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1.
Ann Neurol ; 91(1): 66-77, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34761434

RESUMO

OBJECTIVE: Small fiber neuropathy (SFN) is clinically and etiologically heterogeneous. Although autoimmunity has been postulated to be pathophysiologically important in SFN, few autoantibodies have been described. We aimed to identify autoantibodies associated with idiopathic SFN (iSFN) by a novel high-throughput protein microarray platform that captures autoantibodies expressed in the native conformational state. METHODS: Sera from 58 SFN patients and 20 age- and gender-matched healthy controls (HCs) were screened against >1,600 immune-related antigens. Fluorescent unit readout and postassay imaging were performed, followed by composite data normalization and protein fold change (pFC) analysis. Analysis of an independent validation cohort of 33 SFN patients against the same 20 HCs was conducted to identify reproducible proteins in both cohorts. RESULTS: Nine autoantibodies were screened with statistical significance and pFC criteria in both cohorts, with at least 50% change in serum levels. Three proteins showed consistently high fold changes in main and validation cohorts: MX1 (FC = 2.99 and 3.07, respectively, p = 0.003, q = 0.076), DBNL (FC = 2.11 and 2.16, respectively, p = 0.009, q < 0.003), and KRT8 (FC = 1.65 and 1.70, respectively, p = 0.043, q < 0.003). Further subgroup analysis into iSFN and SFN by secondary causes (secondary SFN) in the main cohort showed that MX1 is higher in iSFN compared to secondary SFN (FC = 1.61 vs 0.106, p = 0.009). INTERPRETATION: Novel autoantibodies MX1, DBNL, and KRT8 are found in iSFN. MX1 may allow diagnostic subtyping of iSFN patients. ANN NEUROL 2022;91:66-77.


Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Neuropatia de Pequenas Fibras/imunologia , Adulto , Idoso , Autoanticorpos/sangue , Estudos de Coortes , Feminino , Humanos , Queratina-8/imunologia , Masculino , Proteínas dos Microfilamentos/imunologia , Pessoa de Meia-Idade , Proteínas de Resistência a Myxovirus/imunologia , Neuropatia de Pequenas Fibras/sangue , Domínios de Homologia de src/imunologia
2.
Muscle Nerve ; 67(4): 259-271, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36448457

RESUMO

Small-fiber neuropathy (SFN) is a disorder that exclusively affects the small nerve fibers, sparing the large nerve fibers. Thinly myelinated Aδ-fibers and unmyelinated C-fibers are damaged, leading to development of neuropathic pain, thermal dysfunction, sensory symptoms, and autonomic disturbances. Although many SFNs are secondary and due to immunological causes or metabolic disturbances, the etiology is unknown in up to half of the patients. Over the years, this proportion of "idiopathic SFN" has decreased, as familial and genetic causes have been discovered, thus shifting a proportion of once "idiopathic" cases to the genetic category. After the discovery of SCN9A-gene variants in 2012, SCN10A and SCN11A variants have been found to be pathogenic in SFN. With improved accessibility of SFN diagnostic tools and genetic tests, many non-SCN variants and genetically inherited systemic diseases involving the small nerve fibers have also been described, but only scattered throughout the literature. There are 80 SCN variants described as causing SFN, 8 genes causing hereditary sensory autonomic neuropathies (HSAN) described with pure SFN, and at least 7 genes involved in genetically inherited systemic diseases associated with SFN. This systematic review aims to consolidate and provide an updated overview on the genetic variants of SFN to date---SCN genes and beyond. Awareness of these genetic causes of SFN is imperative for providing treatment directions, prognostication, and management of expectations for patients and their health-care providers.


Assuntos
Neuralgia , Neuropatia de Pequenas Fibras , Humanos , Neuropatia de Pequenas Fibras/patologia , Neuralgia/etiologia , Fibras Nervosas Amielínicas/patologia , Testes Genéticos , Causalidade , Canal de Sódio Disparado por Voltagem NAV1.7/genética
3.
Curr Pain Headache Rep ; 25(8): 53, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34129112

RESUMO

PURPOSE OF REVIEW: Personal protection equipment (PPE)-associated headache is an unusual secondary headache disorder that predominantly occurs in healthcare workers as a consequence of the donning of protective respirators, face masks and/or eyewear. The appreciation of this entity is important given the significant ramifications upon the occupational health of healthcare workers and could additionally have an impact on persons living with pre-existing headache disorder(s). RECENT FINDINGS: There has been a renewed interest and recognition of PPE-associated headaches amongst healthcare professionals, largely brought about by the ongoing COVID-19 pandemic which has besieged healthcare systems worldwide. De novo PPE-associated headaches may present with migrainous or tension-type features and can be viewed as a subtype of external compression headache. The prognosis of the disorder is generally favourable, given that most headaches are short-lived without long-term sequalae. Several aetiologies have been postulated to account for the development of these headaches. Notably, these headaches can affect the occupational health and work performance of healthcare workers. In this review, we discuss the epidemiology, clinical characteristics, probable etiopathogenesis, management and prognosis of PPE-associated headaches in the context of the COVID-19 pandemic. Future directions for research and PPE development are proposed.


Assuntos
COVID-19/prevenção & controle , Cefaleia/epidemiologia , Cefaleia/terapia , Equipamento de Proteção Individual/efeitos adversos , COVID-19/epidemiologia , COVID-19/transmissão , Cefaleia/diagnóstico , Pessoal de Saúde , Humanos
4.
Mycoses ; 64(10): 1253-1260, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34255907

RESUMO

IMPORTANCE: Coronavirus disease (COVID-19) causes an immunosuppressed state and increases risk of secondary infections like mucormycosis. We evaluated clinical features, predisposing factors, diagnosis and outcomes for mucormycosis among patients with COVID-19 infection. METHODS: This prospective, observational, multi-centre study included 47 consecutive patients with mucormycosis, diagnosed during their course of COVID-19 illness, between January 3 and March 27, 2021. Data regarding demography, underlying medical conditions, COVID-19 illness and treatment were collected. Clinical presentations of mucormycosis, imaging and biochemical characteristics and outcome were recorded. RESULTS: Of the 2567 COVID-19 patients admitted to 3 tertiary centres, 47 (1.8%) were diagnosed with mucormycosis. Mean age was 55 ± 12.8years, and majority suffered from diabetes mellitus (n = 36, 76.6%). Most were not COVID-19 vaccinated (n = 31, 66.0%) and majority (n = 43, 91.5%) had developed moderate-to-severe pneumonia, while 20 (42.6%) required invasive ventilation. All patients had received corticosteroids and broad-spectrum antibiotics while most (n = 37, 78.7%) received at least one anti-viral medication. Mean time elapsed from COVID-19 diagnosis to mucormycosis was 12.1 ± 4.6days. Eleven (23.4%) subjects succumbed to their disease, mostly (n = 8, 72.7%) within 7 days of diagnosis. Among the patients who died, 10 (90.9%) had pre-existing diabetes mellitus, only 2 (18.2%) had received just one vaccine dose and all developed moderate-to-severe pneumonia, requiring oxygen supplementation and mechanical ventilation. CONCLUSIONS: Mucormycosis can occur among COVID-19 patients, especially with poor glycaemic control, widespread and injudicious use of corticosteroids and broad-spectrum antibiotics, and invasive ventilation. Owing to the high mortality, high index of suspicion is required to ensure timely diagnosis and appropriate treatment in high-risk populations.


Assuntos
Corticosteroides/efeitos adversos , COVID-19/epidemiologia , Mucormicose/epidemiologia , Respiração Artificial/efeitos adversos , Corticosteroides/uso terapêutico , Antifúngicos/uso terapêutico , Antivirais/uso terapêutico , COVID-19/mortalidade , Coinfecção/microbiologia , Complicações do Diabetes , Diabetes Mellitus/patologia , Humanos , Índia/epidemiologia , Pessoa de Meia-Idade , Mucormicose/tratamento farmacológico , Mucormicose/mortalidade , Estudos Prospectivos , Ventiladores Mecânicos/efeitos adversos , Tratamento Farmacológico da COVID-19
5.
Muscle Nerve ; 53(5): 671-82, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26872938

RESUMO

Etiological and clinical heterogeneity of small fiber neuropathy (SFN) precludes a unifying approach and necessitates reliance on recognizable clinical syndromes. Symptoms of SFN arise from dysfunction in nociception, temperature, and autonomic modalities. This review focuses on SFN involving nociception and temperature, examining epidemiology, etiology, clinical presentation, diagnosis, pathophysiology, and management. Prevalence of SFN is 52.95 per 100,000 population, and diabetes and idiopathic are the most common etiologies. Dysesthesia, allodynia, pain, burning, and coldness sensations frequently present in a length-dependent pattern. Additional autonomic features in gastrointestinal, urinary, or cardiovascular systems are frequent but poorly objectified. SFN is diagnosed by intraepidermal nerve fiber density and quantitative sensory and autonomic tests in combination with normal nerve conduction. Pathophysiological understanding centers on sodium channel dysfunction, and genetic forms are beginning to be understood. Treatment is directed at the underlying etiology supported by symptomatic treatment using antidepressants and anticonvulsants. Little is known about long-term outcomes, and systematic cohort studies are needed.


Assuntos
Doenças do Sistema Nervoso Autônomo/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Eritromelalgia/fisiopatologia , Hiperalgesia/fisiopatologia , Parestesia/fisiopatologia , Anticonvulsivantes/uso terapêutico , Antidepressivos/uso terapêutico , Doenças do Sistema Nervoso Autônomo/etiologia , Neuropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/terapia , Gerenciamento Clínico , Eritromelalgia/complicações , Eritromelalgia/epidemiologia , Eritromelalgia/terapia , Humanos , Hiperalgesia/etiologia , Condução Nervosa , Nociceptividade/fisiologia , Parestesia/etiologia , Canais de Sódio , Temperatura
6.
7.
Front Neurol ; 14: 1177500, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37325226

RESUMO

Intracranial stenosis is prevalent among Asians and constitutes a common cause of cerebral ischemia. While the best medical therapy carries stroke recurrence rates in excess of 10% per year, trials with intracranial stenting have been associated with unacceptable peri-procedural ischemic events. Cerebral ischemic events are strongly related to the severity of intracranial stenosis, which is high in patients with severe intracranial stenosis with poor vasodilatory reserve. Enhanced External Counter Pulsation (EECP) therapy is known to improve myocardial perfusion by facilitating the development of collateral blood vessels in the heart. In this randomized clinical trial, we evaluate whether EECP therapy may be useful in patients with severe stenosis of intracranial internal carotid (ICA) or middle cerebral artery (MCA). The review of literature, methods of evaluation, status of currently used therapeutic approaches, and trial protocol have been presented. Clinical trial registration: ClinicalTrials.gov, Identifier: NCT03921827.

8.
Front Neurol ; 13: 972336, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061988

RESUMO

Introduction: White matter hyperintensities (WMHs) have been observed with greater frequency in patients with migraine and are thought to be associated with impaired cognition and function. The relationship between WMHs and right-to-left shunt (RLS) in migraine patients is unknown. We performed a systematic review to determine if there is an association between RLS and WMHs in patients with migraine. Methods: A systematic search of the literature was performed in PubMed and Embase using a suitable keyword search strategy from inception up to 16th June 2021. All studies that included patients with migraine and studied RLS and WMHs were included. Results: A total of 8 non-randomized observational studies comprising 1125 patients with migraine were included; 576 had an RLS, compared to 549 patients with no RLS. The mean age of the study populations ranged from 28.4 to 43 years, while the average duration from migraine diagnosis ranged from 5.1 to 19 years. The proportion of female to male patients was consistently higher in all studies (60.0-94.4%). Amongst migraine patients with RLS, 338 patients (58.7%) had WMHs. In contrast, 256 (46.6%) of migraine patients without RLS had WMHs. RLS was significantly associated with the presence of WMHs in migraine patients (OR: 1.56, 95% CI: 1.05-2.34, p = 0.03). Conclusion: In migraine patients, RLS was significantly associated with the presence of WMHs. Longitudinal studies are warranted to establish RLS as a risk factor for WMHs in patients with migraine, and to establish the significance of these changes.

9.
Brain Sci ; 11(8)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34439587

RESUMO

Impaired sense of smell occurs in a fraction of patients with COVID-19 infection, but its effect on cerebral activity is unknown. Thus, this case report investigated the effect of COVID-19 infection on frontotemporal cortex activity during olfactory stimuli. In this preliminary study, patients who recovered from COVID-19 infection (n = 6) and healthy controls who never contracted COVID-19 (n = 6) were recruited. Relative changes in frontotemporal cortex oxy-hemoglobin during olfactory stimuli was acquired using functional near-infrared spectroscopy (fNIRS). The area under curve (AUC) of oxy-hemoglobin for the time interval 5 s before and 15 s after olfactory stimuli was derived. In addition, olfactory function was assessed using the Sniffin' Sticks 12-identification test (SIT-12). Patients had lower SIT-12 scores than healthy controls (p = 0.026), but there were no differences in oxy-hemoglobin AUC between healthy controls and patients (p > 0.05). This suggests that past COVID-19 infection may not affect frontotemporal cortex function, and these preliminary results need to be verified in larger samples.

10.
J Neurol Sci ; 417: 117078, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32768718

RESUMO

BACKGROUND AND AIM: COVID-19 pandemic has resulted in an unprecedented increased usage of Personal protective equipment (PPE) by healthcare-workers. PPE usage causes headache in majority of users. We evaluated changes in cerebral hemodynamics among healthcare-workers using PPE. METHODS: Frontline healthcare-workers donning PPE at our tertiary center were included. Demographics, co-morbidities and blood-pressure were recorded. Transcranial Doppler (TCD) monitoring of middle cerebral artery was performed with 2-MHz probe. Mean flow velocity (MFV) and pulsatility index (PI) were recorded at baseline, after donning N95 respirator-mask, and after donning powered air-purifying respirator (PAPR), when indicated. End-tidal carbon-dioxide (ET-CO2) pressure was recorded for participants donning PAPR in addition to the N95 respirator-mask. RESULTS: A total of 154 healthcare-workers (mean age 29 ± 12 years, 67% women) were included. Migraine was the commonest co-morbidity in 38 (25%) individuals while 123 (80%) developed de-novo headache due to N95 mask. Donning of N95 respirator-mask resulted in significant increase in MFV (4.4 ± 10.4 cm/s, p < 0.001) and decrease in PI (0.13 ± 0.12; p < 0.001) while ET-CO2 increased by 3.1 ± 1.2 mmHg (p < 0.001). TCD monitoring in 24 (16%) participants donning PAPR and N95 respirator mask together showed normalization of PI, accompanied by normalization of ET-CO2 values within 5-min. Combined use of N95 respirator-mask and PAPR was more comfortable as compared to N95 respirator-mask alone. CONCLUSION: Use of N95 respirator-mask results in significant alterations in cerebral hemodynamics. However, these effects are mitigated by the use of additional PAPR. We recommend the use of PAPR together with the N95 mask for healthcare-workers doing longer duties in the hospital wards.


Assuntos
Betacoronavirus , Pessoal de Saúde , Máscaras/efeitos adversos , Doenças Profissionais/prevenção & controle , Pandemias , Dispositivos de Proteção Respiratória , Adulto , Velocidade do Fluxo Sanguíneo , COVID-19 , Dióxido de Carbono/análise , Circulação Cerebrovascular , Infecções por Coronavirus/prevenção & controle , Estudos Transversais , Feminino , Cefaleia/etiologia , Hemodinâmica , Humanos , Masculino , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/fisiopatologia , Doenças Profissionais/etiologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Fluxo Pulsátil , SARS-CoV-2 , Ultrassonografia Doppler Transcraniana , Adulto Jovem
14.
Spine Deform ; 3(2): 151-158, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27927306

RESUMO

STUDY DESIGN: Retrospective reliability study of the coronal curvature measurement on ultrasound (US) imaging in adolescent idiopathic scoliosis (AIS). OBJECTIVES: To determine the intra- and inter-rater reliability and validity of the coronal curvature measurements obtained from US images. SUMMARY OF BACKGROUND DATA: Cobb angle measurements on radiographs are the usual method to diagnose and monitor the progression of scoliosis. Repeated ionizing radiation exposure is a frequent concern of patients and their families. Use of US imaging method to measure coronal curvature in children who have idiopathic scoliosis has not been clinically validated. METHODS: The researchers scanned 26 subjects using a medical 3-dimensional US system. Spinal radiographs were obtained on the same day from the local scoliosis clinic. Three raters used the center of lamina method to measure the coronal curvature on the US images twice 1 week apart. The raters also measured the Cobb angle on the radiographs twice. Intra- and inter-rater reliability of the coronal curvature measurement from the US images was analyzed using intra-class correlation coefficients. The correlation coefficient of the US coronal curvature measurements was compared with the Cobb angles. RESULTS: The intra-class correlation coefficient (2,1) values of intra- and inter-rater reliability on the US method were greater than 0.80. Standard error of measurement on both of the intra- and inter-rater US methods was less than 2.8°. The correlation coefficient between the US and radiographic methods ranged between 0.78 and 0.84 among 3 raters. CONCLUSIONS: The US method illustrated substantial intra- and inter-rater reliability. The measurement difference between radiography and the US method was within the range of clinically acceptable error (5°). The US method may be considered a radiation-free alternative to assess children with scoliosis of mild to moderate severity.

15.
Spine Deform ; 2(3): 168-175, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-27927414

RESUMO

STUDY DESIGN: A reliability analysis of Cobb angle, vertebral rotation (VR), and spinous process angle (SPA) measurements in adolescent idiopathic scoliosis. OBJECTIVE: To determine the intra- and interobserver reliability of semi-automated digital radiograph measurements. SUMMARY OF BACKGROUND DATA: Cobb angle measurements on posteroanterior radiographs are commonly used to determine the severity of scoliosis. Vertebral rotation helps assess scoliosis 3-dimensionally and has a role in predicting curve progression. Recent studies have shown that the spinous process angle is a useful parameter in assessing scoliosis when using ultrasound imaging. Because the reliability of SPA measurements on radiographs has yet to be determined, it is important to compare the reliability of these 3 parameters (Cobb angle, VR, and SPA) using a computer assisted semi-automated method. METHODS: Sixty posteroanterior radiographs of patients with adolescent idiopathic scoliosis were obtained and measured twice by 3 observers who were blinded to their previous measurements, using an in-house developed program. Measurements were obtained using a semi-automated method to minimize variability resulting from observer reliability. The intra- and interobserver reliabilities were analyzed using intra-class correlation coefficients (ICCs) as well as Bland-Altman's bias and limits of agreement. RESULTS: Over 350 (intra) and 90 (inter) sets of curves with an average Cobb angle of 26° ± 9° (range, 10° to 44°) were compared for each parameter. Intra-observer reliabilities for each parameter were excellent (ICC[2,1], .82; 1.00), with mean absolute differences under 3° between most measurements. Interobserver reliability (ICC[2,1], .72; .95) was mostly good to excellent, with mean absolute differences ranging from 2.0° to 5.6°. CONCLUSIONS: Both the intra- and interobserver assessment of the Cobb, VR, and SPA from the semi-automated measurements had clinically acceptable reliability ranges and may be considered for clinical implementation. Additional studies will be conducted to determine the accuracy and sensitivity to change of these scoliosis severity measurements.

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