Publications by authors named "Adrian I Espiritu"

45 Publications

COVID-19 outcomes of 10,881 patients: retrospective study of neurological symptoms and associated manifestations (Philippine CORONA Study).

J Neural Transm (Vienna) 2021 Aug 27. Epub 2021 Aug 27.

Division of Adult Neurology, Office of the Department of Neurosciences, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Taft Avenue, Ermita, 1000, Manila, Philippines.

Our study aimed to determine the effects of new-onset neurological symptoms (NNS) on clinically relevant outcomes in hospitalized patients with COVID-19 infection. We conducted a nationwide, comparative, retrospective, cohort study among adult, hospitalized COVID-19 patients involving 37 hospital sites from various regions in the Philippines. We included a total of 10,881 patients with confirmed COVID-19 infection (2008 had NNS while 8873 did not have NNS). The adjusted hazard ratios (aHRs) for mortality among the mild and severe cases were significantly higher by 1.660 (95% CI 1.132-2.435) and by 1.352 (95% CI 1.042-1.752), respectively, in the NNS group compared to those in the non-NNS group. The aHRs for respiratory failure in the NNS group were significantly increased by 1.914 (95% CI 1.346-2.722), by 1.614 (95% CI 1.260-2.068), and by 1.234 (95% CI 1.089-1.398) among the mild, severe, and critical cases, respectively. The aHRs for ICU admission in the NNS group were still significantly higher by 1.973 (95% CI 1.457-2.673) and by 1.831 (95% CI 1.506-2.226) among the mild and severe cases, respectively. Patients who had NNS were not significantly associated with a longer duration of ventilator dependence (adjusted odds ratio (aOR) 0.954, 95% CI 0.772-1.179), longer ICU stay (aOR 0.983, 95% CI 0.772-1.252) and longer hospital admission (aOR 1.045, 95% CI 0.947-1.153). The presence of NNS significantly increases the risk of mortality, respiratory failure and ICU admission among COVID-19 patients. Registration and associated protocol publication: ClinicalTrials.gov website (NCT04386083); Espiritu AI, Sy MCC, Anlacan VMM, Jamora RDG. The Philippine COVID-19 Outcomes: a Retrospective study Of Neurological manifestations and Associated symptoms (The Philippine CORONA study): a protocol study. BMJ Open. 2020;10:e040944.
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http://dx.doi.org/10.1007/s00702-021-02400-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391861PMC
August 2021

High-dose biotin for multiple sclerosis: A systematic review and meta-analyses of randomized controlled trials.

Mult Scler Relat Disord 2021 Jul 21;55:103159. Epub 2021 Jul 21.

Department of Clinical Epidemiology, College of Medicine, University of the Philippines Manila, Manila, Philippines; Division of Rheumatology, Department of Medicine, University of Toronto and University Health Network Toronto Western Hospital, Toronto, ON M5T 2S8, Canada.

Background: Biotin may activate the acetyl-CoA-, 3-methylcrotonyl-CoA-, propionyl-CoA-, and pyruvate carboxylases to increase myelin repair and/or synthesis, and may enhance the production of adenosine triphosphate (ATP), which may be essential to prevent neurodegeneration. The purpose of this review was to determine the effectiveness and safety of high-dose biotin (HDB) in multiple sclerosis via a systematic review of randomized controlled trials.

Methods: We searched the following electronic databases for relevant articles: MEDLINE, CENTRAL, EMBASE, Scopus, and ClinicalTrials.gov website until April 2021. We considered randomized clinical trials (RCTs) that involved adult patients diagnosed with any phenotype of multiple sclerosis that conforms with the McDonald 2010/2017 criteria or the Lublin 2014 criteria. We included studies employing high-dose biotin or "MD1003" administered orally for at least 300 mg/day and given for at least three months. The methodological quality assessment of the included studies was done using the Cochrane Risk of Bias (RoB) tool. The GRADE approach was used to assess the certainty of evidence [COE].

Results: Out of 366 records identified, three RCTs involving 889 individuals diagnosed with MS (830 participants had progressive MS (PMS); 59 had RRMS) were pooled for analyses. The overall female:male ratio was 1.16:1. All included trials used HDB as an adjunctive treatment. The risks of bias in the three studies were low across the domains. At 12 to 15 months, there is insufficient evidence that the HDB and placebo arms differed in terms of composite improvement of MS-related disability (relative risk (RR) 2.87; 95% CI 0.29-28.40; 2 trials; 796 participants; I = 66%) [low COE], improvement in expanded disability status scale (IEDSS) (RR 2.27; 95% CI 0.25-20.98; 2 trials; 796 participants; I = 63%) [low COE], and both IEDSS and improvement in 25-foot walk time (ITW25) (IEDSS-ITW25) (RR 0.58; 95% CI 0.17-2.00; 2 trials; 796 participants; I = 13%) [moderate COE] among patients with PMS. Pooled data for ITW25 at 12 to 15 months yielded statistical significance (RR 2.06; 95% CI 1.04-4.09; 2 trials; 796 participants; I = 0%) [moderate COE] favoring HDB among patients with PMS. At 12 to 15 months, no significant differences were found in terms of mean change in EDSS (MD -0.06; 95% CI -0.14-0.02; 2 studies; 796 participants; 889 participants; I = 68%) among patients with PMS. Synthesized data on incidence of any AEs (RR 0.98; 95% CI 0.92-1.04; 3 trials; I = 0%) [high COE] and any serious AEs (RR 0.98; 95% CI 0.77-1.24; 3 trials; 889 participants; I = 0%) [moderate COE] were not significantly different between HDB and placebo groups. Out of 662 pooled patients in the HDB group, 31 patients (4.7%) were found to have laboratory test interference compared to zero event in the pooled placebo group [high COE].

Conclusions: A moderate certainty of evidence suggests a potential benefit in favor of HDB administered for 12 to 15 months in terms of ITW25 in patients with PMS. However, an important trade-off of this benefit is the high certainty of evidence suggesting an increased incidence of laboratory test interference when HDB is taken.
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http://dx.doi.org/10.1016/j.msard.2021.103159DOI Listing
July 2021

Autoimmune encephalitis in a tertiary hospital in the Philippines.

J Clin Neurosci 2021 Aug 10;90:191-198. Epub 2021 Jun 10.

Division of Adult Neurology, Department of Neurosciences, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Manila, Philippines.

Background: Autoimmune encephalitis (AE) is an emerging disorder in adults and children. Due to its potentially reversible nature, prompt recognition and intervention are of utmost importance.

Objective: To describe the clinical and paraclinical features, as well as treatment outcomes of patients with AE admitted in a Philippine tertiary hospital.

Methods: Retrospective case series of patients with definite AE.

Results: Eighteen (18) patients were included (12 adults, 6 children), majority of whom had anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. The median age of onset was 32 (IQR: 10.8) years old and 13 (IQR: 4.8) years old in the adult and pediatric population, respectively. In both age groups, most presented with psychiatric symptoms and normal imaging findings. Cerebrospinal fluid (CSF) pleocytosis was detected in 8/12 (66.7%) adults and 2/6 (33.3%) children, while CSF protein elevation was only seen in 6/12 (50%) adults. Most patients presented with seizures, and the most frequent electroencephalography (EEG) abnormality detected was slow activity (70.5%). A high proportion of patients received high dose steroids, alone (35.3%) or in combination with intravenous immunoglobulin (IVIG, 52.9%). Overall, 66.7% had improved outcomes, mostly seen in the pediatric population.

Conclusion: This study highlighted the broad clinical phenotype, as well as the similarities and differences of AE manifestations in adults and children. It demonstrated the limited but supportive role of laboratory investigations in the diagnosis of AE. It also underscored the importance of early intervention in AE and highlighted factors influencing treatment practices and discharge outcomes in the local setting.
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http://dx.doi.org/10.1016/j.jocn.2021.05.052DOI Listing
August 2021

Clinical features and real-world outcomes of Guillain-Barré syndrome in the Philippines.

Neurol Res 2021 Jul 6:1-10. Epub 2021 Jul 6.

Department of Neurosciences, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Manila, Philippines.

Background: Our study aimed to determine the profile of Guillain-Barré syndrome (GBS) in the Philippines, compare the outcomes who received intravenous immunoglobulin (IVIg) and therapeutic plasma exchange (TPE), and determine the factors related to hospital stay and late motor recovery.

Methods: We conducted a retrospective cohort study of adult GBS patients admitted to the Philippine General Hospital from 2009 to 2019.

Results: We included 105 patients with confirmed GBS diagnoses. The median age was 43 years (interquartile range 32 to 56); the female-to-male ratio was 1.62:1; the predominant variant was acute inflammatory demyelinating polyneuropathy (n = 40, 38.1%). The difference in outcomes of patients in the IVIg (n = 44) and TPE (n = 24) groups (walking with aid/GBS-disability scores/ventilator dependency at 1 month, duration dependent on the ventilator, intensive care unit stay, and hospital stay) were not statistically significant, except for mild disability at 1 month (p = 0.009). Pneumonia, urinary tract infection, and dysautonomia were significantly related to a prolonged hospital stay. No predetermined variables were associated with late motor recovery. After adjusting for age and sex, the cumulative hazard risk for late motor recovery was 0.69 (95% CI 0.27-1.74).

Conclusion: Our study presented the first comprehensive information regarding the features and outcomes of GBS patients in the Philippines.

Abbreviations: AIDP - Acute inflammatory demyelinating polyneuropathy; AMAN - Acute motor axonal neuropathy; AMSAN - Acute motor and sensory axonal neuropathy; GBS - Guillain-Barré syndrome; GBS-DS - Guillain-Barré syndrome disability scale; ICU - Intensive care unit; IVIg - Intravenous immunoglobulin; MFS - Miller-Fisher syndrome; PGH - Philippine General Hospital; TPE - Therapeutic plasma exchange.
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http://dx.doi.org/10.1080/01616412.2021.1948750DOI Listing
July 2021

Neuro-oncology in the Philippines: a scoping review on the state of medical practice, deterrents to care and therapeutic gaps.

Ecancermedicalscience 2021 20;15:1238. Epub 2021 May 20.

Division of Adult Neurology, Department of Neurosciences, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Taft Ave, Ermita, Manila 1000, Philippines.

Background: Neoplasms of the brain and spine are relatively uncommon compared to breast, lung and gastrointestinal tumours, which occur at higher rates in the Asian population. Updated guidelines in diagnosis and treatment of neuro-oncologic diseases recommend advanced molecular-based precision-medicine; thus the need for increasingly individualised regimens. It is, therefore, necessary to determine whether there are areas of improvement in the provision of care to these patients, especially in low- to middle-income economies like the Philippines.

Methods: In this study, we identified gaps in the delivery of medical care to Filipino patients with tumours of the central nervous system. We performed a scoping review on the available literature on clinical experience with treatment of neuro-oncologic cases from the Philippines and performed qualitative analysis viewed through the lens of the existing healthcare system.

Results: The medical practice of neuro-oncology in the Philippines lacks robust local data on epidemiology and treatment outcomes. There are existing legislative frameworks to support adequate healthcare delivery and financing to brain tumour patients. However, inequities in the geographic distribution of infrastructure, manpower and medications are roadblocks for accessibility to neuro-oncologic services like specialised molecular markers, neurosurgical procedures, sustained chemotherapy and radiation therapy centres.

Conclusion: There are significant treatment gaps in the care of neuro-oncologic patients in the Philippines that need to be addressed. Early detection and initiation of prognosis-changing therapeutics through reduction of out-of-pocket expenses, access to readily available diagnostic tools and sustainability of management regimens are the main areas that necessitate strengthened partnership between the public and private sectors of Philippine society.
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http://dx.doi.org/10.3332/ecancer.2021.1238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225337PMC
May 2021

Google search behavior for meningitis and its vaccines: an infodemiological study.

BMC Neurol 2021 Jun 23;21(1):232. Epub 2021 Jun 23.

Institute for Neurosciences, St. Luke's Medical Center, Quezon City & Global City, Philippines.

Background: The internet has made significant contributions towards health education. Analyzing the pattern of online behavior regarding meningitis and vaccinations may be worthwhile. It is hypothesized that the online search patterns in meningitis are correlated with its number of cases and the search patterns of its related vaccines.

Methods: This was an infodemiological study that determined the relationship among online search interest in meningitis, its worldwide number of cases and its associated vaccines. Using Google Trends™ Search Volume Indices (SVIs), we evaluated the search queries "meningitis," "pneumococcal vaccine," "BCG vaccine," "meningococcal vaccine" and "influenza vaccine" in January 2021, covering January 2008 to December 2020. Spearman rank correlation was used to determine correlations between these queries.

Results: The worldwide search interest in meningitis from 2008 to 2020 showed an average SVI of 46 ± 8.8. The most searched topics were symptoms, vaccines, and infectious agents with SVIs of 100, 52, and 39, respectively. The top three countries with the highest search interest were Ghana, Kazakhstan, and Kenya. There were weak, but statistically significant correlations between meningitis and the BCG (ρ = 0.369, p < 0.001) and meningococcal (ρ = 0.183, p < 0.05) vaccines. There were no statistically significant associations between the number of cases, influenza vaccine, and pneumococcal vaccine.

Conclusion: The relationships among the Google SVIs for meningitis and its related vaccines and number of cases data were inconsistent and remained unclear. Future infodemiological studies may expand their scopes to social media, semantics, and big data for more robust conclusions.
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http://dx.doi.org/10.1186/s12883-021-02258-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219513PMC
June 2021

Reasons for hospitalization and factors of mortality in patients with Parkinson's disease in the Philippines.

Neurodegener Dis Manag 2021 06 10;11(3):229-238. Epub 2021 May 10.

Department of Neurosciences, College of Medicine & Philippine General Hospital, University of The Philippines Manila, Manila, Philippines.

We aimed to determine the reasons for hospitalizations and factors of mortality of Filipino Parkinson's disease (PD) patients in a tertiary hospital. We conducted a retrospective review of medical records of PD patients admitted to our institution between 2016 and 2018. Demographic and clinical data were analyzed. We included 166 PD patients. The most common cause of admission was infectious (pneumonia, urinary tract, and skin-soft tissue infections) (n = 65, 39.2%). The most common cause of mortality was sepsis (n = 9, 5.4%). Renal comorbidity was a significant factor of mortality (OR: 3.67, 95% CI: 1.11-12.12; p = 0.033). Interventions designed to reduce the risk of complications in PD patients should be prioritized to potentially decrease the probability of eventual hospitalization.
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http://dx.doi.org/10.2217/nmt-2020-0062DOI Listing
June 2021

Primary headache research output and association with socioeconomic factors in Southeast Asia: a bibliometric analysis.

Neurol Sci 2021 Jul 20;42(7):2683-2693. Epub 2021 Apr 20.

Section of Neurology, Institute for Neurosciences, St. Luke's Medical Center, Quezon City and Global City, Philippines.

Background: Although headache is one of the most common neurologic conditions with a high disease burden, primary data on headache research from Southeast Asia (SEA) was hypothesized to be inadequate. This study aimed to evaluate research productivity among the different countries in SEA and to determine the association between specific bibliometric indices and socioeconomic factors.

Methods: A systematic search was conducted until June 10, 2020 in Scopus, PubMed, Embase, Cochrane Central Register of Controlled Trials, and Index Medicus for South-East Asia Region to include all primary headache studies on migraine, tension-type headache, and trigeminal autonomic cephalalgia, with at least one author affiliated with a SEA country. Bibliometric indices, such as the number of publications and PlumX metrics, were obtained and correlated with the country-specific socioeconomic factors.

Results: We identified 153 articles. Most of the publications (n = 43, 28.1%) were epidemiologic studies and case reports/series (n = 25, 16.3%). Migraine was the most studied primary headache subtype. Malaysia, Singapore, and Thailand were the major contributors to primary headache research in SEA. Only the percent gross domestic product for research and development correlated significantly with research productivity.

Conclusion: Despite the high global burden of disease, research productivity on primary headache was low in SEA. The move towards a knowledge-based economy may drive research productivity in SEA.
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http://dx.doi.org/10.1007/s10072-021-05266-3DOI Listing
July 2021

Wernicke-Korsakoff Syndrome in Hyperemesis Gravidarum: A Case Report and Literature Review.

Neurohospitalist 2021 Apr 4;11(2):141-147. Epub 2020 Sep 4.

Department of Neurosciences, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Philippines.

Background: Wernicke-Korsakoff syndrome (WKS) is a triad of ophthalmoplegia, ataxia and memory deficits due to thiamine insufficiency resulting from under- or untreated Wernicke's encephalopathy (WE), which may be associated with hyperemesis gravidarum (HEG).

Case Presentation: We present a case of a 36-year-old Filipino woman in her first trimester with HEG, along with the WKS triad and abnormal hyperintense signals in the bilateral thalami and midbrain, left occipital lobe, periaqueductal gray matter and pontine periventricular areas. Neurologic deficits partially improved but persisted despite intravenous thiamine administration.

Evidence Review: A review of current treatments for WE, and the prevention and neurocognitive recovery of WKS was done. The beneficial effects of thiamine for acute WKS are supported by several case reports and clinical experience. Evidence from one randomized controlled trial wherein thiamine was given in various doses for treating WE or preventing WKS in an alcohol-dependent population is limited by methodological issues. Rehabilitation and pharmacotherapy for neurocognitive recovery seems promising, but they have inadequate evidentiary support. More robust studies on multi-modal strategies are warranted to facilitate the neurocognitive recovery of patients with WKS.
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http://dx.doi.org/10.1177/1941874420953027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958682PMC
April 2021

The association of online search interest with polio cases and vaccine coverage: an infodemiological and ecological study.

Eur J Pediatr 2021 Aug 27;180(8):2435-2441. Epub 2021 Mar 27.

Division of Adult Neurology, Department of Neurosciences, College of Medicine-Philippine General Hospital, University of the Philippines Manila, Manila, Philippines.

Achievement of universal eradication of paralytic poliomyelitis has remained a challenge. Despite the general decline in cases, multiple outbreaks attributed to poor vaccination still occur. Noncompliance from vaccination can be improved through education on various media platforms. In the internet age, online health-seeking behavior plays a significant role in this regard. Hence, our study investigated the association between global online search interest in polio with the number of polio cases and vaccination coverage. This infodemiological and ecological study utilized Google Trends' search volume index (SVI) for "polio" and the World Health Organization data on the number of polio cases (PC) and vaccine coverage rate (VCR) per country between 2006 and 2019. Associations between SVI for "polio" with PC and with VCR were evaluated. From the years 2006 to 2019, the global inquiry for this term was highest (i.e., SVI at 100) last October 2018. There was a direct correlation between the SVI for "polio" and PC while there was an inverse relationship between SVI and VCR per country per year. Both relationships have weak to moderate strength of associations. Based on our models, a one-unit increase in the SVI leads to a 3.8% increase in the number of polio cases. On the other hand, a one-unit increase in the SVI leads to a 0.01% decrease in the VCR.Conclusions: Dynamic changes in global SVIs for polio may reflect fluctuations in the number of polio cases and rates of vaccine coverage. Our study brings into light the largely untapped and potential use of online search behavior for polio to anticipate changes in PC and VCR in real-time. What is Known: •Parental vaccine hesitancy is a strong hindrance to the eradication of vaccine-preventable diseases. •The internet is a major source of information that modifies this attitude. What is New: •Internet health-seeking behavior can be measured using Google Trends' search volume index and can be used to correlate to certain aspects of public health determinants of a certain disease. •Google Trends' search volume index correlates with the number of polio cases/immunization rates, and this provides a basis for considering public health measures online.
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http://dx.doi.org/10.1007/s00431-021-04049-4DOI Listing
August 2021

Efficacy of aspirin for sporadic vestibular schwannoma: a meta-analysis.

Neurol Sci 2021 Mar 26. Epub 2021 Mar 26.

Department of Neurosciences, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Manila, Philippines.

Background: Pharmacologic treatment of vestibular schwannomas (VSs) may increase the success of conservative management for small lesions, and offer an alternative to surgery and stereotactic radiotherapy in symptomatic cases in the high-risk population. Agents that have been studied include aspirin (ASA), but the results of the preliminary studies have been conflicting. In this study, we aimed to systematically review the evidence on the effect of ASA intake on tumor growth in patients with VSs.

Methods: Pubmed, Cochrane, Scopus, Embase, ClinicalTrials.gov , and Web of Science were searched for studies comparing VS tumor growth in patients with aspirin intake and those without. Random-effect meta-analysis was used to evaluate the outcomes in terms of linear and/or volumetric tumor growth.

Results: Four retrospective cohort studies were included in the meta-analysis. No significant difference was found in tumor growth between VS patients with aspirin intake and those without. This result held true for the analysis of linear tumor growth (OR 1.23; 95% CI 0.49, 3.10), volumetric tumor growth (OR 1.41; 95% CI 0.36, 5.59), and both combined (OR 1.02; 95% CI 0.56, 1.86).

Conclusions: Our meta-analysis suggests that there is insufficient evidence to recommend ASA therapy in patients with VSs. High-quality randomized controlled trials are warranted to determine the efficacy of this drug in reducing VS tumor growth.
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http://dx.doi.org/10.1007/s10072-021-05193-3DOI Listing
March 2021

Stroke in Male-to-Female Transgenders: A Systematic Review and Meta-Analysis.

Can J Neurol Sci 2021 Mar 26:1-8. Epub 2021 Mar 26.

Department of Neurosciences, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Manila, Philippines.

Background: The effect of hormonal therapy has been extensively studied in women. However, similar data on male-to-female (MTF) transgenders, another important population that receives hormonal therapy is lacking. Existing studies in MTF transgenders are skewed toward mental health and health-harming behaviors while few have focused on chronic health conditions. Our study aims to review the existing data on stroke in MTF transgenders and perform a quantitative analysis on the frequency of this condition in this special population.

Methods: PubMed, Cochrane, Scopus, Embase, ClinicalTrials.gov, and Web of Science were systematically searched for studies that reported data on the occurrence of cerebrovascular diseases in MTF transgenders. We reported the hormonal regimens, clinical characteristics, and outcomes of stroke in MTF transgenders. A meta-analysis of proportions was performed by the random-effects model to compute for the frequency of cerebrovascular events in MTF transgenders.

Results: Fourteen studies were included in the qualitative analysis while five studies were included in the quantitative analysis. A total of 109 MTF transgenders (Mean 14; range 1-53) suffered a cerebrovascular event. Random-effect modeling analysis showed an overall estimated frequency of 2% for cerebrovascular events in transgenders with a moderate degree of heterogeneity (I2 = 62%).

Conclusion: Hormonal therapy in MTF transgenders may confer cardiovascular risks in this population. However, more population-based studies that include clinical characteristics and outcomes of chronic health diseases in MTF transgenders are warranted. Such studies may be crucial in directing future guidelines on the health care and management of MTF transgenders.
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http://dx.doi.org/10.1017/cjn.2021.54DOI Listing
March 2021

Memantine for Multiple Sclerosis: A Systematic Review and Meta-Analysis of Randomized Trials.

Front Neurol 2020 15;11:574748. Epub 2021 Feb 15.

Department of Neurosciences, College of Medicine, Philippine General Hospital, University of the Philippines Manila, Manila, Philippines.

Multiple sclerosis (MS), a disabling demyelinating disease of the central nervous system, is associated with cognitive impairment, spasticity, and fatigue. There are still no established guidelines on the management of MS-related sequela. Memantine has the potential to reduce glutamate toxicity, thereby reducing consequent cognitive impairment, spasticity, and fatigue. This study aims to determine the efficacy and safety of memantine in preventing cognitive impairment, reducing spasticity and fatigue, and controlling disability in MS patients through a review of relevant randomized trials. MEDLINE, CENTRAL, Scopus, Embase, LILACS, ClinicalTrials.gov, and HERDIN were searched from inception to May 2020 for relevant trials. The search yielded 203 articles; four studies were included in the analysis. Pooled evidence shows that memantine compared with placebo does not significantly improve PASAT, ASS, MFIS, and EDSS scores of patients with MS. Memantine is associated with mild adverse drug events such as dizziness, fatigue, and anxiety. There is not enough evidence to support the efficacy of memantine in preventing cognitive decline, controlling spasticity, reducing fatigue, and preventing disability. Future researches should consider the different MS subtypes, effect of co-administration of disease-modifying therapies, longer duration of administration, and more sensitive outcome measures to evaluate the potential benefit of memantine in MS.
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http://dx.doi.org/10.3389/fneur.2020.574748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917060PMC
February 2021

Neuropathologic findings of patients with COVID-19: a systematic review.

Neurol Sci 2021 Apr 22;42(4):1255-1266. Epub 2021 Jan 22.

Division of Adult Neurology, Department of Neurosciences, College of Medicine-Philippine General Hospital, University of the Philippines Manila, Manila, Philippines.

Background: Despite the expanding literature that discusses insights into the clinical picture and mechanisms by which the SARS-CoV-2 virus invades the nervous system, data on the neuropathologic findings of patients who died following SARS-CoV-2 infection is limited.

Methods: A broad literature search was done for published articles that reported on histopathological findings of the brain in patients with COVID-19 in PubMed by MEDLINE, Embase, CENTRAL by the Cochrane Library, and SCOPUS from December 31, 2019 to October 31, 2020.

Results: The systematic literature search strategy used resulted in a total of 1608 articles of which 14 were included in the analysis (PROSPERO registration number: CRD42020221022). There were ten case series, two case reports, one retrospective cohort, and one prospective cohort. The age of the patients ranged between 38 and 90 years old, most of them older than 65 years old (n=66, 45.2%) and males (n=79, 54.1%). Most tested negative in SARS-CoV-2 immunohistochemistry (n=70, 47.9%). The striking pathologic changes included diffuse edema (n=25, 17.1%), gliosis with diffuse activation of microglia and astrocytes (n=52, 35.6%), infarctions involving cortical and subcortical areas of the brain (n=4, 2.7%), intracranial bleed (subarachnoid hemorrhage and punctate hemorrhages) (n=18, 12.4%), arteriosclerosis (n=43, 29.5%), hypoxic-ischemic injury (n=41, 28.1%), and signs of inflammation (n=52, 35.6%). The cause of death was attributed to the cardiorespiratory system (n=66, 45.2%).

Conclusions: The neuropathologic changes observed likely represent direct cytopathic effects and indirect effects secondary to host-specific inflammatory response induced by the viral infection. Further studies however are required to better elucidate the pathologic mechanism.
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http://dx.doi.org/10.1007/s10072-021-05068-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822400PMC
April 2021

Primary Brain Tumor Research Productivity in Southeast Asia and Its Association With Socioeconomic Determinants and Burden of Disease.

Front Oncol 2020 23;10:607777. Epub 2020 Dec 23.

Division of Adult Neurology, Department of Neurosciences, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Manila, Philippines.

Background: There is an unmet need to assess research productivity from southeast Asia (SEA) regarding primary central nervous system (CNS) tumors. The country's economy, landscape of neurology practice, and disease burden are hypothesized to correlate with scientific output. This study aimed to objectively measure the impact of published studies on primary brain tumors in SEA and to assess for correlation with socioeconomic determinants and burden of disease.

Methods: We systematically searched electronic databases for relevant articles from SEA on primary CNS tumor until July 31, 2020. Bibliometric indices were reported and subjected to correlational analysis with population size, gross domestic product (GDP) per capita, percentage (%) GDP for research and development (R&D), total number of neurologists, disease incidence, deaths, and disability-adjusted life years.

Results: A total of 549 articles were included, consisting primarily of case reports (n=187, 34.06%) and discussed gliomas (n=195, 35.52%). Singapore published the most number of the articles (n=246, 44.8%). Statistical analysis showed a positive correlation between %GDP for R&D and total publication. Additionally, negative relationships were noted between burden of disease and total neurologist with most bibliometric indices. However, GDP per capita was not correlated with measures for research productivity.

Conclusion: The low impact of scientific output on primary CNS tumors in SEA does not address the growing epidemiology and burden of this disease. An increase in the GDP growth and financial and manpower investment to R&D may significantly improve research productivity in SEA.
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http://dx.doi.org/10.3389/fonc.2020.607777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786370PMC
December 2020

Bibliometric analysis of bacterial central nervous system infection research in Southeast Asia.

BMC Neurol 2021 Jan 8;21(1):11. Epub 2021 Jan 8.

Division of Adult Neurology, Department of Neurosciences, College of Medicine - Philippine General Hospital, University of the Philippines Manila, Manila, Philippines.

Background: The status of research and scientific outputs with regards to bacterial central nervous system (CNS) infection in southeast Asia (SEA) is unknown. This study aimed to analyze and compare bacterial CNS infection research output of SEA countries in terms of bibliometric indices.

Methods: The major electronic databases (MEDLINE, Scopus, Embase, CENTRAL, Clinicaltrials.gov and WPRIM) were searched for studies on bacterial CNS infection in SEA until August 31, 2020. Frequencies, percentages and Spearman's rho correlations were used.

Results: There was a total of 648 unique studies on bacterial CNS infection in SEA and it was 657 when double-counted (collaborative studies between SEA countries). Thailand (n=148, 22.5%) and Vietnam (n=142, 21.6%) had the highest number of publications. The most common type of research publication was the case report / case series (n=160, 24.7%). Tuberculous meningitis/tuberculoma (n=176, 26.7%) was the most common topic. This study showed that the %GDP for research and development (R&D) was associated with a higher number of research output. However, the GDP per capita was not associated with any of the bibliometric indices. The total number of neurologists was associated with all of the bibliometric analysis.

Conclusion: Bacterial CNS infection research output in SEA countries was low in terms of quantity. The %GDP for R&D was associated with the number of research publications. The total number of neurologists was associated with all of the bibliometric indices.
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http://dx.doi.org/10.1186/s12883-021-02042-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791854PMC
January 2021

Treatment gaps and challenges in epilepsy care in the Philippines.

Epilepsy Behav 2021 02 13;115:107491. Epub 2020 Dec 13.

Department of Neurosciences, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Manila, Philippines; Institute for Neurosciences, St. Luke's Medical Center, Quezon City and Global City, Philippines. Electronic address:

Objective: Epilepsy is a neurologic disease that carries a high disease burden and likely, a huge treatment gap especially in low-to-middle income countries (LMIC) such as the Philippines. This review aimed to examine the treatment gaps and challenges that burden Philippine epilepsy care.

Materials & Methods: Pertinent data on epidemiology, research, health financing and health systems, pharmacologic and surgical treatment options, cost of care, and workforce were obtained through a literature search and review of relevant Philippine government websites.

Results: The estimated prevalence of epilepsy in the Philippines is 0.9%. Epilepsy research in the Philippines is low in quantity compared with the rest of Southeast Asia (SEA). Inequities in quality and quantity of healthcare services delivered to local government units (LGUs) have arisen because of devolution. Programs for epilepsy care by both government and nongovernment institutions have been implemented. Healthcare expenditure in the Philippines is still largely out-of-pocket, with only partial coverage from the public sector. There is limited access to antiseizure medications (ASMs), mainly due to cost. Epilepsy surgery is an underutilized treatment option. There are only 20 epileptologists in the Philippines, with one epileptologist for every 45,000 patients with epilepsy. In addition, epilepsy care service delivery has been further impeded by the coronavirus disease of 2019 (COVID-19) pandemic.

Conclusion: There is a large treatment gap in epilepsy care in the Philippines in terms of high epilepsy disease burden, socioeconomic limitations and inadequate public support, sparse clinico-epidemiologic research on epilepsy, inaccessibility of health care services and essential pharmacotherapy, underutilization of surgical options, and lack of specialists capable of rendering epilepsy care. Acknowledgment of the existence of these treatment gaps and addressing such are expected to improve the overall survival and quality of life of patients with epilepsy in the Philippines.
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http://dx.doi.org/10.1016/j.yebeh.2020.107491DOI Listing
February 2021

The Philippine OVID-19 utcomes: a etrospective study f eurological manifestations and ssociated symptoms (The Philippine study): a protocol study.

BMJ Open 2020 11 30;10(11):e040944. Epub 2020 Nov 30.

Department of Neurosciences, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Manila, Philippines.

Introduction: The SARS-CoV-2, virus that caused the COVID-19 global pandemic, possesses a neuroinvasive potential. Patients with COVID-19 infection present with neurological signs and symptoms aside from the usual respiratory affectation. Moreover, COVID-19 is associated with several neurological diseases and complications, which may eventually affect clinical outcomes.

Objectives: The Philippine COVID-19 Outcomes: a Retrospective study Of Neurological manifestations and Associated symptoms (The Philippine CORONA) study investigators will conduct a nationwide, multicentre study involving 37 institutions that aims to determine the neurological manifestations and factors associated with clinical outcomes in COVID-19 infection.

Methodology And Analysis: This is a retrospective cohort study (comparative between patients with and without neurological manifestations) via medical chart review involving adult patients with COVID-19 infection. Sample size was determined at 1342 patients. Demographic, clinical and neurological profiles will be obtained and summarised using descriptive statistics. Student's t-test for two independent samples and χ test will be used to determine differences between distributions. HRs and 95% CI will be used as an outcome measure. Kaplan-Meier curves will be constructed to plot the time to onset of mortality (survival), respiratory failure, intensive care unit (ICU) admission, duration of ventilator dependence, length of ICU stay and length of hospital stay. The log-rank test will be employed to compare the Kaplan-Meier curves. Stratified analysis will be performed to identify confounders and effects modifiers. To compute for adjusted HR with 95% CI, crude HR of outcomes will be adjusted according to the prespecified possible confounders. Cox proportional regression models will be used to determine significant factors of outcomes. Testing for goodness of fit will also be done using Hosmer-Lemeshow test. Subgroup analysis will be performed for proven prespecified effect modifiers. The effects of missing data and outliers will also be evaluated in this study.

Ethics And Dissemination: This protocol was approved by the Single Joint Research Ethics Board of the Philippine Department of Health (SJREB-2020-24) and the institutional review board of the different study sites. The dissemination of results will be conducted through scientific/medical conferences and through journal publication. The lay versions of the results may be provided on request.

Trial Registration Number: NCT04386083.
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http://dx.doi.org/10.1136/bmjopen-2020-040944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705427PMC
November 2020

Stroke Research Disparity in Southeast Asia: Socioeconomic Factors, Healthcare Delivery, and Stroke Disease Burden.

J Stroke Cerebrovasc Dis 2021 Feb 27;30(2):105481. Epub 2020 Nov 27.

Division of Adult Neurology, Department of Neurosciences, College of Medicine - Philippine General Hospital, University of the Philippines Manila, Manila, Philippines; Institute for Neurosciences, St. Luke's Medical Center, Quezon City and Global City, Philippines. Electronic address:

Background: Cerebrovascular disease is the second leading cause of death worldwide and provides a heavy burden of disease in Southeast Asia (SEA). Contribution to the collective knowledge of this disease is necessary to address practice and treatment disparities. There is limited data on research productivity in the region. This study aimed to determine research productivity on stroke and other cerebral and spinal vascular diseases among the SEA countries and determine its relationship with bibliometrics, socioeconomic parameters, healthcare delivery indices, and burden of disease.

Methods: A comprehensive literature search was conducted using five major healthcare databases. We included studies published until June 2020 on cerebral and spinal vascular disease with at least one author from SEA. Country-specific socioeconomic parameters, the burden of disease, healthcare delivery indices, and the number of neurologists were collected from international databases and published data. Correlational analysis was done on bibliometric indices and collected data.

Results: A total of 2577 articles were included. Singapore had the most publications (n=1095, 42.5%) and citations (PlumX n=16,592, 55.2%; Scopus n=22,351, 56.7%). Gross domestic product per capita, percent gross domestic product for research and development, universal health care effective coverage index overall and for stroke treatment, and the number of neurologists had a positive correlation to bibliometric indices.

Conclusions: There is a disparity in stroke research productivity among high-income and low-income countries in SEA. Priority must be given to scientific research output and its role in socioeconomic development and policy formulation.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105481DOI Listing
February 2021

Clinical features and outcomes of nonconvulsive status epilepticus in a developing country: A 5-year retrospective study.

Epilepsy Behav 2020 12 24;113:107547. Epub 2020 Nov 24.

Department of Neurosciences, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Manila, Philippines; Electroencephalography Unit, Department of Neurosciences, Philippine General Hospital, University of the Philippines Manila, Manila, Philippines.

Background: This study aimed to determine the frequency of electrographically confirmed nonconvulsive status epilepticus (NCSE) in a cohort suspected with this condition and to determine the demographic/clinical profile, treatment, and outcomes of these patients in the context of a developing country, the Philippines.

Methods: We conducted a retrospective study among patients with suspected with NCSE admitted in the Philippine General Hospital from 2014 to 2019. Using the Salzberg 2013 criteria to diagnose NCSE, three electroencephalographers independently reviewed the electroencephalogram (EEG) tracings of suspected patients and were blinded from the clinical information. Then, we obtained pertinent clinical data from the medical records of EEG-confirmed NCSE cases.

Results: Out of 89 patients suspected with NCSE and with available EEG tracings, information from a total of 14 patients (15.7%) with electrographically confirmed cases were included in the analysis. Median age was 52 ranging from 22 to 77 and female-to-male ratio was 1.3:1. The following conditions were associated with NCSE: intracranial tumor (n = 4), metabolic encephalopathy (n = 4), autoimmune encephalitis (n = 3), intracranial hemorrhage (n = 3), sepsis (n = 3), cardiac arrest (n = 2), hypoxic-ischemic injury (n = 2), antiepileptic withdrawal (n = 1), intracranial abscess (n = 1), head trauma (n = 1), and meningitis (n = 1). Three patients (21.4%) had relatively good clinical outcomes (mRS 0-2) while 6 patients (42.8%) had poor outcomes (mRS 3-5) at discharge. Five patients (35.7%) died due to medical/neurological complications. Our review of the literature showed that the profile of NCSE cases identified in our resource-limited institution strengthens the findings in other populations.

Conclusion: Our data showed that approximately 1 in 6 patients who are suspected with NCSE may have electrographic evidence of NCSE in our setting. The most common etiologies associated with NCSE were intracranial tumors and metabolic conditions. Further studies may entail a prospective collection of data to validate the estimates of our study.
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http://dx.doi.org/10.1016/j.yebeh.2020.107547DOI Listing
December 2020

Scientific impact of movement disorders research from Southeast Asia: A bibliometric analysis.

Parkinsonism Relat Disord 2020 12 31;81:205-212. Epub 2020 Oct 31.

Department of Neurosciences, College of Medicine - Philippine General Hospital, University of the Philippines Manila, Manila, Philippines; Movement Disorders Service, Institute for Neurosciences, St. Luke's Medical Center, Quezon City and Global City, Philippines. Electronic address:

Background: The number of scientific publications on movement disorders from Southeast Asia (SEA) is thought to be low. Thus, we looked at the movement disorders research productivity among SEA countries and its associations with country-specific socioeconomic factors.

Methods: We performed a systematic search for publications indexed in PubMed, Scopus, Embase and Cochrane Central Register of Controlled Trials from January 2000 to December 2019 with at least one author from SEA. Bibliometric indices were used to evaluate research impact. The country-specific socioeconomic characteristics were also obtained.

Results: Of the 9488 identified articles, 1567 met the eligibility criteria. There was an increasing trend in the total number of publications on movement disorders during the last two decades. Singapore had the highest contribution in all aspects, which highlights the impact of knowledge-based economy type in research productivity. Parkinsonism remained the most studied condition, followed by dystonia, chorea, and tremor. Among the socioeconomic factors, only % gross domestic product (GDP) for research and development showed a positive correlation on the number of publications of a country. On the other hand, GDP per capita, population size and the number of neurologist size did not affect research productivity.

Conclusions: An increasing trend in the movement disorders research output over the last 20 years was seen. Singapore had the highest contribution in all aspects which highlights the impact of economy in research productivity. Among the socioeconomic factors, only % GDP for R&D showed a positive impact on the number of publications of a country.
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http://dx.doi.org/10.1016/j.parkreldis.2020.10.043DOI Listing
December 2020

Challenges to the Emergence of Telerehabilitation in a Developing Country: A Systematic Review.

Front Neurol 2020 8;11:1007. Epub 2020 Sep 8.

Department of Rehabilitation Medicine, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Manila, Philippines.

Despite being known abroad as a viable alternative to face-to-face consultation and therapy, telerehabilitation has not fully emerged in developing countries like the Philippines. In the midst of the coronavirus disease 2019 (COVID-19) pandemic, wherein social distancing disrupted the in-clinic delivery of rehabilitation services, Filipinos attempted to explore telerehabilitation. However, several hindrances were observed especially during the pre-implementation phase of telerehabilitation, necessitating a review of existing local evidences. We aimed to determine the challenges faced by telerehabilitation in the Philippines. We searched until March 2020 through PubMed, Scopus, Embase, Cochrane Library, and HeRDIN for telerehabilitation-related publications wherein Filipinos were involved as investigator or population. Because of the hypothesized low number of scientific outputs on telerehabilitation locally, we performed handsearching through gray literature and included relevant papers from different rehabilitation-related professional organizations in the Philippines. We analyzed the papers and extracted the human, organizational, and technical challenges to telerehabilitation or telehealth in general. We analyzed 21 published and 4 unpublished papers, which were mostly reviews (8), feasibility studies (6), or case reports/series (4). Twelve out of 25 studies engaged patients and physicians in remote teleconsultation, teletherapy, telementoring, or telemonitoring. Patients sought telemedicine or telerehabilitation for general medical conditions (in 3 studies), chronic diseases (2), mental health issues (2), orthopedic problems (2), neurologic conditions (1), communication disorders (1), and cardiac conditions (1). Outcomes in aforementioned studies mostly included telehealth acceptance, facilitators, barriers, and satisfaction. Other studies were related to telehealth governance, legalities, and ethical issues. We identified 18 human, 17 organizational, and 18 technical unique challenges related to telerehabilitation in the Philippines. The most common challenges were slow internet speed (in 10 studies), legal concerns (9), and skepticism (9). There is paucity of data on telerehabilitation in the Philippines. Local efforts can focus on exploring or addressing the most pressing human, organizational, and technical challenges to the emergence of telerehabilitation in the country.
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http://dx.doi.org/10.3389/fneur.2020.01007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505991PMC
September 2020

Efficacy and safety of amantadine for the treatment of fatigue in multiple sclerosis: a systematic review and meta-analysis.

Neurodegener Dis Manag 2020 12 5;10(6):383-395. Epub 2020 Oct 5.

Section of Neurology, Department of Internal Medicine, Cardinal Santos Medical Center, San Juan City, Philippines.

Fatigue is a debilitating symptom of multiple sclerosis (MS) affecting at least 75% of patients. Amantadine has been tested for MS-related fatigue treatment but efficacy and safety remain unclear. We performed a systematic review and meta-analysis of qualified literatures searched until 30 April 2020. A total of 11 clinical trials were included. The meta-analysis revealed improvement of MS-related fatigue with amantadine treatment using the patients' subjective responses and validated fatigue scales. Amantadine is the most studied drug that has shown improvement of MS-related fatigue, with mild side effects and good tolerability. Larger studies using a standard measurement for MS-related fatigue are recommended to improve the quality of evidence. Safety and efficacy on long-term use needs further investigation.
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http://dx.doi.org/10.2217/nmt-2020-0030DOI Listing
December 2020

Success and complication rates of endoscopic third ventriculostomy for tuberculous meningitis: a systematic review and meta-analysis.

Neurosurg Rev 2021 Aug 24;44(4):2201-2209. Epub 2020 Sep 24.

Division of Neurosurgery, Department of Neurosciences, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Taft Avenue, Ermita, 1000, Manila, Philippines.

Because ventriculoperitoneal shunt (VPS) insertion for patients with hydrocephalus from tuberculous meningitis (TBM) can be complicated by shunt infection and malfunction, endoscopic third ventriculostomy (ETV) has been proposed as an alternative. The aim of this review was to determine the success, technical failure, and complication rates of ETV in TBM in a meta-analysis and determine which factors are predictive of outcome. The PubMed, Scopus, and CENTRAL databases were searched from inception to April 2020 for case series, cohort studies, or randomized controlled trials reporting success, technical failure, or complication rates. For studies with individual patient data available, logistic regression analysis was done to determine whether age, sex, clinical grade, and type of hydrocephalus on imaging was predictive of outcome. Eight studies with a total of 174 patients were included in the review. Using random-effects modeling, the pooled estimate of success rate was 59% (95% CI 50-68%), with low heterogeneity (I = 30%). The technical failure and complication rates were 5% and 15%, respectively, but these variables had moderate heterogeneity. In 36 patients with individual patient data, a non-communicating type of hydrocephalus on imaging was associated with an odds ratio of 5.90 (95% CI 1.1-32.9, p = 0.043) for success. In summary, ETV for TBM had a pooled success rate of 59%, technical failure rate of 5%, and complication rate of 15%. An imaging finding of non-communicating hydrocephalus was associated with increased success. High-quality randomized, prospective studies using VPS insertion as control are needed to further define the role of ETV in TBM.
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http://dx.doi.org/10.1007/s10143-020-01396-yDOI Listing
August 2021

The current status and challenges in multiple sclerosis management in the Philippines.

Mult Scler Relat Disord 2020 Nov 18;46:102510. Epub 2020 Sep 18.

Department of Neurosciences, College of Medicine - Philippine General Hospital, University of the Philippines Manila, Manila, Philippines. Phone: (+63) 917 8459424, ORCID iD: 0000-0001-7263-8474; Institute for Neurosciences, St. Luke's Medical Center, Quezon City & Global City, Philippines. Electronic address:

Background: The provision of adequate services for individuals living with multiple sclerosis (MS) is an important issue since MS has a chronic and debilitating course.

Objective: We aimed to review the literature on health service delivery for individuals with MS in the Philippines and identify the gaps in adequate provision of healthcare in these individuals.

Methods: We reviewed data from relevant local and international repositories on health service delivery for individuals with MS in the Philippines.

Results: The epidemiology of MS in the Philippine setting remains unknown. Approximately 1 neurologist caters to 175,000 Filipinos aged 15 and above, and nearly half are practicing in the National Capital Region. Physical access to magnetic resonance imaging is severely limited at 0.8 MRI unit per million Filipinos. Household out-of-pocket payment and voluntary health care payment schemes contributed 53.9% and 12.2%, respectively, to the current health expenditures. The average monthly income of a Filipino household is only 519 USD which may not be enough to cover treatment of a single relapse let alone costly disease-modifying treatments.

Conclusion: The Philippines faces challenges in terms of the availability of accurate epidemiologic information, resource allocation, access to services and provision of therapies for individuals with MS.
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http://dx.doi.org/10.1016/j.msard.2020.102510DOI Listing
November 2020

Electroencephalographic findings in antileucine-rich glioma-inactivated 1 (LGI1) autoimmune encephalitis: A systematic review.

Epilepsy Behav 2020 11 22;112:107462. Epub 2020 Sep 22.

Department of Neurosciences, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Manila, Philippines.

Background: Antileucine-rich glioma-inactivated 1 (LGI1) autoimmune encephalitis is a distinct syndrome of early onset faciobrachial dystonic seizures (FBDS) and other focal seizures followed by neuropsychiatric symptoms. The electroclinical syndrome of this condition is yet to be fully understood. The main objective of this study was to determine the frequencies of electroencephalogram (EEG) findings in patients diagnosed with anti-LGI1 autoimmune encephalitis through a systematic review of published relevant articles.

Methods: Major electronic healthcare databases were searched for relevant published articles until July 2020.

Results: From 327 articles, 23 case reports and 14 case series were included in the review after satisfying the eligibility criteria. Data from a total of 151 cases of definite anti-LGI1 encephalitis were analyzed in this systematic review. Epileptiform discharges were the most frequent finding at 57.3%. Focal electroencephalographic abnormalities including slow wave (59.3%) and epileptiform activities (53.5%) most commonly arise from the temporal region. Faciobrachial dystonic seizures often have no ictal electroencephalographic correlate but would show electrodecremental events when seizure duration is prolonged.

Conclusion: Electroencephalogram abnormalities are seen in anti-LGI1 autoimmune encephalitis with epileptiform discharges as the most common finding followed by focal slowing. These findings were most frequently seen arising in the temporal region. Further studies using a standardized protocol focusing on electroencephalographic findings in anti-LGI1 encephalitis with clinical correlation to disease stage and treatment outcomes in terms of seizure control and memory and cognitive function are needed. Particular attention on ictal electrodecremental activity during FBDS should be done in studies with a larger sample size.
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http://dx.doi.org/10.1016/j.yebeh.2020.107462DOI Listing
November 2020

Electroencephalographic findings in COVID-19 patients: A systematic review.

Seizure 2020 Nov 15;82:17-22. Epub 2020 Sep 15.

Department of Neurosciences, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Taft Avenue, Manila, 1000, Philippines. Electronic address:

Background: Growing evidence of neurologic involvement seen in COVID-19 infection necessitates the pooling of neurodiagnostic findings like electroencephalography (EEG) that may guide clinical management. The objective of this study was to review the EEG findings in patients diagnosed with COVID-19 infection through a systematic review of published articles.

Methods: We systematically searched until July 25, 2020 for published articles that reported on descriptive EEG findings in patients diagnosed with COVID-19 in PUBMED by Medline, EMBASE, and CENTRAL by the Cochrane Library.

Results: From a total of 94 identified records, 29 relevant articles were included in this review. A total of 177 patients with COVID-19 with descriptive EEG reports were analyzed. The most common indication for EEG was unexplained altered mental status. Disturbances of background activity such as generalized and focal slowing were seen as well epileptiform abnormalities and rhythmic or periodic discharges. There were no consistent EEG findings specific to COVID-19 infection.

Conclusion: The EEG findings in COVID-19 appear to be non-specific. Further research on the relationship of the EEG findings to the clinical state and short- or long-term prognosis of COVID-19 patients may be conducted to help clinicians discern which patients would necessitate an EEG procedure and would eventually require treatment.
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http://dx.doi.org/10.1016/j.seizure.2020.09.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490625PMC
November 2020

Neurological Manifestations in COVID-19 Infection: A Systematic Review and Meta-Analysis.

Can J Neurol Sci 2021 Jan 15;48(1):66-76. Epub 2020 Jul 15.

Department of Neurosciences, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Manila, Philippines.

Background: Growing evidence showed that coronavirus disease 2019 (COVID-19) infection may present with neurological manifestations. This review aimed to determine the neurological manifestations and complications in COVID-19.

Methods: We conducted a systematic review and meta-analysis that included cohort and case series/reports involving a population of patients confirmed with COVID-19 infection and their neurologic manifestations. We searched the following electronic databases until April 18, 2020: PubMed, Embase, Scopus, and World Health Organization database (PROSPERO registration number: CRD42020180658).

Results: From 403 articles identified, 49 studies involving a total of 6,335 confirmed COVID-19 cases were included. The random-effects modeling analysis for each neurological symptom showed the following proportional point estimates with 95% confidence intervals: "headache" (0.12; 0.10-0.14; I2 = 77%), "dizziness" (0.08; 0.05-0.12; I2 = 82%), "headache and dizziness" (0.09; 0.06-0.13; I2 = 0%), "nausea" (0.07; 0.04-0.11; I2 = 79%), "vomiting" (0.05; 0.03-0.08; I2 = 74%), "nausea and vomiting" (0.06; 0.03-0.11; I2 = 83%), "confusion" (0.05; 0.02-0.14; I2 = 86%), and "myalgia" (0.21; 0.18-0.25; I2 = 85%). The most common neurological complication associated with COVID-19 infection was vascular disorders (n = 23); other associated conditions were encephalopathy (n = 3), encephalitis (n = 1), oculomotor nerve palsy (n = 1), isolated sudden-onset anosmia (n = 1), Guillain-Barré syndrome (n = 1), and Miller-Fisher syndrome (n = 2). Most patients with neurological complications survived (n = 14); a considerable number of patients died (n = 7); and the rest had unclear outcomes (n = 12).

Conclusion: This review revealed that neurologic involvement may manifest in COVID-19 infection. What has initially been thought of as a primarily respiratory illness has evolved into a wide-ranging multi-organ disease.
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http://dx.doi.org/10.1017/cjn.2020.146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492583PMC
January 2021

Dementia Research Productivity and Associations with Socioeconomic Factors and Burden of Disease in Southeast Asia.

J Alzheimers Dis 2020 ;76(3):1151-1160

Department of Neurosciences, Division of Adult Neurology, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Manila, Philippines.

Background: Scientific output in Southeast Asia (SEA) on the topic of dementia is postulated to be low in quality and quantity. It is also speculated that certain socioeconomic variables and measures of disease burden for dementia may play a significant role in driving the research output of a particular country.

Objective: This study aimed to determine the research impact of published journal articles on dementia in SEA and its association with country-level socioeconomic factors and measures of disease burden for dementia.

Methods: A systematic search was conducted using electronic healthcare databases. We included articles published on dementia until August 2019 with at least 1 author affiliated with any SEA institution. We obtained bibliometric indices, relevant socioeconomic factors, and measures of disease burden for dementia from published sources.

Results: One thousand six articles fulfilled the inclusion criteria. The majority of publications were related to Alzheimer's disease (n = 775, 77.0%). Singapore contributed the highest number of publications (n = 457, 45.4%). Gross domestic product (GDP) per capita, % GDP for research and development, and total neurologists significantly correlated with several bibliometric indices. On the other hand, the measures of disease burden for dementia in SEA countries were not significantly associated with research productivity.

Conclusion: Research productivity in SEA on dementia has substantially increased in recent years. Augmenting GDP per capita and expanding the apportionment of resources to research and development (R&D) may have a significant role in the advancement of dementia research in SEA.
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http://dx.doi.org/10.3233/JAD-200355DOI Listing
June 2021

Effects of Citicoline as an Adjunct Treatment for Alzheimer's Disease: A Systematic Review.

J Alzheimers Dis 2020 ;76(2):725-732

Department of Neurosciences, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Manila, Philippines.

Background: A critical strategy in the management of Alzheimer's disease (AD) is optimizing the effects of currently available pharmacologic therapies such as citicoline (CC).

Objective: The purpose of this study was to determine the effects of CC as adjunct therapy to cholinesterase inhibitors (AChEI) in the treatment of AD.

Methods: We identified relevant studies by electronic search until April 2020. We considered studies with a comparator group that enrolled elderly patients with a diagnosis of AD and employed CC as an adjunct therapy to AChEIs compared to AChEI monotherapy or comparisons of different AChEIs combined with CC. Methodological quality assessment was done using the Newcastle-Ottawa Scale.

Results: Out of 149 articles identified, two retrospective cohort studies involving 563 elderly patients affected with AD were included. After 3 months and 9 months, better Mini-Mental Status Examination scores were observed in the "AChEIs + CC" group versus "AChEIs alone" group. CC combined with donepezil may be better in improving cognition than when combined with rivastigmine. No significant difference was noted in terms of activities of daily living (ADL) and instrumental-ADL. Neuropsychiatric Inventory and Geriatric Depression Scale-short form scores appeared to be lower in the combination treatment versus monotherapy. The adverse events of combined treatment were self-limiting and included occasional excitability, gastric intolerance, and headache.

Conclusion: Limited evidence from pooled data of two observational studies suggests that CC used in adjunct with AChEIs in the treatment of AD was well-tolerated and showed improvement in cognition, mood, and behavioral symptoms compared to treating with AChEIs alone.
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http://dx.doi.org/10.3233/JAD-200378DOI Listing
May 2021
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