Hong Ki Song

Bio: Hong Ki Song is an academic researcher from Hallym University. The author has contributed to research in topics: Epilepsy & Adjunctive treatment. The author has an hindex of 9, co-authored 14 publications receiving 243 citations. Previous affiliations of Hong Ki Song include Sacred Heart Hospital.

The effect of topiramate monotherapy on bone mineral density and markers of bone and mineral metabolism in premenopausal women with epilepsy

Abstract: Summary Purpose: To investigate the effect of topiramate on bone mass and metabolism in premenopausal women with epilepsy. Methods: Thirty-six women on long-term (at least 1 year) topiramate monotherapy were compared with 36 women taking carbamazepine, 32 women taking valproate, and 36 age- and sex-matched controls. Subjects completed bone mineral density (BMD) studies. Serum was analyzed for indices of bone metabolism. Key Findings: BMD Z-scores, and serum 25-hydroxyvitamin D and 1alpha,25-dihydroxyvitamin D3 concentrations did not differ among the groups. Serum calcium concentrations were significantly lower in patients receiving topiramate than in those receiving valproate, and in patients receiving carbamazepine than in those receiving valproate and controls. Patients taking topiramate had lower levels of parathyroid hormone compared with controls and those taking carbamazepine or valproate. Patients receiving topiramate had higher levels of bone-specific alkaline phosphatase and osteocalcin when compared with controls and higher levels of C-terminal telopeptide of type 1 collagen when compared with those taking carbamazepine or valproate. Patients receiving carbamazepine had higher levels of bone-specific alkaline phosphatase compared with controls and those receiving valproate. Serum bicarbonate concentrations were significantly lower in patients receiving topiramate than in the other groups. Significance: Our results demonstrate that use of topiramate is associated with lower parathyroid hormone and bicarbonate concentrations along with mild hypocalcemia and increased bone turnover, which suggests that topiramate may have long-term effects on bone.

Multi-center study on migraine and seizure-related headache in patients with epilepsy

Abstract: Purpose The purpose of this study is to investigate the frequency and characteristics of migraine and seizure-related headache (SRH) according to the criteria of the International Headache Society. Materials and Methods A questionnaire was undertaken at the initial evaluation of newly referred patients from 32 epilepsy clinics. Results Of a total of 597 patients, 74 (12.4%) patients had migraine. Age at the onset of epilepsy was lower in patients with migraine than in those without. Twenty-six (4.4%), nine (1.5%), and 146 (24.5%) patients experienced prodromal, ictal, and postictal SRH, respectively (n = 169, 28.3%). A pain intensity of prodromal and postictal SRH was 6.1 ± 1.5 (SD) and 6.3 ± 1.9 (SD) on the visual analogue scale, and their duration was 12.6 ± 26.7 (SD) hours and 9.0 ± 17.4 (SD) hours, respectively. Age at the onset of epilepsy was lower in patients with SRH than in those without, and the risk of occurrence of SRH was significantly greater in patients with longer epilepsy duration. SRH could be classified as a type of migraine in 46.2% of patients with prodromal SRH and in 36.3% of patients with postictal SRH. Prodromal SRH occurred more frequently and was more likely to be a migraine-type in patients with migraine compared with those without. Postictal SRH occurred more frequently and was more likely to be a migraine-type in patients with migraine. Conclusion This study suggests that SRH is a frequent accompanying symptom of epileptic seizures causing major impairment in daily life, and migraine is an important comorbidity of epilepsy, affecting the incidence and characteristics of SRH.

Pregabalin add‐on therapy using a flexible, optimized dose schedule in refractory partial epilepsies: A double‐blind, randomized, placebo‐controlled, multicenter trial

Abstract: Summary Purpose: To evaluate the efficacy and safety of pregabalin (PGB) as adjunctive therapy, using a flexible-dosing schedule in Korean patients with refractory partial-onset seizures. Methods: This randomized, double-blind (DB), placebo-controlled trial consists of a 6-week baseline, a 12-week DB treatment, and a 1-week taper phase. Patients having recurrent partial seizures (≥4 seizures during baseline phase) under adequate pharmacotherapy were recruited to be randomized to PGB or placebo (PLC) in a 2 to 1 ratio. Starting dose was 150 mg/day, increased every 2 weeks by 150-mg/day increments up to maximum dose of 600 mg/day. The primary efficacy parameter was response ratio (RRatio) for all partial seizures. Results: A total of 178 patients (119 in PGB, 59 in PLC) were assigned to the study. Median daily doses of PGB and PLC were 367 and 420 mg/day, respectively. RRatio least squares (LS) mean was −35.8 in the PGB group and −23.2 in the PLC group, with estimated difference in RRatios being −12.6 [95% confidence interval (CI): −22.7 to −2.5, p = 0.015] in the intent-to-treat (ITT) population. Analysis of secondary efficacy measures showed a general trend favoring PGB over PLC. Seventy-seven patients (64.7%) in the PGB group and 18 patients (30.5%) in the PLC group developed adverse events (AEs) related to the study drug. Seven patients (5.9%) in the PGB group discontinued the study prematurely because of AEs. In the post hoc analysis, a significant weight gain (≥7% of baseline body weight) was found in 24.8% of patients taking PGB, which was more frequent in patients with a lower body mass index (BMI ≤20). Discussion: PGB was effective and easily tolerable as add-on treatment in an Asian population with refractory partial-onset seizures.

Cognitive and behavioral effects of lamotrigine and carbamazepine monotherapy in patients with newly diagnosed or untreated partial epilepsy

Abstract: Purpose In this prospective study, we compared the long-term cognitive and behavioral effects of lamotrigine (LTG) and carbamazepine (CBZ) in patients with newly diagnosed or untreated partial epilepsy. Methods This was a multicenter, open-label, randomized study that compared monotherapy with LTG and CBZ in newly diagnosed or untreated patients with partial epilepsy. We employed an 8-week titration period and a 40-week maintenance period. Neuropsychological tests, Symptom Check List-90, and QOLIE-31 were assessed at baseline, 16 weeks, and 48 weeks after drug treatment. A group-by-time interaction was the primary outcome measure and was analyzed by use of the linear mixed model. Results A total of 110 patients were eligible and 73 completed the 48-week study (LTG, n =39; CBZ, n =34). Among the cognitive tests, significant group-by-time interaction was identified only in phonemic fluency of Controlled Oral Word Association Task ( p =0.0032) and Stroop Color–Word Interference ( p =0.0283), with a significant better performance for LTG group. All other neuropsychological tests included did not show significant group-by-time interactions. Among the subscales of Symptom Check List-90, significant group-by-time interactions were identified in Obsessive-Compulsive ( p =0.0005), Paranoid Ideation ( p =0.0454), Global Severity Index ( p =0.0194), and Positive Symptom Total ( p =0.0197), with a significant improvement for CBZ group. QOLIE-31 did not show significant group-by-time interactions. Conclusion Our data suggest that epilepsy patients on LTG have better performance on phonemic fluency and the task of Stroop Color–Word Interference than do patients on CBZ, whereas patients on CBZ had more favorable behavioral effects on two subscales and two global scores of Symptom Check List-90 than did patients on LTG.

Efficacy and safety of levetiracetam as adjunctive treatment of refractory partial seizures in a multicentre open-label single-arm trial in Korean patients.

Abstract: Summary This prospective, open-label study evaluated the efficacy and safety of adjunctive levetiracetam (LEV) in Korean adults with uncontrolled partial epilepsy. Study patients had to have an average of at least 1 and not more than 14 partial seizures per month (averaged over a 3-month historical baseline) despite the use of one or two AEDs. Patients initially received LEV 1000mg/day (administered bid) and could increase to 2000mg/day after 2 weeks, and to 3000mg/day after another 2 weeks, to obtain adequate seizure control. During the 12-week maintenance period, the dose of LEV could be increased or decreased once if seizure control was insufficient or tolerability warranted, respectively. Seizure count and adverse events (AEs) were recorded by patients. Global evaluation scale (GES) and quality of life (QOLIE-31) were also evaluated. A total of 100 patients were enrolled and 92 patients completed the study. The median percent reduction in weekly seizure frequency over the treatment period was 43.2%. The ≥50% and ≥75% responder rates were 45.4% and 36.1%, respectively. Seizure freedom throughout the 16-week treatment period was observed in 17 patients. On investigator's GES, 81 patients were considered improved, with 41 patients showing marked improvement. Most QOLIE-31 scales improved significantly. Treatment-emergent AEs were reported in 59 patients. Three most common AEs were somnolence (36%), dizziness (12%), and headache (8%). Adjunctive LEV therapy was effective and well-tolerated in Korean adults with refractory partial epilepsy.

The cognitive impact of antiepileptic drugs

Abstract: Effective treatment of epilepsy depends on medication compliance across a lifetime, and studies indicate that drug tolerability is a significant limiting factor in medication maintenance. Available antiepileptic drugs (AEDs) have the potential to exert detrimental effects on cognitive function and therefore compromise patient wellbeing. On the other hand, some agents may serve to enhance cognitive function. In this review paper, we highlight the range of effects on cognition linked to a variety of newer and older AEDs, encompassing key alterations in both specific executive abilities and broader neuropsychological functions. Importantly, the data reviewed suggest that the effects exerted by an AED could vary depending on both patient characteristics and drug-related variables. However, there are considerable difficulties in evaluating the available evidence. Many studies have failed to investigate the influence of patient and treatment variables on cognitive functioning. Other difficulties include variation across studies in relation to design, treatment group and assessment tools, poor reporting of methodology and poor specification of the cognitive abilities assessed. Focused and rigorous experimental designs including a range of cognitive measures assessing more precisely defined abilities are needed to fill the gaps in our knowledge and follow up reported patterns in the literature. Longitudinal studies are needed to improve our understanding of the influence of factors such as age, tolerance and the stability of cognitive effects. Future trials comparing the effects of commonly prescribed agents across patient subgroups will offer critical insight into the role of patient characteristics in determining the cognitive impact of particular AEDs.

Use of CTX-I and PINP as bone turnover markers: National Bone Health Alliance recommendations to standardize sample handling and patient preparation to reduce pre-analytical variability

Abstract: The National Bone Health Alliance (NBHA) recommends standardized sample handling and patient preparation for C-terminal telopeptide of type I collagen (CTX-I) and N-terminal propeptide of type I procollagen (PINP) measurements to reduce pre-analytical variability. Controllable and uncontrollable patient-related factors are reviewed to facilitate interpretation and minimize pre-analytical variability. The IOF and the International Federation of Clinical Chemistry (IFCC) Bone Marker Standards Working Group have identified PINP and CTX-I in blood to be the reference markers of bone turnover for the fracture risk prediction and monitoring of osteoporosis treatment. Although used in clinical research for many years, bone turnover markers (BTM) have not been widely adopted in clinical practice primarily due to their poor within-subject and between-lab reproducibility. The NBHA Bone Turnover Marker Project team aim to reduce pre-analytical variability of CTX-I and PINP measurements through standardized sample handling and patient preparation. Recommendations for sample handling and patient preparations were made based on review of available publications and pragmatic considerations to reduce pre-analytical variability. Controllable and un-controllable patient-related factors were reviewed to facilitate interpretation and sample collection. Samples for CTX-I must be collected consistently in the morning hours in the fasted state. EDTA plasma is preferred for CTX-I for its greater sample stability. Sample collection conditions for PINP are less critical as PINP has minimal circadian variability and is not affected by food intake. Sample stability limits should be observed. The uncontrollable aspects (age, sex, pregnancy, immobility, recent fracture, co-morbidities, anti-osteoporotic drugs, other medications) should be considered in BTM interpretation. Adopting standardized sample handling and patient preparation procedures will significantly reduce controllable pre-analytical variability. The successful adoption of such recommendations necessitates the close collaboration of various stakeholders at the global stage, including the laboratories, the medical community, the reagent manufacturers and the regulatory agencies.

The adverse event profile of pregabalin: A systematic review and meta‐analysis of randomized controlled trials

Abstract: Summary Purpose: Despite the widespread use of antiepileptic drugs (AEDs) across different neurologic and psychiatric disorders, no study has systematically reviewed all available randomized controlled trials (RCTs) of a given AED to fully uncover its tolerability profile. We aimed at identifying treatment emergent adverse events (AEs) associated with pregabalin through a systematic review and meta-analysis of all available RCTs. We also assessed the association between serious AEs and pregabalin, and investigated whether pregabalin AEs display a dose–response relationship. Methods: We searched MEDLINE, EMBASE, and Cochrane CENTRAL to February 2010 for RCTs. Additional studies were identified from reference lists of retrieved papers and from online clinical databases. We selected placebo-controlled, double-blind RCTs investigating the therapeutic effects of pregabalin in adults with any condition. Studies had to include at least 20 subjects per arm and have a duration of at least 4 weeks. AEs were assessed for their association with pregabalin after identification/exclusion of synonyms, rare AEs, and nonassessable AEs due to methodologic limitations. We used relative risks (RRs) to assess the association of any [99% confidence intervals (CIs)] or serious AEs (95% CIs) with pregabalin, and risk differences (RDs, 95% CIs) to investigate dose–response relationships of pregabalin AEs. Key findings: Thirty-eight RCTs were included in our study. Of 39 AEs, 20 (51%) were significantly associated with pregabalin (dizziness, vertigo, incoordination, balance disorder, ataxia, diplopia, blurred vision, amblyopia, tremor, somnolence, confusional state, disturbance in attention, thinking abnormal, euphoria, asthenia, fatigue, edema, peripheral edema, dry mouth, constipation). The highest RRs were found for cognition/coordination AEs. There was no significant association between serious AEs and pregabalin. There was a selective dose–response pattern in the onset of pregabalin AEs, with certain AEs appearing at lower doses than others. Significance: Individuals starting treatment with pregabalin are at increased risk for several AEs, particularly those affecting cognition/coordination. Pregabalin AEs appear according to a selective dose–response pattern, possibly reflecting the severity of dysfunction of distinct anatomic structures. These findings may aid clinicians in providing better patient management, and support the value of including in meta-analyses of AED tolerability profiles RCTs performed in different conditions.

Factors determining response to antiepileptic drugs in randomized controlled trials. A systematic review and meta-analysis.

Abstract: Summary Purpose: Because of the lack of head-to-head adjunctive-therapy trials of antiepileptic drugs (AEDs) in refractory partial epilepsy, meta-analyses of placebo-controlled randomized controlled trials (RCTs) represent a potentially important source of evidence to guide treatment decisions However, such indirect comparisons raise various methodologic issues that may hamper their relevance Methods: All RCTs in adult refractory partial epilepsy were analyzed to assess whether efficacy outcomes are influenced by: characteristics of patients and trials ; use of last observation carried forward (LOCF) analysis; evaluation period (entire period versus maintenance period); and year of publication A meta-analysis of these AEDs was then performed taking these factors into consideration Key Findings: Sixty-three RCTs evaluating 20 AEDs were included The following variables influenced efficacy estimates: (1) responder rates correlated positively with duration of the entire treatment period (p = 0038); (2) response to placebo was significantly greater in the maintenance period than in the entire treatment period (p = 0005); (3) responder rates increased over the years both for AEDs (p < 0001) and for placebo (p = 0001); (4) LOCF analysis overestimated responder rates for AEDs (p < 0001) and for placebo (p = 0001) compared with completer-based analysis, and the overestimation correlated positively with withdrawal rates (p < 0001) A meta-analysis of available data showed large differences in efficacy ranking in relation to dose selection and type of analysis, but these were mostly nonsignificant due to statistical power limitations Significance: Several methodologic issues hamper the relevance of indirect comparisons of AEDs in the adjunctive-therapy of refractory partial epilepsy Some of these issues could be overcome by improved standardization in the reporting of efficacy outcomes