Modified ICH score was superior to original ICH score for assessment of 30-day mortality and good outcome of non-traumatic intracerebral hemorrhage.

INTRODUCTION: Intracerebral hemorrhage (ICH) score has been widely used as a consistent and reliable clinical grading scale for predicting mortality. However, ICH score had not been used to predict good outcome or significant disability for those who were alive. We intended to address whether any modifications would increase prediction accuracy for mortality as well as the extent of morbidity for those who survived. METHODS: We conducted a retrospective cohort study, involving all non-traumatic ICH patients admitted to our hospital between September 2018 and July 2020. All non-traumatic ICH patients who were admitted to the stroke unit and registered in our stroke database had their medical records, neuroimaging, and laboratory test results reviewed. Only patients with complete medical records and available CT imaging and laboratory test results were included in our study. Independent predictors of mortality (modified Rankin scale/mRS of 6) or good outcome vs. significant disability (mRS≤2 vs. mRS 3-5, respectively) were identified by logistic regression. A modified ICH (mICH) score was compared with the original ICH (oICH) score for its diagnostic performance (DP). Overall DPs were graded and ranked according to Youden Index (YI). RESULTS: As many as 311 patients were eligible with both 39.9% rate of 30-day mortality and good outcome. Factors independently associated with mortality were low GCS and high NIHSS on admission (P = 0.002, <0.001, respectively), and presence of respiratory failure (P < 0.001). Independent factors for good outcome were low NIHSS on admission and mass effect (midline shift > 5 mm) [both P < 0.001]. A modification of ICH score from the original was made by substituting GCS with NIHSS (0 -10 = 1; 11 - 20 = 2; >20 = 3), changing age cut-off point to > 55 years old (= 1), and adding respiratory failure (= 1), and mass effect (= 1). Overall, mICH scored better over oICH score with respect to sensitivity and had comparable specificity for both 30-day mortality and good outcome (sensitivity 80.6% vs. 50.8%; specificity 88.7% vs. 89.3%; YI 0.69 vs. 0.40, respectively) and good outcome (sensitivity 86.3% vs. 77.4%; specificity 74.6% vs. 77.8%; YI of 0.61 vs. 0.55, respectively). There was only one patient with oICH and none on mICH score of 0, who died and none survived with oICH and mICH score of ≥ 5 and ≥ 7, respectively. The proportion of 30-day mortality and good outcome increased in a more linear fashion with mICH score. CONCLUSIONS: The mICH score was proven to be reliable and consistent as a risk grading assessment for non-traumatic ICH patients. The mICH was statistically superior to oICH score in predicting 30-day mortality and good outcome.

Endocannabinoid and dopaminergic system: the pas de deux underlying human motivation and behaviors.

Endocannabinoid system (ECS) has been identified ever since cannabinoid, an active substance of Cannabis, was known to interact with endogenous cannabinoid (endocannabinoid/eCB) receptors. It later turned out that eCB was more intricate than previously thought. It has a pervasive role and exerts a multitude of cellular signaling mechanisms, regulating various physiological neurotransmission pathways in the human brain, including the dopaminergic (DA) system. eCB roles toward DA system were robust, clearly delineated, and reproducible with respect to physiological as well as pathological neurochemical and neurobehavioral manifestations of DA system, particularly those involving the nigrostriatal and mesocorticolimbic pathways. The eCB-DA system regulates the basics in the Maslow's pyramid of hierarchy of needs required for individual survival such as food and sexual activity for reproductive purpose to those of higher needs in the pyramid, including self-actualization behaviors leading to achievement and reward (e.g., academic- and/or work-related performance and achievements). It is, thus, interesting to specifically discuss the eCB-DA system, not only on the molecular level, but also its tremendous potential to be developed as a future therapeutic strategy for various neuropsychiatric problems, including obesity, drug addiction and withdrawal, pathological hypersexuality, or low motivation behaviors.

Neurocysticercosis presented as a solitary cystic parenchymal lesion mimicking primary brain tumor: A case report.

INTRODUCTION: Neurocysticercosis (NCC) is an infection of the central nervous system by the larval stage of pork tapeworm (Taenia solium/T. solium). Diagnosing NCC can be challenging, particularly among those who reside in areas with rare occurrence of NCC and atypical manifestation such as a solitary parenchymal lesion. We treated a patient whose initially was diagnosed with brain abcess and later, brain tumor, only finally revealed to be an NCC case. CASE REPORT: A 25-year old male suffered from multiple focal-to-bilateral tonic clonic seizures, was initially diagnosed as brain abscess. He was given antibiotics and anti-seizure medication but the seizure relapsed with a typical semiology. Physical examination demonstrated grade I papilledema, grade 4+ hemiparesis, and headache of vascular origin. Patient was suspected to have oligodendroglioma after underwent head MRI examination and subsequent tumor resection was performed. Pathological anatomy evaluation demonstrated multiple cystic segments containing larva of tapeworm, supporting a diagnosis of active NCC infection. After 14-day course of antheminthic treatment and resumed AED, patient was seizure-free and NCC was not found upon follow-up CT scan. CONCLUSION: NCC, with respect to clinical and radiological manifestations, can be protean. A high index of suspicion towards NCC should always be maintained, particularly among patients originated from endemic area. Appropriate treatment with anthelminthic may result in full disease resolution, thus precluding unnecessary invasive approach.

Neurocysticercosis cases identified at Sanglah Hospital, Bali, Indonesia from 2014 to 2018.

Neurocysticercosis (NCC) was first reported in the province of Bali, Indonesia in 1975. Since this time, sporadic cases have been reported annually. This study reports information on 29 NCC cases (20 males and 9 females) admitted to a referral hospital in Denpasar, Bali from 2014 until 2018. Twenty-four cases were from Bali, 2 were from the province of East Nusa Tenggara, and 3 were from the Democratic Republic of Timor-Leste. Mean patient age was 37.2 years and 69.0% (20/29) were male. Epileptic seizures were the most common clinical manifestation (65.5%, 19/29). Serology (ELISA) was used in 14 cases (48.2%, 14/29), but only 6 cases, including one case with an inactive calcified lesion, were positive (42.9%, 6/14). Two cases underwent surgical resection after their lesions were initially misdiagnosed as brain tumors. These hospital-based findings are discussed along with the present status of NCC in Bali.

Alzheimer's Disease: Lessons Learned from Amyloidocentric Clinical Trials.

Alzheimer's disease (AD) is one of the most debilitating neurodegenerative diseases and is predicted to affect 1 in 85 people by 2050. Despite much effort to discover a therapeutic strategy to prevent progression or to cure AD, to date no effective disease-modifying agent is available that can prevent, halt, or reverse the cognitive and functional decline of patients with AD. Several underlying etiologies to this failure are proposed. First, accumulating evidence from past trials suggests a preventive as opposed to therapeutic paradigm, and the precise temporal and mechanistic relationship of ß-amyloid (Aß) and tau protein should be elucidated to confirm this hypothesis. Second, we are in urgent need of revised diagnostic criteria to support future trials. Third, various technical and methodological improvements are required, based on the lessons learned from previous failed trials.

Bone marrow-derived stem cells as an adjunctive treatment for acute myocardial infarction: a systematic review and meta-analysis.

AIM: to confirm the beneficial effect of BMCs therapy over placebo in AMI patients with inclusion only to the randomized double blind placebo-controlled trials. METHODS: we searched multiple database (MEDLINE, CENTRAL, CINAHL) through January 2011 for randomized, double-blind, placebo-controlled trials evaluating the efficacy and safety of BMCs for the treatment of AMI. We subsequently performed a random-effect meta-analysis to assess the eligible studies included related to the primary outcomes (mean LVEF, LVESV, and LVEDV changes from baseline) and secondary outcomes (all-cause mortality, recurrent MI, rehospitalization for HF). RESULTS: ten RCTs (total=906 patients) were included. BMCs therapy was proven superior to placebo regarding mean LVEF change (2.07%; 95% CI, 0.55% to 3.59%; [I2=57%; p=0.008]), LVESV (5.52 mL; 95% CI, -7.68 mL to -3.36 mL; [I2=16%; p<0.00001]), and LVEDV (3.08 mL; 95% CI, -5.57 mL to -0.58 mL; [I2=23%, p=0.02]) from baseline. BMCs therapy showed no difference with regards to mortality events when compared to placebo (OR 1.01; 95% CI, 0.35 to 2.94; [I2=0%; p=0.98]), but exerts protective effects toward recurrent MI (OR 0.45; 95% CI, 0.09 to 2.16; [I2=8%; p=0.32]) and rehospitalization for HF (OR 0.39; 95% CI, 0.08 to 1.85; [I2=0%; p=0.24]). All outcomes were sustained for a long period of time (up to 5 years). CONCLUSION: the resulting meta-analysis concluded that BMCs therapy consistently improves cardiac performance parameters (LVEF, LVESV, and LVEDV) when compared to placebo, even after the establishment of primary intervention. It is also safe to use and prevents the development of recurrent MI and HF.

The prospect of induced pluripotent stem cells for diabetes mellitus treatment.

A continuous search for a permanent cure for diabetes mellitus is underway with several remarkable discoveries over the past few decades. One of these is the potential of pancreatic stem/progenitor cells to rejuvenate functional ß cells. However, the existence of these cell populations is still obscure and a lack of phenotype characterization hampers their use in clinical settings. Cellular reprogramming through induced pluripotent stem (iPS) cell technology can become an alternative strategy to generate insulin-producing cells in a relatively safe (autologous-derived cells, thus devoid of rejection risk) and efficient way (high cellular proliferation) but retain a precise morphological and genetic composition, similar to that of the native ß cells. iPS cell technology is a technique of transducing any cell types with key transcription factors to yield embryonic-like stem cells with high clonogenicity and is able to give rise into all cell lineages from three germ layers (endoderm, ectoderm, and mesoderm). This approach can generate ß-like pancreatic cells that are fully functional as proven by either in vitro or in vivo studies. This novel proof-of-concept stem cell technology brings new expectations on applying stem cell therapy for diabetes mellitus in clinical settings.

Clinical applications of stem cell therapy for regenerating the heart.

An immediate reperfusion therapy after acute myocardial infarction (AMI) is a prerequisite to prevent further cardiac damage and minimize ventricular remodelling. Although a rigorous and sophisticated set of therapeutic procedure has been applied in the disease management, mortality rate has yet unchanged during the last twenty years. This fact necessitates an alternative or adjuvant therapy that is critically safe and capable of repairing the injured vascular as well as regenerating the infarcted myocardium without omitting the ethical considerations. Stem cell therapy could be the answer. It has gained major basic and clinical research interest, ever since its discovered potential to repair the injured vascular in 1997. Multiple cell types across lineages have been shown to be able to transdifferentiate into mature functioning cardiomyocytes either in vitro through similar phenotypical and genotypical characteristics or in vivo by regenerating the infarcted myocardium and improve contractile function. Although the exact repairing mechanisms are still in a major debate, numerous clinical trials have demonstrated favorable effects toward the use of autologous stem cells in AMI patients with considerably low side effects. Despite the relatively novel discovery, stem cell therapy offers a promising prospect to confer a better protection, prevent later complications, and perhaps reduce the mortality among patients with ischemic heart disease. This ultimate outcome would likely be achieved through a stringent and coordinated of either basic and clinical research.

The therapeutic potential of RNA interference in controlling HIV-1 replication.

Human immunodeficiency virus type 1 (HIV-1) has long been a major problem to handle. Its existence is incurable (yet) and has reached pandemic proportions despite strictly-controlled epidemiological surveillance. The current treatment regimen involves the use of multiple antiretroviral agents (known as HAART) is very complex and may harm patients through its serious risk of toxicities. Moreover, the continuing emergence of drug resistance further threaten the future therapy, thereby necessitates another treatment strategy i.e. specific and efficient with low or minimal toxicity. RNAi is a potent candidate for the future treatment of HIV-1. It involves an immune-based silencing mechanism (post transcriptional gene silencing/PTGS) that uses small sequence of RNA (21-25 nucleotides in length) to inhibit almost every genes expression, including HIV-1 RNA and its mRNA byproducts. Since RNAi uses sequence of base pairs, it can be designed very specific and homologues to silence the genes in favor. RNAi works either through binding with HIV-1 to inhibit provirus integration into cellular genome or with mRNA products to inhibit certain genes expression (e.g. p24/Gag, Vif, Rev) that plays an important role in HIV-1 infectivity to knockdown its virulence capacity. Given the need for a treatment modality that are sequence-specific and able to overcome the highly mutation rate of virus like HIV-1, also by its enormous power to inhibit HIV-1 expression through various target sites, it is considered essential to discuss the molecular mechanism of RNAi, progresses that have been achieved, and future directions for its use in clinical settings.