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.

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 DN patients, 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, 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.

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.

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.

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.

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.

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.

Dual attack: targeting the rare co-occurrence of myasthenia gravis and Graves' disease with radioactive iodine therapy.

SUMMARY: Occasionally, autoimmune disorders can come in twos. This double trouble creates unique challenges. Myasthenia gravis co-existing with autoimmune thyroid disease occurs in only about 0.14-0.2% of cases. The patient is a 27-year-old man with a 2-month history of bilateral ptosis, diplopia, with episodes of easy fatigability, palpitations, and heat intolerance. On physical exam, the patient had an enlarged thyroid gland. Myasthenia gravis was established based on the presence of ptosis with weakness of the intraocular muscles, abnormal fatigability, and a repetitive nerve stimulation study indicated neuromuscular junction disease. Episodes of fluctuating right shoulder weakness were also noted. He was also found to have elevated FT3, FT4, and a suppressed TSH. Thyroid ultrasound revealed thyromegaly with diffused parenchymal disease. Thyroid scintigraphy showed increased uptake function at 72.4% uptake at 24 h. TRAb was positive at 4.1 U/L. Patient was started on pyridostigmine which led to a significant reduction in the frequency of ocular muscle weakness. Methimazole was also initiated. Radioactive iodine at 14.9 mci was instituted for the definitive management of hyperthyroidism. After RAI, there was abatement of the hyperthyroid symptoms, as well as improvement in the status of the myasthenia gravis, with ptosis, diplopia, and right arm weakness hardly occurring thereafter despite the reduction of the pyridostigmine dose based on a symptom diary and medication intake record. Two distinct autoimmune conditions displayed a markedly improved clinical course with the institution of radioactive iodine therapy for Graves' disease. LEARNING POINTS: The presence of ptosis, diplopia, and fluctuating muscle weakness are atypical in Graves' disease and should prompt an investigation on the existence of concurrent myasthenia gravis. A prompt diagnosis of both conditions will enable the institution of appropriate management that would target both rare and challenging autoimmune diseases. Selecting the therapeutic options with minimal risk of morbidity and mortality, which could lead to maximal benefit especially in a resource-limited setting is paramount. Targeted non-surgical management can lead to the remission of two autoimmune diseases which can result in patient satisfaction and improved quality of life.

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

BACKGROUND: Our study aimed to determine the profile of Guillain-Barré syndrome (GBS) in the Philippines, compare the outcomes who received intravenous immunoglobulin (IVIg) and therapeutic plasma exchange (TPE), and determine the factors related to hospital stay and late motor recovery. METHODS: We conducted a retrospective cohort study of adult GBS patients admitted to the Philippine General Hospital from 2009 to 2019. RESULTS: We included 105 patients with confirmed GBS diagnoses. The median age was 43 years (interquartile range 32 to 56); the female-to-male ratio was 1.62:1; the predominant variant was acute inflammatory demyelinating polyneuropathy (n = 40, 38.1%). The difference in outcomes of patients in the IVIg (n = 44) and TPE (n = 24) groups (walking with aid/GBS-disability scores/ventilator dependency at 1 month, duration dependent on the ventilator, intensive care unit stay, and hospital stay) were not statistically significant, except for mild disability at 1 month (p = 0.009). Pneumonia, urinary tract infection, and dysautonomia were significantly related to a prolonged hospital stay. No predetermined variables were associated with late motor recovery. After adjusting for age and sex, the cumulative hazard risk for late motor recovery was 0.69 (95% CI 0.27-1.74). CONCLUSION: Our study presented the first comprehensive information regarding the features and outcomes of GBS patients in the Philippines. ABBREVIATIONS: AIDP - Acute inflammatory demyelinating polyneuropathy; AMAN - Acute motor axonal neuropathy; AMSAN - Acute motor and sensory axonal neuropathy; GBS - Guillain-Barré syndrome; GBS-DS - Guillain-Barré syndrome disability scale; ICU - Intensive care unit; IVIg - Intravenous immunoglobulin; MFS - Miller-Fisher syndrome; PGH - Philippine General Hospital; TPE - Therapeutic plasma exchange.

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.

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.

Efficacy and safety of mexiletine in amyotrophic lateral sclerosis: a systematic review of randomized controlled trials.

Background: Mexiletine is a potential drug in amyotrophic lateral sclerosis (ALS) that has been tested in clinical trials. The objective of this study was to determine the efficacy and safety of mexiletine in ALS via systematic review of existing evidences. Materials & methods: Relevant records were searched using major healthcare electronic databases. Data on functional disability, impairment, survival, muscle cramp frequency and severity, and adverse events were obtained. Results & conclusion: Three relevant randomized controlled trials with 141 patients were included in this review. Mexiletine has no effect on the functional disability, impairment and survival in ALS. However, significant improvement in reducing muscle cramp severity and frequency was shown. The most common adverse effect associated with mexiletine intake among ALS patients are nausea (n = 11, 7.8%) and tremors (n = 5, 3.6%).

Efficacy and tolerability of subcutaneously administered immunoglobulin in myasthenia gravis: A systematic review.

Subcutaneous immunoglobulin (SCIg) is an emerging therapeutic alternative in the management of myasthenia gravis (MG) due to its potential efficacy, safety, cost effectiveness and ease of administration. At present, there are no systematic reviews that summarized the effects of SCIg in patients with MG. The objective of this study is to determine the efficacy and safety of SCIg in the treatment of adult patients with myasthenia gravis. Relevant records were identified from August 2018 to January 2019 systematic search. Five relevant articles with a total of 34 patients with MG were included in this review. Data on functional disability score and adverse events were obtained. Based on the included uncontrolled studies, the functional disability scores of adult MG patients after SCIg administration showed consistent improvement. Headache and local site injection reactions were the most common adverse events reported. The evidence from limited uncontrolled studies gathered in this review showed that SCIg may improve functional disability in patients with MG. Local and mild adverse events were reported with its administration, but no systemic and serious adverse events were noted.