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Dravet syndrome (DS) is an uncommon epilepsy syndrome that may negatively affect the patients and their caregivers. However, reliable and valid measures of its impact on caregivers and the characteristics of patients with DS in Taiwan are lacking. This study aimed to describe the characteristics of patients with DS and concerns of their caregivers and establish a baseline frequency of disease characteristics using a cross-sectional survey in Taiwan. We assessed the caregivers of patients with DS using an online anonymous questionnaire. The seizure frequency decreased with age, although lacking statistical significance. Vaccines show no influence on the condition of patients with DS. Our findings revealed the highest impact on the domains affecting the caregivers' daily life, including additional household tasks, symptom observation, further medical plan, and financial issues. Caregivers also expressed concerns regarding the lack of independence/constant care, seizure control, speech/communication, and impacts on siblings because of long-term care of the patients in parents' absence. Our findings highlight the significant effects of caring for a child with DS on the lives of their caregivers in Taiwan; these findings will help raise awareness regarding the needs of these families. Furthermore, we discussed the possible pathophysiological mechanisms of associated comorbidities. [ABSTRACT FROM AUTHOR]

The aims were to develop an integrated electronic medication reconciliation (ieMR) platform, evaluate its effects on preventing potential duplicated medications, analyze the distribution of the potential duplicated medications by the Anatomical Therapeutic and Chemical (ATC) code for all inpatients, and determine the rate of 30-day medication-related hospital revisits for a geriatric unit. The study was conducted in a tertiary medical center in Taiwan and involved a retrospective quasi pre-intervention (July 1–November 30, 2015) and post-intervention (October 1–December 31, 2016) study design. A multidisciplinary team developed the ieMR platform covering the process from admission to discharge. The ieMR platform included six modules of an enhanced computer physician order entry system (eCPOE), Pharmaceutical-care, Holistic Care, Bedside Display, Personalized Best Possible Medication Discharge Plan, and Pharmaceutical Care Registration System. The ieMR platform prevented the number of potential duplicated medications from pre (25,196 medications, 2.3%) to post (23,413 medications, 3.8%) phases (OR 1.71, 95% CI, 1.68–1.74; p <.001). The most common potential duplicated medications classified by the ATC codes were cardiovascular system (28.4%), alimentary tract and metabolism (26.4%), and nervous system (14.9%), and by chemical substances were sennoside (12.5%), amlodipine (7.5%), and alprazolam (7.4%). The rate of medication-related 30-day hospital revisits for the geriatric unit was significantly decreased in post-intervention compared with that in pre-intervention (OR = 0.12; 95% CI, 0.03–0.53; p <.01). This study indicated that the ieMR platform significantly prevented the number of potential duplicated medications for inpatients and reduced the rate of 30-day medication-related hospital revisits for the patients on the geriatric unit. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to improve medication reconciliation and reduce the occurrence of duplicate prescriptions by pharmacists and physicians within 72 hours of hospital admission using an intelligent prescription system combined with the National Health Insurance PharmaCloud system to integrate the database with the medical institution computerized physician order entry (CPOE) system. Methods: This 2‐year intervention study was implemented in the geriatric ward of a hospital in Taiwan. We developed an integrated CPOE system linked with the PharmaCloud database and established an electronic platform for coordinated communication with all healthcare professionals. Patients provided written informed consent to access their PharmaCloud records. We compared the intervention effectiveness within 72 hours of admission for improvement in pharmacist medication reconciliation, increased at‐home medications documentation and decreased costs from duplicated at‐home prescriptions. Results: The medication reconciliation rate within 72 hours of admission increased from 44.0% preintervention to 86.8% postintervention (relative risk = 1.97, 95% confidence interval [CI]: 1.69–2.31; P < .001). The monthly average of patients who brought and took home medications documented in the CPOE system during hospitalization increased by 7.54 (95% CI 5.58–20.49, P = .22). The monthly average of home medications documented increased by 102.52 (95% CI 38.44–166.60; P = .01). Savings on the monthly average prescription expenditures of at‐home medication increased by US$ 2,795.52 (95% CI US$1310.41–4280.63; P < .01). Conclusion: Integrating medication data from PharmaCloud to the hospital's medical chart system improved pharmacist medication reconciliation, which decreased duplicated medications and reduced in‐hospital medication costs. [ABSTRACT FROM AUTHOR]

Transient hypothyroidism is common in premature infants and increases the risk of adverse neurodevelopmental outcomes. Thyroid hormone (TH) is involved in oligodendrocyte development and myelination, however, whether transient hypothyroidism is associated with oligodendrocyte dysplasia and abnormal myelination is unclear. The aim of the present study was to investigate correlations among TH levels, neurodevelopmental outcomes and white matter (WM) microstructure in premature infants. The authors designed a cohort study recruiting 81 premature infants (age, 23-35 weeks). A total of 17 were born with a gestational age (GA) <30 weeks (early preterm group) and 64 of them were born with a GA ≥30 weeks (late preterm group). For outcome measurement, thyroid stimulating hormone (TSH) levels at 0, 18, and 24 h of admission were measured. Neurodevelopmental outcomes were assessed using Bayley III test. Diffusion tensor imaging was used to explore the characterization of WM microstructure. The data demonstrated that GA, however not TSH level was associated with neurodevelopmental outcomes in the following 2 years. Fractional anisotrophy (FA) increased with TSH0 levels over anterior limb of internal capsule, while axial diffusivity decreased with TSH0 levels over splenium of corpus callosum (CC). The late preterm group had more intact WM integrity over the internal and external capsule (EC) in FA compared with the early preterm group. Infants with motor dysfunction had significantly increased mean diffusivity (MD) values at regions of interest in the genu and splenium of CC. The results of the present study demonstrated that GA, however not transient hypothyroidism influenced neurodevelopmental outcomes in the premature infants. FA increased with age in a regionally-specific manner over regions of the internal capsule and EC. MD may act as a potential predictor for motor function in premature babies. [ABSTRACT FROM AUTHOR]

In this 16-year (1986-2001) retrospective study, 23 childhood patients were identified with Guillain-Barre´ syndrome. According to clinical and electrophysiologic findings, 18 patients manifested acute inflammatory demyelinating polyradiculoneuropathy, 2 had Miller Fisher syndrome, 1 had axonal forms, and 2 were unclassified. Seasonal preponderance was evident in 39% of patients with Guillain-Barre´ syndrome, developing the disease in the winter (November to January) with upper respiratory infection the most frequent preceding event. The most common manifestation was limb weakness, with various degrees of motor weakness in 22 patients. Bulbar involvement was the most common cranial palsy, and it was evident in 30% of the episodes. Only one of these progressed to mechanical ventilation during hospitalization. Altogether, approximately 61% of the episodes exhibited sensory symptoms. At a follow-up of 1 year or more, 20 patients recovered and 3 had residua. Furthermore, no fatality occurred in our study. Our study also demonstrates that the clinical course of childhood Guillain-Barre´ syndrome has a shorter recovery time as compared with an adult patient group. Therapeutic outcome is favorable for patients who receive prompt treatment. [Copyright &y& Elsevier]

Adenosine is an endogenous modulator that has an inhibitory effect on neuronal activity. The aim of this work was to investigate the role of aminophylline, an adenosine receptor antagonist, on the long-term effects of status epilepticus (SE) in the developing brain. Four groups of rats at the postnatal age of 12 days were intraperitoneally administered with saline, aminophylline (50 mg/kg), lithium–pilocarpine (Li–PC) (3 mEq/kg–60 mg/kg), and Li–PC plus aminophylline, respectively. The four groups were tested for spatial memory using the Morris water maze task at P80 and motor performance by the Rotarod test at P100. The brains were then analyzed with cresyl violet stain for histological lesions and evaluated for mossy fiber sprouting with the Timm stain. At the acute stage, all rats subjected to Li–PC developed SE and no seizures were elicited in the saline-treated or aminophylline-treated rats. The seizure duration was longer in the Li–PC plus aminophylline group (346.9±32.7 min) as compared with that in the Li–PC group (265.2±9.8 min). The difference of mortality was not significant. Rats without seizures exhibited no motor imbalance, spatial deficits, or morphological changes. The rats with Li–PC-induced SE demonstrated spatial memory deficits without motor incoordination or morphological changes. However, the rats subjected to Li–PC plus aminophylline exhibited motor impairment and morphological changes, including neuronal cell loss in CA1 area and increased mossy fiber sprouting in CA3 area. In addition, the rats of Li–PC plus aminophylline had greater spatial memory deficits than that seen in rats with Li–PC. We concluded that an adenosine receptor antagonist, such as aminophylline, had synergistic effects on the SE-induced long-term deficit of cognition and motor performance in the developing brain. The present study may provide experimental evidence and lead to novel therapeutic interventions. [Copyright &y& Elsevier]

Patients with Rett syndrome (RTT) show severe difficulties with communication, social withdrawl, and learning. Music-based interventions improve social interaction, communication skills, eye contact, and physical skills and reduce seizure frequency in patients with RTT. This study aimed to investigate the mechanism by which music-based interventions compromise sociability impairments in mecp2 null/y mice as an experimental RTT model. Male mecp2 null/y mice and wild-type mice (24 days old) were randomly divided into control, noise, and music-based intervention groups. Mice were exposed to music or noise for 6 h/day for 3 consecutive weeks. Behavioral patterns, including anxiety, spontaneous exploration, and sociability, were characterized using open-field and three-chamber tests. BDNF, TrkB receptor motif, and FNDC5 expression in the prefrontal cortex (PFC), hippocampus, basal ganglia, and amygdala were probed using RT-PCR or immunoblotting. mecp2 null/y mice showed less locomotion in an open field than wild-type mice. The social novelty rather than the sociability of these animals increased following a music-based intervention, suggesting that music influenced the mecp2-deletion-induced social interaction repression rather than motor deficit. Mechanically, the loss of BDNF signaling in the prefrontal cortex and hippocampal regions, but not in the basal ganglia and amygdala, was compromised following the music-based intervention in mecp2 null/y mice, whereas TrkB signaling was not significantly changed in either region. FNDC5 expression in the prefrontal cortex region in mecp2 null/y mice also increased following the music-based intervention. Collective evidence reveals that music-based interventions improve mecp2-loss-induced social dysfunction. BDNF and FNDC5 signaling in the prefrontal cortex region mediates the music-based-intervention promotion of social interactions. This study gives new insight into the mechanisms underlying the improvement of social behaviors in mice suffering from experimental Rett syndrome following a music-based intervention. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal shock wave therapy (ESWT) is reportedly effective for improving spasticity and motor function in children with cerebral palsy (CP). Because late-stage Rett syndrome has a similar presentation, this study aimed to investigate the effects of ESWT on these two diseases. Material and Methods: Patients diagnosed with spastic CP and Rett syndrome received 1500 impulses of ESWT at 4 Hz and 0.1 mJ/mm2, on their spastic legsonce weekly for a total of 12 weeks. Outcomes were assessed before and 4 and 12 weeks after ESWT. Clinical assessments included the Modified Ashworth Scale (MAS), passive range of motion (PROM), and Gross Motor Function Measure 88 (GMFM-88). Ultrasonographic assessments included muscle thickness, acoustic radiation force impulse (ARFI), and strain elastography. Results: Fifteen patients with CP and six with Rett syndrome were enrolled in this study. After ESWT, patients with CP showed significant clinical improvement in the MAS (P = 0.011), ankle PROM (P = 0.002), walking/running/jumping function (P = 0.003), and total function (P < 0.001) of the GMFM-88. The patients with Rett syndrome showed improved MAS scores (P = 0.061) and significantly improved total gross motor function (P = 0.030). Under ARFI, patients with CP demonstrated decreased shear wave speed in the gastrocnemius medial head (P = 0.038). Conversely, patients with Rett syndrome show increased shear-wave speeds after ESWT. Conclusion: Our study provides evidence that a weekly course of low-dose ESWT for 12 weeks is beneficial for children with both CP and Rett syndrome, with the clinical effects of reducing spasticity and improving the gross motor function of the lower limbs. The ARFI sonoelastography reveals improvement of muscle stiffness in patients with CP after ESWT, but deteriorated in patients with Rett syndrome. The diverse therapeutic response to ESWT may be caused by the MECP2 mutation in Rett syndrome, having a continuous impact and driving the pathophysiology differently as compared to CP, which is secondary to a static insult. Trial registration IRB 201700462A3. Registered 22March 2017, https://cghhrpms.cgmh.org.tw/HRPMS/Default.aspx. [ABSTRACT FROM AUTHOR]

Background: Periventricular white-matter (WM) injury is a prominent feature of brain injury in preterm infants. Thyroxin (T4) treatment reduces the severity of hypoxic-ischemic (HI)-mediated WM injury in the immature brain. This study aimed to delineate molecular events underlying T4 protection following periventricular WM injury in HI rats. Methods: Right common-carotid-artery ligation, followed by hypoxia, was performed on seven-day-old rat pups. The HI pups were injected with saline, or 0.2 or 1 mg/kg of T4 at 48–96 h postoperatively. Cortex and periventricular WM were dissected for real-time (RT)-quantitative polymerase chain reactions (PCRs), immunoblotting, and for immunofluorescence analysis of neurotrophins, myelin, oligodendrocyte precursors, and neointimal. Results: T4 significantly mitigated hypomyelination and oligodendrocyte death in HI pups, whereas angiogenesis of periventricular WM, observed using antiendothelium cell antibody (RECA-1) immunofluorescence and vascular endothelium growth factor (VEGF) immunoblotting, was not affected. T4 also increased the brain-derived neurotrophic factors (BDNFs), but not the nerve growth factor (NGF) expression of injured periventricular WM. However, phosphorylated extracellular signal regulated kinase (p-ERK) and phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB) concentrations, but not the BDNF downstream pathway kinases, p38, c-Jun amino-terminal kinase (c-JNK), or Akt, were reduced in periventricular WM with T4 treatment. Notably, T4 administration significantly increased BDNF and phosphorylated CREB in the overlying cortex of the HI-induced injured cortex. Conclusion: Our findings reveal that T4 reversed BNDF signaling to attenuate HI-induced WM injury by activating ERK and CREB pathways in the cortex, but not directly in periventricular WM. This study offers molecular insight into the neuroprotective actions of T4 in HI-mediated WM injury in the immature brain. [ABSTRACT FROM AUTHOR]

This meta-analysis was a systematic review of evidence on the effects of mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT) on quality of life (QOL), pain, fatigue, anxiety, and depression in cancer patients. Until July 2020, PubMed, Cochrane Library, and Embase were searched for randomized controlled trials (RCTs). The study included 18 RCTs. The MBSR/MBCT intervention resulted in a significant effect on QOL (SMD 0.80, CI 0.28, 1.32, I2 = 94%). In subgroup analysis, MBSR/MBCT interventions had a significant effect in the early cancer stage on anxiety (SMD − 3.48, CI − 4.07, − 2.88), and QOL (SMD 4.30, CI 3.62, 4.99); in alleviating decreasing pain (SMD − 0.42, CI − 0.70, − 0.14) within 4 weeks after the end of intervention, and alleviating fatigue in younger participants (SMD − 0.64, CI − 1.09, − 0.19). MBSR/MBCT has short-term effects on cancer patients, especially in younger patients and early cancer stages. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Paraneoplastic neurological diseases (PND) are rare, but potentially treatable disorders. Paraneoplastic encephalitis is rapidly emerging as an important but likely under-recognized condition in children. The aim of this study was to assess the prevalence and spectrum of PND in children with benign ovary tumor and the long-term outcome. Patients and methods: We retrospectively reviewed the charts of all female patients below 18years of age diagnosed with a benign ovarian tumor proven by pathology between January 1993 and December 2010. All the clinical symptoms developed within 5years of tumor diagnosis and the related investigations were recorded. Results: There were total 133 children and adolescents with benign ovarian tumors, mostly mature teratoma. Six patients (4.5%) had neuropsychiatric manifestations and all but one were beyond age 10years. The most common neuropsychiatric presentations were depression or low mood (84%), headache (50%), mutism (50%), hypoventilation (50%), seizures (30%), hallucination (30%), vomiting and hypersalivation (30%). Three patients (2.2%) had serious PND including acute disseminated encephalomyelitis in 1 and anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis in 2. Although all of three improved after tumor removal, one without immunotherapy had neurological sequelae and prolonged ICU stay. Conclusion: The prevalence of PND in benign ovary tumor is not so uncommon in children. It is important to survey ovary tumors in female adolescents with subacute presentation of multiple-level involvement of neuraxis where no clear alternate diagnosis is possible. Treatment of serious PND associated with ovary tumors should include immunotherapy in addition to tumor removal. [Copyright &y& Elsevier]

Maternal nutrient intake influences the health of the offspring via microenvironmental systems in digestion and absorption. Maternal high fructose diet (HFD) impairs hippocampus-dependent memory in adult female rat offspring. However, the underlying mechanisms remain largely unclear. Maternal HFD causes microbiota dysbiosis. In this study, we find that the plasma level of butyrate, a major metabolite of microbiota, is significantly decreased in the adult female maternal HFD offspring. In these rats, GPR43, a butyrate receptor was downregulated in the hippocampus. Moreover, the expressions of mitochondrial transcription factor A (TFAM), and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) were downregulated in the hippocampus. The decreases of these functional proteins were reversed by fructooligosaccharides (FOS, a probiotic) treatment in adulthood. Astrocytes are critical for energy metabolism in the brain. Primary astrocyte culture from female maternal HFD offspring indicated that GPR43 and the mitochondrial biogenesis were significantly suppressed, which was reversed by supplemental butyrate incubation. The oxygen consumption rate (OCR) was reduced in the HFD group and rescued by butyrate. Intriguingly, the nuclear histone deacetylase 4 (HDAC4) was enhanced in the HFD group, suggesting an inhibitory role of butyrate on histone deacetylase activity. Inhibition of HDAC4 effectively restored the OCR, bioenergetics, and biogenesis of mitochondria. Together, these results suggested that the impaired butyrate signaling by maternal HFD could underlie the reduced mitochondrial functions in the hippocampus via HDAC4-mediated epigenetic changes. [ABSTRACT FROM AUTHOR]

Intellectual disability (ID) has emerged as the commonest manifestation of underlying genomic abnormalities. Given that molecular genetic tests for diagnosis of ID usually require high costs and yield relatively low diagnostic rates, identification of additional phenotypes or comorbidities may increase the genetic diagnostic yield and are valuable clues for pediatricians in general practice. Here, we enrolled consecutively 61 children with unexplained moderate or severe ID and performed chromosomal microarray (CMA) and sequential whole-exome sequencing (WES) analysis on them. We identified 13 copy number variants in 12 probands and 24 variants in 25 probands, and the total diagnostic rate was 60.7%. The genetic abnormalities were commonly found in ID patients with movement disorder (100%) or with autistic spectrum disorder (ASD) (93.3%). Univariate analysis showed that ASD was the significant risk factor of genetic abnormality (P = 0.003; OR 14, 95% CI 1.7–115.4). At least 14 ID-ASD associated genes were identified, and the majority of ID-ASD associated genes (85.7%) were found to be expressed in the cerebellum based on database analysis. In conclusion, genetic testing on ID children, particularly in those with ASD is highly recommended. ID and ASD may share common cerebellar pathophysiology. [ABSTRACT FROM AUTHOR]

• KD is a promising alternative therapy for refractory epilepsy in infants under 2 years old. • The starting keto ratio should be lower, and the keto ratio titration period should be longer in this age group. • Adverse effects were mildly symptomatic and could be reversible by adjusting the keto ratio. • Growth retardation, the major concerns of KD treatment under 2 years old, is rare under the non-fasting, low starting keto ratio and gradually titrating energy demand KD program. Ketogenic diet Therapy (KDT) has been reported as a possible beneficial management strategy for controlling seizures in infants aged <2 years, but the safety and efficacy of this therapy remain to be investigated. We investigated the achievability, tolerability, efficacy, and safety of KDT for patients under 2 years old. Infants younger than 2 years old with pharmacoresistant epilepsy were enrolled in this prospective study. We divided cases into three age groups: I) neonates; II) infants aged 1–12 months; III) infants aged 12–24 months. KDT initiation protocol were administration through parenteral route, enteral route or oral feeding. Seizure reduction rate, physical growth, and adverse effects were assessed at monthly visit. Thirteen patients who completed 6 months of KDT were recruited. There was one neonate in group I, 9 infants in group II, and 3 infants in group III. Eleven of them (11/13, 84.6%) were responders to KDT. All infants with underlying genetic etiology were seizure free after treating with KDT. The starting keto ratio was 1.1 mmol/L in group I, 2.3 mmol/L in group II, and 2.8 mmol/L in group III, which gradually approached 3:1–4:1 over 5–7 days. There were no symptomatic adverse effects or growth retardation in any of the study subjects. KDT is a promising alternative therapy with high feasibility, safety, and efficacy for pharmacoresistant epilepsy in infants under 2 years old, especially for those with genetic etiology. The starting keto ratio should be lower, and the keto ratio titration period should be longer than for children older than 2 years. [ABSTRACT FROM AUTHOR]

We report on a 7-year-old immunocompetent boy initially presenting with right-sided frontal cephalalgia, painful ophthalmoplegia, and ptosis for 1 month. Initial cerebrospinal fluid analysis produced normal results. Magnetic resonance imaging revealed an inflammatory pseudotumor of the right cavernous sinus after intravenous gadolinium administration, indicating a rare idiopathic inflammatory disorder of the cavernous sinus, i.e., Tolosa-Hunt syndrome. Ptosis and cephalalgia resolved after steroid treatment, although right-sided ophthalmoplegia remained. Breakthrough headache, associated with signs of meningeal irritation, developed 6 weeks later. Follow-up contrast-enhanced computed tomography revealed no enhancing cavernous soft tissue mass. A further lumbar puncture disclosed central nervous system infection with Staphylococcus saprophyticus. After 6 weeks of vancomycin, the headache resolved completely, and neuroimaging produced normal results. A diagnosis of Tolosa-Hunt syndrome should be rendered cautiously, because the etiology may involve a rare but not “idiopathic” infection. Moreover, if clinical signs are not fully responsive to steroid treatment, the underlying problems should receive careful investigation. [ABSTRACT FROM AUTHOR]

In this study, 116 patients, at least 1 month of age but younger than 5 years, were identified with culture-proven bacterial meningitis. A comparison was made between the clinical data of the patients with and without seizures during hospitalization. Seizures during acute bacterial meningitis accounted for 47% (55/116) of the episodes. Time interval between the onset of bacterial meningitis and that of seizures was 1 to 20 days (mean, 4 days). Twelve of these 55 patients had one or more afebrile seizures after completing the treatment. At follow-up of at least 1 year after completing treatment, 26 patients had good outcomes, whereas the other 29 patients had poor outcomes. A strong correlation between the findings of abnormalities through neuroimaging and the occurrence of seizures during hospitalization was observed. The long-term outcomes of patients with infantile and childhood bacterial meningitis, who had seizures during the acute phase of bacterial meningitis, were worse than the outcomes of those who did not have such seizures. No child developed late seizures unless there were acute seizures. Factors associated with seizures during acute bacterial meningitis include disturbed consciousness on admission, abnormal neuroimaging findings, and low glucose and high concentration of total proteins in cerebrospinal fluid. [Copyright &y& Elsevier]

This 16-year (1986–2001) retrospective study enrolled 80 infantile patients (aged, 30–365 days old) with culture-proven bacterial meningitis. The most prevalent pathogens were Salmonellaspecies, Streptococcus (S.) agalactiae, Escherichia (E.) coli, and Haemophilus (H.) influenzae, accounting for about 59% of the episodes. Meningitis caused by Salmonella species, E. coli and H. influenzae occurs more often in the older infants, while that caused by S. agalactiae occurs more often in young infants. Our study revealed a decrease in the proportion of Salmonella meningitis from 27% in the first 8 years to 9% in the second 8 years with E. coli replacing Salmonella species as the leading pathogen of this disease during the second period. Overall mortality rate for both periods of time was 11%. However, if we take those with undesirable poor outcomes into account, 43% of patients could be considered treatment failures. The study also reveals a high prevalence of neurological complications when this disease is caused by H. influenzae, S. pneumoniae, and Salmonella species. Stepwise logistic regression analysis revealed that only initial changing levels of consciousness (P=0.006) were independently associated with treatment failure. The most frequent neurological complications associated with this disease included subdural empyema, hydrocephalus, cerebral infarctions, and seizures. Because therapeutic regimens may require attention to the eradication of bacterial pathogen but also the neurological complications, early diagnosis and choice of appropriate antibiotics are essential to increasing the possibility of survival. [Copyright &y& Elsevier]

To determine the epidemiologic trends, prognostic factors, and therapeutic results of neonatal bacterial meningitis, 60 neonatal patients with culture-proven neonatal bacterial meningitis were enrolled in this study. To compare changes over time, the appearance of disease among the patients was divided into two equal periods (1986-1993 and 1994-2001). Group B streptococci were the most common causative pathogens, accounting for approximately 32% of the episodes. Escherichia coli, the next most common pathogen, was more frequently observed in the second period. Seventy-seven percent of gram-negative bacilli isolates were resistant to ampicillin. Moreover, oxacillin-resistant Staphylococcus and ampicillin-resistant group B streptococci strains occurred in the second periods as late-onset neonatal bacterial meningitis. The overall mortality rates for the first and second study period were 17% and 8%, respectively. However, if individuals with poor outcomes were taken into account, 38% of patients were considered treatment failures. Significant prognostic factors included the presence of seizures, thrombocytopenia, and high cerebrospinal fluid protein and low cerebrospinal fluid glucose concentration. Although the mortality rate was significantly reduced in the second period, there has been increasing incidence of the emergence of resistant strains presenting a therapeutic challenge. The presentation in neonatal bacterial meningitis might be nonspecific, and blood culture results were negative in 45% of the episodes. Early diagnosis, choice of appropriate antibiotics, and correction of metabolic derangement are essential to improving outcomes. Chang C-J, Chang W-N, Huang L-T, Huang S-C, Chang Y-C, Hung P-L, Tasi C-Y, Lu C-H, Cheng B-C, Lee P-Y, Chang H-W. Neonatal bacterial meningitis in southern Taiwan. [Copyright &y& Elsevier]

Summary: Purpose: Maternal deprivation is stressful for the neonate. The aim of this study was to investigate the short- and long-term effects of maternal separation on recurrent seizures in the developing brain. Methods: Rats were divided into four groups according to whether the rat pups were treated with maternal deprivation from postnatal day 2 (P2) to P9 or neonatal seizures induced by intraperitoneal (i.p.) injection of pentylenetetrazol (PTZ) from P10 to P14. Rats in the control group received saline i.p. injection from P10 to P14; rats in the isolation group underwent daily separation from their dams from P2 to P9; rats in the PTZ-treated group were subjected to PTZ-induced recurrent seizures from P10 to P14; rats in the isolation plus PTZ–treated group were subjected to maternal deprivation from P2 to P7 followed by serial seizures from P10 to P14. In addition, subsets of rats at P15 were killed and the brains assessed for acute neuronal degeneration. Visual–spatial memory test using the Morris water maze task was performed at P80. After testing, the hippocampus was evaluated for histologic lesions and cyclic adenosine monophosphate (cAMP)-responsive element-binding protein phosphorylation at serine-133 (p CREBSer-133 ), an important transcription factor underlying learning and memory. Results: All rats given PTZ developed recurrent seizures. After PTZ administration, rats with a history of maternal deprivation had more intense impairment than did rats with maternal deprivation and neonatal seizures than those without deprivation. Neuronal degeneration was most prominent in the rats exposed to maternal deprivation plus recurrent seizures. Rats receiving maternal deprivation or PTZ-induced recurrent seizures exhibited only spatial deficits, but no morphologic changes in the hippocampus. However, rats with maternal deprivation plus PTZ-induced recurrent seizures exhibited worse visual–spatial learning compared with rats... [ABSTRACT FROM AUTHOR]

The lack of specific symptoms and signs in patients with tuberculous meningitis makes early diagnosis difficult. To our knowledge, there has been no report in the literature focusing on tuberculous meningitis patients younger than 1 year of age. In this report, we reviewed the clinical features and laboratory findings of seven infants with tuberculous meningitis encountered during a 15-year period. All patients had fever, cough, and alternation of consciousness at presentation. Five patients had bulging anterior fontanel, and five had generalized tonic-clonic seizures. The purified protein derivative skin test was positive in six patients. Six patients had hyponatremia. All seven patients had abnormal cerebrospinal fluid findings, and six of them demonstrated cell counts less than 500 cells/mm3 with lymphocytic predominance. Brain sonography examination revealed hydrocephalus in all seven patients. Therefore we conclude that antituberculosis therapy should be promptly initiated in any young infant with a clinical impression of meningitis in the context of cerebrospinal fluid white cell count of less than 500 cells/mm3 and lymphocytic predominance, hyponatremia, and hydrocephalus. [Copyright &y& Elsevier]

Summary: Purpose: Recurrent seizures in infants are associated with a high incidence of neurocognitive deficits. Animal models have suggested that the immature brain is less vulnerable to seizure-induced injury than is that in adult animals. We studied the effects of recurrent neonatal seizures on cognitive tasks performed when the animals were in adolescence and adulthood. Methods: Seizures were induced by intraperitoneal injection of pentylenetetrazol (PTZ) for 5 consecutive days, starting from postnatal day 10 (P10). At P35 and P60, rats were tested for spatial memory by using the Morris water maze task. In adulthood, motor performance was examined by the Rotarod test, and activity level was assessed by the open field test. Seizure threshold was examined by inhalant flurothyl. To assess presence or absence of spontaneous seizures, rats were video recorded for 4 h/day for 10 consecutive days for the detection of spontaneous seizures. Finally, brains were examined for histologic evidence of injury with cresyl violet stain and Timm staining in the supragranular zone and CA3 pyramidal cell layers of the hippocampus. Results: PTZ-treated rats showed significant spatial deficits in the Morris water maze at both P35 and P60. There were no differences in seizure threshold, motor balance, or activity level during the open field test. Spontaneous seizures were not recorded in any rat. The cresyl violet stain showed no cell loss in either the control or experimental rats. PTZ-treated rats exhibited more Timm staining in the CA3 subfield. However, the control and experimental rats showed similar Timm staining within the supragranular zone. Conclusions: Our findings indicate that recurrent PTZ-induced seizures result in long-term cognitive deficits and morphologic changes in the developing brain. Furthermore, these cognitive deficits could be detected during pubescence. [ABSTRACT FROM AUTHOR]

Abstract: Here, we investigated whether aminophylline, an adenosine receptor antagonist used usually as a treatment for premature apnea, had synergistic effects on status epilepticus in the developing brain. On postnatal day 14 (P14), four groups of rats intraperitoneally received saline, aminophylline, lithium–pilocarpine (Li-PC), and Li-PC plus aminophylline, respectively. Subsequently, the Morris water maze task was performed at P80. The brains were then analyzed with cresyl violet stain for histological lesions and evaluated for mossy fiber sprouting with the Timm stain. No seizures were elicited in the saline-treated or aminophylline-treated rats. Both the Li-PC-treated and aminophylline plus Li-PC-treated rats exhibited seizures and there was no significant difference in mortality between the two groups. More interestingly, as in adulthood (P80), aminophylline aggravated the spatial deficits and histological damages seen in Li-PC-treated rats. In summary, this present study suggests that the use of adenosine receptor antagonists, such as aminophylline, exacerbates seizure-induced damage in the developing brain. [Copyright &y& Elsevier]

Recurrent neonatal seizures are associated with a high risk of neurological sequelae. The major concern is whether recurrent neonatal seizures induce adverse effects on long-term cognition and/or motor performance. Rats were treated with intraperitoneal (ip) bicuculline for 3 consecutive days, starting from Postnatal Day 5 (P5). Kainic acid (KA, 4 mg/kg ip) was injected at P53 to investigate the susceptibility to a second insult, and then cognitive function was tested using the Morris water maze, and motor performance using the Rotarod test, in adulthood (P60). Finally, histological assessments of brains were performed. The rats treated with bicuculline had no deficits in cognition function and pathology findings, but had worse motor performance and increased susceptibility to later KA challenge. Our findings indicate that recurrent bicuculline-induced seizures in the developing brain result in long-term motor deficits and increase the risk of subsequent cognitive damage in response to a second insult. [Copyright &y& Elsevier]

Dysfunction of mitochondria causes defects in oxidative phosphorylation system (OXPHOS) and increased production of reactive oxygen species (ROS) triggering the activation of the cell death pathway that underlies the pathogenesis of aging and various diseases. The process of autophagy to degrade damaged cytoplasmic components as well as dysfunctional mitochondria is essential for ensuring cell survival. We analyzed the role of autophagy inpatient-specific induced pluripotent stem (iPS) cells generated from fibroblasts of patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) with well-characterized mitochondrial DNA mutations and distinct OXPHOS defects. MELAS iPS cells recapitulated the pathogenesis of MELAS syndrome, and showed an increase of autophagy in comparison with its isogenic normal counterpart, whereas mitophagy is very scarce at the basal condition. Our results indicated that the existence of pathogenic mtDNA alone in mitochondrial disease was not sufficient to elicit the degradation of dysfunctional mitochondria. Nonetheless, oxidative insults induced bulk macroautophagy with the accumulation of autophagosomes and autolysosomes upon marked elevation of ROS, overload of intracellular calcium, and robust depolarization of mitochondrial membrane potential, while mitochondria respiratory function was impaired and widespread mitophagy compromised cell viability. Collectively, our studies provide insights into the dysfunction of autophagy and activation of mitophagy contributing to the pathological mechanism of mitochondrial disease. [ABSTRACT FROM AUTHOR]