingested in the GCB series were 10-13 orders of magnitude smaller than those reported to cause toxic reactions in humans. There was poor correlation between symptoms with GCB and toxic profiles of the components. A nonsignificant, inverse relationship between dose and severity of reaction was observed. Conversely, four GCB components (in homeopathic doses) had a high propensity to produce at least one of five symptoms which define ALTE, two of which had intermediate to high propensity to produce three symptoms. CONCLUSIONS: It is unlikely that the ALTE following ingestion of GCB was a toxic reaction to any of the drug's component. Homeopathic theory may explain this linkage, though further research is needed to understand the pathogenic effects of highly diluted homeopathic compounds.

Sir Victor Horsley's contributions to the study and treatment of gunshot wounds of the head.

Sir Victor Horsley'S many contributions to neurological surgery include experimental and clinical studies of gunshot wounds (GSW) of the head. Horsley's publications from 1894 to 1897 and 1914 to 1915 on GSWs were reviewed. Horsley described GSWs in animal and clay models, illustrating characteristics of the primary missile tract and secondary cavitation. A transcranial GSW model in 67 dogs related intracranial damage to the projectile's velocity and sectional area, producing a marked sudden increase in intracranial pressure that presumably "tunneled" to the medullary respiratory and cardiac centers. If the resultant sudden apnea was treated with artificial respiration and prompt surgical decompression, the animal often survived. In these animal experiments, Horsley clearly described increased intracranial pressure, hypertension, and bradycardia-later recognized as the Cushing response or triad. With the onset of World War I, Horsley again reviewed the ballistics of military weaponry, emphasizing projectile spin and velocity as the main wounding mechanisms. He was outspoken against the "wicked tradition" of neglecting cranial GSWs and personally treated cases with aggressive respiratory support and prompt decompression of devitalized tissue. Horsley's contributions to the experimental and clinical aspects of GSWs to the head are consistent with his other important contributions to neurosurgery and have largely stood the test of time.

Injury severity determines Purkinje cell loss and microglial activation in the cerebellum after cortical contusion injury.

Clinical evidence suggests that the cerebellum is damaged after traumatic brain injury (TBI) and experimental studies have validated these observations. We have previously shown cerebellar vulnerability, as demonstrated by Purkinje cell loss and microglial activation, after fluid percussion brain injury. In this study, we examine the effect of graded controlled cortical impact (CCI) injury on the cerebellum in the context of physiologic and anatomical parameters that have been shown by others to be sensitive to injury severity. Adult male rats received mild, moderate, or severe CCI and were euthanized 7 days later. We first validated the severity of the initial injury using physiologic criteria, including apnea and blood pressure, during the immediate postinjury period. Increasing injury severity was associated with an increased incidence of apnea and higher mortality. Severe injury also induced transient hypertension followed by hypotension, while lower grade injuries produced an immediate and sustained hypotension. We next evaluated the pattern of subcortical neuronal loss in response to graded injuries. There was significant neuronal loss in the ipsilateral cortex, hippocampal CA2/CA3, and laterodorsal thalamus that was injury severity-dependent and that paralleled microglial activation. Similarly, there was a distinctive pattern of Purkinje cell loss and microglial activation in the cerebellar vermis that varied with injury severity. Together, these findings emphasize the vulnerability of the cerebellum to TBI. That a selective pattern of Purkinje cell loss occurs regardless of the type of injury suggests a generalized response that is a likely determinant of recovery and a target for therapeutic intervention.

[Attacks of apnea in a newborn aged 18 days]. / Apnoe-Anfälle bei einem 18 Tage alten Neugeborenen.

Clinical case of an 18-day-old newborn of the 40th + 1 pregnancy week with postpartum respiratory adjustment disorder including periodical decreases in blood oxygen saturation. On day 8 postpartum the newborn developed myoclonic cramps of unknown origin combatted with phenobarbital. 6 days later Cheyne-Stokes breathing began under normal phenobarbital level being the cause for an additional homeopathic therapy trial. After a single dose of opium C 30 the breathing improved significantly, suspending the breaks in breathing and the decreases in blood oxygen saturation.

[Systematic review of the effects of therapy in infants with the KISS-syndrome (kinetic imbalance due to suboccipital strain)]. / Systematisch literatuuronderzoek naar de effecten van behandeling bij zuigelingen met 'kopgewrichteninvloed bij storingen in de symmetrie' ('KISS-syndroom').

OBJECTIVE: To establish the effects of manual therapy, chiropractic, or osteopathic treatment of the KISS-syndrome (kinetic imbalance due to suboccipital strain) in infants with positional preference, plagiocephaly, and colic. DESIGN: Systematic review of the literature. METHOD: PubMed, Embase and the Cochrane Library were searched for articles on the effects of manual therapy, chiropractic and osteopathy on the KISS-syndrome. Experts in the field of manual medicine and osteopathy were asked to provide relevant articles. The bibliography in a textbook of manual therapy for children was hand-searched for additional references to the KISS-syndrome. RESULTS: No clinical trials were found that evaluated the effects of manual therapy or osteopathy on either the KISS-syndrome or its symptoms. Pooled analysis of two randomised clinical trials on the effects of chiropractic in infantile colic showed no statistically significant difference between active and control treatments. In addition, we found that 22% of infants showed short episodes of apnoea during manual therapy of the spine, and that one case has been described in which such apnoea resulted in death. CONCLUSION: Given the absence of evidence of beneficial effects of spinal manipulation in infants and in view of its potential risks, manual therapy, chiropractic and osteopathy should not be used in infants with the KISS-syndrome, except within the context of randomised double-blind controlled trials.

Heart rate changes in response to mild mechanical irritation of the high cervical spinal cord region in infants.

Alterations in the heart rate were monitored before, during and after the application of a unilateral mechanical impulse to the high cervical spinal cord region which was administered strictly in connection with the so called manual therapy (diagnosis= KISS). The investigation is based on a survey of 695 infants between the ages of 1 and 12 months. A notable change in the heart rate was evident in 47.2% of all examined infants (n= 695). In 40.1% of these infants, the change in heart rate was characterized by heart rate decrease of 15-83% compared to control conditions. Infants in their first 3 months of life responded more often with a severe bradycardia (50-83% decrease), older infants (7-12 months) more often with a mild bradycardia (15-49.9% decrease). This comparison revealed a significantly increased occurrence of severe bradycardia in the younger age group compared to the group of children >3 months (significance 0.0017). In 12.1% (n= 84) of the infants, the bradycardia was accompanied by an apnea. We discuss the hypothesis that mechanical irritation of the high-cervical region serves as a trigger that may be involved in sudden infant death (SID).

Apnea during spinal anesthesia in an unsedated patient with central sleep apnea syndrome.

We describe a case of apnea during spinal anesthesia in an unsedated patient with central sleep apnea syndrome. When spinal anesthesia is planned for a patient who is suspected of having this syndrome, apnea may be induced, even if no sedative was administered and the level of anesthesia is only moderate.

Morbid hypocalcemia associated with phosphate enema in a six-week-old infant.

A 6-week-old premature infant who was born at 29 weeks of gestation presented to the emergency department with a several-hour history of stiffness and increased alarms on his apnea monitor at home. On arrival he was noted to have generalized seizures, apnea, and bradycardia. He was intubated and required cardiopulmonary resuscitation including chest compressions and medications. After stabilization he was transferred to the neonatal intensive care unit for further management. His initial laboratory tests revealed a serum calcium level of 2.4 mg/dL (normal range: 8.4-10.2 mg/dL) and a serum phosphorus level of 28.5 mg/dL (normal range: 2.4-4.5 mg/dL). During the first week of admission, the infant's mother reported that she had administered a full pediatric Fleets enema (CB Fleet Company Inc, Lynchburg, VA) to him. The infant was discharged after 12 days of hospitalization. Anticipatory guidance on the stool patterns and behavior of infants can prevent misconceptions about constipation that are especially prevalent in new parents. Proper management of constipation, should it arise, should be addressed with all parents at early well-child visits to avoid hazardous complications of treatments. hypocalcemia, seizures, premature infants, enema.

A case of infantile spasms: epileptic apnea as partial seizures at onset.

We report a 2-month-old boy who presented with apneic attacks as a manifestation of epileptic seizures at onset and eventually progressed to infantile spasms. At onset, at 2 months of age, apneic attacks were the sole symptom of epileptic fits. Although these seizures were accompanied by cyanosis, bradycardia was not noted. An ictal electroencephalogram showed focal paroxysmal discharges in the temporal area. Treatment with sodium valproate was not effective to control his seizures. By 6 months of age, he progressed to infantile spasms. Although his seizures could be completely controlled with the use of zonisamide, vitamin B6 or high-dose immunoglobulin, his mental and behavioral development was retarded severely. There have been no previously published cases with infantile spasms that evolved from epileptic apnea as partial seizures.

Improved recovery from laryngeal-stimulation-induced apnea by alpha-adrenergic blockade in adult rabbits.

The apnea triggered by laryngeal stimulation (LS) is associated with a redistribution of blood flow towards the heart and the brain that depends upon peripheral vasoconstriction. The circulatory component of the response to LS has been shown to be reduced following injection of large dose of beta-adrenergic agonist that more intriguingly blunted the ventilatory response as well. To test whether the reduction of LS-induced apnea could be related to the decreased magnitude of the peripheral vasoconstruction, the effects of the alpha-adrenergic antagonist urapidil on the ventilatory and blood pressure responses to LS were studied in 6 adult rabbits. alpha-Adrenergic blockade reduced both the rise in blood pressure and the magnitude of hypopnea induced by LS. These results suggest that the circulatory component of the laryngeal chemoreflex, i.e. the peripheral vasoconstruction, contributes to the magnitude of the ventilatory depression.

Upper airway oedema following autologous blood transfusion from a wound drainage system.

We report a case of a 70-yr-old white woman who underwent a revision of a total hip arthroplasty under general anaesthesia. The intraoperative course was stable without any complications and the estimated blood loss was 2500 ml. The patient received an autologous transfusion of blood from a wound drainage system in the recovery room. The transfusion was followed immediately by marked respiratory distress and upper airway oedema. She required emergency tracheal intubation and mechanical pulmonary ventilation. A coagulopathy also developed which was treated and resolved within 12 hr of the capillary leak phenomenon. The trachea was extubated on the first postoperative day and she had an uneventful course until discharge from the hospital two days later. We discuss the possible, aetiology of such a reaction to autologous blood including complement and platelet activation. It is suggested that reinfusion of nonwashed shed blood from a wound drainage system may present a hazard even though the fluid was autologous in origin.