Neonatal Hypotonia Following in Utero Exposure to Antidepressant Drugs.

Associations between fetal exposure to antidepressants and neonatal hypotonia were studied using VigiBase and the French PharmacoVigilance Database. We identified significant associations between neonatal hypotonia and clomipramine, venlafaxine, and imipramine. Reports from the French database implicated prolonged fetal exposure. Neonatal hypotonia may be associated with in utero exposure to antidepressants.

Unintentional cannabis poisoning in toddlers: A one year study in Marseille.

France is the country with the highest prevalence of cannabis use in Europe, despite the fact that cannabis has not been legalized. This prevalence is still increasing along with THC content in cannabis products. In the meantime, unintentional cannabis poisoning by ingestion in toddlers is constantly rising. The aim of this study was to document children's cannabis poisoning biologically and clinically. Plasma and urine samples were extracted by solid phase extraction and analyzed by liquid chromatography coupled to tandem mass spectrometry. Children under 4 years old admitted in pediatric emergency departments for cannabis intoxication between February 1st 2019 and January 31st 2020 were included in this study. Twenty-six children were included (14 female and 12 male), the mean age was 17 months (10-41 months). THC, 11-OH-THC and THC-COOH plasma concentrations ranged from 2.9 to 93 ng/mL, 2.6-65 ng/mL and 29-914 ng/mL, respectively. The most frequent symptoms were drowsiness and hypotonia. Six critical cases were observed: 5 coma and 1 respiratory depression. All children having THC plasma concentrations over 60 ng/mL were in coma. Cannabis poisoning in toddlers become more frequent, 9 cases/year were reported in Marseille in 2007 and 26 cases/year in this study. There is a rising in severe clinical cases, particularly coma. These observations could be explained by an increase in THC content in cannabis products, and a trivialization of cannabis consumption. The unintentional ingestion of cannabis by children is a serious public health concern, and cannabis legalization could worsen this problem.

Episodio de hipotonía-hiporrespuesta tras administracion de la vacuna antimeningococo B 4CMenB / Hypotonic-hyporesponsive episode after antimeningococcal B vaccine, 4CMenB

El episodio hipotonía-hiporrespuesta (EHH) es un tipo muy inusual de efecto adverso después de la vacunación. Se ha observado con mayor frecuencia tras las vacunas de células enteras contra la tosferina. El EHH se caracteriza por el inicio repentino de hipotonía, hiporrespuesta y el cambio de color de la piel (palidez o cianosis) en las primeras 48 horas después de la administración de una vacuna en niños. Se ha descrito que los episodios pueden durar entre 6 y 30 minutos. Se desconoce la patogénesis. Aunque se ha clasificado dentro de las reacciones adversas graves, no se han demostrado efectos a largo plazo y no se contraindica la administración de una nueva dosis de la vacuna, si así está indicado para completar el calendario de vacunación del niño. Presentamos el caso de una lactante de 5 meses de edad que presentó un EHH tres horas después de la administración de una segunda dosis de la vacuna antimeningocócica B 4CMenB (Bexsero)

Hypotonic-hyporesponsive episode (HHE) is a very unusual type of adverse effect following immunization. HHE has been observed more frequently following whole-cell pertussis vaccines. HHE is characterized by sudden onset of reduced muscle tone, hyporesponsiveness and change of skin colour (paleness or cyanosis) in the first 48 hours after the administration of a vaccine in children. It has been shown that episodes can last between 6 and 30 minutes. The pathogenesis is unknown. Although it has been classified within the severe adverse reactions, long-term effects have not been shown and it does not contraindicate the administration of a new dose of the vaccine, as well as for the vaccination schedule of the child. Introducing the case of a 5-month-old breastfeeding infant who presented a HHE 3 hours after the administration of a second dose of the antimeningococcal B vaccine, 4CMenB (Bexsero)

Transplacental lidocaine intoxication.

Neonatal seizures are frequent in neonatal intensive care and the most common cause is perinatal asphyxia. Among other causes, toxin exposure is rare.We present a boy with an uneventful vaginal birth, who presented one hour after birth with apnea, hypotonia, mydriasis, tongue fasciculation, and tonic seizures. There was no hypoxic ischemic encephalopathy and brain imaging was normal. Toxicology screening revealed a toxic concentration of lidocaine in his blood. The intoxication was transplacental, as a cord blood sample confirmed the toxic level. This was probably due to maternal perineal nerve block with lidocaine.Perineal local infiltration of lidocaine is not without risk for the newborn. Toxicology screen remains an important tool in the work-up of neonatal seizures and sudden unexpected postnatal collapse.

Hypotonic-hyporesponsive episodes after administration of hexavalent DTP-based combination vaccine: A description of 12 cases.

Hypotonic-hyporesponsive (HHE) episodes are known and recognized phenomena, which typically occur within 48 hours of immunisation..Our aim is to describe 12 cases of HHE brought to the Center of Pediatric Sleep Medicine, with attention to the clinical features of the episode and their follow-up. Medical charts of infants visited between 2005-2015 were reviewed. Twelve infants showed a HHE using HHE using Brighton Collaboration Criteria. All infants received a Hexavalent diphtheria -tetanus -pertussis acellular component -hepatitis B-,inactivated poliovirus- Haemophilus influenzae type-b conjugate vaccine. Five out of 12 were brought to Emergency Department, where 2 were symptomatic (one was hyporeactive, the other had fever). No infant died during the episode, or the follow-up, nor developed neurological disease after subsequent vaccinations. HHE are confirmed as benign events, even after administration of hexavalent vaccination, devoid of negative neuropsychomotor outcome.

Chronic GABAergic blockade in the spinal cord in vivo induces motor alterations and neurodegeneration.

Inhibitory GABAergic and glycinergic neurotransmission in the spinal cord play a central role in the regulation of neuronal excitability, by maintaining a balance with the glutamate-mediated excitatory transmission. Glutamatergic agonists infusion in the spinal cord induce motor neuron death by excitotoxicity, leading to motor deficits and paralysis, but little is known on the effect of the blockade of inhibitory transmission. In this work we studied the effects of GABAergic and glycinergic blockade, by means of microdialysis perfusion (acute administration) and osmotic minipumps infusion (chronic administration) of GABA and glycine receptors antagonists directly in the lumbar spinal cord. We show that acute glycinergic blockade with strychnine or GABAergic blockade with bicuculline had no significant effects on motor activity and on motor neuron survival. However, chronic bicuculline infusion, but not strychnine, induced ipsilateral gait alterations, phalange flaccidity and significant motor neuron loss, and these effects were prevented by AMPA receptor blockade with CNQX but not by NMDA receptor blockade with MK801. In addition, we demonstrate that the chronic infusion of bicuculline enhanced the excitotoxic effect of AMPA, causing faster bilateral paralysis and increasing motor neuron loss. These findings indicate a relevant role of GABAergic inhibitory circuits in the regulation of motor neuron excitability and suggest that their alterations may be involved in the neurodegeneration processes characteristic of motor neuron diseases such as amyotrophic lateral sclerosis.

Self-induced drug intoxication in baclofen: of the calm hypotonic coma in the status epilepticus.

Baclofen is an agonist of peripheral and central B gamma-aminobutyric acid receptors, whose activation causes a myorelaxation and a powerfull depression of the central nervous system. Moreover, it has an action against addiction, in reducing craving. Commercialized since 1975 in France, to control muscle spasticity due to medullar affection or multiple sclerosis, it receives a temporary recommendation of use in march 2014, as a last-line adjuvant treatment in alcohol withdrawal. Beyond its therapeutic use, baclofen is involved in many self-induced intoxications. We report the case of a patient who develops, after a massive ingestion of baclofen (supposed dose ingested: 1 200 mg), a hypotonic and calm coma, requiring her admission in our intensive care unit, and then a status epilepticus.

Parenteral nutrition solution in cerebrospinal fluid in preterm newborn - a case report and review of the literature.

INTRODUCTION: Percutaneously inserted central venous catheters (epicutaneo-cava-catheter - ECC) are widely used in neonatal intensive care, facilitating the parenteral nutrition and the treatment of critically ill newborns. This invasive procedure is regarded as safe and associated with low complication rate. Possible life-threatening complications may result from malpositioning of ECC. Paraspinal misplacement of ECC is one of the most serious complications. CASE PRESENTATION: The authors report a case of misplacement of ECC inserted via left saphenous vein for intravenous feeding. A plane radiograph performed after the procedure showed the line tip at L3-L4 level, supposed to indicate location of the catheter in the vena cava inferior. Three days later, the infant developed neurologic symptoms (lethargy, hypotonia, seizures). Lumbar puncture revealed milky fluid containing parenteral nutrition solution. The infusion was stopped. X-ray with contrast showed the catheterization of the left ascending lumbar vein draining the vertebral venous plexuses. The contrast was highlighting the epidural space. The line was immediately removed resulting in improvement in patient's condition and resolution of all neurological symptoms. There was no sequela of this infiltration and the baby had an uneventful recovery. Follow-up at the age of 12 months showed normal development. CONCLUSIONS: A percutaneous catheter inserted via a lower limb may inadvertently enter the ascending lumbar vein. As previously reported, a catheter inserted via the left lower limb is a risk factor of this malposition. The life-threatening complications may be avoided by careful verification of ECC position (lateral x-ray, contrast examination). Plain radiography alone may not be sufficient for tip localization.

Does magnesium exposure affect neonatal resuscitation?

OBJECTIVE: Research on immediate neonatal resuscitation suggests that maternal magnesium exposure may be associated with increased risk of low Apgar scores, hypotonia, and neonatal intensive care unit admission. However, not all studies support these associations. Our objective was to determine whether exposure to magnesium at the time of delivery affects initial neonatal resuscitation. STUDY DESIGN: This is a secondary analysis of the Randomized Controlled Trial of Magnesium Sulfate for the Prevention of Cerebral Palsy that evaluated whether the study drug (magnesium or placebo) that was administered at the time of delivery was associated with increased risk for a composite adverse neonatal resuscitation outcome (5-minute Apgar score <7, oxygen administration in the delivery room, intubation, chest compressions, hypotension, and hypotonicity). A subgroup analysis was performed among patients who delivered at ≥30 weeks of gestation. Log-linear regression was used to control for possible confounders. RESULTS: Data for 1047 patients were analyzed, of whom 461 neonates (44%) were exposed to magnesium. There was no increased risk for the primary composite outcome associated with magnesium exposure. Individual adverse neonatal outcomes and other secondary short-term neonatal outcomes that were evaluated also did not demonstrate an association with magnesium exposure. CONCLUSION: Exposure to magnesium sulfate did not affect neonatal resuscitation or other short-term outcomes. These findings may be useful in planning neonatal care and patient counseling.

Encephalopathy and hypotonia due to baclofen toxicity in a patient with end-stage renal disease.

BACKGROUND: Baclofen is a centrally acting gamma-aminobutyric acid agonist used for the symptomatic relief of skeletal muscle spasm and spasticity in traumatic spinal cord lesions, multiple sclerosis, cerebral palsy, and stroke. It is also used in the treatment of chronic hiccups and cocaine abuse. Baclofen-induced central nervous system depression is rare at the usual therapeutic doses. However, patients with impaired renal function are at a higher risk of developing baclofen toxicity, even at a lower dose. CASE REPORT: A 57-year-old woman with end-stage renal disease on hemodialysis was admitted to our emergency department with progressive confusion and a generalized decrease in muscular tone. There was no obvious metabolic or infectious etiology that could have explained her condition. A comprehensive laboratory and imaging workup was negative. A review of her medication showed that she had recently been prescribed baclofen for muscular spasm. She was diagnosed with baclofen toxicity and was treated with emergent hemodialysis, which improved her mental status and her decreased muscle tone. Repeated sessions of hemodialysis administered on her second and third days of admission ultimately produced sustained clinical improvement and a complete return to her baseline mental status. She was subsequently discharged home with instructions to stay off baclofen. CONCLUSIONS: Baclofen toxicity is an under-diagnosed condition, especially in patients with renal dysfunction. Physicians should consider baclofen toxicity in patients with suboptimal kidney function on baclofen who present with altered mental status. Emergent hemodialysis and intensive care unit monitoring is recommended.

[Intoxication from accidental ingestion of cannabis: analysis of eight cases]. / À propos de 8 cas d'intoxication accidentelle au cannabis chez des nourrissons.

Consultations at pediatric emergency units for acute consciousness alterations is frequent. Miscellaneous causes include cranial trauma, meningoencephalitis, metabolic disorders, drugs, or other intoxications. We report here eight cases of infants who were brought to the emergency division due to acute consciousness failure after accidental ingestion of hashish, confirmed by urinary dosage of Δ9-tetrahydrocannabinol. This series of under 24-month-old infants only emphasizes the value of screening for cannabis in urine in cases of abnormal consciousness and/or abnormal behavior in an infant.

Antidepressants Increase REM Sleep Muscle Tone in Patients with and without REM Sleep Behavior Disorder.

STUDY OBJECTIVES: REM sleep behavior disorder (RBD) is associated with antidepressant treatment, especially in younger patients; but quantitative REM sleep without atonia (RSWA) analyses of psychiatric RBD patients remain limited. We analyzed RSWA in adults receiving antidepressants, with and without RBD. DESIGN: We comparatively analyzed visual, manual, and automated RSWA between RBD and control groups. RSWA metrics were compared between groups, and regression was used to explore associations with clinical variables. SETTING: Tertiary-care sleep center. PARTICIPANTS: Participants included traditional RBD without antidepressant treatment (n = 30, 15 Parkinson disease [PD-RBD] and 15 idiopathic); psychiatric RBD receiving antidepressants (n = 30); and adults without RBD, including antidepressant-treated psychiatric (n = 30), untreated psychiatric (n = 15), and OSA (n = 60) controls. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: RSWA was highest in traditional and psychiatric RBD, intermediate in treated psychiatric controls, and lowest in untreated psychiatric and OSA controls (P < 0.01). RSWA distribution and type also differed between antidepressant-treated patients having higher values in anterior tibialis, and PD-RBD with higher submentalis and tonic RSWA. Psychiatric RBD had significantly younger age at onset than traditional RBD patients (P < 0.01). CONCLUSIONS: Antidepressant treatment was associated with elevated REM sleep without atonia (RSWA) even without REM sleep behavior disorder (RBD), suggesting that antidepressants, not depression, promote RSWA. Differences in RSWA distribution and type were also seen, with higher anterior tibialis RSWA in antidepressant-treated patients and higher tonic RSWA in Parkinson disease-RBD patients, which could aid distinction between RBD subtypes. These findings suggest that antidepressants may mediate different RSWA mechanisms or, alternatively, that RSWA type and distribution evolve during progressive neurodegeneration. Further prospective RSWA analyses are necessary to clarify the relationships between antidepressant treatment, psychiatric disease, and RBD.

Baclofen and γ-hydroxybutyrate (GHB), a dangerous combination.

Baclofen is a γ-aminobutyric acid (GABA)-ß receptor agonist with a muscle relaxant effect. It increases GABA activity and reduces the production of glutamate and dopamine. The GABA precursor γ-hydroxybutyrate (GHB) has gained popularity as a drug of abuse. For the first time, we report a case of a GHB-dependent patient, who ingested several days' doses of baclofen (80 mg) simultaneously with 0.3 L (215 g) of illicit GHB. Baclofen (40 mg/d) was prescribed to prevent relapse after a successful detoxification. The patient developed a rapid coma (E2M5V1 with oxygen support), bradypnea, and hypotonia. Physicians should be alert to the danger of this combination because of the hazards of coma and respiratory distress.

[Transplacental or breast milk intoxication to clonidine: a case of neonatal hypotonia and drowsiness]. / Intoxication transplacentaire ou par lait maternel à la clonidine : un cas de somnolence et d'hypotonie néonatale.

We report a case of clonidine poisoning in a breastfed newborn. At 2 days of life, this boy presented a consciousness deficit with drowsiness, hypotonia, and suspected generalized seizures. There were no cardiorespiratory problems outside of progressive central apneas beginning the 5th day. Further initial investigations were normal (extensive biological exams, cranial ultrasonography and transfontanellar Doppler, electroencephalography, and brain MRI study), excluding the main causes of neonatal hypotonia (encephalitis, infection, metabolic disorder). However, new medical questioning revealed maternal daily intake of 0.15 mg clonidine for hypertension during and after pregnancy. Since it was impossible to quantify clonidine quantification in newborn serum and breast milk, a weaning test was performed the 9th day. Twenty-four hours after cessation of breastfeeding, complete regression of symptoms was obtained. Poisoning by clonidine after fetal and neonatal exposure through breast milk is rare but severe enough to simulate a neurological disease. Diagnosis is based on the search for drug use and the cessation of breastfeeding if doubt persists. Recovery of normal examination results is then rapid and complete.

Hypotonic hyporesponsive episode and the 13-valent pneumococcal vaccine.

Hypotensive-hyporesponsive episodes are rare events after immunizations performed for diphtheria, tetanus, Haemophilus influenzae type b and hepatitis B virus vaccines, but most of the reported episodes have been associated with pertussis-containing vaccines. We report the case of a 3-month-old girl, previously healthy otherwise, presenting with the unusual event of a hypotonic-hyporesponsive episode after vaccination with the 13-valent pneumococcal vaccine. Diagnosis was established after a thorough evaluation of the patient and by exclusion of other clinical conditions.

Can ophthalmic drops cause central nervous system depression and cardiogenic shock in infants?

Topical ocular medications have been widely prescribed and successfully used in children for the management of different ophthalmic disorders. We present 2 infants admitted to our pediatric intensive care unit who developed altered state of consciousness, hypotonia, hypothermia, bradycardia, and apnea after instillation of ophthalmic drops. The second infant also had hypotension and broncho-obstruction. Few days before admission, both infants were diagnosed with congenital glaucoma, and topical antiglaucoma treatment was initiated. Ophthalmic drops with brimonidine and brinzolamide were prescribed to both patients, whereas the second infant also received topical timolol. After elimination of other possible causes, the diagnosis of intoxication with topical antiglaucoma medications was established. After discontinuation of eye drops and vigorous symptomatic treatment, both infants recovered without sequels. Topically applied ophthalmic drops may cause life-threatening systemic adverse effects in infants, such as central nervous system depression and cardiogenic shock. Moreover, these 2 patients illustrate the importance of careful evaluation of all topical medications and their consideration as possible causes of the derangements in critically ill infants.