Methylphenidate Overdose Causing Secondary Polydipsia and Severe Hyponatremia in an 8-Year-Old Boy.

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is an increasingly common diagnosis of childhood that manifests with symptoms that affect cognitive, academic, behavioral, emotional, and social functioning. There are a multitude of pharmaceutical therapies to choose from when managing this condition, and though many studies on the safety and efficacy of these medications have been published, adverse effects still occur. CASE: This case discusses a previously healthy 8-year-old boy who had been prescribed 20-mg lisdexamfetamine dimesylate for ADHD however mistakenly took his brother's 36-mg methylphenidate extended-release tablets, resulting in hyperhidrosis, excessive thirst, polydipsia, and combative behavior that began within 3 hours of ingestion. He was evaluated at a community hospital emergency department and given lorazepam due to agitation and combativeness before discharge. However, he returned with hypothermia, hyponatremia, and status epilepticus resulting in intubation. Patient was transferred to our facility where a computer tomography of his head was negative and hyponatremia was corrected with 3% NaCl saline solution. A lumbar puncture was performed due to temperature instability before starting broad-spectrum antibiotics. Cerebrospinal fluid findings were normal, and he was extubated at 18 hours postingestion. Patient was discharged home after 3 days with no residual symptoms. DISCUSSION/CONCLUSIONS: Though both lisdexamfetamine dimesylate and methylphenidate are widely used among pediatricians today for treatment of ADHD, reports of life-threatening water intoxication as a result of overdose is rare. Studies have reported that severe 3,4-methylenedioxymethamphtamine toxicity in adults is associated with syndrome of inappropriate diuretic hormone (SIADH) secretion, hyponatremia, and seizures, along with serotonin-induced transient elevation in antidiuretic hormone. Adult schizophrenics who receive psychostimulants have also been shown to develop polydipsia with hyponatremia. Although the use of psychostimulants in adult schizophrenic patients has been studied, literature on toxicity and effects in the pediatric psychiatric population is scarce. We would suggest that this patient's polydipsia and hyponatremia are most likely a result of his ingestion of a toxic dose of a long-acting agent known to cause secondary psychosis.

Does MAP2 have a role in predicting the development of anti-NMDAR encephalitis associated with benign ovarian teratoma? A report of six new pediatric cases.

Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is a potentially fatal neurologic syndrome in which patients present with a spectrum of central nervous system deficits. Sixty percent of the cases can be attributed to the presence of tumors, most often ovarian teratomas. This report examines 6 pediatric patients who presented with neurologic deficits associated with the presence of such tumors. These cases illustrate a perplexing phenomenon, where benign teratomas could have a possible association with anti-NMDAR encephalitis. The purpose of this study was to compare the histology and immunohistochemistry of tumors associated with this syndrome to ovarian teratomas found in patients presenting with no neurologic symptoms. After obtaining institutional review board approval, 57 cases of ovarian teratomas were identified at our institution over 12 years. Six patients were identified with anti-NMDAR encephalitis. A panel of immunostains, including S100, GFAP, MAP2, and NeuN was applied to patients' tumor sections as well as the 6 controls from age-matched patients. No qualitative histologic or immunohistochemical differences were seen between the study cases and control group. Because no qualitative differences were identified between the study cases and the control group, testing of paired serum and cerebrospinal fluid remains the best method for diagnosis of anti-NMDAR encephalitis. Tumor banking with molecular analysis of ovarian teratomas, including whole-genome sequencing and comparative genomic hybridization between ovarian tissue saved from patients with and without anti-NMDAR encephalitis, is necessary to fully understand the etiopathogenesis of anti-NMDAR encephalitis.

Vitamin D Deficiency in Pediatric Critical Illness.

INTRODUCTION: The potential role for vitamin D in infection has been well described in adults. The objective of our study was to determine the prevalence of vitamin D insufficiency and to evaluate the relationship between vitamin D status and markers of innate immunity and infection in critically ill children. HYPOTHESIS: Vitamin D deficiency was highly prevalent in children with critical illness and correlated with the severity of illness and dysfunction in innate immunity. METHODS: We performed a prospective clinical observational study with both case and control groups in the pediatric intensive care unit (PICU). Vitamin D status was defined as vitamin D sufficient (25-hydroxyvitamin D (25(OH)D≥ 20 ng/mL), vitamin D insufficient (25(OH)D 10 to 20 ng/mL), and vitamin D deficient (25(OH)D <10 ng/mL). Vitamin D status, severity of illness scores, and cathelicidin, and other clinical data were collected. RESULTS: Sixty-one PICU patients and 46 control patients were enrolled. Over 60% of the PICU cases were found to be vitamin D insufficient while less than 1/3 of the controls were insufficient (p < 0.0001). No significant correlation was seen between plasma 25(OH)D and any severity of illness scores. Cases with asthma had a significantly lower median level 25(OH)D (16.9 ng/mL) than cases without asthma (18.7 ng/mL). Over 50% of patients hospitalized during the fall and winter were considered vitamin D deficient or insufficient whereas in the sunnier seasons (spring and summer) the prevalence of vitamin D deficiency/insufficiency decreased to about 30% (p = 0.003). CONCLUSIONS: The overall finding of profound vitamin D deficiency in the pediatric critical care population is an important finding. Significant seasonal differences were noted even in the critically ill. Certain diseases like asthma in critically ill children merit further study.

Safety of drug-eluting stents in patients with left ventricular dysfunction undergoing percutaneous coronary intervention.

Recent studies have reported a higher incidence of late stent thrombosis in patients undergoing drug-eluting stent (DES). Reduced left ventricular (LV) ejection fraction (EF) is considered a risk factor for this complication after both bare-metal stent (BMS) and DES implantation. Therefore, the aim of this study was to evaluate the safety of DES on long-term follow-up in patients with LV dysfunction undergoing percutaneous coronary intervention. We retrospectively selected all patients with an EF <45% undergoing percutaneous coronary intervention with implantation of > or =1 sirolimus- or paclitaxel-eluting stent at our institution. The primary endpoint of the study was all-cause mortality, retrieved using both Social Security Database and hospital records. We also compared the results of this group with a historical cohort of patients with LV dysfunction undergoing BMS implantation; 121 patients who received > or =1 DES were enrolled. The mean LVEF was 36 +/- 8%, with 20 patients (16%) with a LVEF < or =25%; 36 patients (30%) had diabetes mellitus, and DES implantation was considered off-label in 100 patients (83%). Survival at 1-, 2-, and 3-year follow-up was 94% (95% confidence interval [CI] 88 to 100), 90% (95% CI 82 to 98) and 88% (95% CI 80 to 96), respectively. In conclusion, the favorable results of this study demonstrate the safety of DES in patients with LV dysfunction.

Vardenafil: a novel type 5 phosphodiesterase inhibitor reduces myocardial infarct size following ischemia/reperfusion injury via opening of mitochondrial K(ATP) channels in rabbits.

cGMP and opening of mitochondrial K(ATP) channel play an important role in preconditioning of the heart following ischemia/reperfusion (I/R) injury. We investigated the cardioprotective effect of vardenafil (VAR) (Levitra), a highly selective and biochemically potent inhibitor of phosphodiesterase-5 (PDE-5) that enhances erectile function in men through up-regulation of cGMP. Rabbits were treated with VAR (0.014 mg/kg, iv) or volume-matched saline, 30 min prior to 30 min of sustained regional ischemia followed by 3 h of reperfusion. 5-hydroxydecanoate (5-HD, 5 mg/kg, iv) or HMR 1098 (HMR, 3 mg/kg, iv), the respective blockers of mitochondrial or sarcolemmal K(ATP) channels were administered 10 min before I/R. Infarct size was measured by computer morphometry of tetrazolium stained sections. Vardenafil treatment caused decrease in mean arterial blood pressure from 93.5+/-2.6 to 82.2+/-1.5 mmHg and increase in heart rate from baseline value of 151+/-20 to 196+/-4.6 bpm (mean+/-standard error of mean (S.E.M.), P<0.05) within 5 min. The infarct size (% of risk area) was reduced from 33.8+/-1.3 in control rabbits to 14.3+/-2.2 (58% reduction, P<0.05). 5-HD abolished VAR-induced protection as demonstrated by increase in infarct size to 34.5+/-2.3 (P<0.05, N=6 per group). In contrast, HMR failed to block the protective effect of VAR (infarct size, 14.3+/-2.2 versus 16.3+/-1.0 in VAR + HMR, P>0.05). Neither inhibitors of the K(ATP) channel influenced the infarct size in the control rabbits, as shown by infarct size of 34.9+/-1.1 and 33.3+/-1.4 in animals treated with 5-HD and HMR, respectively. For the first time, we demonstrate that VAR induces protective effect against I/R injury via opening of mitochondrial K(ATP) channel. These results further support our hypothesis that the novel class of PDE-5 inhibitors induce protective effect in the ischemic heart, in addition to their well known clinical effects in the treatment of erectile dysfunction in men.

Pharmacological preconditioning with sildenafil: Basic mechanisms and clinical implications.

The phosphodiesterase type-5 (PDE5) inhibitor, sildenafil, is the first drug developed for treatment of erectile dysfunction in patients. Experimental data in animals show that sildenafil has a preconditioning-like cardioprotective effect against ischemia/reperfusion injury in the intact heart. Mechanistic studies suggest that sildenafil exerts cardioprotection through NO generated from eNOS/iNOS, activation of protein kinase C/ERK signaling and opening of mitochondrial ATP-sensitive potassium channels. Additional studies show that the drug attenuates cell death resulting from necrosis and apoptosis, and increases the Bcl2/Bax ratio through NO signaling in adult cardiomyocytes. Emerging new data also suggest that sildenafil may be used clinically for treatment of pulmonary arterial hypertension and endothelial dysfunction. Future demonstration of the cardioprotective effect in patients with the relatively safe and effective FDA-approved PDE5 inhibitors such as sildenafil could have an enormous impact on bringing the long-studied phenomenon of ischemic and pharmacologic preconditioning to the clinical forefront.

A comparison of pulmonary vein ostial anatomy by computerized tomography, echocardiography, and venography in patients with atrial fibrillation having radiofrequency catheter ablation.

Accurate assessment of pulmonary vein anatomy is important to procedures that isolate these structures in patients with atrial fibrillation. Various modalities of pulmonary vein (PV) imaging are employed in clinical practice; however, the consistency of findings among the different modalities is unknown. The purpose of this study is to compare PV ostial anatomy by 4 common imaging techniques. Twenty-four patients undergoing catheter-based PV isolation procedures for atrial fibrillation had their PV ostial anatomy determined by cardiac computerized tomography (CT) and transesophageal echocardiography (TEE) before ablation and by intracardiac echocardiography (ICE) and venography during the ablation procedure. The number and maximal dimension of the PV ostia were determined by each imaging modality. In the 24 patients, 98 PV ostia were visualized by CT, 93 by ICE, 81 by TEE, and 71 by venography. The average ostial diameters were similar between CT (1.45 +/- 0.29 cm) and ICE (1.51 +/- 0.22 cm, p = 0.066). Compared with CT or ICE, the ostial diameters were larger with venography (1.67 +/- 0.32 cm) and smaller with TEE (1.16 +/- 0.28 cm, all p <0.001). PV ostial diameters as determined by ICE were significantly correlated with CT measurements (r = 0.57, p <0.001) and venography (r = 0.52, p <0.001). Venography measures of PV diameter were correlated with measures by CT (r = 0.33, p = 0.03). TEE measures were not correlated with any other modality (all p >/=0.43). CT identifies the greatest number of PV ostia followed by ICE. Venography overestimates and TEE underestimates ostial diameters compared with CT or ICE. The PV ostial dimensions obtained by ICE, CT, and venography are all significantly correlated.