Pi-Lien Hung

Maternal Deprivation Stress Exacerbates Cognitive Deficits in Immature Rats with Recurrent Seizures

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.

Pentylenetetrazol-induced recurrent seizures in rat pups: Time course on spatial learning and long-term effects

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.

Bacterial meningitis in infants: the epidemiology, clinical features, and prognostic factors.

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.

Tuberculous meningitis in infancy.

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/mm(3) 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/mm(3) and lymphocytic predominance, hyponatremia, and hydrocephalus.

A clinical and electrophysiologic survey of childhood Guillain-Barré syndrome

In this 16-year (1986-2001) retrospective study, 23 childhood patients were identified with Guillain-Barré 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-Barré 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-Barré syndrome has a shorter recovery time as compared with an adult patient group. Therapeutic outcome is favorable for patients who receive prompt treatment.

Guillain–Barré syndrome in southern Taiwan: clinical features, prognostic factors and therapeutic outcomes

To determine the clinical features, prognostic factors, and therapeutic results of Guillain–Barré syndrome (GBS) in order to improve the therapeutic strategy for this disease. We retrospectively reviewed the electrodiagnostic study and medical records of patients with GBS admitted to Chang Gung Memorial Hospital, Kaohsiung, between January 1986 and December 2000. Outcomes and prognosis were followed‐up after 1 year. Ninety‐six patients were enrolled in this study. According to the clinical and electrophysiological findings, 77 patients were acute inflammatory demyelinating polyradiculoneuropathy, seven were Miller Fisher syndrome, and six were axonal forms, and six were unclassified. At a follow‐up of 1 year, 61 patients (64%) recovered, 30 (31%) had residua and five (5%) died. Amongst these 30 had residua, including unassisted gait in 19, assisted gait in four, and wheel/bed bound in seven. According to the statistical analysis, disabilities at the nadir (P < 0.0001) and at admission (P = 0.014) were significant prognostic factors. Variables used for the stepwise logistic regression, and the results revealed that after analysis for all the above variables, only disability at the nadir (P < 0.0001) was independently associated with the treatment failure rate. Our study revealed 27% of cases in need of respiratory support during hospitalization, and 5% of hospital‐treated patients die from the complications. Furthermore, 31% had residua at a follow‐up of 1 year or more. If prognostic factors are considered, disability at the nadir during hospitalization demonstrates consistently poor therapeutic outcomes. Therefore, early diagnosis, choice of appropriate treatment, and preventing complications during acute stages are essential to maximize the potential for survival.

Neonatal bacterial meningitis in southern Taiwan.

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.

Adult Streptococcus pneumoniae meningitis in Southern Taiwan: epidemiologic trends and prognostic factors

The clinical features of 22 adult patients with Streptococcus pneumoniae meningitis, retrospectively collected over a 16-year period, were reviewed. Otopharyngeal infection, haematogenous spread and cranial neurosurgery continue to be the predominant routes of infection. Most patients acquired the infection in the community, and predisposing underlying conditions are common. The proportion of S. pneumoniae meningitis compared to all microorganisms causing meningitis in adults declined dramatically from 17% in the first 8 study years to 4% in the last 8 study years. However, all penicillin-resistant S. pneumoniae strains were found in the second half of the study period, accounting for 25% of these episodes. The overall mortality rates for the first and second halves of the study period were 43% and 63%, respectively. Third-generation cephalosporins were the antibiotics of choice for the treatment of S. pneumoniae meningitis in this study, however, the emergence of resistant strains may create a therapeutic challenge in the future. To avoid treatment failure, early diagnosis, careful monitoring of the clinical course and the choice of appropriate antibiotics according to the in vitro antimicrobial susceptibilities, are necessary.

Aminophylline exacerbates status epilepticus-induced neuronal damages in immature rats: a morphological, motor and behavioral study

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.

Prognostic factors and therapeutic outcome of isolated symptomatic middle cerebral artery stenosis.

To analyze the prognostic factors and therapeutic outcome of adult patients with isolated symptomatic stenosis of the middle cerebral artery (MCA). Forty‐nine patients were retrospectively verified with isolated symptomatic stenosis of the MCA through both magnetic resonance angiogram and transcranial color‐coded duplex sonography. Therapeutic outcome at 1 year or more was determined using a modified Barthel index (BI). For the purpose of analysis, the patients were divided into two groups: a good outcome group (BI ≥ 12) and a poor outcome group (BI < 12 or recurrent stroke). The association between different therapeutic regimens and the percent free of recurrent stroke after the first event of cerebral infarction was assessed with Kaplan–Meier plots compared by a log‐rank test. These patients accounted for 2.8% of all patients with the first event of cerebral infarction during the same period. At follow‐up of 1 year or more, 63% had good outcomes whilst the other 37% had poor outcomes. Overall, 26.5% suffered from recurrent strokes during the follow‐up period. According to the statistical analysis, the stepwise logistic regression revealed that only the National Institutes of Health Stroke Scale (NIHSS) at the time of admission was independently associated with a poor outcome. Furthermore, Kaplan–Meier analysis showed a significantly higher percentage of patients free of recurrent stroke events amongst those who were treated with warfarin. The NIHSS at the time of admission was a predictor of outcome amongst our patients, and stenosis of the MCA implies the danger of recurrent cerebral events. Our study also demonstrates the efficacy of oral anticoagulants in the secondary prevention in this specific group of patients. Therefore, we look forward to more prospective multicenter investigations in evaluating the efficiency of therapy in the future.