INTRODUCTION: Seizures are the most common neurologic emergency in the neonatal period. Phenobarbital and levetiracetam are the most commonly used anti-epileptic agents. However, there is conflicting evidence regarding their efficacy and safety. This review aims to synthesize data from randomized trials evaluating levetiracetam versus phenobarbital as a first-line antiepileptic drug for seizures in the newborn. METHODS: A systematic review and meta-analysis following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines was performed. The review considered randomized clinical trials (RCTs) providing information about the efficacy and safety of levetiracetam vs phenobarbital as first line treatment of neonatal seizures. Medline by PubMed, CENTRAL by Cochrane, Embase, Google Scholar, and grey literature for RCTs were searched. RESULTS: Four randomized controlled trials met the criteria for inclusion. A total of 312 neonates (levetiracetam n=167, phenobarbital n=145) comprised the pooled sample. Seizure freedom did not significantly favour one particular drug. This was also seen throughout subgroup analysis comprising clinical determination of seizure onset and cessation and neonates with hypoxic-ischemic encephalopathy. Significant heterogeniety was seen throughout the analyses. Hypotension was seen more in patients given phenobarbital. No significant association of either drug was seen for respiratory abnormalities and requirement for ventilation. Mortality was not significantly associated with either drug. CONCLUSION This meta-analysis combined and synthesized data from four randomized controlled trials comparing levetiracetam and phenobarbital in efficacy and safety for neonatal seizures. The statistical analysis did not lend evidence to support the use of one drug over the over. More studies that employ stringent techniques to minimize bias are needed for a more robust conclusion.

There is a paucity of published literature on the different oral medications tried for X-linked dystonia parkinsonism (XDP). In practice, most XDP patients are tired on medication typically used for patients with generalized dystonia. These drugs include anticholinergic agents, baclofen, clonazepam and other ben-zodiazepines, tetrabenazine, and clozapine. Although several articles have shown that these classess of drugs are beneficial for patients with generalized dystonia, none been systematically studied specifically for XDP patients. We are currently conducting the first randomized, placebo-controlled trial on the medications that have been used in XDP.

Human ; Baclofen ; Cholinergic Antagonists ; Clonazepam ; Clozapine ; Dystonia ; Dystonic Disorders ; Genetic Diseases, X-linked ; Parkinsonian Disorders ; Tetrabenazine ; Levodopa

BACKGROUND AND OBJECTIVE: X-linked dystonia parkinsonism (XDP, DYT3, MIM #314250) is a neurodegenerative movement disorder found endemically in the Philippines. An SVA retrotransposon insertion mutation has been described in patients with XDP, which requires Southern analysis for detection. However, this method is costly and time-consuming. Hence we developed a PCR-based method and validated it among our local population.

METHODS AND RESULTS: A total of 58 samples from 58 patients with a clinical diagnosis of XDP were collected. Other samples were from an obligate female carrier, two unaffected male relatives, and two patients with typical Parkinson’s disease. Primers designed to amplify the SVA retrotransposon found in the DYT3-TAF1 gene (NCBI Accession Number AB191243) were used. All patients were positive for the expected 3229-bp product after PCR amplification. The normal control showed a 599-bp product, while the female carrier showed both the 3229 and 599-bp product. Subsequent RFLP analysis using BamHI verified the presence of the SVA retrotransposon insertion mutation. CONCLUSION: Our results show that large-scale PCR-based testing to screen for genetic diseases with a relatively high prevalence such as XDP is possible in our setting. When followed by RFLP analysis, this can provide genetic confirmation of the diagnosis of XDP and facilitate proper genetic counselling and therapy.
Dystonia 3, Torsion, X-Linked

BACKGROUND: XDP is an X-linked recessive disorder characterized by parkinsonism and dystonia described among Filipinos. Oral medications are frequently ineffective. Lately, DBS have been promising. However these are not generally available or affordable for the vast majority of patients. We then decided to evaluate the effectiveness of levodopa-carbidopa for XDP.
OBJECTIVE: To compare the efficacy, safety and tolerability of levodopa-carbidopa vs. placebo in XDP patients.
METHODS: After informed consent and randomization, the BFM and the UPDRS parts III and IV were performed at baseline and monthly up to 6 months. Patients were randomized to receive either levodopa-carbidopa at a starting dose of 125 mg levodopa/ day in 2 divided doses or corresponding placebo. Gradual uptitration was done to a maximum of 1000 mg levodopa/ day or until side effects appeared.
Homogeneity of the characteristics of patients in the 2 groups was determined using Independent t-test and Chi-square test. To determine the significance of changes in the efficacy parameters within each group, Wilcoxon Matched Pairs Signed Ranks Test was used. To compare the scores of the different efficacy parameters of the 2 groups, Mann Whitney U Test was applied to the data. A p?0.050 was considered significant.
RESULTS: A total of 107 patients were recruited. There were 13 screen failures, and 94 were subsequently enrolled. The baseline characteristics (age, duration of illness, baseline BFM and UPDRS (motor) scores were not significant between levodopa and placebo (age in years: 47 + 9.35 vs. 50 + 9.51; duration of illness in years 6.3 + 7 vs. 6.2 + 5.2; BFM score: 32.8 + 24.5 vs. 28.4 + 26.5; UPDRS score 29.9 + 20.7 vs. 34.8 + 26.8).
There was a decrease in BFM scores from baseline to all follow-up periods in patients given levodopa but were statistically significant only on visit 2 and visit 9. In the placebo group, decrease in scores was also observed in some observation periods but no statistical significance was shown. A comparison of the 2 groups showed that the magnitude of decrease in the levodopa group was statistically greater than the placebo group on the second visit. There were no significant differences observed in all other follow-up periods. Both groups showed a decrease in UPDRS scores but significant decrease was observed in visits 2, 5, 6, 7, 9 of the levodopa group. While in the placebo group, a significant decrease was observed only on visit 2. Comparison of the 2 groups did not show any significant differences.
There were 17 patients from the levodopa group who reported adverse events (most common: increased involuntary movements, nausea/ vomiting/ dizziness, headache, and generalized weakness. In the placebo group, there were 11 patients (most common: increased involuntary movements, abdominal pain). There were 9 patients who dropped out (levodopa: 4, placebo: 5).
CONCLUSION: There was a significant decrease in the BFM and UPDRS scores in XDP patients given levodopa compared to placebo. Levodopa is a safe and effective drug that may be considered in patients with XDP.
NOTE: This study was supported by an unrestricted grant by Torrent Pharma Philippines, Inc.

Human ; Abdominal Pain ; Carbidopa ; Dyskinesias ; Dystonia ; Dystonic Disorders ; Headache ; Levodopa ; Nausea ; Parkinsonian Disorders ; Statistics, Nonparametric ; Vomiting

The X-linked dystonia-parkinsonism (XDP) is a severe progressive, adult-onset X-linked endemic disorder in Filipinos, which is characterized by dystonic movements that start in the third of fourth decade, and replaced by parkinsonism beyond the 10th year of illness. Understanding the pathophysiology of XDP and development of rational therapies will depend on observations from imaging pathological and genetic studies. In this paper we summarize the results of these studies on patients with XDP. The cranial magnetic resonance imaging shows hy-perintense putaminal rim in both dystonic and parkinsonian stages, and atrophy of the caudate head or putamen in the parkinsonian stage. Neuropathological findings show atrophy of the caudate nucleus and putamen, with mild to severe neuronal loss and gliosis. In the neostriatum, the dystonic phase of XDP shows the involvement of striosomes and matrix sparing, while the later, i.e., p[arkinsonian phase, shows matrix involvement as well. In the dystonic phase, the loss of striosomal inhibitory projections lead to disinhibition of nigral dopaminergic neurons, perhaps resulting in a hyperkinetic state; while in the parkinsonian phase, severe and critical reduction of matrix-based projection may result in extranigral parkinsonism. Genetic sequencing of the XDP critical region in Xq13.1 has revealed an SVA retronsposon insertion in an intron of TAF1. This may reduce neuron-specific expression of the TAF1 isoform in the caudade nucleus, and subsequently interfere with the transcription of many neuronal genes, including DRD2. Findings from imaging, pahtology, and genetics studies are gradually shedding light on the pathophysiology of XDP, which hopefully will lead to mare rational and directed therapies.

Human ; Adult ; Atrophy ; Caudate Nucleus ; Dopaminergic Neurons ; Dystonic Disorders ; Genetic Diseases, X-linked ; Gliosis ; Introns ; Parkinsonian Disorders ; Protein Isoforms ; Putamen

OBJECTIVES: The objectives of the research study were to determine ethical guidelines and principles applicable in the practice and research of eHealth and telehealth in the Philippines, how these are applicable to the Philippines, and to differentiate between the ethical issues in research and in clinical practice of eHealth.

METHODS: This research study used: 1) review of ethics manuscripts, guidelines and literature; 2) focused group discussion and key informant interviews of experts; and 3) triangulation. The information sought for the review were- 1) relevant policies, guidelines in eHealth that are pertinent to the discussion of eHealth ethics in the Philippines; 2) components of ethics in eHealth research; and 3) components of ethics in eHealth practice. The framework of the consultation with experts was to identify mechanisms and strategies in incorporating ethics in both eHealthpractice and eHealth research within the following- 1) in reference to existing laws, policies, and guidelines on ethics in medicine and health; and 2) in the context of the Philippine setting.

RESULTS: Based on the review, there are pertinent codes of ethics, applicable laws, policies and guidelines in eHealth, both in the international and local settings. The focus group discussion and key informant interview with experts yielded significant and deeper understanding on how to address the gaps and lapses of ethics applied to eHealth in the country. These recommendations were given which distinguish between the ethics in clinical practice and ethics in the planning and implementation of eHealth systems. There is also a need to resolve the problem of whose primary responsibility the patient is- the referring, commonly referred to as the attending physician in the local community, or the specialist from the center. The proposed resolution was also presented.

CONCLUSION: The study has shown how important eHealth in potentially promoting timely and improved health care access. However, there are still lapses and gaps in the implementation of policies and guidelines on and relating to eHealth in the Philippines as shown by the data culled from the review and the focus group discussions with the experts. With more specific ethical guidelines and relevant policies, the development and practice of eHealth and telehealth will be on its way in bridging the gap and aiding in health systems development in the Philippines, especially with the support of the national government and collaboration of various agencies and stakeholders.

Human ; Federal Government ; Focus Groups ; Codes Of Ethics ; Philippines ; Telemedicine ; Delivery Of Health Care ; Referral And Consultation

BACKGROUND: Locally, understanding and communicating sensory neuropathy may be confounded by a "comprehension gap" during consults and limited "nerve literacy" or knowledge of patients about nerves. This may affect the effectiveness of healthcare.
OBJECTIVE: The study aims to describe the Filipino patients' experience of sensory neuropathy in local terms and their understanding of its causation.
METHODS: A cross-sectional, descriptive study among 24 patients with sensory neuropathy was done using semi-structured individual interviews. The first part elicited Filipino terms and descriptions used to explain their experience. The second part elicited perceived cause pre- and post- consult and perceived body part affected.
RESULTS: The most common descriptors of sensory neuropathy include "manhid", "kuryente", "tinutusuk-tusok", "ngalay", "kirot", and "naninigas". Many would initially identify "pasma" as a cause. Post-consult, many would cease to see it as part of natural ageing and would identify structural explanations such as impingement. They would however attribute it to an affectation of "ugat" which most defined as blood vessels.
CONCLUSION: The abovementioned terms are commonly used to describe sensory neuropathy and can be clinically useful in eliciting symptoms. There is existing confusion with regards to the nerve as a structure involved even after consultation.

Sex-linked dystonia parkinsonism (XDP, DYT3, "Lubag") is an adult-onset, progressive, debilitating movement disorder first described in Filipino males from Panay Island in 1975. XDP manifests predominantly as torsion dystonia, later combined with or sometimes replaced with parkinsonism. Within the Island of Panay, the preva-lence rate is highest in the province of Capiz, where 1:4000 men suffer from the disorder. There is a high degree of penetrance and generalization. While women often serve as carriers, XDP is not limited to men. An updated XDP Philippine registry (as of January 2010) has identified 505 cases, with 500 males and 5 females. While some report that females may carry a milder form of the disorder, in our experience, both sexes generally follow a similar progressive clinical course.

Human ; Male ; Female ; Aged ; Adult ; Dystonia ; Dystonia Musculorum Deformans ; Dystonic Disorders ; Genetic Diseases, X-linked ; Islands ; Parkinsonian Disorders ; Penetrance

BACKGROUND: Migraine is a highly common disorder that can cause significant disability on an individual, which collectively may lead to a substantial burden for the society. Various expert societies have recommended Acetaminophen/Aspirin/Caffeine (AAC) combination regimen as the first-line drug treatment for migraine attacks; however, there were no pooled evidences summarizing the effectiveness and tolerability of this regimen.
OBJECTIVE: To determine the effectiveness and tolerability assessment of oral AAC combination regimen as an acute treatment for migraine in adults.
METHODS: Relevant studies from inception to March 2014 were searched in Cochrane CENTRAL, MEDLINE, LILACS, Scopus and metaRegister of Controlled Trials. The Cochrane Collaboration's tool for the assessment of risk of bias was employed. Trials that were randomized, double-blind, parallel-group, placebo and active-controlled were included and the data were employed for meta-analysis. To evaluate the quality of evidence, the GRADE approach was utilized for outcomes with sufficient studies and data.
RESULTS: From 225 records identified, 4 trials were included in this review, with a total of 3,608 participants with recorded baseline characteristics. Patient-reported migraine intensity was moderate-severe and the AAC dose used was at 500/500/130 mg. At 2 hours, AAC regimen was statistically different and found to be superior to placebo in terms of pain-free, headache relief, nausea-free, photophobia-free, phonophobia-free and functional disability reduction rates using intension-to-treat analysis. Missing data did not alter the outcome measures generating robust results. Sumatriptan 100 mg was found to be better than AAC in pain-free rate, and phonophobia-free rates at 2 hours. Statistically more patients in the AAC arm experienced "any adverse event" compared to placebo and complaints were commonly nausea and nervousness.
CONCLUSION: For adult individuals with moderate-severe migraine, a fixed oral dose of Acetaminophen/Aspirin/Caffeine (AAC 500/500/130 mg) may be used as first-line therapy for the acute treatment of migraine and is only associated with mild, infrequent adverse events.

Acetaminophen ; Aspirin ; Caffeine ; Migraine without Aura ; Migraine with Aura ; Migraine Disorders

BACKGROUND: Dysphagia is common among post-stroke patients,causing disability due to malnutrition and pneumonia. Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment modality to address this complication.

OBJECTIVE: The study aimed to compare real versus sham rTMS in treating post-stroke dysphagia.

METHODS: PubMed, Ovid, ClinicalKey, Herdin, and Google Scholar databases were searched from their earliest record to 31 July 2015 for randomized controlled trials that used rTMS to treat post-stroke dysphagia. The Jadad scale was used to assess the quality of the studies. The weighted mean difference (WMD) between baseline and post-treatment mean for Penetration Aspiration Scores (PAS) measured in the experimental and control groups were extracted for subsequent meta-analyses.

RESULTS: Three studies were analyzed. The WMD in PAS score between rTMS and control using liquid bolus two weeks after treatment in two good quality studies was -1.14 (95% confidence interval (CI) = -1.80 - -0.48, P = 0.001, I2 = 0.0%), and after four weeks was -1.83 (CI = -3.22 - -0.44, P = 0.010, I2 = 0.0%).

CONCLUSION: Treatment of post-stroke dysphagia with rTMS improved PAS on subgroup analyses of studies using liquid bolus after two weeks, and between real and sham treatment after four weeks.?

Human ; Male ; Female ; Aged 80 And Over ; Aged ; Middle Aged ; Adult ; Deglutition Disorders ; Transcranial Magnetic Stimulation ; Stroke ; Pubmed ; Qualitative Research ; Pneumonia ; Malnutrition