Prenatal and perinatal determinants of neonatal seizures occurring in the first week of life

To evaluate prenatal and perinatal risk factors for early neonatal seizures, we conducted a case-control study including 100 newborns with neonatal seizures in the first week of life and 204 controls randomly selected from a list of healthy newborns born in the same hospital during the study period. Generalized tonic seizures were the most common seizures observed (29%), although the majority of newborns (71%) experienced more than one type of seizure. The most frequent presumed etiology of neonatal seizures was hypoxic-ischemic encephalopathy (30%). A history of epilepsy in first-degree relatives was found only for cases. Neonatal seizures were found to be associated with maternal disease in the 2 years before pregnancy, mother's weight gain > 14 kg during pregnancy, placental pathology, preeclampsia, low birthweight, low gestational age, and jaundice in the first 3 days of life. The need for cardiopulmonary resuscitation was found only for cases (37%). The causal pathways for neonatal seizures often begin before birth, and some of the factors identified may be preventable.     

Effect of intravenous tropisetron on modulation of pain and central hypersensitivity in chronic low back pain patients

The activation of 5-hydroxytryptamine-3 (5-HT-3) receptors in spinal cord can enhance intrinsic spinal mechanisms of central hypersensitivity, possibly leading to exaggerated pain responses. Clinical studies suggest that 5-HT-3 receptor antagonists may have an analgesic effect. This randomized, double-blind, placebo-controlled crossover study tested the hypothesis that the 5-HT-3 receptor antagonist tropisetron attenuates pain and central hypersensitivity in patients with chronic low back pain. Thirty patients with chronic low back pain, 15 of whom were women (aged 53 ± 14 years) and 15 men (aged 48 ± 14 years), were studied. A single intravenous injection of 0.9% saline solution, tropisetron 2 mg, and tropisetron 5 mg was administrated in 3 different sessions, in a double-blind crossover manner. The main outcome was the visual analogue scale (VAS) score of spontaneous low back pain before, and 15, 30, 60, and 90 minutes after drug administration. Secondary outcomes were nociceptive withdrawal reflexes to single and repeated electrical stimulation, area of reflex receptive fields, pressure pain detection and tolerance thresholds, conditioned pain modulation, and area of clinical pain. The data were analyzed by analysis of variance and panel multiple regressions. All 3 treatments reduced VAS scores. However, there was no statistically significant difference between tropisetron and placebo in VAS scores. Compared to placebo, tropisetron produced a statistically significant increase in pain threshold after single electrical stimulation, but no difference in all other secondary outcomes was found. A single-dose intravenous administration of tropisetron in patients with chronic low back pain had no significant specific effect on intensity of pain and most parameters of central hypersensitivity.     

Single-injection thoracic paravertebral block for postoperative pain treatment after thoracoscopic surgery

Background. Thoracoscopic surgery can be associated with considerablepostoperative pain. While the benefits of paravertebral blockon pain after thoracotomy have been demonstrated, no investigationson the effects of paravertebral block on pain after thoracoscopyhave been conducted. We tested the hypothesis that a single-injectionthoracic paravertebral block, performed preoperatively, reducespain scores after thoracoscopic surgery. Methods. Of 45 patients recruited, 40 completed the study. Theywere randomly allocated to two groups: the paravertebral groupreceived i.v. patient-controlled analgesia (PCA) with morphineplus single-injection thoracic paravertebral block with bupivacaine0.375% and adrenaline 1:200 000 0.4 ml kg^–1 (n=20). Thecontrol group was treated with a back puncture without injectionand morphine PCA (n=20). Results. The main outcomes recorded during 48 h after surgerywere pain scores using the visual analogue scale (VAS, 0–100).Secondary outcomes were cumulative morphine consumption andpeak expiratory flow rate (PEFR). Half an hour and 24 h aftersurgery, median (25th–75th percentiles) VAS on coughingin the paravertebral group was 31.0 (20.0–55.0) and 30.5(17.5–40.0) respectively and in the control group it was70.0 (30.0–100.0) and 50.0 (25.0–75.0) respectively.The difference between the groups over the whole observationperiod was statistically significant (P<0.05). Twenty-fourand 48 h after surgery, median (25th–75th percentiles)cumulative morphine consumption (mg) was 49.0 (38.3–87.0)and 69.3 (38.8–118.5) respectively in the paravertebralgroup and 51.2 (36.0–84.1) and 78.1 (38.4–93.1)in the control group (statistically not significant). No differenceswere found in PEFR or the incidence of any side-effects betweengroups. Conclusion. We conclude that single-shot preoperative paravertebralblock improves post-operative pain treatment after thoracoscopicsurgery in a clinically significant fashion.      

A neurocutaneous disorder with a severe course: Wyburn-Mason's syndrome

Wyburn-Mason's syndrome is a rare neurocutaneous disorder consisting mainly of unilateral arteriovenous malformations of the midbrain and retina with multiple cutaneous nevi. The authors report on the clinical presentation, neurologic phenotype, and long-term neurologic follow-up of two unrelated children. The first patient had recurrent epistaxis during early childhood. At the age of 7 years, he developed acute hemianopsia and right hemiplegia. Angiography revealed large bilateral arteriovenous malformations involving the midbrain thalamic area and the right optic nerve. During the following years, he had recurrent episodes of headache, right hemiplegia, and cognitive deterioration. The second patient had some episodes of epistaxis in the first years of life. At the age of 5 years, he presented with sudden onset of headache, followed by a loss of consciousness, vomiting, and, subsequently, visual disturbances. Angiography revealed deeply located arteriovenous malformations involving the right temporal, frontobasal, capsulonuclear, insular, and parietal areas and the right optic nerve. During the following years, he had an acute strokelike episode followed by transient hemiplegia and slow progressive signs, with mild worsening of cognitive abilities. Early onset of neurologic manifestations is a poor prognostic factor for long-term outcome.     

Drug polymorphism and dosage form design: a practical perspective

Formulators are charged with the responsibility to formulate a product which is physically and chemically stable, manufacturable, and bioavailable. Most drugs exhibit structural polymorphism, and it is preferable to develop the most thermodynamically stable polymorph of the drug to assure reproducible bioavailability of the product over its shelf life under a variety of real-world storage conditions. There are occasional situations in which the development of a metastable crystalline or amorphous form is justified because a medical benefit is achieved. Such situations include those in which a faster dissolution rate or higher concentration are desired, in order to achieve rapid absorption and efficacy, or to achieve acceptable systemic exposure for a low-solubility drug. Another such situation is one in which the drug remains amorphous despite extensive efforts to crystallize it. If there is no particular medical benefit, there is less justification for accepting the risks of intentional development of a metastable crystalline or amorphous form. Whether or not there is medical benefit, the risks associated with development of a metastable form must be mitigated by laboratory work which provides assurance that (a) the largest possible form change will have no substantive effect on product quality or bioavailability, and/or (b) a change will not occur under all reasonable real-world storage conditions, and/or (c) analytical methodology and sampling procedures are in place which assure that a problem will be detected before dosage forms which have compromised quality or bioavailability can reach patients.     

Modulation of remifentanil-induced analgesia,hyperalgesia, and tolerance by small-dose ketamine in humans

Adding a small dose of ketamine to opioids may increase the analgesic effect and prevent opioid-induced hyperalgesia and acute tolerance to opioids. In this randomized, double-blinded, placebo-controlled crossover study, we investigated the effect of remifentanil combined with small concentrations of ketamine on different experimental pain models. Pain detection thresholds to single and repeated IM electrical stimulation and to repeated transcutaneous electrical stimulation, pressure pain tolerance threshold, and sedative, respiratory, and cardiovascular side effects were assessed in 14 healthy volunteers. Saline, remifentanil alone, and remifentanil combined with ketamine at target plasma concentrations of 50 or 100 ng/mL were administered in four study sessions. The ketamine infusion was started after baseline testing at a constant target concentration. Remifentanil was started after testing with ketamine alone at an initial target concentration of 1 ng/mL and then increased to 2 ng/mL and decreased to 1 ng/mL. The last test series were started 10 min after discontinuation of remifentanil. Acute remifentanil-induced hyperalgesia and tolerance were detected only by the pressure pain test and were not suppressed by ketamine. Remifentanil alone induced significant analgesia with all pain tests. Ketamine further increased the remifentanil effect only on IM electrical pain. Remifentanil at a 2 ng/mL target concentration induced a slight respiratory depression that was antagonized by ketamine. We conclude that ketamine effects on opioid analgesia are pain-modality specific. IMPLICATIONS: Coadministration of ketamine and morphine for pain relief is still controversial. Our experimental pain study with volunteers showed that ketamine enhances opioid analgesia without increasing sedation and reduces respiratory depression. Opioid-induced hyperalgesia and tolerance were not affected by ketamine and depended on the type of nociceptive stimulus. This may explain the conflicting results on opioid tolerance in previous studies.     

Neurologic aspects of adenylosuccinate lyase deficiency

Adenylosuccinate lyase deficiency is an autosomal-recessive disorder of the purine de novo synthesis pathway, diagnosed up to now in approximately 40 patients. The clinical presentation is characterized by severe neurologic involvement including seizures, developmental delay, hypotonia, and autistic features. Neonatal seizures and a severe infantile epileptic encephalopathy are often the first manifestations of this disorder. The existence of genetic heterogeneity for the adenylosuccinate lyase defect could account for variability of the clinical presentation. Deficiency of purine nucleotides, impairment of energy metabolism, and toxic effects are potential mechanisms of cerebral damage. Laboratory investigations show the presence in urine and cerebrospinal fluid of succinylpurines, which are normally undetectable. Currently, no effective treatment is available for adenylosuccinate lyase deficiency. A search for this disorder should be included in the screening program of children with unexplained neonatal seizures or severe infantile epileptic encephalopathy.     

Chronic HPV correlated lymphedema of external genitals: a case report

The Authors describe an unusual case of association between skin lymphangiomas and HPV infection in external genitals. The encountered difficulties in diagnosis represented an excellent example of efficient integration among specialists of different medical branches