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.

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.

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.

Characteristic and management motor neuron disease in the largest tertiary hospital in the Philippines: A one-year period cross sectional analytic study.

BACKGROUND: Motor neuron disease (MND) is largely understudied in many underdeveloped and developing countries, including the Philippines. The practice and management of MND is generally insufficient, and thus, the quality of life of these patients are consequently compromised. OBJECTIVES: The aim of this study is to determine the clinical profile and describe the management of MND patients seen in the largest tertiary hospital in the Philippines for one year. METHODS: This is a cross-sectional study of MND patients diagnosed clinically and via electromyogram-nerve conduction study (EMG NCS) in the Philippine General Hospital (PGH) from January to December 2022. Clinical characteristics, diagnostics and management information were obtained and summarized. RESULTS: The incidence of MND in our neurophysiology unit was 4.3% (28/648), with amyotrophic lateral sclerosis (ALS) being the most common variant (67.9%, n = 19). Male to Female ratio was 1:1, with the median age of onset of 55 (36-72) years old and median onset duration to diagnosis of 1.5 (0.25-8) years. Limb onset was more prevalent (82.14%, n = 23) with upper limbs initially involved (79.1%, n = 18). Split hand syndrome was found in almost half (53.6%) of the patients. The median ALS functional rating score-revised (ALSFRS-R) and medical research council (MRC) scores were 34 (8-47) and 42(16-60) respectively while the median King's clinical stage was 3 (1-4). Only half of the patients were able to undergo magnetic resonance imaging (MRI) and only one had neuromuscular ultrasound. Only one of the 28 patients was able to take riluzole, and only one was on oxygen support. None had gastrostomy and none used non-invasive ventilation. CONCLUSION: This study showed that the management of MND in the Philippines is largely inadequate and further improvement in the health care system in handling rare neurologic cases must be implemented to enhance their quality of life.

Neuromuscular Ultrasound Findings of Myokymia in a Young Woman With Generalized Anti-LGI-1 and Anti-Caspr2 Antibodies Negative Isaac Syndrome.

ABSTRACT: Isaac syndrome is one of the rare peripheral nerve hyperexcitability (PNH) syndromes, which manifests with gross fasciculations, muscle undulation, twitching, and cramps, with or without autonomic and sensory symptoms. The diagnosis relies on characteristic electromyogram findings and the presence of anti-leucine-rich glial inactivated 1 and anti-contactin-associated protein 2 antibodies in the serum. Here, we report the case of a 21-year-old woman, who presented with extremities and tongue myokymia whose electromyogram findings were compatible with PNH, albeit seronegative for antibodies. Neuromuscular ultrasound was performed showing high-frequency rotatory, to-and-fro, high-amplitude movement of superficial and deep muscle fascicles, more prominent in the proximal than distal muscles. Neuromuscular ultrasound may be a useful adjunct in the diagnosis of PNH.

Chronic Myopathy as the Initial Manifestation of Thyrotoxicosis: A Report of 2 Cases.

INTRODUCTION: Rarely, hyperthyroidism will initially present with chronic myopathy characterized by progressive and sometimes fluctuating proximal muscle weakness, along with elevated creatine kinase and myopathic pattern in the electromyogram, mimicking other muscle and neuromuscular junction disorders with poorer prognosis. CASES: Here, we present 2 young patients who complained of 1-4 months duration of chronic proximal muscle lower extremity weakness, supported by elevated creatine kinase and myopathic pattern in electromyogram, who later found to have markedly low thyroid-stimulating hormone, high free T3 and free T4, enlarged thyroid gland on ultrasound, and elevated anti-thyroid-stimulating hormone receptor antibody, characteristic of Grave disease. CONCLUSIONS: Although rare, thyrotoxicosis should always be ruled out in a patient with chronic myopathy because this has better prognosis than other primary muscle conditions presenting similarly.

Facial Diplegia as the Sole Manifestation of Post-Vaccination Guillain-Barre Syndrome: A Case Report and Literature Review.

Introduction: Recently, a large study concluded that certain brands of vaccines may increase the risk of Bell's palsy and Guillain Barre Syndrome (GBS). As to whether vaccination after COVID-19 modify the risk of Bell's palsy or GBS has not yet been studied. Case: Here we report a 35 years old COVID-19 survivor whom in less than 2 weeks after his second dose of inactivated SARS-CoV2 vaccine, developed bilateral facial nerve paralysis. In addition, he had hyperacusis, dysgeusia and decreased lacrimation without any signs of sensory and motor deficits in the limbs. His limb nerve conduction study (NCS) was unremarkable in contrast to bilaterally abnormal facial NCS and blink reflexes. Although he had negative anti-GM1 IgG and IgM antibodies, he has marked albuminocytologic dissociation, classic of acute inflammatory demyelinating polyneuropathy. Conclusion: To date, there were no similar case reports which published the occurrence of facial diplegia as sole manifestation of GBS in a post COVID-19 patient who recently completed vaccination. We believe that molecular mimicry, induced by magnified immune response from both COVID-19 and vaccination may have caused the symptom.

Neuroleptic Malignant Syndrome in a Patient With Anti-N-Methyl-D-Aspartate Receptor Encephalitis: Case Report and Review of Related Literature.

INTRODUCTION: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe but treatable disease that presents with symptoms similar to neuroleptic malignant syndrome (NMS). CASE REPORT: We describe a 28-year old female who initially presented with headaches, behavioral changes, anxiety, lip tremors, and rigidity of extremities. She was prescribed with olanzapine and later manifested with neuroleptic malignant syndrome symptoms such as decrease in sensorium, muscle rigidity, hyperthermia and tachycardia. Further investigation showed presence of bilateral ovarian teratoma and anti-NMDAR antibodies in her serum and cerebrospinal fluid. Symptoms resolved after intravenous high-dose methylprednisolone, bilateral oophoro-cystectomy, and intravenous immunoglobulin administration. Overlapping pathological mechanisms of anti- NMDAR encephalitis and NMS were discussed. Ten patients with anti- NMDAR encephalitis and NMS were noted in a review of literature. Prognosis was favorable and intervention ranged from supportive to methylprednisolone and intravenous immunoglobulin administration, plasma exchange and teratoma resection. CONCLUSION: Anti- NMDAR encephalitis patients are at risk for NMS due to antipsychotic intolerance and other interrelated pathophysiological mechanisms. The overlap between the signs and symptoms of anti-NMDAR encephalitis and NMS poses a diagnostic dilemma and warrants a careful investigation and management.

Corticobasal syndrome etiologies in a young Filipino patient: A case report and literature review.

While corticobasal syndrome (CBS) has long been associated with corticobasal degeneration (CBD), only 24-57% of CBS patients will have the classic histopathologic findings of CBD postmortem. Here, we present a 28-year-old male who had a 3-year history of progressive right sided predominant, atypical parkinsonism, limb dystonia, stimulus sensitive myoclonus, apraxia, aphasia, alien limb phenomenon, and cognitive impairment, typical of CBS, who, based on Armstrong criteria will qualify as possible CBD. In conclusion, among young patients presenting with CBS, tauopathies are still the most common causes, but inherited metabolic and white matter diseases as well as other non-tau associated neurodegenerative conditions should also be ruled out. Nevertheless, since most of these are diagnosed histopathologically, accurate and complete clinical findings, in addition to extensive metabolic work ups, imaging and genetic tests may be needed to clinch the cause of this syndrome.

Choriocarcinoma Presenting as Recurrent Intracranial Hemorrhage in an Adolescent Patient.

BACKGROUND: Due to its highly metastatic and invasive nature, choriocarcinoma may affect other organ systems and mimic conditions not typical of gynecologic cancers. Recurrent intracranial hemorrhage secondary to rupture of multiple oncotic aneurysms is one of its rare initial presentations. CASE: We report a 2-month postpartum, 16-year old girl who initially presented with sudden-onset left-sided weakness. Her plain cranial computed tomography scan showed a 16-mL hematoma in the right parietal area, and her 4-vessel angiogram (4VA) disclosed 4 saccular aneurysms in bilateral distal middle cerebral arteries (MCA). The ß-human chorionic gonadotrophin (ß-hCG) done 2 weeks later was 356,684.5 mIU, and her transvaginal ultrasound showed an ill-defined heterogenous myometrial mass measuring 1.6 × 1.3 × 1.2 cm. Due to the multiplicity of aneurysms and the patient's young age, surgical excision and brain irradiation were deferred. Nonetheless, she received chemotherapy with a regimen of etoposide, methotrexate, actinomycin-D, cyclophosphamide, and vincristine/oncovin. SUMMARY AND CONCLUSION: Early consideration of oncotic aneurysm secondary to choriocarcinoma in a postpartum presenting with multiple intracranial hemorrhages may lead to earlier administration of proper chemotherapy and, in turn, to a better prognosis. Age and the number of aneurysms should be considered in choosing the appropriate therapy.

Anti-GM1 IgM antibody positive axonal variant of Guillain-Barre-syndrome in a pediatric patient with dengue fever.

INTRODUCTION: While children of all ages may be affected by Guillain-Barre-Syndrome (GBS), there are no reports of Dengue Fever (DF) as the preceding or concurrent infection in this age group. In addition, the presence of anti-GM1 IgM antibody, commonly seen in Multifocal Motor Neuropathy, is rarely encountered in both axonal and demyelinating variants of GBS. Moreover, only few neuromuscular ultrasound findings of the axonal variant in children were reported in the literature. CASE: Here we present a nine-year-old female who developed the classic signs, symptoms and neurophysiologic findings of axonal type of GBS during DF. She had elevated anti-GM1 IgM antibody atypical of this variant and diffusely enlarged nerves via neuromuscular ultrasound. CONCLUSION: In a pediatric patient with DF and acute flaccid paralysis, GBS should always be one of the considerations. Although rare, anti-ganglioside GM1 IgM antibody can still be found in axonal variant of GBS.

Autoimmune encephalitis associated with two antibodies.

•In patients presenting with clinical manifestations of encephalitis without clinical or laboratory signs of infection, an autoimmune etiology should be suspected.•Antibodies for various neural antigens may coexist, thus a complete and clinically-guided autoimmune panel must be done in suspected cases of autoimmune encephalitis.•Tumor resection, if applicable, combined with high dose steroids and immunotherapy are effective treatment strategies for autoimmune encephalitis with coexisting antibodies.