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1.
Mov Disord ; 2024 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-38616406

RESUMEN

BACKGROUND: X-Linked dystonia-parkinsonism (XDP) is an adult-onset neurodegenerative disorder characterized by rapidly progressive dystonia and parkinsonism. Mosaic Divergent Repeat Interruptions affecting motif Length and Sequence (mDRILS) were recently found within the TAF1 SVA repeat tract and were shown to associate with repeat stability and age at onset in XDP, specifically the AGGG [5'-SINE-VNTR-Alu(AGAGGG)2AGGG(AGAGGG)n] mDRILS. OBJECTIVE: This study aimed to investigate the stability of mDRILS frequencies and stability of (AGAGGG)n repeat length during transmission in parent-offspring pairs. METHODS: Fifty-six families (n = 130) were investigated for generational transmission of repeat length and mDRILS. The mDRILS stability of 16 individuals was assessed at two sampling points 1 year apart. DNA was sequenced with long-read technologies after long-range polymerase chain reaction amplification of the TAF1 SVA. Repeat number and mDRILS were detected with Noise-Cancelling Repeat Finder (NCRF). RESULTS: When comparing the repeat domain, 51 of 65 children had either contractions or expansions of the repeat length. The AGGG frequency remained stable across generations at 0.074 (IQR: 0.069-0.078) (z = -0.526; P = 0.599). However, the median AGGG frequency in children with an expansion (0.072 [IQR: 0.066-0.076]) was lower compared with children with retention or contraction (0.080 [IQR: 0.073-0.083]) (z = -0.007; P = 0.003). In a logistic regression model, the AGGG frequency predicted the outcome of either expansion or retention/contraction when including repeat number and sex as covariates (ß = 80.7; z-score = 2.63; P = 0.0085). The AGGG frequency varied slightly over 1 year (0.070 [IQR: 0.063-0.080] to 0.073 [IQR: 0.069-0.078]). CONCLUSIONS: Our results show that a higher AGGG frequency may stabilize repeats across generations. This highlights the importance of further investigating mDRILS as a disease-modifying factor with generational differences. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

2.
J Mov Disord ; 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38500249

RESUMEN

Objectives: Since the release of vaccines against COVID-19, there have been reports of vaccine-related neurologic complications. This study aimed to create a descriptive systematic review of movement disorders associated with COVID-19 vaccines. Methods: We described the demographics, clinical presentation, management, outcomes, and proposed patho-mechanism. A systematic review was performed according to the PRISMA guidelines. A standardized tool was used to assess the quality of the cases. Results: We have identified 8 articles that met our inclusion criteria consisting of 10 patients who developed movement disorders after vaccination. The majority were males (n = 8), with a median age of 64.5 years. The most common movement disorder was hemichorea. The rest presented with generalized chorea with myoclonus, cervical dystonia, and akathisia. Most cases responded with immunotherapy. The standardized tool used showed that most studies have a low risk of bias. Conclusion: The reported incidence of vaccine-related movement disorders was low in occurrence based on available published cases that were found.

3.
Med Sci (Basel) ; 12(1)2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38535157

RESUMEN

BACKGROUND: Pituitary adenomas are benign brain tumors that impose a heavy burden on patients worldwide. The local burden of disease is yet to be established due to scarcity of data. In line with this, this study aims to present the challenges and gaps in the treatment of pituitary adenomas in the Philippines. METHODS: A scoping review of available relevant literature on epidemiology, clinical experience with treatment, health financing, and healthcare delivery system based on the Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines extension for Scoping Reviews was conducted. RESULTS: The scarcity of updated local clinical data, inequity of distribution of resources, inadequate government support, and lack of affordable diagnostic testing, medications, and neurosurgical procedures are the factors that hinder provision of adequate care of pituitary adenomas in the Philippines. CONCLUSION: There are notable treatment gaps in the management of pituitary adenomas in the Philippines, which may be addressed by strengthening universal healthcare. Strategies to address these gaps were proposed, including improving public-private insurance coverage, increasing manpower, enhancing accessibility to resources, and spreading more awareness.


Asunto(s)
Adenoma , Neoplasias Encefálicas , Neoplasias Hipofisarias , Humanos , Filipinas , Gobierno
4.
J Alzheimers Dis ; 97(4): 1533-1543, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38306035

RESUMEN

Background: Dementia prevalence is increasing in low- and middle-income countries such as the Philippines. Objective: This study aimed to give an overview of dementia care in the Philippines and to identify gaps in terms of local epidemiology, research, financial coverage, diagnostics, pharmacotherapy, manpower, and caregiver support. Methods: This scoping review was conducted using the Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines extension for scoping reviews. Six international and two local databases, and government and non-government websites were searched. Data published in the English or Filipino language on dementia epidemiology, research, diagnostics, management, manpower, and training were extracted from the earliest indexed record until June 2022. Results: The prevalence of dementia in the Philippines is high and research output on all aspects of dementia is low. Cost is a major barrier as health care coverage is limited, with reliance mainly on out-of-pocket payments, leading to challenges in the proper diagnosis and treatment of dementia. There is a low specialist-to-population ratio, with shortages beyond manpower and training. Conclusions: Gaps in dementia care include limited published local data, high healthcare costs, inadequate health financing, and limited manpower.


Asunto(s)
Demencia , Servicios de Salud , Humanos , Filipinas/epidemiología , Costos de la Atención en Salud , Prevalencia , Demencia/diagnóstico , Demencia/epidemiología , Demencia/terapia
5.
BMC Res Notes ; 17(1): 14, 2024 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-38178236

RESUMEN

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) and coronary artery disease (CAD) or heart failure (HF) are more likely to have poor outcomes. This study aimed to determine the characteristics and outcomes of COVID-19 patients with CAD/HF across various institutions in the Philippines. METHODS: We utilized the data from the Philippine CORONA Study and compared the outcomes of admitted COVID-19 patients with CAD/HF versus those without. The Student's t test, Mann-Whitney U test, binary logistic regression and multivariate regression analysis were utilized. Odds ratios (OR) and Kaplan-Meier curves were generated. RESULTS: We included a total of 512 patients with COVID-19 had CAD/HF and 10,369 were without. CAD/HF was significantly associated with COVID severity, all-cause mortality, death from cardiac causes, respiratory failure, and prolonged hospitalization. After adjusting for confounders, the presence of CAD/HF was still associated with death from a cardiac cause (OR 2.22, 95% CI 1.49-3.3, p < 0.01). CONCLUSIONS: The presence of CAD or HF was significantly associated with severity of COVID disease, all-cause mortality, death from cardiac causes, respiratory failure, and prolonged hospitalization.


Asunto(s)
COVID-19 , Enfermedad de la Arteria Coronaria , Insuficiencia Cardíaca , Insuficiencia Respiratoria , Humanos , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/epidemiología , Filipinas/epidemiología , COVID-19/complicaciones , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/etiología , Insuficiencia Respiratoria/complicaciones
6.
Parkinsonism Relat Disord ; 119: 105949, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38072720

RESUMEN

INTRODUCTION: X-linked dystonia-parkinsonism (XDP) is a progressive neurodegenerative disorder that has been studied well in recent years. OBJECTIVES: This scoping review aimed to describe the current state of knowledge about the diagnosis and treatment of XDP, to provide clinicians with a concise and up-to-date overview. METHODS: We conducted a scoping review of pertinent literature on the diagnosis and treatment of XDP using Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. RESULTS: There were 24 articles on diagnostic methods and 20 articles on therapeutic interventions for XDP, with 7 review articles describing both. The detection of the SVA retrotransposon insertion within the TAF1 gene is confirmatory for XDP. Oral medications are marginally effective. Chemodenervation with botulinum toxin is an effective treatment. Pallidal deep brain stimulation (DBS) has been shown to provide significant improvement in the dystonia and quality of life of patients with XDP for a longer time. A less invasive surgical option is the transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS), which has shown promising effects with the limited number of case reports available. CONCLUSION: XDP is a geneti disorder characterized by striatal symptoms and pathology on neuroimaging. No effective oral medications are available for the management of XDP. The use of botulinum toxin is limited by its cost and duration of effects. As of now, pallidal DBS is deemed to be the best option. Another promising option is the tcMRgFUS but still has limited studies on its safety and efficacy in XDP.


Asunto(s)
Toxinas Botulínicas , Distonía , Trastornos Distónicos , Enfermedades Genéticas Ligadas al Cromosoma X , Humanos , Trastornos Distónicos/diagnóstico , Trastornos Distónicos/genética , Trastornos Distónicos/terapia , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/terapia , Calidad de Vida
7.
Clin Pract ; 13(6): 1383-1392, 2023 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-37987425

RESUMEN

BACKGROUND: The global pandemic caused by the coronavirus disease 2019 (COVID-19) resulted in many deaths from fulminant respiratory failure. Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality worldwide. There has been great concern regarding the impact of COPD on the COVID-19 illness. METHODS: Data from the Philippine CORONA study were analyzed to determine the association of COPD and COVID-19 in terms of mortality, disease severity, respiratory failure, mechanical ventilation, and lengths of stay in the intensive care unit (ICU) and hospital. RESULTS: A total of 10,881 patients were included in this study, and 156 (1.4%) patients had been diagnosed with COPD. A majority of COVID-19 patients with COPD had other existing comorbidities: hypertension, diabetes mellitus, chronic cardiac disease, and chronic kidney disease. COPD patients were 2.0× more likely to present with severe to critical COVID-19 disease. COVID-19 patients with COPD in our study have a 1.7× increased mortality, 1.6× increased respiratory failure, and 2.0× increased risk for ICU admission. Smokers with COVID-19 were 1.8× more likely to present with more severe disease and have a 1.9× increased mortality. CONCLUSION: Our study supports the growing evidence that COPD among COVID-19 patients is a risk factor for higher mortality, more severe form of COVID-19, higher ICU admission, and higher respiratory failure needing ventilatory support.

8.
Pediatr Int ; 65(1): e15623, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37767858

RESUMEN

BACKGROUND: A dengue vaccine, dengvaxia, was licensed for the first time in 2015. It was approved for use in 11 countries where dengue infection is endemic, including the Philippines. In November 2017, controversy arose in the Philippines regarding the dengvaxia vaccine. We hypothesized that the dengvaxia controversy might be correlated with immunization coverage in the Philippines. METHODS: We performed an analytical and infodemiological study on web-based interest in dengvaxia, both globally and in 18 dengue endemic countries, from 2015 to 2020 using Google Trends™. Comparisons were made with search trends for the components of the National Immunization Program (NIP) and vaccine coverage by computing the Pearson product-moment correlation coefficient (r) between each variable. RESULTS: Among the 18 countries included, the Philippines had the highest search volume index for dengvaxia, with peaks in searches coinciding with that of worldwide search trends. There was no correlation between the relative search volume for dengvaxia with that of vaccines included in the NIP in the Philippines from 2015 to 2020. There was no significant correlation between web-based interest in dengvaxia and the estimated immunization coverage from 2015 to 2019. CONCLUSION: There was no significant correlation between web-based interest in dengvaxia, the vaccines in the NIP, and national immunization coverage.


Asunto(s)
Vacunas contra el Dengue , Dengue , Vacunas , Humanos , Dengue/epidemiología , Dengue/prevención & control , Cobertura de Vacunación , Vacunación , Filipinas , Programas de Inmunización
9.
BMC Neurol ; 23(1): 306, 2023 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-37596524

RESUMEN

Transcranial magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive method for controlling tremor and has recently been used in patients with X-linked dystonia-parkinsonism (XDP). This study aims to determine the improvement in dystonia and parkinsonism in patients with XDP after MRgFUS pallidothalamic tractotomy. This prospective study will be conducted at the Philippine General Hospital, University of the Philippines Manila. The primary outcome measure is the change in the pre- and post-treatment XDP-Movement Disorder Society of the Philippines Scale scores. In addition, demographic and clinical data will be collected, including the Burke-Fahn-Marsden Dystonia Rating Scale, Part III of the Movement Disorder Society-Unified Parkinson's disease Rating Scale score, XDP clinical and functional stage, the five-level EuroQol five-dimensional questionnaire, Montreal Cognitive Assessment scores, MRgFUS treatment parameters, and adverse events. Patients will be assessed within 24 hours of treatment, then at 2 weeks, 3 months, 6 months, 9 months, and 12 months post-treatment. This protocol was approved by the University of the Philippines Manila Research Ethics Board (UPMREB 2022-0271-01). Data collection began in January 2023. This protocol has been registered with ClinicalTrials.gov: Trial Registration number: NCT05592028.


Asunto(s)
Distonía , Trastornos del Movimiento , Humanos , Espectroscopía de Resonancia Magnética , Filipinas , Estudios Prospectivos
10.
Heliyon ; 9(7): e18335, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37519698

RESUMEN

Background: Stokes-Adams attacks presenting as convulsions may be difficult to distinguish from epilepsy. Stokes-Adams Syndrome is a transient abrupt collapse into unconsciousness due to a sudden but pronounced decrease in cardiac output caused by change in heart rate and rhythm, resulting in syncope. Case presentation: We report a patient who presented with multiple convulsive episodes managed as epilepsy, until she was found to have paroxysmal total atrioventricular block. Previously, she had been treated with anti-seizure medications without relief. Ventricular standstill was seen on cardiac monitoring and the convulsive episodes were determined as Stokes-Adams attacks. She underwent percutaneous coronary intervention and has been free of convulsive episodes since. Conclusion: Awareness of distinction between seizures/epilepsy and convulsive syncope is important and may be life-saving. A good clinical history as well as simple non-invasive tests such as electroencephalogram and electrocardiogram are important in establishing correct diagnosis.

11.
Ann Neurol ; 94(4): 684-695, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37376770

RESUMEN

OBJECTIVE: The purpose of this study was to characterize a metabolic brain network associated with X-linked dystonia-parkinsonism (XDP). METHODS: Thirty right-handed Filipino men with XDP (age = 44.4 ± 8.5 years) and 30 XDP-causing mutation negative healthy men from the same population (age = 37.4 ± 10.5 years) underwent [18 F]-fluorodeoxyglucose positron emission tomography. Scans were analyzed using spatial covariance mapping to identify a significant XDP-related metabolic pattern (XDPRP). Patients were rated clinically at the time of imaging according to the XDP-Movement Disorder Society of the Philippines (MDSP) scale. RESULTS: We identified a significant XDPRP topography from 15 randomly selected subjects with XDP and 15 control subjects. This pattern was characterized by bilateral metabolic reductions in caudate/putamen, frontal operculum, and cingulate cortex, with relative increases in the bilateral somatosensory cortex and cerebellar vermis. Age-corrected expression of XDPRP was significantly elevated (p < 0.0001) in XDP compared to controls in the derivation set and in the remaining 15 patients (testing set). We validated the XDPRP topography by identifying a similar pattern in the original testing set (r = 0.90, p < 0.0001; voxel-wise correlation between both patterns). Significant correlations between XDPRP expression and clinical ratings for parkinsonism-but not dystonia-were observed in both XDP groups. Further network analysis revealed abnormalities of information transfer through the XDPRP space, with loss of normal connectivity and gain of abnormal functional connections linking network nodes with outside brain regions. INTERPRETATION: XDP is associated with a characteristic metabolic network associated with abnormal functional connectivity among the basal ganglia, thalamus, motor regions, and cerebellum. Clinical signs may relate to faulty information transfer through the network to outside brain regions. ANN NEUROL 2023;94:684-695.


Asunto(s)
Distonía , Trastornos Distónicos , Enfermedades Genéticas Ligadas al Cromosoma X , Masculino , Humanos , Adulto , Persona de Mediana Edad , Trastornos Distónicos/diagnóstico por imagen , Trastornos Distónicos/genética , Trastornos Distónicos/complicaciones , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico por imagen , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Distonía/diagnóstico por imagen , Distonía/genética , Biomarcadores
12.
Cureus ; 15(2): e35388, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36994271

RESUMEN

Research productivity on viral infections of the nervous system in Southeast Asia (SEA) is unknown. We aimed to determine the research productivity of SEA in terms of bibliometric indices and PlumX metrics and their correlation with socioeconomic factors. A comprehensive search of major electronic databases was done to identify studies on viral infections of the nervous system with at least one author from SEA. Socioeconomic factors and collaborations outside SEA were determined. Correlational analysis was done on bibliometric indices and socioeconomic factors. A total of 542 articles were analyzed. The majority came from Thailand (n = 164, 30.2%). Most articles used a descriptive study design (n = 175, 32.2%). The most common topic was Japanese encephalitis (n = 170, 31.3%). The % gross domestic product allotted for research, number of neurologists, and number of collaborations outside SEA correlated with the bibliometric indices and PlumX metrics. In conclusion, the number of research from SEA was low but the quality was comparable to the global benchmark. Improving resource allocation and collaboration between SEA nations and other countries may support this endeavor.

13.
Parkinsonism Relat Disord ; 108: 105319, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36774704

RESUMEN

INTRODUCTION: Although genetic factors are known to play a role in the pathogenesis of Parkinson's disease (PD), true prevalence of familial PD is unknown. We conducted this pilot study to identify genes implicated in familial Parkinson's disease among Filipinos. METHODS: Eighteen Filipino patients belonging to 11 families with personal and family history of PD underwent thorough evaluation by movement disorders specialists. Samples were analyzed in Juntendo University, Tokyo, Japan. Sanger sequencing of polymerase chain reaction products was performed. Each sample was screened for 23 genes (SNCA, PARK 2, UCHL1, PINK 1, DJ-1, LRRK2, ATP13A2, GIGYF2, HTRA2, PLA266, FBX07, VPS35, EIF461, DNAJC13, CHCHD2, GCH1, MAPT, NR4A2, VPS13c, PSEN1, and GRN). RESULTS: Out of 18 patients, six harbored Parkinson-related gene mutations. Five individuals from three families were positive for PINK1 c.10140T > C(p.L347P) mutation while one had heterozygous variant PRKN c.136G>T(p.A465) gene mutation. Three families displayed autosomal recessive pattern while one family with PINK1 mutation showed autosomal dominant mode of inheritance. Bradykinesia and tremor were predominant symptoms. Mean age at onset of symptoms was 40.4 years among those with PINK1 mutations. CONCLUSION: In this study, we presented the clinical profiles and identified two genetic mutations among a small group of Filipino patients with familial PD. They were congruent with most studies showing these mutations as the most common causes of autosomal recessive early-onset PD. Preliminary data from this pilot study will guide planning for larger scale studies, such as collaborative projects including The Global Parkinson's Genetics Program (GP2).


Asunto(s)
Enfermedad de Parkinson , Humanos , Adulto , Enfermedad de Parkinson/genética , Proyectos Piloto , Pruebas Genéticas , Mutación , Temblor/genética , Proteínas de Unión al ADN/genética , Factores de Transcripción/genética
14.
Vaccines (Basel) ; 11(2)2023 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-36851103

RESUMEN

OBJECTIVE: Our study determined the association of pregnancy with various clinical outcomes among women with COVID-19 infection. METHODS: We conducted a retrospective, cohort, subgroup analysis of the Philippine CORONA Study datasets comparing the clinical/neurological manifestations and outcomes of pregnant and nonpregnant women admitted in 37 Philippine hospitals for COVID-19 infection. RESULTS: We included 2448 women in the analyses (322 pregnant and 2.126 nonpregnant). Logistic regression models showed that crude odds ratio (OR) for mortality (OR 0.26 [95% CI 0.11, 0.66]), respiratory failure [OR 0.37 [95% CI 0.17, 0.80]), need for intensive care (OR 0.39 [95% CI 0.19, 0.80]), and prolonged length of hospital stay (OR 1.73 [95% CI 1.36, 2.19]) among pregnant women were significant. After adjusting for age, disease severity, and new-onset neurological symptoms, only the length of hospital stay remained significant (adjusted OR 1.99 [95% CI 1.56,2.54]). Cox regression models revealed that the unadjusted hazard ratio (HR) for mortality (HR 0.22 [95% CI 0.09, 0.55]) among pregnant women was statistically significant; however, after adjustment, the HR for mortality became nonsignificant. CONCLUSION: We did not find a significantly increased risk of mortality, respiratory failure, and need for ICU admission in pregnant women compared with nonpregnant women with COVID-19. However, the likelihood of hospital confinement beyond 14 days was twice more likely among pregnant women than nonpregnant women with COVID-19.

15.
Eur J Med Res ; 28(1): 62, 2023 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-36732874

RESUMEN

OBJECTIVE: To describe the association between hypertension and clinical outcomes in a cohort of patients with coronavirus disease 2019 (COVID-19). DESIGN: Retrospective cohort study. SETTING: Thirty-seven (37) hospitals in the Philippines. PATIENTS: 10,881 patients admitted for COVID-19 from February to December 2020. MEASUREMENTS AND MAIN RESULTS: Among the 10,881 patients included in the Philippine CORONA Study, 3647 (33.5%) had hypertension. On regression analysis adjusted for confounders (age group, sex, smoking history, diabetes, chronic cardiac disease, chronic kidney disease, chronic respiratory disease, chronic neurologic disease, chronic liver disease, HIV/AIDS, and malignancy), patients with hypertension had significantly greater odds of in-hospital mortality (OR 1.33, 95% CI 1.17-1.52), respiratory failure (OR 1.99, 95% CI 1.75-2.28), ICU admission (OR 2.16, 95% CI 1.90-2.45) and severe/critical disease (OR 1.57, 95% CI 1.41-1.75), compared to patients without hypertension. The time-to-event analysis with confounder adjustment also showed that hypertension was significantly associated with shorter time-to-event outcomes of in-hospital mortality (HR 1.13, 95% CI 1.01-1.26), respiratory failure (HR 1.86, 95% CI 1.65-2.10), and ICU admission (HR 1.99, 95% CI 1.76-2.23). CONCLUSIONS: Our analysis of nationwide data confirmed previous findings that hypertension is an independent risk factor for worse clinical outcomes among patients hospitalized for COVID-19, with increased odds of in-hospital mortality, respiratory failure, ICU admission, and severe/critical COVID-19. More specific studies should be done to elucidate the impact of hypertension characteristics, such as chronicity, severity, drug therapy, and level of control on these clinical outcomes.


Asunto(s)
COVID-19 , Hipertensión , Insuficiencia Respiratoria , Humanos , Filipinas/epidemiología , SARS-CoV-2 , Estudios Retrospectivos , Hipertensión/complicaciones , Hipertensión/epidemiología , Factores de Riesgo , Mortalidad Hospitalaria , Unidades de Cuidados Intensivos
16.
Brain ; 146(3): 1075-1082, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-35481544

RESUMEN

While many genetic causes of movement disorders have been identified, modifiers of disease expression are largely unknown. X-linked dystonia-parkinsonism (XDP) is a neurodegenerative disease caused by a SINE-VNTR-Alu(AGAGGG)n retrotransposon insertion in TAF1, with a polymorphic (AGAGGG)n repeat. Repeat length and variants in MSH3 and PMS2 explain ∼65% of the variance in age at onset (AAO) in XDP. However, additional genetic modifiers are conceivably at play in XDP, such as repeat interruptions. Long-read nanopore sequencing of PCR amplicons from XDP patients (n = 202) was performed to assess potential repeat interruption and instability. Repeat-primed PCR and Cas9-mediated targeted enrichment confirmed the presence of identified divergent repeat motifs. In addition to the canonical pure SINE-VNTR-Alu-5'-(AGAGGG)n, we observed a mosaic of divergent repeat motifs that polarized at the beginning of the tract, where the divergent repeat interruptions varied in motif length by having one, two, or three nucleotides fewer than the hexameric motif, distinct from interruptions in other disease-associated repeats, which match the lengths of the canonical motifs. All divergent configurations occurred mosaically and in two investigated brain regions (basal ganglia, cerebellum) and in blood-derived DNA from the same patient. The most common divergent interruption was AGG [5'-SINE-VNTR-Alu(AGAGGG)2AGG(AGAGGG)n], similar to the pure tract, followed by AGGG [5'-SINE-VNTR-Alu(AGAGGG)2AGGG(AGAGGG)n], at median frequencies of 0.425 (IQR: 0.42-0.43) and 0.128 (IQR: 0.12-0.13), respectively. The mosaic AGG motif was not associated with repeat number (estimate = -3.8342, P = 0.869). The mosaic pure tract frequency was associated with repeat number (estimate = 45.32, P = 0.0441) but not AAO (estimate = -41.486, P = 0.378). Importantly, the mosaic frequency of the AGGG negatively correlated with repeat number after adjusting for age at sampling (estimate = -161.09, P = 3.44 × 10-5). When including the XDP-relevant MSH3/PMS2 modifier single nucleotide polymorphisms into the model, the mosaic AGGG frequency was associated with AAO (estimate = 155.1063, P = 0.047); however, the association dissipated after including the repeat number (estimate = -92.46430, P = 0.079). We reveal novel mosaic divergent repeat interruptions affecting both motif length and sequence (DRILS) of the canonical motif polarized within the SINE-VNTR-Alu(AGAGGG)n repeat. Our study illustrates: (i) the importance of somatic mosaic genotypes; (ii) the biological plausibility of multiple modifiers (both germline and somatic) that can have additive effects on repeat instability; and (iii) that these variations may remain undetected without assessment of single molecules.


Asunto(s)
Trastornos Distónicos , Enfermedades Genéticas Ligadas al Cromosoma X , Enfermedades Neurodegenerativas , Humanos , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto , Trastornos Distónicos/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética
17.
Artículo en Inglés | MEDLINE | ID: mdl-36554618

RESUMEN

Due to the real-time acquisition of big data from the Internet, analysis of Google queries is now recognized as a valuable tool to explore and predict human behavior and interests. It was suggested that online data can be correlated with actual health data. Although the data are not structured nor systematic, the huge data from search engines can easily identify trends concerning diseases and other health concepts from a population perspective. Moreover, Internet data with the use of web search advertising nowadays may not only reveal the interest of the general population but also of the healthcare industry as reflected by the bid prices in search terms for medications. We aimed to compare the interests of the general population using monthly search volumes from Google and the healthcare industry using bid prices in web searches. Data used in this study were obtained from the Google Ads Application Programming Interface (API). This study evaluated the population's interest in neurological disorders by using search volumes related to neurology, either disease diagnosis or medications. Bid values generated in API were used as a proxy for the interests of the healthcare industry. Spearman's rank-order correlation was performed between search volumes and bid prices to determine significance. Among the neurologic diseases listed, the most searched were attention deficit hyperactivity disorder, migraine, and Alzheimer's disease. The most commonly searched drugs were oral antihypertensives (amlodipine, losartan, carvedilol), lipid-lowering agents (atorvastatin, simvastatin, rosuvastatin), and antiplatelets (acetylsalicylic acid, clopidogrel). The other most searched drugs were analgesics such as acetaminophen, tramadol, diclofenac, and morphine. The correlational analysis did not reveal a statistically significant correlation between search volume and bid price for both neurologic diseases and medications. Web searches may reflect the interest of the general population and the healthcare industry. However, there was disagreement in the search interests of the general population and the scientific community, including the pharmaceutical industry. Further studies are necessary in order to align these interests for the common benefit of all stakeholders.


Asunto(s)
Enfermedades del Sistema Nervioso , Humanos , Filipinas/epidemiología , Motor de Búsqueda , Internet
18.
Artículo en Inglés | MEDLINE | ID: mdl-36497702

RESUMEN

Philippine research productivity in neurology has not been fully characterized. We investigated the research output of adult and child neurologists in the Philippines and correlated this to the Philippine socioeconomic and healthcare indices among different regions. We used electronic databases to retrieve studies published by Filipino neurologists using the 2022 Philippine Neurological Association website as reference. We included all studies published until December 2021. Official government region-specific socioeconomic indices were used. Correlational analysis was completed on bibliometric indices and collected data. We retrieved 746 articles from 274 of 526 Filipino neurologists which were published in 245 publications over 45 years with 12,409 citations. The National Capital Region (NCR) had the most publications (n = 662, 88.7%) and citations (n = 10,377, 83.6%). Research productivity was positively correlated with population, gross domestic product (GDP), health expenditure, number of healthcare establishments, neurologists, and research personnel. The Philippine research landscape is dominated by articles of neurologists belonging to institutions in the NCR, which has the greatest number of neurologists, training institutions, and highest GDP. There is a need to address the disparity seen in other regions to bridge gaps in healthcare, health human resources, and health information through research.


Asunto(s)
Investigación Biomédica , Humanos , Bibliometría , Costo de Enfermedad , Atención a la Salud , Eficiencia
19.
J Stroke Cerebrovasc Dis ; 31(11): 106776, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36113391

RESUMEN

BACKGROUND: While most large studies on the possible association of COVID-19 and stroke were done in high-income countries, only a few studies consisting of small sample populations have been done in low- to middle-income countries like the Philippines. OBJECTIVES: To determine the risk factors of stroke among hospitalized COVID19 patients in the Philippines; to determine the possible association between these risk factors and stroke among the same cohort; and to determine if there is an association between mortality and stroke in this same group. METHODOLOGY: We obtained relevant clinical and neurological, including stroke data from the Philippine CORONA study, an observational study involving 10,881 patients with COVID-19 admitted in 37 referral hospitals from all over the Philippines. RESULTS: The incidence of stroke among patients with COVID-19 was 3.4% (n = 367). There were more deaths among patients with stroke and COVID-19 than those without stroke and COVID-19 (42.2% vs 14.7%, p < 0.01). In addition, more patients with stroke were admitted in the ICU (43.3% vs 15.0%, p < 0.01) regardless of cause. Smoking (OR: 1.5, 95% CI: 1.3 to 1.7, p < 0.0001), hypertension (OR:1.75, 95% CI:1.53 to 1.97, p < 0.0001), presence of heart failure (OR: 1.4, 95% CI: 1.07 to 1.86, p = 0.01), presence of any neurologic co-morbidities (OR: 1.4, 95% CI:1.11 to 1.46, p = 0.004), and history of stroke (OR:2.3, 95% CI:1.82 to 2.97, p < 0.0001) had direct significant correlation with stroke; while being a health care worker (OR: 0.5, 95% CI: 0.33 to 0.70, p < 0.0004) had an inverse significant association with stroke. CONCLUSION: COVID-19 stroke patients in the Philippines have a higher mortality and ICU admission rates than patients with COVID-19 alone or COVID-19 stroke patients from developed countries. Our cohort has similar cardiovascular and metabolic risk factors to western patients with stroke, highlighting that COVID-19 may only have a small contribution to stroke incidence.


Asunto(s)
COVID-19 , Accidente Cerebrovascular , Humanos , Incidencia , Filipinas/epidemiología , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/complicaciones , Factores de Riesgo , Estudios Retrospectivos
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