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BACKGROUND AND PURPOSE: Myasthenia gravis (MG) is clinically heterogeneous and can be classified into subgroups according to the clinical presentation, antibody status, age at onset, and thymic abnormalities. This study aimed to determine the clinical characteristics and outcomes of generalized MG (GMG) patients based on these subgroups. METHODS: Medical records of MG patients from 1976 to 2023 were reviewed retrospectively. Patients with pure ocular MG were excluded. Data on demographic, clinical characteristics, laboratory features, and outcomes were analyzed. RESULTS: This study included 120 GMG patients. There was a slight preponderance of female patients over male patients (male:female ratio=1:1.3), with the age at onset exhibiting a bimodal distribution. Female patients peaked at a lower age (21-30 years) whereas male patients peaked at a higher age (61-70 years). Most (92%, 105 of 114) patients had positive anti-acetylcholine receptor antibodies. Five patients were also tested for anti-muscle-specific tyrosine kinase antibodies, with two showing positivity. Thymectomy was performed in 62 (52%) patients, of which 30 had thymoma, 16 had thymic hyperplasia, 7 had an involuted thymus, and 6 had a normal thymus. There were significantly more female patients (68% vs. 45%, p=0.011) with early-onset disease (<50 years old) and thymic hyperplasia (33% vs. 0%, p<0.025). Most (71%) of the patients had a good outcome based on the Myasthenia Gravis Foundation of America postintervention status. GMG patients with early-onset disease had a significantly better outcome than patients with a late onset in univariate (58% vs. 37%, p=0.041) and multivariate (odds ratio=4.68, 95% confidence interval=1.17-18.64, p=0.029) analyses. CONCLUSIONS: Female patients with early-onset MG and thymic hyperplasia had significantly better outcomes, but only early-onset disease was independently associated with a good outcome. These findings are comparable with those of other studies.
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BACKGROUND AND PURPOSE: Multiple acyl-CoA dehydrogenase deficiency (MADD) is an inherited disorder of fatty acid oxidation that causes lipid storage myopathy (LSM). This is the first report on MADD that describes the phenotypic and genetic features of a Malaysian cohort. METHODS: Among the >2,500 patients in a local muscle biopsy database, patients with LSM were identified and their genomic DNA were extracted from muscle samples and peripheral blood. All 13 exons of the electron-transfer flavoprotein dehydrogenase gene (ETFDH) were subsequently sequenced. Fifty controls were included to determine the prevalence of identified mutations in the normal population. RESULTS: Fourteen (82%) of the 17 LSM patients had MADD with ETFDH mutations. Twelve (86%) were Chinese and two were Malay sisters. Other unrelated patients reported that they had no relevant family history. Nine (64%) were females. The median age at onset was 18.5 years (interquartile range=16-37 years). All 14 demonstrated proximal limb weakness, elevated serum creatine kinase levels, and myopathic changes in electromyography. Three patients experienced a metabolic crisis at their presentation. Sanger sequencing of ETFDH revealed nine different variants/mutations, one of which was novel: c.998A>G (p.Y333C) in exon 9. Notably, 12 (86%) patients, including the 2 Malay sisters, carried a common c.250G>A (p.A84T) variant, consistent with the hotspot mutation reported in southern China. All of the patients responded well to riboflavin therapy. CONCLUSIONS: Most of our Malaysian cohort with LSM had late-onset, riboflavin-responsive MADD with ETFDH mutations, and they demonstrated phenotypic and genetic features similar to those of cases reported in southern China. Furthermore, we report a novel ETFDH mutation and possibly the first ever MADD patients of Malay descent.
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BACKGROUND AND PURPOSE: Various electrodiagnostic criteria have been developed in Guillain-Barré syndrome (GBS). Their performance in a broad representation of GBS patients has not been evaluated. Motor conduction data from the International GBS Outcome Study (IGOS) cohort were used to compare two widely used criterion sets and relate these to diagnostic amyotrophic lateral sclerosis criteria. METHODS: From the first 1500 patients in IGOS, nerve conduction studies from 1137 (75.8%) were available for the current study. These patients were classified according to nerve conduction studies criteria proposed by Hadden and Rajabally. RESULTS: Of the 1137 studies, 68.3% (N = 777) were classified identically according to criteria by Hadden and Rajabally: 111 (9.8%) axonal, 366 (32.2%) demyelinating, 195 (17.2%) equivocal, 35 (3.1%) inexcitable and 70 (6.2%) normal. Thus, 360 studies (31.7%) were classified differently. The areas of differences were as follows: 155 studies (13.6%) classified as demyelinating by Hadden and axonal by Rajabally; 122 studies (10.7%) classified as demyelinating by Hadden and equivocal by Rajabally; and 75 studies (6.6%) classified as equivocal by Hadden and axonal by Rajabally. Due to more strictly defined cutoffs fewer patients fulfilled demyelinating criteria by Rajabally than by Hadden, making more patients eligible for axonal or equivocal classification by Rajabally. In 234 (68.6%) axonal studies by Rajabally the revised El Escorial (amyotrophic lateral sclerosis) criteria were fulfilled; in axonal cases by Hadden this was 1.8%. CONCLUSIONS AND DISCUSSION: This study shows that electrodiagnosis in GBS is dependent on the criterion set utilized, both of which are based on expert opinion. Reappraisal of electrodiagnostic subtyping in GBS is warranted.
Subject(s)
Electrodiagnosis , Guillain-Barre Syndrome , Neural Conduction , Humans , Guillain-Barre Syndrome/diagnosis , Guillain-Barre Syndrome/classification , Guillain-Barre Syndrome/physiopathology , Neural Conduction/physiology , Electrodiagnosis/methods , Male , Female , Middle Aged , Adult , Amyotrophic Lateral Sclerosis/diagnosis , Amyotrophic Lateral Sclerosis/classification , Amyotrophic Lateral Sclerosis/physiopathology , Aged , Cohort StudiesABSTRACT
This chapter discusses comprehensive neurophysiological biomarkers utilised in motor neuron disease (MND) and, in particular, its commonest form, amyotrophic lateral sclerosis (ALS). These encompass the conventional techniques including nerve conduction studies (NCS), needle and high-density surface electromyography (EMG) and H-reflex studies as well as novel techniques. In the last two decades, new methods of assessing the loss of motor units in a muscle have been developed, that are more convenient than earlier methods of motor unit number estimation (MUNE),and may use either electrical stimulation (e.g. MScanFit MUNE) or voluntary activation (MUNIX). Electrical impedance myography (EIM) is another novel approach for the evaluation that relies upon the application and measurement of high-frequency, low-intensity electrical current. Nerve excitability techniques (NET) also provide insights into the function of an axon and reflect the changes in resting membrane potential, ion channel dysfunction and the structural integrity of the axon and myelin sheath. Furthermore, imaging ultrasound techniques as well as magnetic resonance imaging are capable of detecting the constituents of morphological changes in the nerve and muscle. The chapter provides a critical description of the ability of each technique to provide neurophysiological insight into the complex pathophysiology of MND/ALS. However, it is important to recognise the strengths and limitations of each approach in order to clarify utility. These neurophysiological biomarkers have demonstrated reliability, specificity and provide additional information to validate and assess lower motor neuron dysfunction. Their use has expanded the knowledge about MND/ALS and enhanced our understanding of the relationship between motor units, axons, reflexes and other neural circuits in relation to clinical features of patients with MND/ALS at different stages of the disease. Taken together, the ultimate goal is to aid early diagnosis, distinguish potential disease mimics, monitor and stage disease progression, quantify response to treatment and develop potential therapeutic interventions.
Subject(s)
Amyotrophic Lateral Sclerosis , Biomarkers , Electromyography , Motor Neuron Disease , Motor Neurons , Neural Conduction , Humans , Amyotrophic Lateral Sclerosis/physiopathology , Amyotrophic Lateral Sclerosis/diagnostic imaging , Motor Neurons/physiology , Motor Neuron Disease/physiopathology , Motor Neuron Disease/diagnostic imaging , Motor Neuron Disease/diagnosis , Electromyography/methods , Neural Conduction/physiologyABSTRACT
BACKGROUND AND PURPOSE: There is increasing evidence that the anterior visual pathways are involved in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). This study investigated longitudinal changes in retinal nerve fiber layer (RNFL) thickness in patients with ALS and PD with the aim of better understanding their roles as biomarkers of disease progression. METHODS: This study recruited 21 ALS patients, 19 age-matched PD patients, and 21 agematched healthy controls. Patient demographics and clinical scores relating to the respective diseases were documented. The RNFL thickness was measured using optical coherence tomography at baseline and after 6 months. RESULTS: At baseline, the RNFL in the superior quadrant was significantly thinner in the patients with ALS than in healthy controls (109.90±22.41 µm vs. 127.81±17.05 µm [mean±standard deviation], p=0.008). The RNFL thickness did not differ significantly between the ALS and PD patients or between the PD patients and healthy controls. At 6 months, there was further significant RNFL thinning in patients with ALS, for both the overall thickness (baseline: median=94.5 µm, range=83.0-106.0 µm; follow-up: median=93.5 µm, range=82.5-104.5 µm, p=0.043) and the thickness in the inferior quadrant (median=126 µm, range=109.5-142.5 µm; and median=117.5 µm, range=98.5-136.5 µm; respectively, p=0.032). However, these changes were not correlated with the ALS functional scores. In contrast, the patients with PD did not demonstrate a significant change in RNFL thickness between the two time points. CONCLUSIONS: The RNFL thickness is a promising biomarker of disease progression in patients with ALS but not in those with PD, which has a slower disease progression.
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INTRODUCTION/AIMS: Muscle strength, functional status, and muscle enzymes are conventionally used to evaluate disease status in idiopathic inflammatory myopathies (IIM). This study aims to investigate the role of quantitative muscle ultrasound in evaluating disease status in IIM patients. METHODS: Patients with IIM, excluding inclusion body myositis, were recruited along with age- and sex-matched healthy controls (HC). All participants underwent muscle ultrasound and clinical assessments. Six limb muscles were unilaterally scanned using a standardized protocol, measuring muscle thickness (MT) and echo intensity (EI). Results were compared with HC, and correlations were made with outcome measures. RESULTS: Twenty IIM patients and 24 HC were recruited. The subtypes of IIM were dermatomyositis (6), necrotizing myositis (6), polymyositis (3), antisynthetase syndrome (3), and nonspecific myositis (2). Mean disease duration was 8.7 ± 6.9 years. There were no significant differences in demographics and anthropometrics between patients and controls. MT of rectus femoris in IIM patients was significantly lower than HC. Muscle EI of biceps brachii and vastus medialis in IIM patients were higher than HC. There were moderate correlations between MT of rectus femoris and modified Rankin Scale, Physician Global Activity Assessment, and Health Assessment Questionnaire, as well as between EI of biceps brachii and Manual Muscle Testing-8. DISCUSSION: Muscle ultrasound can detect proximal muscle atrophy and hyperechogenicity in patients with IIM. The findings correlate with clinical outcome measures, making it a potential tool for evaluating disease activity of patients with IIM in the late phase of the disease.
Subject(s)
Myositis, Inclusion Body , Myositis , Polymyositis , Humans , Myositis/complications , Myositis/diagnostic imaging , Muscle, Skeletal , Polymyositis/pathology , Myositis, Inclusion Body/pathology , Muscular Atrophy/pathologyABSTRACT
INTRODUCTION: There is an increasing need for a reproducible and sensitive outcome measure in patients with hereditary transthyretin amyloidosis (ATTRv) with polyneuropathy (PN) due to the emergence of disease modifying therapies. In the current study, we aimed to investigate the role of quantitative muscle ultrasound (QMUS) as a disease biomarker in ATTRv-PN. METHODS: Twenty genetically confirmed ATTRv amyloidosis patients (nine symptomatic, 11 pre-symptomatic) were enrolled prospectively between January to March 2023. Muscle ultrasound was performed on six muscles at standardized locations. QMUS parameters included muscle thickness (MT) and muscle echo intensity (EI). Twenty-five age- and sex-matched healthy controls were recruited for comparison. Significant QMUS parameters were correlated with clinical outcome measures. RESULTS: Muscle volume of first dorsal interosseus (FDI) muscle [measured as cross-sectional area (CSA)] was significantly lower in symptomatic patients compared to healthy controls and pre-symptomatic carriers (98.3 ± 58.0 vs. 184.4 ± 42.5 vs. 198.3 ± 56.8, p < 0.001). EI of biceps and FDI for symptomatic ATTRv-PN patients were significantly higher compared to the other two groups (biceps: 76.4 ± 10.8 vs. 63.2 ± 11.5 vs. 59.2 ± 9.0, p = 0.002; FDI: 48.2 ± 7.5 vs. 38.8 ± 7.5 vs. 33.0 ± 5.3, p < 0.001). CSA of FDI and EI of biceps and FDI correlated with previous validated outcome measures [polyneuropathy disability score, neuropathy impairment score, Karnofsky performance scale, Rasch-built overall disability scale, European quality of life (QoL)-5 dimensions and Norfolk QoL questionnaire-diabetic neuropathy]. CONCLUSION: QMUS revealed significant difference between ATTRv amyloidosis patients and healthy controls and showed strong correlation with clinical outcome measures. QMUS serves as a sensitive and reliable biomarker of disease severity in ATTRv-PN.
Subject(s)
Amyloid Neuropathies, Familial , Muscle, Skeletal , Polyneuropathies , Ultrasonography , Humans , Amyloid Neuropathies, Familial/diagnostic imaging , Male , Female , Middle Aged , Muscle, Skeletal/diagnostic imaging , Muscle, Skeletal/pathology , Polyneuropathies/diagnostic imaging , Aged , Biomarkers , AdultABSTRACT
Background and Objectives: Studies have suggested that, by applying certain nerve ultrasound scores, demyelinating and axonal polyneuropathies can be differentiated. In the current study, we investigated the utility of ultrasound pattern sub-score A (UPSA) and intra- and internerve cross-sectional area (CSA) variability in the diagnostic evaluation of demyelinating neuropathies. Materials and Methods: Nerve ultrasound was performed in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and acute inflammatory demyelinating polyneuropathy (AIDP) and compared to patients with axonal neuropathies. The UPSA, i.e., the sum of ultrasound scores at eight predefined measurement points in the median (forearm, elbow and mid-arm), ulnar (forearm and mid-arm), tibial (popliteal fossa and ankle) and fibular (lateral popliteal fossa) nerves, was applied. Intra- and internerve CSA variability were defined as maximal CSA/minimal CSA for each nerve and each subject, respectively. Results: A total of 34 CIDP, 15 AIDP and 16 axonal neuropathies (including eight axonal Guillain-Barré syndrome (GBS), four hereditary transthyretin amyloidosis, three diabetic polyneuropathy and one vasculitic neuropathy) were included. A total of 30 age- and sex-matched healthy controls were recruited for comparison. Significantly enlarged nerve CSA was observed in CIDP and AIDP with significantly higher UPSA in CIDP compared to the other groups (9.9 ± 2.9 vs. 5.9 ± 2.0 vs. 4.6 ± 1.9 in AIDP vs. axonal neuropathies, p < 0.001). A total of 89.3% of the patients with CIDP had an UPSA score ≥7 compared to the patients with AIDP (33.3%) and axonal neuropathies (25.0%) (p < 0.001). Using this cut-off, the performance of UPSA in differentiating CIDP from other neuropathies including AIDP was excellent (area under the curve of 0.943) with high sensitivity (89.3%), specificity (85.2%) and positive predictive value (73.5%). There were no significant differences in intra- and internerve CSA variability between the three groups. Conclusion: The UPSA ultrasound score was useful in distinguishing CIDP from other neuropathies compared to nerve CSA alone.
Subject(s)
Diabetic Neuropathies , Guillain-Barre Syndrome , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating , Humans , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/diagnostic imaging , Guillain-Barre Syndrome/diagnostic imaging , Ultrasonography , ForearmABSTRACT
BACKGROUND AND OBJECTIVES: To investigate CSF findings in relation to clinical and electrodiagnostic subtypes, severity, and outcome of Guillain-Barré syndrome (GBS) based on 1,500 patients in the International GBS Outcome Study. METHODS: Albuminocytologic dissociation (ACD) was defined as an increased protein level (>0.45 g/L) in the absence of elevated white cell count (<50 cells/µL). We excluded 124 (8%) patients because of other diagnoses, protocol violation, or insufficient data. The CSF was examined in 1,231 patients (89%). RESULTS: In 846 (70%) patients, CSF examination showed ACD, which increased with time from weakness onset: ≤4 days 57%, >4 days 84%. High CSF protein levels were associated with a demyelinating subtype, proximal or global muscle weakness, and a reduced likelihood of being able to run at week 2 (odds ratio [OR] 0.42, 95% CI 0.25-0.70; p = 0.001) and week 4 (OR 0.44, 95% CI 0.27-0.72; p = 0.001). Patients with the Miller Fisher syndrome, distal predominant weakness, and normal or equivocal nerve conduction studies were more likely to have lower CSF protein levels. CSF cell count was <5 cells/µL in 1,005 patients (83%), 5-49 cells/µL in 200 patients (16%), and ≥50 cells/µL in 13 patients (1%). DISCUSSION: ACD is a common finding in GBS, but normal protein levels do not exclude this diagnosis. High CSF protein level is associated with an early severe disease course and a demyelinating subtype. Elevated CSF cell count, rarely ≥50 cells/µL, is compatible with GBS after a thorough exclusion of alternative diagnoses. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that CSF ACD (defined by the Brighton Collaboration) is common in patients with GBS.
Subject(s)
Guillain-Barre Syndrome , Adult , Female , Humans , Male , Middle Aged , Cell Count , Cerebrospinal Fluid/cytology , Cohort Studies , Disease Progression , Guillain-Barre Syndrome/cerebrospinal fluid , Guillain-Barre Syndrome/diagnosis , Guillain-Barre Syndrome/pathology , Guillain-Barre Syndrome/physiopathology , Internationality , Miller Fisher Syndrome/cerebrospinal fluid , Miller Fisher Syndrome/diagnosis , Miller Fisher Syndrome/pathology , Miller Fisher Syndrome/physiopathology , Prognosis , Treatment OutcomeABSTRACT
Neuromuscular ultrasound has become an integral part of the diagnostic workup of neuromuscular disorders at many centers. Despite its growing utility, uniform standard scanning techniques do not currently exist. Scanning approaches for similar diseases vary in the literature creating heterogeneity in the studies as reported in several meta-analysis. Moreover, neuromuscular ultrasound experts including the group in this study have different views with regards to technical aspects, scanning protocols, and the parameters that should be assessed. Establishing standardized neuromuscular scanning protocols is essential for the development of the subspeciality to ensure uniform clinical and research practices. Therefore, we aimed to recommend consensus-based standardized scanning techniques and protocols for common neuromuscular disorders using the Delphi approach. A panel of 17 experts participated in the study, which consisted of three consecutive electronic surveys. The first survey included voting on six scanning protocols addressing the general scanning technique and five common categories of suspected neuromuscular disorders. The subsequent surveys focused on refining the protocols and voting on new steps, rephrased statements, or areas of non-agreement. A high degree of consensus was achieved on the general neuromuscular ultrasound scanning technique and the scanning protocols for focal mononeuropathies, brachial plexopathies, polyneuropathies, amyotophic lateral sclerosis, and muscle diseases. In this study, a group of neuromuscular ultrasound experts developed six consensus-based neuromuscular ultrasound scanning protocols that may serve as references for clinicians and researchers. The standardized protocols could also aid in achieving high-quality uniform neuromuscular ultrasound practices.
Subject(s)
Brachial Plexus Neuropathies , Motor Neuron Disease , Neuromuscular Diseases , Polyneuropathies , Humans , Neuromuscular Diseases/diagnostic imaging , Ultrasonography/methods , Meta-Analysis as TopicABSTRACT
BACKGROUND: With progress made in neurogenetics and neuroinflammation, the indications and value of nerve biopsies in the diagnostic evaluation of peripheral neuropathies are less clear. In this study, we aimed to evaluate the diagnostic yield of nerve biopsies in patients with peripheral neuropathies. METHODS: We performed a retrospective review of nerve biopsy reports from April 1998 to June 2021 of patients with peripheral neuropathies presenting to the Department of Pathology, University of Malaya Medical Centre, Kuala Lumpur, Malaysia. The diagnostic value of the biopsies was determined based on the criteria by Midroni and Bilbao as follows: contributive (essential and helpful), non-contributive and inadequate. RESULTS: A total of 107 nerve biopsies were analysed. Sixty-four (60 %) were males and the mean age was 52 years, ranging from 13 to 86 years. Ninety-four (88 %) were sural nerve biopsies; and only one patient (1 %) each had superficial peroneal and superficial radial nerve biopsy. The indications for the procedure were vasculitis (34 %), peripheral neuropathy of unknown aetiology (34 %), amyloidosis (14 %) and chronic inflammatory demyelinating polyneuropathy (10 %). In 68 (63 %) biopsies, the diagnostic value was contributive. Of these, 28 (26 %) were essential and 40 (37 %) were helpful. In contrast, 35 (33 %) biopsies were non-contributive and 4 (4 %) were inadequate. In 66 % (71/107) of cases, the nerve biopsy did not reveal a definite pathological diagnosis. However, in the remainder, a diagnosis of vasculitis (18 %, 19/107), followed by amyloidosis (10 %, 11/107) could be determined. For 32/71 biopsies with undetermined pathological diagnosis, neuropathy remained cryptogenic in 22 % (7/32) upon follow up. CONCLUSIONS: With the exception of vasculitis and amyloidosis, there is limited value in performing nerve biopsies in the evaluation of patients with peripheral neuropathy. However, this should be interpreted with caution as the number of patients with a clinical diagnosis of vasculitis and amyloidosis were relatively larger than patients with other diagnosis. Refinement and careful selection of cases are required to increase the diagnostic yield of nerve biopsy.
Subject(s)
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating , Vasculitis , Male , Humans , Middle Aged , Female , Biopsy/methods , Radial Nerve/pathology , Vasculitis/diagnosis , Retrospective Studies , Sural Nerve/pathologyABSTRACT
Background: Severe dysautonomia is typically seen during acute phase of Guillain-Barré syndrome (GBS). Objective: To investigate the relationship of cardiovascular autonomic dysfunction with motor recovery in GBS. Materials and Methods: Consecutive GBS patients presented to our hospital were recruited. Clinical assessment was evaluated with the Medical Research Council (MRC) sum score and GBS disability score (GDS). All patients had series of autonomic testing on admission and after treatment at 6 and 24 weeks. Both computation-dependent tests (heart rate variability [HRV] and baroreflex sensitivity [BRS]) and autonomic maneuvers were performed. Age- and gender-matched healthy controls (HC) were recruited. The data obtained at admission, 6 weeks and 24 weeks were compared within groups for statistical difference. Results: Six patients (4 men; mean age 39.5 ± 14.3 years) were recruited over one year. Five had GBS and one Miller Fisher syndrome. The mean MRC sum score and GDS on admission were 52.3 ± 4.3 and 3.5 ± 0.8 respectively. During admission, time-domain average RR interval (AVNN) and BRS were significantly poorer among cases compared to HC. Active standing 30:15 ratio and cold pressor test at admission were also significantly abnormal when compared with HC. All the autonomic parameters had normalized by 6 weeks and these were significant for the high frequency-HRV, BRS, and active standing 30:15 ratio. For MRC and GDS, there were significant improvements in the scoring over a period of 24 weeks. Conclusions: Dysautonomia in GBS improved gradually and in keeping with motor and disability recovery.
Subject(s)
Guillain-Barre Syndrome , Miller Fisher Syndrome , Primary Dysautonomias , Male , Humans , Adult , Middle Aged , Longitudinal Studies , Guillain-Barre Syndrome/complications , Guillain-Barre Syndrome/diagnosis , Heart Rate/physiology , Primary Dysautonomias/diagnosis , Primary Dysautonomias/etiologyABSTRACT
Electrodiagnostic (EDx) studies are helpful in diagnosing and subtyping of Guillain-Barré syndrome (GBS). Published criteria for differentiation into GBS subtypes focus on cutoff values, but other items receive less attention, although they may influence EDx subtyping: (a) extensiveness of EDx testing, (b) nerve-specific considerations, (c) distal compound muscle action potential (CMAP)-amplitude requirements, (d) criteria for conduction block and temporal dispersion. The aims of this study were to investigate how these aspects were approached by neuromuscular EDx experts in practice and how this was done in previously published EDx criteria for GBS. A completed questionnaire was returned by 24 (of 49) members of the electrophysiology expertise group from the International GBS Outcome Study. Six published EDx criteria for GBS subtyping were compared regarding these aspects. The indicated minimal number of motor nerves to study varied among respondents and tended to be more extensive in equivocal than normal studies. Respondents varied considerably regarding usage of compression sites for subtyping (median/wrist, ulnar/elbow, peroneal/fibular head): 29% used all variables from all sites, 13% excluded all sites, and 58% used only some sites and/or variables. Thirty-eight percent of respondents required a minimal distal CMAP amplitude to classify distal motor latency as demyelinating, and 58% did for motor conduction velocity. For proximal/distal CMAP-amplitude ratio and F-wave latency, a requisite minimal CMAP amplitude was more often required (79%). Also, the various published criteria sets showed differences on all items. Practical use of EDx criteria for subtyping GBS vary extensively across respondents, potentially lowering the reproducibility of GBS subtyping.
Subject(s)
Guillain-Barre Syndrome , Neural Conduction , Guillain-Barre Syndrome/diagnosis , Humans , Neural Conduction/physiology , Reproducibility of Results , Surveys and QuestionnairesABSTRACT
This paper presents results from the first survey of training and education undertaken by the Europe-Middle East-Africa (EMEAC), the Latin America (LAC) and the Asia-Oceania (AOC) Chapters of the International Federation of Clinical Neurophysiology (IFCN). The survey was conducted initially by the EMEAC in 2012 and updated in 2016, 2019, and 2020. It had the following categories: status of specialty and training in member country (21 questions), competency and accreditation (12 questions), practice and concerns (23 questions). An abbreviated version of the survey was conducted by the LAC and AOC in 2018-2019. Clinical neurophysiology (CN) was a single specialty in a minority of member societies' countries: 8/33 EMEAC, 2/12 AOC and 2/10 LAC. In others it was usually a subspecialty of neurology. Training periods in CN were split fairly evenly between 1, 2, 3, 4 and 5â¯years in EMEAC, while neurology takes 4 to 5â¯years. In the AOC, neurology training was for 3 to 4â¯years and CN for up to 2â¯years. In LAC a majority of countries trained for 2 to 3â¯years in both neurology and CN. An exit exam was performed in 16/30 EMEAC respondents, 8/12 in the AOC and 3/10 in the LAC. Competence was considered to require a wide range of numbers of tests performed under supervision, fromâ¯<250 toâ¯>750 in EMEAC and AOC, with the EMEAC tending to require more. The main concerns were in recruitment and workload in EMEAC, training in AOC and the need for more recognition of the specialty in some countries within the LAC. This survey, the first across the three chapters, revealed considerable differences in training durations and numbers of tests performed for competence between national societies.
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BACKGROUND AND AIM: Percutaneous endoscopic gastrostomy (PEG) placement is recommended in patients with amyotrophic lateral sclerosis (ALS), but the procedure is considered high risk. In this study, we aimed to compare the outcome of ALS patients with and without PEG. The success of the procedure and complications of PEG insertion were also explored. METHODS: Patients with ALS who met the criteria for enteral feeding support were consecutively recruited. Patients who consented had PEG insertion using the modified technique of introducer method with transoral ultra-slim endoscopy. RESULTS: A total of 64 patients were recruited, of which 36 (56%) patients consented to PEG. The median age of all patients was 65 years and 59% were male. There was no difference in demographic and clinical characteristics between patients who agreed to a PEG and those who did not. The mortality rate at 6 and 12 months was lower in the PEG cohort compared with non-PEG, but this was not statistically significant (6 months: 28.6% vs 32.2%, P = 0.561; 12 months: 38.9% vs 50.0%, P = 0.374). Amongst the PEG cohort, 61% were stratified high risk and 31% moderate risk. Thirty-one percent of them required long-term home noninvasive ventilation. All patients (100%) underwent successful PEG insertion at single attempt using the modified approach. The complications reported over a period of 6 months were infected PEG site (17%), dislodged gastrostomy tube (14%), and minor bleeding (8%). CONCLUSION: In ALS patients with moderate to high risk of PEG insertion, the introducer technique utilizing ultra-slim endoscopy guidance was well tolerated and safe.
Subject(s)
Amyotrophic Lateral Sclerosis , Gastrostomy , Aged , Amyotrophic Lateral Sclerosis/complications , Endoscopy, Gastrointestinal/adverse effects , Endoscopy, Gastrointestinal/methods , Enteral Nutrition , Female , Gastrostomy/methods , Humans , Male , Retrospective StudiesABSTRACT
We report on our cohort of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) who fulfilled the 2010 diagnostic criteria of CIDP. Patients were consecutively recruited and their demographics, clinical features and serological analysis of autoantibodies against neurofascin (NF)-155, NF-186, contactin-1 (CNTN1) and contactin-associated protein 1 were obtained. A total of 26 patients for which there was serologic testing were included: 22 typical CIDP, 3 distal CIDP and 1 multifocal CIDP. Of these, 2 patients had previously reported paranodal antibodies; one with autoantibodies IgG4 against NF155 and one with IgG4 against CNTN1. The patient with IgG4 anti-NF155 had young-onset, predominantly distal phenotype with associated tremor and sensory ataxia and poor response to intravenous immunoglobulin (IVIG). The patient with IgG4 anti-CNTN1 antibodies had a subacute onset, sensory ataxia, membranous nephropathy but responded poorly to IVIG. Autoimmune nodopathies represented 8% of our CIDP cohort. The clinical features and treatment response of patients with IgG4 anti-NF155 and anti-CNTN1 were similar to previous reports. Detecting the presence of autoimmune nodopathies was crucial in refining the diagnosis and determining the prognosis.
Subject(s)
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating , Ataxia , Autoantibodies , Cell Adhesion Molecules , Contactin 1 , Humans , Immunoglobulin G , Immunoglobulins, Intravenous , Nerve Growth Factors , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/diagnosisABSTRACT
OBJECTIVE: To describe the heterogeneity of electrodiagnostic (EDx) studies in Guillain-Barré syndrome (GBS) patients collected as part of the International GBS Outcome Study (IGOS). METHODS: Prospectively collected clinical and EDx data were available in 957 IGOS patients from 115 centers. Only the first EDx study was included in the current analysis. RESULTS: Median timing of the EDx study was 7 days (interquartile range 4-11) from symptom onset. Methodology varied between centers, countries and regions. Reference values from the responding 103 centers were derived locally in 49%, from publications in 37% and from a combination of these in the remaining 15%. Amplitude measurement in the EDx studies (baseline-to-peak or peak-to-peak) differed from the way this was done in the reference values, in 22% of motor and 39% of sensory conduction. There was marked variability in both motor and sensory reference values, although only a few outliers accounted for this. CONCLUSIONS: Our study showed extensive variation in the clinical practice of EDx in GBS patients among IGOS centers across the regions. SIGNIFICANCE: Besides EDx variation in GBS patients participating in IGOS, this diversity is likely to be present in other neuromuscular disorders and centers. This underlines the need for standardization of EDx in future multinational GBS studies.
Subject(s)
Guillain-Barre Syndrome , Neural Conduction , Electrodiagnosis/methods , Guillain-Barre Syndrome/diagnosis , Humans , Neural Conduction/physiology , Outcome Assessment, Health Care , Reference ValuesABSTRACT
BACKGROUND AND OBJECTIVES: The clinical course and outcome of the Guillain-Barré syndrome (GBS) are diverse and vary among regions. The modified Erasmus GBS Outcome Score (mEGOS), developed with data from Dutch patients, is a clinical model that predicts the risk of walking inability in patients with GBS. The study objective was to validate the mEGOS in the International GBS Outcome Study (IGOS) cohort and to improve its performance and region specificity. METHODS: We used prospective data from the first 1,500 patients included in IGOS, aged ≥6 years and unable to walk independently. We evaluated whether the mEGOS at entry and week 1 could predict the inability to walk unaided at 4 and 26 weeks in the full cohort and in regional subgroups, using 2 measures for model performance: (1) discrimination: area under the receiver operating characteristic curve (AUC) and (2) calibration: observed vs predicted probability of being unable to walk independently. To improve the model predictions, we recalibrated the model containing the overall mEGOS score, without changing the individual predictive factors. Finally, we assessed the predictive ability of the individual factors. RESULTS: For validation of mEGOS at entry, 809 patients were eligible (Europe/North America [n = 677], Asia [n = 76], other [n = 56]), and 671 for validation of mEGOS at week 1 (Europe/North America [n = 563], Asia [n = 65], other [n = 43]). AUC values were >0.7 in all regional subgroups. In the Europe/North America subgroup, observed outcomes were worse than predicted; in Asia, observed outcomes were better than predicted. Recalibration improved model accuracy and enabled the development of a region-specific version for Europe/North America (mEGOS-Eu/NA). Similar to the original mEGOS, severe limb weakness and higher age were the predominant predictors of poor outcome in the IGOS cohort. DISCUSSION: mEGOS is a validated tool to predict the inability to walk unaided at 4 and 26 weeks in patients with GBS, also in countries outside the Netherlands. We developed a region-specific version of mEGOS for patients from Europe/North America. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the mEGOS accurately predicts the inability to walk unaided at 4 and 26 weeks in patients with GBS. TRIAL REGISTRATION INFORMATION: NCT01582763.