Acute Peripheral Neuropathy Research Articles

Clinical application of phage immunoprecipitation sequencing to diagnose enterovirus D68 as the underlying etiology in a case of Gullain-Barré syndrome.

Gullain-Barré syndrome (GBS) is an acute peripheral neuropathy often preceded by respiratory or gastrointestinal infections, though molecular testing of cerebrospinal fluid (CSF) is often inconclusive. In a recent case of severe pediatric GBS in British Columbia, Canada, we detected CSF antibodies against enterovirus D (EV-D) to link GBS with prior EV-D68 respiratory infection.

Anti-sulfatide antibody associated GBS with headache and abdominal pain: a case report

BackgroundGuillain‒Barre syndrome (GBS) is an acute inflammatory peripheral neuropathy caused by autoimmunity. Gangliosides and sulfatides are important components of peripheral nerves. Anti-sulfatide antibody-mediated complement is associated with acute sensorimotor peripheral neuropathy in GBS, which is characterized by pain and paresthesias.Case presentationThe child was a 7-year-old girl with headache and abdominal pain, followed by limb numbness and pain. Cranial imaging showed ventricular dilatation, peripheral nerve function conduction examination showed polyradiculopathy, and cerebrospinal fluid tests showed normal cell counts but elevated protein levels, all of which led to the diagnosis of GBS. After treatment with intravenous immunoglobulin (400 mg/kg × 5 days), the symptoms did not improve, and muscle strength progressively worsened, accompanied by paroxysmal complexion flushing, heart rate fluctuation, hyperhidrosis, and a progressive increase in cerebrospinal fluid protein (up to 3780.1 mg/L). On the basis of these findings combined with serum anti-sulfatide IgM positivity, anti-sulfatide antibody-related GBS was considered, and treatment with low-dose prednisolone (1 mg/kg/d) led to symptom improvement.ConclusionsAnti-sulfatide antibody-associated GBS is associated with small fiber peripheral neuropathy. The main manifestations are pain, paresthesias and autonomic dysfunction. In addition to the dysfunction of spinal nerve root absorption caused by increased cerebrospinal fluid protein, autonomic dysfunction may be involved in pain. When the therapeutic effect of immunoglobulin is not satisfactory, a low dose and short course of corticosteroids can be considered, and the prognosis is good.

Superacute onset of Guillain-Barré syndrome after elective spinal surgery: A case report and literature review.

Guillain-Barré syndrome (GBS) epitomizes an acute peripheral neuropathy hallmarked by an autoimmune retort directed at the myelin sheath enwrapping peripheral nerves. While it is widely acknowledged that a majority of GBS patients boast a history of antecedent infections, the documentation of postoperative GBS occurrences is progressively mounting. Drawing upon an exhaustive compendium of recent case reports, the disease's inception spans a gamut from within 1 hour to 1.2 years. At this juncture, we proffer a singular case: an instance involving a 51-year-old gentleman who underwent lumbar spine surgery, only to encounter immediate debilitation of limb and respiratory musculature. Post elimination of variables linked to anesthetic agents, encephalon, and spinal cord pathologies, a potent suspicion of superacute GBS onset emerged. Subsequent to immunoglobulin therapy, plasmapheresis, and adjunctive support, the patient's ultimate demise became manifest. No progress was found to date. Given GBS's potential to instigate paralysis, respiratory collapse, and autonomic nervous system aberrations, alongside other pernicious sequelae, coupled with the exceptional rarity of the temporal onset in this particular instance, it undeniably proffers an imposing conundrum for anesthetists in the realm of differential diagnosis and therapeutic conduct. During the postoperative convalescence phase under anesthesia, should the patient evince deviant limb musculature vigor and compromised respiratory sinews, the prospect of GBS must not be consigned to oblivion. Precision in diagnosis conjoined with apt therapeutic measures could well be the harbinger of a divergent denouement for the afflicted patient.

Effects of acupuncture for Bell's palsy patients in the acute phase and its impact on facial nerve edema: a study protocol for a randomized, controlled trial.

Bell's palsy is an acute peripheral facial neuropathy, which is one of the most common causes of facial palsy of lower motor neurons. Facial nerve swelling is commonly observed in Bell's palsy. Acupuncture therapy has been widely used in the treatment of Bell's palsy. However, whether acupuncture can be effectively used in the acute stage is still controversial. There are no clinical trials conducted previously to evaluate the effect of acupuncture on facial nerve edema in Bell's palsy patients. The study aims to evaluate the potential efficacy of different acupuncture modalities on Bell's palsy patients in the acute phase, its effect on facial nerve edema, and to preliminarily explore its possible mechanism. In this randomized, controlled trial, 165 Bell's palsy patients with unilateral onset within 3 days will be recruited and randomly assigned to either the electroacupuncture group (n = 33), the acupuncture group (n = 33), the sham acupuncture group (n = 33), the blank control group (n = 33), or the acupuncture control group (n = 33) in a 1:1:1:1:1 ratio. The participants will receive 4 weeks of treatment and 8 weeks of follow-up. The five groups of participants will receive the following treatments: A: Electroacupuncture + Medication (prednisone acetate tablets, mecobalamin tablets, and vitamin B1 tablets); B: Acupuncture + Medication; C: Sham Acupuncture + Medication; D: Medication only; and E: Acupuncture only. The primary outcome will be the effectiveness rate of different acupuncture modalities in improving facial nerve function after the intervention period. The secondary outcomes will be the recovery speed, the diameter of the facial nerve, the echo intensity and thickness of facial muscles, blood flow parameters of the facial artery, the serum inflammatory level, safety evaluation, and adverse events. Preliminary exploration of its mechanism of action occurs through inflammation and immune response. The difference between groups will be assessed using repeated measure analysis of covariance (ANCOVA) and trend chi-square. The trial will evaluate the efficacy and facial nerve edema of acupuncture for Bell's palsy patients in the acute phase and preliminarily explore its possible mechanism. The results thus may provide evidence for clinical application. https://www.chictr.org.cn/bin/project/edit?pid=133211, identifier ChiCTR2100050815.

Exploration for Blood Biomarkers of Human Long Non-coding RNAs Predicting Oxaliplatin-Induced Chronic Neuropathy Through iPS Cell-Derived Sensory Neuron Analysis.

Oxaliplatin, a platinum-based chemotherapeutic agent, frequently causes acute and chronic peripheral sensory neuropathy, for which no effective treatment has been established. In particular, chronic neuropathy can persist for years even after treatment completion, thus worsening patients' quality of life. To avoid the development of intractable adverse effects, a predictive biomarker early in treatment is awaited. In this study, we explored extracellular long non-coding RNAs (lncRNAs) released from primary sensory neurons as biomarker candidates for oxaliplatin-induced peripheral neuropathy. Because many human-specific lncRNA genes exist, we induced peripheral sensory neurons from human induced pluripotent stem cells. Oxaliplatin treatment changed the levels of many lncRNAs in extracellular vesicles (EVs) released from cultured primary sensory neurons. Among them, the levels of release of lncRNAs that were considered to be selectively expressed in dorsal root ganglia were correlated with those of lncRNAs in plasma EV obtained from healthy individuals. Several lncRNAs in plasma EVs early after the initiation of treatment showed greater changes in patients who did not develop chronic neuropathy that persisted for more than 1year than in those who did. Therefore, these extracellular lncRNAs in plasma EVs may represent predictive biomarkers for the development of chronic peripheral neuropathy induced by oxaliplatin.

Role of TRPA1 in Painful Cold Hypersensitivity.

Transient receptor potential ankyrin 1 (TRPA1) is a polymodal cation channel that plays a pivotal role in pain generation after exposure to irritant chemicals and is involved in the sensation of a wide variety of pathological pain. TRPA1 was first reported to be sensitive to noxious cold, but its intrinsic cold sensitivity still remains under debate. To address this issue, we focused on cold hypersensitivity induced by oxaliplatin, a platinum-based chemotherapeutic drug, as a peculiar adverse symptom of acute peripheral neuropathy. We and other groups have shown that oxaliplatin enhances TRPA1 sensitivity to its chemical agonists and reactive oxygen species (ROS). Our in vitro and animal model studies revealed that oxaliplatin, or its metabolite oxalate, inhibits hydroxylation of a proline residue within the N-terminus of human TRPA1 (hTRPA1) via inhibition of prolyl hydroxylase domain-containing protein (PHD), which induces TRPA1 sensitization to ROS. Although hTRPA1 is insensitive to cold, PHD inhibition endows hTRPA1 with cold sensitivity through sensing the small amount of ROS produced after exposure to cold. Hence, we propose that PHD inhibition can unveil the cold sensitivity of hTRPA1 by converting ROS signaling into cold sensitivity. Furthermore, in this review, we summarize the role of TRPA1 in painful cold hypersensitivity during peripheral vascular impairment.

Evidence-Based Application of the Plasma Exchange to Improve Muscle Power and Disability Grade in Patients with Guillain-Barré Syndrome

<p>格林-巴利症候群是罕見且病程進展快速的急性周邊神經系統病變，未及時治療，將導致四肢癱瘓及呼吸衰竭。本文描述一位71歲男性，接種AstraZeneca（AZ）疫苗後，出現對稱性肢體無力及右側顏面麻痺，經檢查確診為AZ疫苗誘發格林-巴利症候群的急性發炎性脫髓鞘多發性神經病變合併右側貝爾氏麻痺。筆者以神經科專科護理師角度，評估病人與家屬對治療方案之選擇呈現意見分歧，故運用實證方法探討血漿置換術對改善肌肉力量與殘疾程度之成效。 於Cochrane、Embase、MEDLINE、PubMed、 CINAHL及華藝等資料庫，使用“Guillain-Barre Syndrome”、“plasma exchange”、“intravenous immunoglobulin”、“muscle power”及“disability grade”之關鍵字，搜尋2013 年1月至2023 年2月之中英文文獻。經篩選後共計納入3篇研究進行分析，使用OCEBM評讀文獻，結果顯示治療第2週後，接受血漿置換術之介入措施對於殘疾等級和肌肉力量之改善高於靜脈注射免疫球蛋白。本實證應用結果，病人於住院期間確實恢復肌肉力量及改善殘疾程度。希冀藉由此案例分享，做為爾後照護之參考。</p> <p> </p><p>Guillain-Barré syndrome is a rare and rapidly progressing disease characterized by acute peripheral neuropathy. If left untreated, it can lead to quadriplegia and respiratory failure. In this case, a 71-year-old male developed symmetric limb weakness and right facial palsy after receiving the AstraZeneca (AZ) vaccine. The case was diagnosed with acute inflammatory demyelinating polyneuropathy, a form of Guillain-Barré syndrome, along with right Bell’s palsy. The author, a neurological nurse practi-tioner, was trying to resolve the differences in treatment preferences between the patient and his fami-ly members. Therefore, an evidence-based approach was employed to explore the effectiveness of plas-ma exchange in improving muscle strength and disability grade. An electronic literature search was conducted in databases including Cochrane, Embase, MEDLINE, PubMed, CINAHL, and Airiti Li-brary. Keywords such as “Guillain-Barré Syndrome,” “Plasma Exchange,” “Intravenous Immunoglob-ulin,” “Muscle Power,” and “Disability Grade” were applied. Studies in Chinese or English published between January 2013 and February 2023 were screened and three relevant studies were included in the analysis. The Oxford Centre for Evidence-Based Medicine criteria were further applied to review the literature. The results showed that plasma exchange intervention resulted in a greater improvement in disability grade and muscle power compared to intravenous immunoglobulin after the second week of treatment. Empirical evidence indicated that the patient indeed regained muscle strength and im-proved their disability grade during hospitalization. This case is shared as a reference for future care considerations.</p> <p> </p>

Construction and evaluation of a prognostic prediction model based on the mEGOS score for patients with Guillain-Barré syndrome

BackgroundGuillain-Barré syndrome (GBS) is an immune-mediated acute peripheral neuropathy in which up to 20% patients remain unable to walk independently after 6 months of onset. This study aimed to develop a clinical prognostic model based on the modified Erasmus GBS Outcome Score (mEGOS) for predicting the prognosis of GBS patients at 6 months of onset.MethodsThe clinical data of 201 GBS patients were retrospectively analyzed. According to the GBS disability score (GBS-DS) at 6 months of onset, patients were divided into a good prognosis group (GBS-DS <3 points) and a poor prognosis group (GBS-DS≥3 points). Univariate and multivariate analysis was used to screen out independent risk factors for poor prognosis, and a prediction model was accordingly constructed for GBS prognosis.ResultsThe mEGOS score, serum albumin (ALB) and fasting plasma glucose (FPG) were independent risk factors for poor prognosis in patients with GBS, and the above risk factors were used to construct a prognostic model of mEGOS-I and a nomogram. The receiver operating characteristic (ROC) curve showed that the area under curve (AUC) of mEGOS-I at admission and at 7 days of admission to predict poor prognosis at 6 months of GBS onset was 0.891 and 0.916, respectively, with sensitivities of 82.7% and 82.6% and specificities of 86.5% and 86.6%, respectively. Decision curve analysis showed that the nomogram had a very high clinical benefit.ConclusionTo our knowledge, this is the first report of the construction of a prognostic prediction model based on the mEGOS score, ALB, and FPG that can accurately and stably predict the prognosis of GBS patients at 6 months of onset.

Nervous System Involvement in Hospitalized Patients With COVID-19

Abstract Background COVID-19 patients with neurological manifestations have poorer outcomes. We investigated the association between clinicodemographic and laboratory findings with poorer outcomes among COVID-19 inpatients with neurological manifestations. Methods This was a retrospective study of consecutive medical records (March–April 2020). Neurological manifestations (altered level of consciousness, acute cerebrovascular disease, ataxia, seizure, headaches, dizziness/vertigo, muscle weakness, and peripheral neuropathies) were categorized into serious and nonserious. Results Of 119 COVID-19 inpatients, 38 with neurological manifestations were included (age, 63.7 ± 13.4 years; male, 65.8%), of whom 27 (71.1%) had serious manifestations. Muscle weakness (57.9%), impaired consciousness (47.4%), and acute cerebrovascular disease (23.7%) were the most frequent manifestations. The in-hospital mortality rate was 28.9%. Patients with serious manifestations were significantly older (66.9 vs 55.7, P = 0.018), with significantly higher white blood cell count (6.8 vs 5.1 × 103/μL, P = 0.023), direct bilirubin (0.3 vs 0.2 mg/dL, P = 0.030), prothrombin time (PT) (15.4 vs 14.4 seconds, P = 0.006), international normalized ratio (1.2 vs 1.1, P = 0.005), and model for end-stage liver disease (MELD) scores (10 vs 7, P = 0.011), compared with those with nonserious manifestations. In addition, the nonsurvivors had higher potassium (4.5 vs 4.0 mEq/L, P = 0.021), total bilirubin (1.1 vs 0.6 mg/dL, P = 0.008), and MELD scores (12 vs 8, P = 0.025) compared with the survivors. After adjustment, we found significant impacts of age (adjusted odds ratio [aOR], 1.11; P = 0.032), PT (aOR, 5.04; P = 0.019), and MELD score (aOR, 1.27, P = 0.047) on poorer outcomes. Conclusions Older age, higher white blood cell count, bilirubin, PT, international normalized ratio, potassium, and MELD scores were associated with poorer outcomes in COVID-19 inpatients with neurological manifestations.

Role of pattern recognition receptors in chemotherapy-induced neuropathic pain.

Progress in the development of effective chemotherapy is producing a growing population of patients with acute and chronic painful chemotherapy-induced peripheral neuropathy (CIPN), a serious treatment-limiting side effect for which there is currently no US Food and Drug Administration-approved treatment. CIPNs induced by diverse classes of chemotherapy drugs have remarkably similar clinical presentations, leading to the suggestion they share underlying mechanisms. Sensory neurons share with immune cells the ability to detect damage associated molecular patterns (DAMPs), molecules produced by diverse cell types in response to cellular stress and injury, including by chemotherapy drugs. DAMPs, in turn, are ligands for pattern recognition receptors (PRRs), several of which are found on sensory neurons, as well as satellite cells, and cells of the immune system. In the present experiments, we evaluated the role of two PRRs, TLR4 and RAGE, present in dorsal root ganglion (DRG), in CIPN. Antisense (AS)-oligodeoxynucleotides (ODN) against TLR4 and RAGE mRNA were administered intrathecally before ('prevention protocol') or 3 days after ('reversal protocol') the last administration of each of three chemotherapy drugs that treat cancer by different mechanisms (oxaliplatin, paclitaxel and bortezomib). TLR4 and RAGE AS-ODN prevented the development of CIPN induced by all three chemotherapy drugs. In the reversal protocol, however, while TLR4 AS-ODN completely reversed oxaliplatin- and paclitaxel-induced CIPN, in rats with bortezomib-induced CIPN it only produced a temporary attenuation. RAGE AS-ODN, in contrast, reversed CIPN induced by all three chemotherapy drugs. When a TLR4 antagonist was administered intradermally to the peripheral nociceptor terminal, it did not affect CIPN induced by any of the chemotherapy drugs. However, when administered intrathecally, to the central terminal, it attenuated hyperalgesia induced by all three chemotherapy drugs, compatible with a role of TLR4 in neurotransmission at the central terminal but not sensory transduction at the peripheral terminal. Finally, since it has been established that cultured DRG neurons can be used to study direct effects of chemotherapy on nociceptors, we also evaluated the role of TLR4 in CIPN at the cellular level, using patch-clamp electrophysiology in DRG neurons cultured from control and chemotherapy-treated rats. We found that increased excitability of small-diameter DRG neurons induced by in vivo and in vitro exposure to oxaliplatin is TLR4-dependent. Our findings suggest that in addition to the established contribution of PRR-dependent neuroimmune mechanisms, PRRs in DRG cells also have an important role in CIPN.

Acute Onset Peripheral Neuropathy in a Patient with Scrub Typhus

The neurological complications of scrub typhus can have a wide spectrum of presentations involving both central and peripheral nervous system, meningoencephalitis and meningitis being the most common. Involvement of the peripheral nervous system in scrub infection is not commonly reported, here we present a case of A 70-year-old male diagnosed with scrub typhus fever and presented with peripheral neuropathy. Duloxetine and methyl cobalamin combination along with gabapentin were used for management and the patient was partially improved gradually over a period of six days. Keywords: scrub typhus, scrub infection, scrub typhus fever, orientia tsutsugamushi.

Integrated gene expression profiling and functional enrichment analyses to discover biomarkers and pathways associated with Guillain-Barré syndrome and autism spectrum disorder to identify new therapeutic targets

Guillain-Barré syndrome (GBS) is one of the most prominent and acute immune-mediated peripheral neuropathy, while autism spectrum disorders (ASD) are a group of heterogeneous neurodevelopmental disorders. The complete mechanism regarding the neuropathophysiology of these disorders is still ambiguous. Even after recent breakthroughs in molecular biology, the link between GBS and ASD remains a mystery. Therefore, we have implemented well-established bioinformatic techniques to identify potential biomarkers and drug candidates for GBS and ASD. 17 common differentially expressed genes (DEGs) were identified for these two disorders, which later guided the rest of the research. Common genes identified the protein-protein interaction (PPI) network and pathways associated with both disorders. Based on the PPI network, the constructed hub gene and module analysis network determined two common DEGs, namely CXCL9 and CXCL10, which are vital in predicting the top drug candidates. Furthermore, coregulatory networks of TF-gene and TF-miRNA were built to detect the regulatory biomolecules. Among drug candidates, imatinib had the highest docking and MM-GBSA score with the well-known chemokine receptor CXCR3 and remained stable during the 100 ns molecular dynamics simulation validated by the principal component analysis and the dynamic cross-correlation map. This study predicted the gene-based disease network for GBS and ASD and suggested prospective drug candidates. However, more in-depth research is required for clinical validation. Communicated by Ramaswamy H. Sarma

COVID-19 vaccine safety in Scotland – background rates of adverse events of special interest

ObjectivesMass COVID-19 vaccination commenced in December 2020 in Scotland. Monitoring vaccine safety relies on accurate background incidence rates (IRs) for health outcomes potentially associated with vaccination. This study aimed to quantify IRs in Scotland of adverse events of special interest (AESI) potentially associated with COVID-19 vaccination. Study design and methodsIRs and 95% confidence intervals (CIs) for 36 AESI were calculated retrospectively for the pre-COVID-19 pandemic period (01 January 2015–31 December 2019) and the COVID-19 pandemic period (01 April 2020–30 November 2020), with age-sex stratification, and separately by calendar month and year. Incident cases were determined using International Classification of Diseases-10th Revision (ICD-10)–coded hospitalisations. ResultsPrepandemic population-wide IRs ranged from 0.4 (0.3–0.5 CIs) cases per 100,000 person-years (PYRS) for neuromyelitis optica to 478.4 (475.8–481.0 CIs) cases per 100,000 PYRS for acute renal failure. Pandemic population-wide IRs ranged from 0.3 (0.2–0.5 CIs) cases per 100,000 PYRS for Kawasaki disease to 483.4 (473.2–493.7 CIs) cases per 100,000 PYRS for acute coronary syndrome. All AESI IRs varied by age and sex. Ten AESI (acute coronary syndrome, acute myocardial infarction, angina pectoris, heart failure, multiple sclerosis, polyneuropathies and peripheral neuropathies, respiratory failure, rheumatoid arthritis and polyarthritis, seizures and vasculitis) had lower pandemic than prepandemic period IRs overall. Only deep vein thrombosis and pulmonary embolism had a higher pandemic IR. ConclusionLower pandemic IRs likely resulted from reduced health-seeking behaviours and healthcare provision. Higher IRs may be associated with SARS-CoV-2 infections. AESI IRs will facilitate future vaccine safety studies in Scotland.

Oxaliplatin causes increased offset analgesia during chemotherapy- a feasibility study.

Offset analgesia (OA) is the phenomenon where the perceived pain intensity to heat stimulation disproportionally decreases after a slight decrease in stimulation temperature. The neural mechanisms of OA are not fully understood, but it appears that both peripheral and central temporal filtering properties are involved. Chemotherapy with oxaliplatin often causes acute peripheral sensory neuropathy, and manifests primarily as a cold induced allodynia. The aim of this exploratory patient study was to investigate if OA was affected by the neurotoxic effects of adjuvant oxaliplatin treatment. OA was assessed in 17 colon cancer patients during 12 cycles of adjuvant oxaliplatin treatment. The OA response was estimated as the decrease in pain intensity caused by a temperature decrease from 46 °C to 45 °C. Changes in the OA during the treatment period was estimated using a mixed linear model and corrected for multiple comparisons by Sidak's test. OA was increased significantly when assessed before the 2nd, 3rd, 5th, 6th, 9th, and 10th treatment cycle compared to the first (baseline) treatment (p<0.05). OA is generally decreased in persons suffering from chronic pain or peripheral neuropathy as compared tohealthy controls. But in the present study, OA increased during chemotherapy with oxaliplatin. The underlying mechanism of this unexpected increase should be further explored.

Adult-onset seizures as the initial presentation of acute intermittent porphyria

Acute intermittent porphyria (AIP) is a rare metabolic disorder caused by the deficiency of enzyme porphobilinogen deaminase used in haeme biosynthesis. Nonspecific abdominal pain is the classical presentation of AIP. Patients rarely present with rapid-onset neurological manifestations such as acute peripheral neuropathy or seizures. The knowledge on the management of seizures in AIP is important as some antiepileptic drugs may exacerbate acute attack. Hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion is a recognised cause of seizures in AIP. We report a case of a 20-year-old woman presenting to a tertiary care hospital in Sri Lanka with seizures due to hyponatremia who was eventually diagnosed with AIP. Although AIP is not frequently reported in Sri Lanka, it’s important to have a strong clinical suspicion as an early diagnosis will reduce mortality and morbidity.

Anti-GT1a and anti-GQ1b immunoglobulin G antibody positivity with overlapping Miller Fisher/Guillain-Barré syndromes and prominent headache: a case report.

Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) are acute immune-mediated peripheral neuropathies. In addition to their classic presentations, a variety of other signs and symptoms have been reported; however, headache appears to be relatively uncommon. We describe a 53-year-old woman who presented with acute bulbar palsy as the first symptom of overlapping MFS/GBS accompanied by severe headache. The first important clinical impairment of the patient was acute bulbar palsy along with prominent headache, without limb weakness. Although her initial diagnosis was acute bulbar palsy plus, she subsequently developed lower limb diffuse weakness, and her final clinical diagnosis was overlapping MFS/GBS. Anti-ganglioside antibodies were positive for anti-GQ1b and anti-GT1a immunoglobulin G. The patient received intravenous immunoglobulin on day 2 of admission. Early identification of these overlapping syndromes is important for the management of patients, to avoid respiratory failure or severe weakness with axonal degeneration. We therefore remind clinicians of the importance of further examination in patients with headache and acute bulbar palsy of unknown origin.

Pattern of Autonomic Involvement in Adult Patients with Guillain Barre Syndrome in a Tertiary Hospital

Background: Guillain Barre Syndrome (GBS) is an acute post infectious immune mediated peripheral neuropathy with a marked variation in pathology, clinical presentation and prognosis. Autonomic dysfunction is one of the important manifestations of GBS which may lead to significant morbidity and mortality. Objective: The aim of the study is to assess the autonomic involvement, to determine its frequency and pattern of involvement in adult patients with GBS Methods: An observational, descriptive, cross sectional study was carried out in the Department of Neurology, BSMMU, Dhaka from March, 2015 to September, 2017. Total 43 patients of GBS and 35 apparently healthy controls were recruited as the study population. On the basis of nerve conduction study patients were classified into different groups: acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN) and acute motor sensory axonal neuropathy (AMSAN) and other variants. Disability status at the time of autonomic testing was measured by Hughes functional grading scale. The following tests of autonomic nervous system were performed in both patients and controls 1) resting heart rate and heart rate on changing posture (30: 15 ratio) 2) supine blood pressure and blood pressure on changing posture 3) heart rate response to valsalva maneuver 4) heart rate response to deep breathing and E: I ratio 5) sphincter disturbance by symptoms questionnaire. Results: The mean age of patients was 35±12 years (range18 to 65 years) and 58.1% were male. Around 88.4 % of patients showed some sort of autonomic dysfunction. Variation of heart rate by different maneuver like posture change, deep breathing and valsalva maneuver was found commonly. Among them 30:15 ratio was abnormal in majority of the patients (82.4%) followed by abnormal max-min HR/min (58.1%) and abnormal valsalva ratio (37.2%). Other abnormalities were postural hypotension (38.2%), sinus tachycardia (25.6%), hypertension (16.3%), hypotension (2.7%), sinus arrhythmia (4.7%), constipation (30%), urinary retention (7%) and urinary incontinence (4.7%). Conclusion: In this study different patterns of autonomic dysfunction was found in 88.4% of patients with GBS involving both sympathetic and parasympathetic components. The present study found no significant association between autonomic dysfunction and motor disability scores. Thus autonomic function assessment is essential in every patient with GBS in addition to motor &amp; sensory function. Bangladesh Medical Res Counc Bull 2022; 48(3): 174-179

Detection of anti-ganglioside antibodies in Guillain-Barré syndrome.

Gangliosides are a class of glycosphingolipid molecules that are highly enriched in cellular membranes of the nervous system. The gangliosides associated with autoimmune diseases of the nervous system are mainly GM1, GD1a, GalNAc-GD1a, GM1b, GD3, CD1b, GT1a, and GQ1b. Multiple antibodies recognizing gangliosides are associated with some acute or chronic peripheral neuropathies, especially Guillain-Barré syndrome (GBS) and its clinical variants. Antibodies binding to gangliosides can activate complement system and recruit macrophages on the axolemma at the nodes of Ranvier of motor fibers, which are found in the course of GBS, causing axonal degeneration and reversible conduction block or conduction failure. Testing of anti-gangliosides autoantibodies is helpful for diagnosis of autoimmune peripheral neuropathies or support the diagnosis of the subtypes. These anti-gangliosides antibodies are usually detected by several qualitative or quantitative methods, particularly enzyme-linked immunosorbent assay (ELISA) and immunodot assays, which have been commercialized or established in-house worldwide. Herein, we introduce the methods and clinical applications of these assays in the diagnosis of autoimmune peripheral neuropathies. Anti-gangliosides antibodies are diagnostic markers of GBS subtypes. We use GBS as an example to explain the role of anti-gangliosides antibodies in the pathogenesis and diagnostic classification of neuropathies.

Variable sensitivity to diethylene glycol poisoning is related to differences in the uptake transporter for the toxic metabolite diglycolic acid

Introduction/Context Poisonings with diethylene glycol are characterized by acute kidney injury and peripheral neuropathy. In animal studies on the toxicities of diethylene glycol and its metabolite diglycolic acid, remarkable differences in susceptibility to acute kidney injury were observed in identically-dosed rats. In those studies, only about 60% showed acute kidney injury, yet all rats with acute kidney injury showed marked diglycolic acid accumulation in tissues, while no diglycolic acid accumulated in rats without injury. Diglycolic acid is taken into renal cells via sodium-dependent dicarboxylate transporters. When sodium-dependent dicarboxylate transporter-1 is inhibited or knocked down in human kidney cells, diglycolic acid uptake and toxicity are reduced. We hypothesize that the variation in sensitivity to tissue diglycolic acid retention and to diethylene glycol/diglycolic acid toxicity is explained by differential expression of sodium-dependent dicarboxylate transporter-1 in rat kidneys. Methods Using kidney tissue from previous studies, we performed rt-PCR analysis of sodium-dependent dicarboxylate transporter-1 mRNA. In those studies, Wistar-Han rats were either gavage with diethylene glycol 6 g/kg every 12 h for 7 days or with single doses of diglycolic acid 300 mg/kg. Kidney tissue was harvested after euthanasia and preserved in formalin. Tissue slices were homogenized and RNA was isolated using an RNAstorm FFPE RNA Isolation Kit. The expression of sodium-dependent dicarboxylate transporter-1 mRNA was compared between groups that showed diglycolic acid accumulation and acute renal injury with those that showed no diglycolic acid accumulation or toxicity. Results Significantly higher expression of sodium-dependent dicarboxylate transporter-1 mRNA was present in the kidneys of rats with acute kidney injury and diglycolic acid accumulation compared to those in rats that had no diglycolic acid in their kidneys and no acute kidney injury. Discussion The likelihood of acute kidney injury after dosing of rats with diethylene glycol or diglycolic acid is linked with an enhanced ability to take up diglycolic acid into renal cells via the sodium-dependent dicarboxylate transporter-1. The variability in diethylene glycol toxicity in humans, as reported in epidemiological studies, may also be linked with differences in tissue uptake of diglycolic acid. Conclusions Animals with acute kidney injury after exposure to diethylene glycol or diglycolic acid had higher sodium-dependent dicarboxylate transporter-1 expression and greater diglycolic acid accumulation in renal tissues than animals without acute kidney injury.

Case Series of Acute Peripheral Neuropathies in Individuals Who Received COVID-19 Vaccination

Background and Objectives: Vaccination has been critical to managing the COVID-19 pandemic. Autoimmunity of the nervous system, especially among a select set of high-risk groups, can be triggered or enhanced by the contents of vaccines. Here, we report a case series of acute peripheral neuropathies following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report on 11 patients (range: 30-90 years old) who presented at our center between January 2021 and February 2022. Methods: We obtained the patients' history and performed clinical neurological examination and electromyoneurography on all subjects. If necessary, magnetic resonance imaging and laboratory testing, including cerebrospinal fluid analysis and specific antibody testing, were performed. Results: Patients presented with peripheral neuropathies of acute onset between 1 and 40 days after vaccination with different types of COVID-19 vaccines. Most cases (9/11) resolved with a rapid, complete or partial recovery. Conclusions: We found acute peripheral neuropathies in a set of individuals after they received vaccines against SARS-CoV-2. Albeit our observation shows that during extensive vaccination programs, negative side effects on the peripheral nervous system might occur, most of them showed benign clinical evolution. Thus, potential side effects should not hinder the prescription of vaccines. More extensive studies are needed to elucidate populations at risk of developing peripheral neuropathies and mechanisms of autoimmune response in the nervous system.