Clinical profile and outcomes of tetanus patients in a tertiary hospital in the Philippines: a ten-year retrospective study.

BACKGROUND: Tetanus is a life-threatening but preventable neurologic disorder characterized by trismus and muscle spasms. Despite its decreasing global incidence, it remains to be endemic in resource-limited settings such as the Philippines. This study aimed to determine the incidence, demographic characteristics, risk factors, clinical presentation, management, complications, and outcomes of non-neonatal tetanus cases in a tertiary hospital in the Philippines. It also aimed to compare the clinical profile and outcomes between the adult and pediatric subgroups. METHODS: This study used a retrospective cross-sectional design including all adult and pediatric non-neonatal tetanus patients admitted at the University of the Philippines - Philippine General Hospital from January 2012 to June 2023. Data was extracted from department censuses and inpatient charts. RESULTS: One hundred thirty-eight cases were included. The incidence rate was 0.03%, while mortality rate was 29%. Majority of patients were males presenting with trismus and spasms after sustaining a puncture wound. Chronic hypertension was associated with an increased hazard of death by 4.5 times (p = 0.004), while treatment with magnesium sulfate was associated with a decreased hazard of death by 35 times (p = 0.005). The mode of infection and the medications administered differed between the adult and pediatric subgroups. CONCLUSIONS: Although the total number of cases has decreased over the past decade, tetanus remains to have a high incidence and mortality rate in the Philippines. Increasing vaccination coverage, improving public awareness, and educating health professionals can help reduce morbidity and mortality from this disease.

Subchronic Graphene Exposure Reshapes Skin Cell Metabolism.

In recent years, the toxicity of graphene-related materials (GRMs) has been evaluated in diverse models to guarantee their safety. In most applications, sublethal doses of GRMs contact human barriers such as skin in a subchronic way. Herein, the subchronic effect (30 day exposure) of three GRMs (GO 1, GO 2, and FLG) with different oxidation degrees and sizes was studied. The effects of these materials on human skin cells, HaCaTs, were assayed through high-throughput metabolic-based readout and other cell-based assays. A differential effect was found between the different GRMs. GO 2 induced a metabolic remodeling in epithelial cells, increasing the level of tricarboxylic acid components, mirrored by increased cell proliferation and changes in cell phenotype. The oxidation degree, size, and method of manufacture of GRMs dictated harmful effects on cell metabolism and behavior generated by nontoxic exposures. Therefore, a "safe by design" procedure is necessary when working with these nanomaterials.

Relationship between motor cortical and peripheral axonal hyperexcitability in amyotrophic lateral sclerosis.

BACKGROUND: Previous studies have shown that patients with amyotrophic lateral sclerosis (ALS) have hyperexcitability in both the motor cortex and peripheral motor axons, but the relationship between central and peripheral excitability has not been fully disclosed. METHODS: Threshold tracking transcranial magnetic stimulation (TMS) and motor nerve excitability testing were prospectively performed in 53 patients with ALS and 50 healthy subjects, and their relations to compound muscle action potential (CMAP) amplitude and revised ALS Functional Rating Scale were cross-sectionally analysed. RESULTS: Compared with controls, patients with ALS showed both cortical and peripheral hyperexcitability; TMS showed reduced short-interval intracortical inhibition (interstimulus interval 1-7 ms) (p<0.001) and shortened silent period (p<0.05), and median nerve excitability testing revealed greater changes in depolarising threshold electrotonus (TEd) and greater superexcitability (p<0.0001, both), suggesting reduced axonal potassium currents. Significant correlations between cortical and peripheral excitability indices were not found. Greater changes in TEd (90-100 ms) (R=-0.33, p=0.03) and superexcitability (R=0.36, p=0.01) were associated with smaller amplitude of CMAP, whereas cortical excitability indices had no correlation with CMAP amplitude. More rapid motor functional decline was associated with only greater TEd (90-100 ms) (ß=0.46, p=0.001). CONCLUSIONS: Our results suggest that in ALS, cortical excitability is continuously high regardless of the extent of the peripheral burden, but peripheral hyperexcitability is associated with the extent of the peripheral burden and disease evolution speed. Alterations of ion channel function may play an important role in ALS pathophysiology.

Different patterns of sensory nerve involvement in chronic inflammatory demyelinating polyneuropathy subtypes.

INTRODUCTION/AIMS: Among subtypes of chronic inflammatory demyelinating polyneuropathy (CIDP), different immune pathophysiologies have been proposed. In this study, sensory nerve conduction studies were compared among clinical subtypes to attempt to better understand the underlying pathophysiology. METHODS: A total of 138 patients with CIDP was classified into clinical subtypes: typical CIDP (N = 68), multifocal CIDP (N = 27), or other (N = 2). Patients with immunoglobulin M (IgM) neuropathy anti-myelin-associated glycoprotein neuropathy (MAG; N = 19) were also included as disease controls. Sensory nerve action potentials (SNAPs) were recorded in the median, ulnar, and superficial radial and sural nerves. RESULTS: SNAP amplitudes (P < .05) and conduction velocities (P < .01) in the median nerve and conduction velocities (P < .05) in the ulnar nerve were lower in typical CIDP than in multifocal CIDP, whereas those in the radial and sural nerves were comparable in each group. Low median and normal sural SNAP amplitudes were more common in typical CIDP (P < .005) than in multifocal CIDP, suggesting predominant involvement at terminal portions of the nerves. DISCUSSION: Terminal portions of sensory nerves are preferentially affected in typical CIDP compared with multifocal CIDP. These findings might be partially explained by the hypothesis of antibody-mediated demyelination in typical CIDP at the regions where the blood-nerve barrier is anatomically deficient, whereas multifocal CIDP predominantly affects the nerve trunks, largely due to cell-mediated demyelination, with disruption of the blood-nerve barrier.

Fasciculation intensity and limb dominance in amyotrophic lateral sclerosis: a muscle ultrasonographic study.

BACKGROUND AND PURPOSE: Muscle ultrasonography has been increasingly recognized as a useful tool for detection of fasciculations. Separately, concordance between dominant hand and onset side has been reported in amyotrophic lateral sclerosis (ALS). The aim of this study was to reveal the distribution of fasciculations in the whole body, focusing on handedness. METHODS: In 106 consecutive patients with ALS, muscle ultrasonography was systematically performed in 11 muscles (the tongue, and bilateral biceps brachii, 1st dorsal interosseous [FDI], T10-paraspinalis, vastus lateralis and tibialis anterior muscles). The fasciculation intensity was scored from 0 to 3 for each muscle. RESULTS: Fasciculations were more frequently found in the limb muscles than the tongue and paraspinalis. Side and handedness analyses revealed that fasciculation intensity in FDI was significantly more prominent on the right (median [inter-quartile range] 2 [0 - 3]) than left (1.5 [0 - 3]; p = 0.016), and in the dominant hand (2 [1 - 3]) than non-dominant side (1.5 [0 - 3]; p = 0.025). The differences were greater in patients with upper limb onset. There were no side differences in the lower limb muscles. Multivariate analyses showed that male patients had more frequent fasciculations in the dominant FDI (ß = 0.22, p < 0.05). CONCLUSION: More intensive fasciculations are present in the FDI in the dominant hand and gender might be associated with fasciculation intensities. This distribution pattern of fasciculations might be associated with pathogenesis of ALS.

Perampanel for amyotrophic lateral sclerosis: A systematic review and meta-analysis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease. There is still no established cost-effective treatment that can improve functional status and survival of ALS patients. Perampanel, by inhibiting neuronal calcium ion influx and preventing dyslocalization of nuclear proteins, has the potential to ameliorate ALS neurodegeneration. OBJECTIVES: This study aims to determine the efficacy and safety of perampanel among ALS patients in terms of improvement in functional status using a review of relevant studies. METHODS: MedLine, Cochrane Central Register for Controlled Trials, Scopus, Embase, Literatura Latino-Americana e do Caribe em Ciências da Saúde, ClinicalTrials.gov website, and HERDIN databases were searched from inception to August 2021 for relevant studies. RESULTS: The search yielded 132 articles; 3 studies were included in the analysis. Pooled evidence shows that perampanel compared to placebo significantly improves cortical motor hyperexcitability but not the ALS functional rating scale-revised score. Perampanel is associated with adverse events such as aggression, somnolence, anger, and dysarthria. CONCLUSION: There is no sufficient evidence to support the role of perampanel in improving functional status of ALS patients. Although it can ameliorate motor cortical hyperexcitability, its clinical benefit has not yet been elucidated. Perampanel is not well tolerated among ALS patients as it is associated with adverse events such as aggression, somnolence, anger, and dysarthria. Further studies investigating the role of perampanel early in the ALS disease course, excluding ALS patients with frontotemporal lobe degeneration features and C9ORF72 repeat expansion, and using gradual drug titration schedule are needed to evaluate the potential benefit of perampanel in ALS.

Incidence and risk factors for stroke in patients with COVID-19 in the Philippines: An analysis of 10,881 cases.

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.

Acetylcholinesterase inhibitor responsive myasthenia in a Filipino male with X-linked recessive spinal and bulbar muscular atrophy.

We report a 51-year-old male diagnosed with X-linked recessive spinal and bulbar muscular atrophy (SBMA) by genetic testing who presented with 30 years history of progressive proximal and bulbar weakness responsive to cholinesterase inhibitor. Although the anti-acetylcholine receptor antibody (anti-AChR Ab) was negative, the myasthenic state was confirmed by decremental response in repetitive nerve stimulation and increased jitter frequency and blocking in single fiber-electromyography. While myasthenia gravis and SBMA may co-exist independently in an individual having the signs and symptoms of both conditions, the absence of anti-AChR Ab may imply that myasthenia can be an exaggerated activity-induced fatigue or weakness from the latter.

Acetylcholinesterase Inhibitors in Myasthenic Crisis: A Systematic Review of Observational Studies.

Current myasthenia gravis guidelines recommend intravenous immunoglobulin or plasmapheresis and discontinuation of pyridostigmine during myasthenic crisis. However, intravenous immunoglobulin or plasmapheresis is expensive and frequently not available in developing countries. This study aims to summarize the evidence of giving an acetylcholinesterase inhibitor in myasthenic crisis. Medline, Embase, and Cochrane databases and references were searched for observational studies that determined the use of acetylcholinesterase inhibitor in myasthenic crisis. The eligibility criteria were as follows: population, patients with myasthenic crisis, intervention (acetylcholinesterase inhibitor administration), and outcome (clinical improvement and complications). In total, 106 studies were identified, 92 through database searching (after removing duplicates) and 14 through other sources. Only eight were analyzed in the present systematic review. In five, acetylcholinesterase inhibitor was given at the start of the crisis, whereas in the other three, acetylcholinesterase inhibitor was discontinued initially and then restarted prior to extubation. Two observational analytic studies and three case reports showed improvement in different outcome measures. In the other three, improvement of outcome measures was also observed. Overall, a small proportion of patients developed cardiac arrhythmia and pneumonia after administration of acetylcholinesterase inhibitor alone, although this was not statistically different compared with those subjected to plasmapheresis. In summary, continuous intravenous infusion of pyridostigmine or neostigmine can be a substitute for intravenous immunoglobulin or plasmapheresis if these are not available during crisis; however, caution should be observed because of the aforementioned possible complications.

A comprehensive systematic review of CSF proteins and peptides that define Alzheimer's disease.

BACKGROUND: During the last two decades, over 100 proteomics studies have identified a variety of potential biomarkers in CSF of Alzheimer's (AD) patients. Although several reviews have proposed specific biomarkers, to date, the statistical relevance of these proteins has not been investigated and no peptidomic analyses have been generated on the basis of specific up- or down- regulation. Herein, we perform an analysis of all unbiased explorative proteomics studies of CSF biomarkers in AD to critically evaluate whether proteins and peptides identified in each study are consistent in distribution; direction change; and significance, which would strengthen their potential use in studies of AD pathology and progression. METHODS: We generated a database containing all CSF proteins whose levels are known to be significantly altered in human AD from 47 independent, validated, proteomics studies. Using this database, which contains 2022 AD and 2562 control human samples, we examined whether each protein is consistently present on the basis of reliable statistical studies; and if so, whether it is over- or under-represented in AD. Additionally, we performed a direct analysis of available mass spectrometric data of these proteins to generate an AD CSF peptide database with 3221 peptides for further analysis. RESULTS: Of the 162 proteins that were identified in 2 or more studies, we investigated their enrichment or depletion in AD CSF. This allowed us to identify 23 proteins which were increased and 50 proteins which were decreased in AD, some of which have never been revealed as consistent AD biomarkers (i.e. SPRC or MUC18). Regarding the analysis of the tryptic peptide database, we identified 87 peptides corresponding to 13 proteins as the most highly consistently altered peptides in AD. Analysis of tryptic peptide fingerprinting revealed specific peptides encoded by CH3L1, VGF, SCG2, PCSK1N, FBLN3 and APOC2 with the highest probability of detection in AD. CONCLUSIONS: Our study reveals a panel of 27 proteins and 21 peptides highly altered in AD with consistent statistical significance; this panel constitutes a potent tool for the classification and diagnosis of AD.

Split hand and motor axonal hyperexcitability in spinal and bulbar muscular atrophy.

OBJECTIVE: The 'split hand' sign refers to preferential wasting of the thenar and first dorsal interosseous muscles with relatively sparing of the hypothenar muscles in amyotrophic lateral sclerosis (ALS) and both cortical and spinal/peripheral excitotoxic mechanisms have been proposed. We aimed to study split hand and axonal excitability in spinal and bulbar muscular atrophy (SBMA) in which cortical motor neurons are intact. METHODS: In 35 patients with genetically confirmed SBMA, 55 with ALS, 158 with other neuromuscular diseases and 90 normal controls; split hand was strictly determined by amplitudes of compound muscle action potentials. Nerve excitability testing of median motor axons was performed in 35 SBMA and 55 patients with ALS and 45 normal controls. RESULTS: Split hand was as frequently found for patients with SBMA (57%) and ALS (62%), compared with disease (20%) and normal (0%) controls. Excitability testing showed that in both SBMA and ALS, strength-duration time constant was longer, and threshold changes in depolarising threshold electrotonus and superexcitability in the recovery cycle were greater than in normal controls (p<0.01). CONCLUSIONS: Split hand is not specific to ALS and can be caused by the peripheral mechanism alone in SBMA, whereas the effect of upper motor neuron lesion cannot be excluded in ALS. Our results also suggest that SBMA and ALS share common axonal excitability changes; increased nodal persistent sodium and reduced potassium currents that may accelerate motor neuronal death and differently affect axons-innervating different muscles. Ion channel modulators could be a therapeutic option for both SBMA and ALS.

Vasoactive Intestinal Peptide Ameliorates Acute Myocarditis and Atherosclerosis by Regulating Inflammatory and Autoimmune Responses.

Vasoactive intestinal peptide (VIP) is a neuropeptide that exerts various vascular and cardioprotective functions and regulates immune function and inflammatory response at multiple levels. However, its role in inflammatory cardiovascular disorders is largely unknown. Myocarditis and atherosclerosis are two inflammatory and autoimmune cardiovascular diseases that cause important adverse circulatory events. In this study, we investigate the therapeutic effects of VIP in various well-established preclinical models of experimental autoimmune myocarditis and atherosclerosis. Intraperitoneal injection of VIP during the effector phase of experimental autoimmune myocarditis in susceptible BALB/c mice significantly reduced its prevalence, ameliorated signs of heart hypertrophy and injury, attenuated myocardial inflammatory infiltration, and avoided subsequent profibrotic cardiac remodeling. This effect was accompanied by a reduction of Th17-driven cardiomyogenic responses in peripheral lymphoid organs and in the levels of myocardial autoantibodies. In contrast, acute and chronic atherosclerosis was induced in apolipoprotein E-deficient mice fed a hyperlipidemic diet and subjected to partial carotid ligation. Systemic VIP treatment reduced the number and size of atherosclerotic plaques in carotid, aorta, and sinus in hypercholesterolemic mice. VIP reduced Th1-driven inflammatory responses and increased regulatory T cells in atherosclerotic arteries and their draining lymph nodes. VIP also regulated cholesterol efflux in macrophages and reduced the formation of foam cells and their presence in atherosclerotic plaques. Finally, VIP inhibited proliferation and migration of smooth muscle cells and neointima formation in a mouse model of complete carotid ligation. These findings encourage further studies aimed to assess whether VIP can be used as a pharmaceutical agent to treat heart inflammation and atherosclerosis.

Sex-dependent co-occurrence of hypoxia and ß-amyloid plaques in hippocampus and entorhinal cortex is reversed by long-term treatment with ubiquinol and ascorbic acid in the 3 × Tg-AD mouse model of Alzheimer's disease.

Structural and functional abnormalities in the cerebral microvasculature have been observed in Alzheimer's disease (AD) patients and animal models. One cause of hypoperfusion is the thickening of the cerebrovascular basement membrane (CVBM) due to increased collagen-IV deposition around capillaries. This study investigated whether these and other alterations in the cerebrovascular system associated with AD can be prevented by long-term dietary supplementation with the antioxidant ubiquinol (Ub) stabilized with Kaneka QH P30 powder containing ascorbic acid (ASC) in a mouse model of advanced AD (3 × Tg-AD mice, 12 months old). Animals were treated from prodromal stages of disease (3 months of age) with standard chow without or with Ub + ASC or ASC-containing vehicle and compared to wild-type (WT) mice. The number of ß-amyloid (Aß) plaques in the hippocampus and entorhinal cortex was higher in female than in male 3 × Tg-AD mice. Extensive regions of hypoxia were characterized by a higher plaque burden in females only. This was abolished by Ub + ASC and, to a lesser extent, by ASC treatment. Irrespective of Aß burden, increased collagen-IV deposition in the CVBM was observed in both male and female 3 × Tg-AD mice relative to WT animals; this was also abrogated in Ub + ASC- and ASC-treated mice. The chronic inflammation in the hippocampus and oxidative stress in peripheral leukocytes of 3 × Tg-AD mice were likewise reversed by antioxidant treatment. These results provide strong evidence that long-term antioxidant treatment can mitigate plasma oxidative stress, amyloid burden, and hypoxia in the AD brain parenchyma.

Cortistatin inhibits migration and proliferation of human vascular smooth muscle cells and decreases neointimal formation on carotid artery ligation.

RATIONALE: Proliferation and migration of smooth muscle cells (SMCs) are key steps for the progression of atherosclerosis and restenosis. Cortistatin is a multifunctional neuropeptide belonging to the somatostatin family that exerts unique functions in the nervous and immune systems. Cortistatin is elevated in plasma of patients experiencing coronary heart disease and attenuates vascular calcification. OBJECTIVE: To investigate the occurrence of vascular cortistatin and its effects on the proliferation and migration of SMCs in vitro and in vivo and to delimitate the receptors and signal transduction pathways governing its actions. METHODS AND RESULTS: SMCs from mouse carotid and human aortic arteries and from human atherosclerotic plaques highly expressed cortistatin. Cortistatin expression positively correlated with the progression of arterial intima hyperplasia. Cortistatin inhibited platelet-derived growth factor-stimulated proliferation of human aortic SMCs via binding to somatostatin receptors (sst2 and sst5) and ghrelin receptor, induction of cAMP and p38-mitogen-activated protein kinase, and inhibition of Akt activity. Moreover, cortistatin impaired lamellipodia formation and migration of human aortic SMCs toward platelet-derived growth factor by inhibiting, in a ghrelin-receptor-dependent manner, Rac1 activation and cytosolic calcium increases. These effects on SMC proliferation and migration correlated with an inhibitory action of cortistatin on the neointimal formation in 2 models of carotid arterial ligation. Endogenous cortistatin seems to play a critical role in regulating SMC function because cortistatin-deficient mice developed higher neointimal hyperplasic lesions than wild-type mice. CONCLUSIONS: Cortistatin emerges as a natural endogenous regulator of SMCs under pathological conditions and an attractive candidate for the pharmacological management of vascular diseases that course with neointimal lesion formation.

Porcine sst1 can physically interact with other somatostatin receptors, and its expression is regulated by metabolic/inflammatory sensors.

The majority of the biological actions attributed to somatostatin (SST) are thought to be mediated by SST receptor 2 (sst2), the most ubiquitous sst, and, to a lesser extent, by sst5. However, a growing body of evidence suggests a relevant role of sst1 in mediating SST actions in (patho)physiological situations (i.e., endometriosis, type 2 diabetes). Moreover, sst1 together with sst2 and sst5 is involved in the well-known actions of SST on pituitary somatotropes in pig and primates. Here, we cloned the porcine sst1 (psst1) and performed a structural and functional characterization using both primary and heterologous models. The psst1 sequence presents the majority of signature motifs shared among G protein-coupled receptors and, specifically, among ssts and exhibits a high homology with other mammalian sst1, with only minor differences in the amino-terminal domain, reinforcing the idea of an early evolutive divergence between mammalian and nonmammalian sst1s. psst1 is functional in terms of decreasing cAMP levels in response to SST when transfected in heterologous models. The psst1 receptor is expressed in several tissues, and analyses of gene cis elements predict regulation by multiple transcription factors and metabolic stimuli. Finally, psst1 is coexpressed with other sst subtypes in various tissues, and in vitro data demonstrate that psst1 can interact with itself forming homodimers and with other ssts forming heterodimers. These data highlight the functional importance of sst1 on the SST-mediated effects and its functional interaction with different ssts, which point out the necessity of exploring the consequences of such interactions.

Utility and Prognostic Value of Intraoperative Blink Reflex in Trigeminal or Facial Nerve Monitoring in Skull Base Surgeries: A Systematic Review.

BACKGROUND: Blink reflex (BR) is an oligosynaptic reflex that involves the ophthalmic branch of the trigeminal nerve (TN), ipsilateral main sensory and trigeminospinal nuclei, bilateral facial nuclei, and the facial nerves (FNs). Theoretically, as BR tests the function of both TN and FNs simultaneously, it is an ideal tool for monitoring the status of TN and FNs during skull base surgeries. Nevertheless, it has been used only recently in surgeries as the use of anesthesia limits its use. METHODS: For this systematic review, 2 authors input the search terms [(Blink Reflex) AND (Intraoperative Neuromonitoring OR Neuro Intraoperative Monitoring OR Intraoperative OR NIOM OR IONM) AND (skull base surgery OR Facial Nerve OR Trigeminal Nerve OR Microvascular Decompression OR Hemifacial Spasm)] in MEDLINE through its PubMed interface and other search engines. Articles that fulfilled the inclusion and exclusion criteria were obtained and scrutinized. RESULTS: Seven observational articles with a total of 437 participants were included. All 5 studies that described the use of BR in FN surgery noted that intraoperative BR is beneficial, safe, sensitive, specific, and predictive of outcomes, while 2 articles describing patients with trigeminal neuralgia recommended use of BR in microvascular decompression of TN. CONCLUSIONS: Intraoperative BR is a sensitive, specific, and safe monitoring technique that has good predictability of facial paresis and paresthesia among patients undergoing MVD for trigeminal neuralgia and primary hemifacial spasm and patients undergoing cerebellopontine angle tumor resection.

Ranking Alpha Lipoic Acid and Gamma Linolenic Acid in Terms of Efficacy and Safety in the Management of Adults With Diabetic Peripheral Neuropathy: A Systematic Review and Network Meta-analysis.

OBJECTIVES: Current medications for diabetic neuropathy (DN) recommended by the American Diabetes Association and American Academy of Neurology do not address the pathologic process of denervation among patients with DN, because ancillary treatments, such as reactive oxygen scavengers, may be needed. The purpose of this work was to summarize the available evidence about the efficacy and safety of alpha lipoic acid (ALA) and gamma linolenic acid (GLA) in the management of DN. METHODS: Using the search terms [(alpha lipoic acid or ALA or thioctic acid or thioctacid) or (gamma linolenic acid or GLA)] AND [(diabetes or diabetes mellitus) AND (polyneuropathy or neuropathy or sensorimotor polyneuropathy or radiculopathy)], 11 studies were included in this review and combined meta-analysis. RESULTS: Eight of the 11 articles (73%) reported significant benefit of ALA vs placebo. In the meta-analysis, the Total Symptom Score (TSS) for ALA 600 mg/day (ALA600) was 1.05 points lower (standard mean difference [SMD] -1.05, 95% confidence interval [CI] -2.07 to -0.04, p=0.04, I2=98.18%) compared with control at the end of the study. In the network meta-analysis, ALA600 (SMD -1.68, 95% CI -2.8 to -0.6) and GLA (SMD -2.39, 95% CI -4.3 to -0.5) had significantly lower TSSs compared with placebo. Moreover, GLA had the highest probability of being the best (52.7%) for improving DN symptoms. In all studies, most adverse events include gastrointestinal disturbances. In terms of tolerability, no differences were detected between ALA and control groups. CONCLUSION: ALA and GLA appear to be safe and efficacious biofactors for improvement of DN symptoms.

Chronological Changes in Transcranial Motor Evoked Potential during Anterior Temporal Lobectomy in Patients with Temporal Lobe Epilepsy: A Single Center Cross-Sectional Analytic Study.

OBJECTIVE: Despite the benefits of anterior temporal lobectomy with amygdalohippocampectomy (ATL+AH) in patients with temporal lobe epilepsy (TLE), approximately up to 5% may have hemiparesis as its postoperative complication. This paper aims to describe which step/s of the ATL with AH have the highest probability of having greatest decrease in MEP amplitude. METHODS: This study utilized a cross-sectional design of obtaining data from TLE patients who underwent ATL+AH with TcMEP monitoring. Each of the following steps were evaluated for reduction in MEP amplitude: 1) Dural Opening, 2) Opening the inferior horn, 2) Vertical temporal lobe resection 3) Subpial dissection, 4) Temporal lobe stem resection, 5) Lateral temporal lobe resection, 6) Hippocampal Resection, 7) Amygdala Resection, 8) Uncus resection and 9) Dural Closure. RESULTS: Nineteen patients were included in the study. Based on Friedman Test, one or more steps had significantly different average MEP amplitude reductions (Friedman=50.7, p=0.0001). When compared to baseline (100%, cut off p=0.005), hippocampal resection (z=-3.81, p<0.0001), T1 subpial dissection (z=-3.2, p=0.0010), uncus resection (z=-3.48, p=0.0002), temporal stem resection (z=-3.26, p=0.001), lateral temporal lobe resection (z=-3.13, p=0.002) and amygdalectomy (-z=-3.37, p=0.0005) were significantly lower. Of these, hippocampal resection, uncus resection and amygdalectomy were deemed highly significant. CONCLUSIONS: MEP amplitude tends to decrease during amygdala, hippocampal and uncal resection because of surgical manipulation of choroidal arteries which can potentially cause hemiparesis so careful attention should be paid to changes in MEP during these steps.

Efficacy and safety of intravenous immunoglobulin retreatment amongst Guillain-Barré syndrome patients who poorly responded to initial IVIG cycle: a systematic review.

INTRODUCTION: Small cross-sectional studies and case reports observed improvement after administration of second IVIG dose (SID) amongst Guillain-Barré Syndrome (GBS) patients not responsive to initial IVIG cycle. Nevertheless, recent clinical trial and larger observational studies did not find any positive effects of SID. Instead, an increased risk of thromboembolism and mortality was noted. The conclusions of these studies however were not robust as confounding and selection bias were present. METHODOLOGY: Two neurologists conducted the search process (KBA and MBP) using the following terms in Medline: [(" Guillain-Barré Syndrome"[MeSH Terms] or GBS or Acute Motor Axonal Neuropathy or Acute Motor Axonal Neuropathy or Acute Inflammatory Demyelinating Polyneuropathy) AND (Poorly Responsive or Poor Prognosis or Progressive)] AND [("Intravenous Immunoglobulin"[MeSH Terms] or IVIG or IGIV) AND (second dose or retreatment or SID)]. RESULTS: Only 7 articles were included in this review. In terms of primary outcomes, although the cross-sectional study found improvement in GBS DS score at 4 weeks (Median GBS DS: 3 vs 5, p = 0.033) and the 2 case series observed improvement after SID, no significant differences between the control and intervention groups were found in the cohort [Early SIV OR: 0.7 (95% CI 0.16-3.04), Late SIV OR: 0.66 (CI: 0.18-2.5)] and clinical trial studies (Adjusted OR: 1.4 (95% CI:0.6-3.3, p = 0.45). Moreover, 4 patients who died in the clinical trial were from the intervention group. CONCLUSION: Based on studies with research designs of higher quality, SID is not effective in the management of GBS patients who poorly responded to initial IVIG. Nevertheless, an adequately powered, randomized, double-blinded, placebo-controlled clinical trial, using GBS-DS of 3 and above after first IVIG dose should be done to effectively establish the efficacy and safety of SID as intervention for this cohort of patients.

Methotrexate in generalized myasthenia gravis: a systematic review.

Current myasthenia gravis guidelines recommend the use of azathioprine as first-line steroid sparing agent. However, due to its high cost, compliance to azathioprine is low in developing countries. To determine the efficacy and safety of the cheaper methotrexate as an alternative immunosuppressant, Medline/Pubmed, Embase and Cochrane databases and references were searched for clinical trials and observational studies using the search terms: "Myasthenia OR Myasthenia Gravis OR anti AchR antibody positive Myasthenia Gravis OR anti-MuSK antibody Myasthenia Gravis OR MG" AND "Methotrexate". Of 78 possible articles, only 4 were selected using the following eligibility criteria: population: generalized MG patients; intervention: methotrexate; and outcome: effectiveness, steroid sparing efficacy and adverse effects. Two clinical trials and one observational study noted improvement in different MG outcomes in patients given methotrexate. While one randomized controlled clinical trial concluded that methotrexate has no steroid sparing benefit, a single blinded clinical trial established that methotrexate was a better steroid sparing agent than azathioprine starting at 10th month of use. Adverse effects were rare with non-specific pain and elevated transaminases as the most common complaints. Based on available evidence, MTX may be a safe and effective alternative to AZA as steroid sparing agent in developing countries.