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BACKGROUND: The novel optic neuritis (ON) diagnostic criteria include intereye differences (IED) of optical coherence tomography (OCT) parameters. IED has proven valuable for ON diagnosis in multiple sclerosis but has not been evaluated in aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders (AQP4+NMOSD). We evaluated the diagnostic accuracy of intereye absolute (IEAD) and percentage difference (IEPD) in AQP4+NMOSD after unilateral ON >6 months before OCT as compared with healthy controls (HC). METHODS: Twenty-eight AQP4+NMOSD after unilateral ON (NMOSD-ON), 62 HC and 45 AQP4+NMOSD without ON history (NMOSD-NON) were recruited by 13 centres as part of the international Collaborative Retrospective Study on retinal OCT in Neuromyelitis Optica study. Mean thickness of peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell and inner plexiform layer (GCIPL) were quantified by Spectralis spectral domain OCT. Threshold values of the ON diagnostic criteria (pRNFL: IEAD 5 µm, IEPD 5%; GCIPL: IEAD: 4 µm, IEPD: 4%) were evaluated using receiver operating characteristics and area under the curve (AUC) metrics. RESULTS: The discriminative power was high for NMOSD-ON versus HC for IEAD (pRNFL: AUC 0.95, specificity 82%, sensitivity 86%; GCIPL: AUC 0.93, specificity 98%, sensitivity 75%) and IEPD (pRNFL: AUC 0.96, specificity 87%, sensitivity 89%; GCIPL: AUC 0.94, specificity 96%, sensitivity 82%). The discriminative power was high/moderate for NMOSD-ON versus NMOSD-NON for IEAD (pRNFL: AUC 0.92, specificity 77%, sensitivity 86%; GCIP: AUC 0.87, specificity 85%, sensitivity 75%) and for IEPD (pRNFL: AUC 0.94, specificity 82%, sensitivity 89%; GCIP: AUC 0.88, specificity 82%, sensitivity 82%). CONCLUSIONS: Results support the validation of the IED metrics as OCT parameters of the novel diagnostic ON criteria in AQP4+NMOSD.
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Aquaporinas , Neuromielite Óptica , Neurite Óptica , Humanos , Neuromielite Óptica/diagnóstico , Estudos Retrospectivos , Benchmarking , Neurite Óptica/diagnóstico , Tomografia de Coerência Óptica/métodos , Autoanticorpos , Aquaporina 4RESUMO
BACKGROUND: Patients with anti-aquaporin-4 antibody seropositive (AQP4-IgG+) neuromyelitis optica spectrum disorders (NMOSDs) frequently suffer from optic neuritis (ON) leading to severe retinal neuroaxonal damage. Further, the relationship of this retinal damage to a primary astrocytopathy in NMOSD is uncertain. Primary astrocytopathy has been suggested to cause ON-independent retinal damage and contribute to changes particularly in the outer plexiform layer (OPL) and outer nuclear layer (ONL), as reported in some earlier studies. However, these were limited in their sample size and contradictory as to the localisation. This study assesses outer retinal layer changes using optical coherence tomography (OCT) in a multicentre cross-sectional cohort. METHOD: 197 patients who were AQP4-IgG+ and 32 myelin-oligodendrocyte-glycoprotein antibody seropositive (MOG-IgG+) patients were enrolled in this study along with 75 healthy controls. Participants underwent neurological examination and OCT with central postprocessing conducted at a single site. RESULTS: No significant thinning of OPL (25.02±2.03 µm) or ONL (61.63±7.04 µm) were observed in patients who were AQP4-IgG+ compared with patients who were MOG-IgG+ with comparable neuroaxonal damage (OPL: 25.10±2.00 µm; ONL: 64.71±7.87 µm) or healthy controls (OPL: 24.58±1.64 µm; ONL: 63.59±5.78 µm). Eyes of patients who were AQP4-IgG+ (19.84±5.09 µm, p=0.027) and MOG-IgG+ (19.82±4.78 µm, p=0.004) with a history of ON showed parafoveal OPL thinning compared with healthy controls (20.99±5.14 µm); this was not observed elsewhere. CONCLUSION: The results suggest that outer retinal layer loss is not a consistent component of retinal astrocytic damage in AQP4-IgG+ NMOSD. Longitudinal studies are necessary to determine if OPL and ONL are damaged in late disease due to retrograde trans-synaptic axonal degeneration and whether outer retinal dysfunction occurs despite any measurable structural correlates.
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Aquaporina 4/sangue , Neuromielite Óptica/fisiopatologia , Retina/fisiopatologia , Adulto , Astrócitos/patologia , Autoanticorpos , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia de Coerência ÓpticaRESUMO
BACKGROUND: Admittedly, little is known about the epidemiological signatures of familial multiple sclerosis (FMS) in different geographical regions of Iran. OBJECTIVE: To determine the epidemiology and the risk of FMS incidence in several provinces of Iran with a different ethnic population including, Fars, Tehran, Isfahan (Persians), and Mazandaran (Mazanis), Kermanshah (Kurds), and Chaharmahal and Bakhtiari (Lors). METHODS: This cross-sectional registry-based study was performed on nationwide MS registry of Iran (NMSRI) data collected from 2018 to 2021. This system, registers baseline characteristics, clinical presentations and symptoms, diagnostic and treatments at regional and national levels. RESULTS: A total of 9200 patients including, 7003 (76.1%) female and 2197 (23.9%) male, were participated. About 19% of patients reported a family history of MS; the order from highest to lowest FMS prevalence was as follows: Fars (26.5%), Chaharmahal and Bakhtiari (21.1%), Tehran (20.5%), Isfahan (20.3%), Mazandaran (18.0%), and Kermanshah (12.5%). Of all FMS cases, 74.7% (1308 cases) were female and 25.3% (442 cases) were male. FMS occurrence was much more common in females than males (P-value = 0.001). Further, the mean age at onset was 30 years among FMS cases. A substantially higher probability of relapsing-remitting MS and secondary-progressive MS was found among FMS cases than sporadic MS (SMS) (P_value = 0.001). There was no significant difference in Expanded Disability Status Scale (EDSS) scores between FMS and SMS. The majority of FMS cases were observed among first-degree relatives, with the highest rate in siblings. There was a significant association between MS risk and positive familial history in both maternal and paternal aunt/uncle (P_value = 0.043 and P_value = 0.019, respectively). Multiple sclerosis occurrence among offspring of females was higher than males (P_value = 0.027). CONCLUSIONS: In summary, our findings imply a noteworthy upward trend of FMS in Iran, even more than the global prevalence, which suggests a unique Atlas of FMS prevalence in this multi-ethnic population. Despite the highest rate of FMS within Persian and Lor ethnicities, no statistically significant difference was observed among the provinces.
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Esclerose Múltipla , Estudos Transversais , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Esclerose Múltipla/epidemiologia , Prevalência , Sistema de RegistrosRESUMO
Background: Ponticulus posticus (PP) (arcuate foramen) is an abnormal bony bridge in the posterior arch of the atlas, which could possibly cause certain complications such as headache. Our goal was to assess the prevalence and size of PP on lateral cephalometric radiographs and its relationships with cervicogenic headache and migraine. Materials and Methods: This cross-sectional study was a descriptive-analytical type and was performed in Isfahan Azad Dental University. Lateral cephalometric radiographs of 150 patients referred to the radiology department were selected to assess the prevalence and size of the anomaly. A checklist was prepared to evaluate cervicogenic headache and migraine among patients. Results: Our sample consisted of 97 females and 53 males with an age range between 5 and 56 years. The prevalence of PP was 21.3% (12% complete and 9.3% incomplete), and an insignificant difference was noted between the prevalence of complete and incomplete foramen (P > 0.05). The prevalence of foramen was higher in women (59.4%), but it was not significant. The mean width of complete foramen was 6.40 mm, and the mean heights in individuals with complete and incomplete foramen were 4.71 and 4.84 mm, respectively. Among patients with the anomaly, 43.8% had cervicogenic headache and 9.4% had migraine. There was a significant association between the presence of foramen and both types of headaches (P < 0.05). However, there was no significant correlation between the shape of anomaly and the presence of cervicogenic headache and migraine (P > 0.05). Conclusion: Our study showed a high prevalence of PP and its significant association with cervicogenic headache and migraine.
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Background: Interleukin-6 (IL-6) is an important mediator in the acute phase of inflammatory diseases such as neuromyelitis optica (NMO) and multiple sclerosis (MS). The level of IL-6 is higher in cerebrospinal fluid and serum of NMO patients compare to MS. Vitamin D has a regulatory effect on IL-6, so it may have a negative correlation with IL-6 in the acute phase of these diseases. This study was performed to evaluate the serum levels of IL-6 and Vitamin D in NMO and MS patients at the onset of disease to find differences that may help in early diagnosis. Materials and Methods: This case-control study was done on patients with the first episode of optic neuritis, transverse myelitis, and area postrema syndrome who were referred to Kashani MS Center in Isfahan, Iran, between January 2018 and January 2020. The serum levels of Vitamin D and IL-6 were assessed using enzyme-linked immunosorbent assay in blood sample taken at the time of first presentation in patients who had a definitive diagnosis of NMO and MS during subsequent workup. Results: During a 2-year follow-up, definitive diagnosis of NMO was given in 25 cases, and they were compared with 25 cases that were randomly selected from patients with definite MS. Nineteen patients in the NMO group and 21 patients in the MS group were female. The mean age of patients in the NMO and MS groups was 29.64 ± 1.47 and 30.20 ± 1.42, respectively (P = 0.46). The mean of serum level of Vitamin D was 24.88 ± 15.2 in NMO patients and 21.56 ± 18.7 in MS patients without significant difference (P = 0.48). The mean of IL-6 was 30.1 ± 22.62 in the NMO group and 23.35 ± 18.8 in the MS group without significant difference (P = 0.28). The serum levels of Vitamin D were insufficient in both groups. No correlation between Vitamin D and IL-6 levels was found in our study (P > 0.05). Conclusion: Our results showed that serum IL-6 levels were higher at the onset of NMO disease compared with MS. The serum levels of Vitamin D were low in both groups and there was no association between serum levels of Vitamin D and IL-6 in either group. Future studies with large sample size are needed to confirm these findings.
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Dysphagia and symptoms of depression, anxiety and stress are common in persons with multiple sclerosis (MS). We posited a relationship between dysphagia and increased frequency of psychological symptoms. Therefore, the aim of the present study was to examine associations between symptoms of psychological difficulties, use of emotional suppression and cognitive reappraisal strategies, and dysphagia status in persons with MS. One hundred persons with MS were prospectively assessed in multiple domains of functioning: cognitive, psychological, and dysphagia-related. Participants underwent cognitive screening with the Mini Mental State Examination and completed two psychological inventories: The depression, anxiety and stress scale (DASS)-21 and the Emotion Regulation Questionnaire. Further, they completed the dysphagia in Multiple Sclerosis questionnaire. A speech-language pathologist evaluated persons suspected of having dysphagia with the Mann Assessment of Swallowing Ability. Dysphagia was present in 29 persons with MS, and the sample was split accordingly. The two groups differed at baseline with respect to Expanded Disability Status Scale scores. There were significant between-group differences for mental health symptoms and for use of emotional regulation strategies. Accordingly, multivariate logistic regressions showed that increased symptoms of psychological stress, decreased use of cognitive reappraisal strategies, and increased indicators of emotional suppression independently predicted the presence of dysphagia. There was a clear pattern towards poorer psychological well-being in persons with dysphagia compared to those without. Psychological difficulties may contribute to the manifestation or worsening of dysphagia and should be addressed in treatment planning and future investigations. Therapeutic interventions that promote improvement in mental state alongside swallowing function may be highly beneficial.
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Transtornos de Deglutição , Esclerose Múltipla , Ansiedade/etiologia , Deglutição , Transtornos de Deglutição/etiologia , Depressão/etiologia , Humanos , Esclerose Múltipla/complicaçõesRESUMO
BACKGROUND: Although cognitive impairment is common in multiple sclerosis (MS) patients, language difficulties are controversy and little information is available on nonEnglish languages. Therefore, the present cross-sectional study was conducted to assess the naming accuracy in Persian relapsing-remitting MS (RRMS) patients. MATERIALS AND METHODS: Thirty RRMS patients were recruited from Kashani Comprehensive MS Center, Isfahan, Iran. Their performance on measures of mini mental state examination (MMSE), Expanded Disability Status Scale, and Naming Test was compared with control participants. RESULTS: MS patients were found to have much more naming errors than the control group (2.1 ± 1.8 vs. 0.54 ± 1.1 P = 0.02). Average MMSE score of MS patients was 27.23 (range = 18-30, standard deviation [SD] = 2) versus 28.96 (range = 19-30, SD = 3.2) in controls. CONCLUSION: The present study suggests that naming ability can be impaired in RRMS regardless of disability score. Specific language function tests including naming should be considered in the process of evaluating and rehabilitating patients with MS.
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Cerebral phaeohyphomycosis is frequently a fatal disease caused by truly neurotropic dematiaceous fungi. Although rare, this infection occurs especially among immunocompetent patients, and the clinical symptoms are often misdiagnosed as a cerebral tumour or bacterial brain abscess. The appropriate diagnosis and therapy of cerebral infections by melanized fungi are very challenging if they are caused by mysterious fungi with unknown ecological niche. We reported the second case of cerebral phaeohyphomycosis due to Rhinocladiella mackenziei in Iran and the first culture-confirmed case. In this report, the differential diagnosis and histopathological findings are discussed and a review of the literature is provided.
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Ascomicetos/isolamento & purificação , Feoifomicose Cerebral/diagnóstico , Feoifomicose Cerebral/patologia , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Diagnóstico Diferencial , Feminino , Histocitoquímica , Humanos , Irã (Geográfico) , Imageamento por Ressonância Magnética , Técnicas Microbiológicas , MicroscopiaRESUMO
BACKGROUND: Gender issues and the female preponderance in neuromyelitis optica spectrum disorder (NMOSD) have been investigated before, yet the interplay between NMOSD and menstrual characteristics has remained unknown. Thus, the aim was to compare menstrual cycle patterns and their symptoms in NMOSD patients and healthy women. METHODS: This cross-sectional study was conducted during 2015-2016 in Isfahan, Iran, and included female patients aged>14years with a diagnosis of NMOSD and healthy subjects as controls. Data regarding age at menarche, menstrual characteristics, history of premenstrual syndrome (PMS) and possible perimenstrual symptoms were collected. Also, NMOSD patients were asked to report changes in their menstrual cycles after onset of the disorder. RESULTS: The final study population included 32 NMOSD and 33 healthy controls. These groups did not differ regarding their demographics (P>0.05), and age at menarche in the NMOSD and control groups was 13.31±1.49 years and 13.48±1.44 years, respectively (P=0.637). The controls experienced PMS more frequently (78.8% vs. 40.6% in the NMOSD patients; P=0.03), with no significant differences in other menstrual features between groups (P>0.05). However, changes in menstruation after NMOSD onset were reported by 43.8% of patients, with an increase in menstrual irregularities from 15.6% to 43.7% (P=0.012); other menstrual characteristics did not differ after disease onset (P>0.05). CONCLUSION: Menstruation do not differ between healthy controls and NMOSD patients before the onset of disease whereas, after its onset, those affected experienced more irregularities in their menstrual cycles. This may be an effect of NMOSD and its underlying disorders on menstruation and suggests that further interventions may be required for affected women.
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Menstruação/fisiologia , Neuromielite Óptica/fisiopatologia , Adolescente , Adulto , Azatioprina/uso terapêutico , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Distúrbios Menstruais/epidemiologia , Distúrbios Menstruais/etiologia , Neuromielite Óptica/complicações , Neuromielite Óptica/tratamento farmacológico , Neuromielite Óptica/epidemiologia , Síndrome Pré-Menstrual/complicações , Síndrome Pré-Menstrual/epidemiologia , Rituximab/uso terapêutico , Adulto JovemRESUMO
BACKGROUND: Accumulating evidences from experimental, epidemiologic and clinical studies support the potential linkage between poor vitamin D status and the risk of developing Multiple Sclerosis (MS), as well as, an adverse disease course. However, the results of the trials on the clinical outcomes of vitamin D supplementation in MS patients are less consistent which brought many discrepancies in routine practice. In this article we presented a summary of a symposium on vitamin D and MS. In this symposium we aim to review the current data about the relationship between vitamin D and MS, and suggest management guides for practicing neurologists. DISCUSSION: Generally, supplementation seems to be reasonable for all MS and clinically isolated syndrome (Rinaldi et al., Toxins 7:129-37, 2015) patients with serum 25(OH)D level below 40 ng/ml. In patients with vitamin D insufficiency or deficiency, a large replacing dose (e.g. 50,000 IU capsules of D per week for 8-12 week) is recommended. Panel also suggested: the checking of the serum vitamin D, and calcium level, as well as, patients' compliance after the initial phase; a maintenance treatment of 1500-2000 IU daily or equivalent intermittent (weekly, biweekly or monthly) Dose, considering the patient's compliance; routine check of serum vitamin D level at least two times a year especially at the beginning of spring and autumn; Serum vitamin D evaluation for first degree relatives of MS patients at high risk age and supplementation in case of insufficiency (25(OH)D less than 40 ng/ml); correction of vitamin D deficiency and insufficiency before pregnancy, as well as, a daily dose of 1500-2000 IU or equivalent biweekly intake in 2nd and 3rd trimesters; stopping supplementation if 25(OH)D serum level exceeds 100 ng/ml. Although the results of high power studies are not available, correcting vitamin D status seems plausible in all MS and CIS patients. Maintaining the serum 25(OH)D level between 40 and 100 ng/ml is not known to exert adverse effect. More ever, it might be associated with lower disease activity.
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Consenso , Esclerose Múltipla/tratamento farmacológico , Vitamina D/uso terapêutico , Feminino , Humanos , Irã (Geográfico) , Esclerose Múltipla/complicações , Gravidez , Vitamina D/sangueRESUMO
BACKGROUND: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. Vitamin D has been related to the prevention of MS and to modulating its course. Recent studies have shown the safety of high-dose vitamin D in MS. OBJECTIVE: This study compared the effects of high-dose vitamin D on interleukin 10 (IL-10) levels in MS patients in a double-blind, randomized clinical trial. METHODS: Ninety-four patients with relapsing remitting MS (RRMS) were randomized into a treatment and a placebo group. Both groups received conventional MS treatment. The intervention group received 50,000 IU of vitamin D every 5 days for 3 months. IL-10 was measured at baseline and after 3 months. RESULTS: Serum levels of IL-10 were (median ± IQR): 12.58 ± 11.97 and 10.97 ± 9.97 pg/ml in the intervention and placebo groups, respectively, at baseline (p = 0.161); after 3 months, these levels were 13.76 ± 18.95 and 11.31 ± 19.63 pg/ml, respectively (p = 0.158). The IL-10 level increased significantly after receiving high-dose vitamin D for 3 months (ß = 0.737, p = 0.015 and R2 = 0.91). CONCLUSION: IL-10 levels increased significantly in RRMS patients after taking high-dose vitamin D3 for 3 months. High-dose vitamin D might be useful in promoting an anti-inflammatory state in RRMS patients.
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Interleucina-10/sangue , Esclerose Múltipla/sangue , Esclerose Múltipla/dietoterapia , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Adolescente , Adulto , Cálcio/sangue , Avaliação da Deficiência , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: To date, few results on well-being in individuals with neurological disease have been published, while several studies in other groups have indicated that well-being may not be the only absence of psychological distress, but also positive psychological function. The aim of the present study was to compare the psychological well-being (PWB) between the people with Multiple sclerosis (MS) and normal individuals and identify correlated demographic factors to PWB in people with MS disorder. MATERIALS AND METHODS: A case-control study was performed in July 2012 on 55 people with MS who were referred to MS clinic (located at the Kashani Hospital), Isfahan Neurosciences Research Centre and 83 normal individuals with matched mean of age, level of education, and gender. The participants filled up the 18-item Ryff's PWB and demographic profile. The data were analyzed by SPSS software based on the independent t-test, and ANOVA. RESULTS: There is significant different in all PWB dimensions between people with MS and normal groups. There were no significant differences in PWB in people with MS in relation to gender and marital status, but individuals with higher level of education scored higher in total PWB, positive relationship with others and purpose in life. CONCLUSION: People with MS are at risk of lower level of PWB. Interventional programs for improving PWB are strongly recommended.
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BACKGROUND: Month-long daytime Ramadan fasting pose s major challenges to multiple sclerosis (MS) patients in Muslim countries. Physicians should have practical knowledge on the implications of fasting on MS. We present a summary of database searches (Cochrane Database of Systematic Reviews, PubMed) and a mini-symposium on Ramadan fasting and MS. In this symposium, we aimed to review the effect of fasting on MS and suggest practical guidelines on management. DISCUSSION: In general, fasting is possible for most stable patients. Appropriate amendment of drug regimens, careful monitoring of symptoms, as well as providing patients with available evidence on fasting and MS are important parts of management. Evidence from experimental studies suggests that calorie restriction before disease induction reduces inflammation and subsequent demyelination and attenuates disease severity. Fasting does not appear to have unfavorable effects on disease course in patients with mild disability (Expanded Disability Status Scale (EDSS) score ≤3). Most experts believed that during fasting (especially in summer), some MS symptoms (fatigue, fatigue perception, dizziness, spasticity, cognitive problems, weakness, vision, balance, gait) might worsen but return to normal levels during feasting. There was a general consensus that fasting is not safe for patients: on high doses of anti-convulsants, anti-spastics, and corticosteroids; with coagulopathy or active disease; during attacks; with EDSS score ≥7. SUMMARY: These data suggest that MS patients should have tailored care. Fasting in MS patients is a challenge that is directly associated with the spiritual belief of the patient.
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Jejum/efeitos adversos , Jejum/fisiologia , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/epidemiologia , Animais , Progressão da Doença , Fadiga/diagnóstico , Fadiga/epidemiologia , Fadiga/fisiopatologia , Humanos , Esclerose Múltipla/fisiopatologiaRESUMO
BACKGROUND: Sexual dysfunction (SD) is a common reported problem in patients with multiple sclerosis (MS). AIMS: to examine frequency and distribution of SD dimensions and to determine whether SD is related to various clinical and demographic variables in female patients. MATERIALS AND METHODS: A total of 271 MS women (age: 19-50 years) participated in this cross-sectional study. We used a structured demographic and clinical interview and Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19). Disability was rated by Expanded Disability Status Score (EDSS). RESULTS: 63.5% (n = 173) of women had SD included 142 (52.4%) women with primary SD, 102 (37.5%) women with secondary SD and 120 (41%) women with tertiary SD. The most common SD-related complaint was orgasmic problem (41.2%). Women with primary SD were significantly older and had higher EDSS score. No significant relationship was found between primary SD and disease duration. Fatigue (OR = 2.69, 95% CI: 1.352-5.385, P = 0.005), memory and concentration complaints (OR = 1.915, 95% CI: 1.034-3.546, P = 0.039) and some of urinary symptoms such as frequency (OR = 2.108, 95% CI: 1.015-4.375, P = 0.045) were seem to be the significant predictors. Fatigue was also found to be the most powerful predicting factor for tertiary SD (OR = 2.793, 95% CI: 1.358-5.744 P = 0.005). CONCLUSION: SD, a common multifactorial problem among MS women, can arise at any time during the disease and with any level of disability. However, we found relationships between SD and some of clinical variables and symptoms. Understanding these relationships would help us to develop practical approach and treatment for SD.
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OBJECTIVE: Optical coherence tomography (OCT) investigations have revealed that the thickness of inner retinal layers becomes decreased in multiple sclerosis (MS) patients, compared to healthy control (HC) individuals. To date, a number of studies have applied machine learning to OCT thickness measurements, aiming to enable accurate and automated diagnosis of the disease. However, there have much less emphasis on other less common retinal imaging modalities, like infrared scanning laser ophthalmoscopy (IR-SLO), for classifying MS. IR-SLO uses laser light to capture high-resolution fundus images, often performed in conjunction with OCT to lock B-scans at a fixed position. METHODS: We incorporated two independent datasets of IR-SLO images from the Isfahan and Johns Hopkins centers, consisting of 164 MS and 150 HC images. A subject-wise data splitting approach was employed to ensure that there was no leakage between training and test datasets. Several state-of-the-art convolutional neural networks (CNNs), including VGG-16, VGG-19, ResNet-50, and InceptionV3, and a CNN with a custom architecture were employed. In the next step, we designed a convolutional autoencoder (CAE) to extract semantic features subsequently given as inputs to four conventional ML classifiers, including support vector machine (SVM), k-nearest neighbor (K-NN), random forest (RF), and multi-layer perceptron (MLP). RESULTS: The custom CNN (85 % accuracy, 85 % sensitivity, 87 % specificity, 93 % area under the receiver operating characteristics [AUROC], and 94 % area under the precision-recall curve [AUPRC]) outperformed state-of-the-art models (84 % accuracy, 83 % sensitivity, 87 % specificity, 92 % AUROC, and 94 % AUPRC); however, utilizing a combination of the CAE and MLP yields even superior results (88 % accuracy, 86 % sensitivity, 91 % specificity, 94 % AUROC, and 95 % AUPRC). CONCLUSIONS: We utilized IR-SLO images to differentiate between MS and HC eyes, with promising results achieved using a combination of CAE and MLP. Future multi-center studies involving more heterogenous data are necessary to assess the feasibility of integrating IR-SLO images into routine clinical practice.
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Esclerose Múltipla , Oftalmoscopia , Humanos , Esclerose Múltipla/diagnóstico por imagem , Oftalmoscopia/métodos , Adulto , Feminino , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Tomografia de Coerência Óptica/métodos , Sensibilidade e EspecificidadeRESUMO
Background: Appropriate treatment reduces the severity and duration of relapses in demyelinating diseases of Central Nervous System (CNS). If high-dose corticosteroids treatment fails, therapeutic plasma exchange (TPE) is considered as a rescue treatment. Objectives: This study aimed to investigate early clinical response and complications of TPE and prognostic factors in CNS demyelinating relapses. Design: This prospective observational study was designed in a tertiary center during one year. Methods: All adult patients diagnosed corticosteroid-resistant Multiple Sclerosis (MS), NeuroMyelitis Optica Spectrum Disorder (NMOSD), idiotypic Transverse Myelitis or Clinical Isolated Syndrome relapses, were eligible. Clinical response is defined based on Expanded Disability Status Scale (EDSS) at discharge. Clinical and laboratory complications recorded. Results: Seventy-two patients were analyzed which 58.3% patients were female. MS was diagnosed for 61.1% of cases. Thirty-five patients (48.6%) responded and the mean differences of EDSS significantly decreased 0.60 score (CI95%:0.44-.77). Electrolyte imbalances and thrombocytopenia occurred in 80.6% and 55.6% of cases respectively and 40.3% of patients had systemic reactions. However, 26.4% patients experienced moderate to severe complications. In patients with moderate to severe disability, responders were younger (MD: 8.42 years, CI95%: 1.67-15.17) and had lower EDSS score at admission (median:6, IQR: 5.5-6 against 7.5 IQR: 6.5-8). The risk of failure was higher in active progressive MS patients compared with RRMS patients (OR: 6.06, CI 95%:1.37-26.76). Patients with thrombocytopenia were hospitalized more than others (MD: 1.5 days, CI 95%: 0-3). Females were more prone to hypokalemia and systemic reactions (OR: 3.11, CI 95%:1.17-8.24 and OR: 6.67, CI 95%:2.14-20.81 respectively). Conclusion: The most common indication of TPE was corticosteroid-resistant severe MS relapses. About half of the patients presented an early clinical response. Lower disability, younger age and RRMS diagnosis are prognostic factors of better response. One out of four patients experienced moderate to severe complications, mainly electrolyte imbalances and systemic reactions. Appropriate interventions against these complications should be considered during TPE, especially in females.
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Purpose: Several machine learning studies have used optical coherence tomography (OCT) for multiple sclerosis (MS) classification with promising outcomes. Infrared reflectance scanning laser ophthalmoscopy (IR-SLO) captures high-resolution fundus images, commonly combined with OCT for fixed B-scan positions. However, no machine learning research has utilized IR-SLO images for automated MS diagnosis. Methods: This study utilized a dataset comprised of IR-SLO images and OCT data from Isfahan, Iran, encompassing 32 MS and 70 healthy individuals. A number of convolutional neural networks (CNNs)-namely, VGG-16, VGG-19, ResNet-50, ResNet-101, and a custom architecture-were trained with both IR-SLO images and OCT thickness maps as two separate input datasets. The highest performing models for each modality were then integrated to create a bimodal model that receives the combination of OCT thickness maps and IR-SLO images. Subject-wise data splitting was employed to prevent data leakage among training, validation, and testing sets. Results: Overall, images of the 102 patients from the internal dataset were divided into test, validation, and training subsets. Subsequently, we employed a bootstrapping approach on the training data through iterative sampling with replacement. The performance of the proposed bimodal model was evaluated on the internal test dataset, demonstrating an accuracy of 92.40% ± 4.1% (95% confidence interval [CI], 83.61-98.08), sensitivity of 95.43% ± 5.75% (95% CI, 83.71-100.0), specificity of 92.82% ± 3.72% (95% CI, 81.15-96.77), area under the receiver operating characteristic (AUROC) curve of 96.99% ± 2.99% (95% CI, 86.11-99.78), and area under the precision-recall curve (AUPRC) of 97.27% ± 2.94% (95% CI, 86.83-99.83). Furthermore, to assess the model generalization ability, we examined its performance on an external test dataset following the same bootstrap methodology, achieving promising results, with accuracy of 85.43% ± 0.08% (95% CI, 71.43-100.0), sensitivity of 97.33% ± 0.06% (95% CI, 83.33-100.0), specificity of 84.6% ± 0.10% (95% CI, 71.43-100.0), AUROC curve of 99.67% ± 0.02% (95% CI, 95.63-100.0), and AUPRC of 99.65% ± 0.02% (95% CI, 94.90-100.0). Conclusions: Incorporating both modalities improves the performance of automated diagnosis of MS, showcasing the potential of utilizing IR-SLO as a complementary tool alongside OCT. Translational Relevance: Should the results of our proposed bimodal model be validated in future work with larger and more diverse datasets, diagnosis of MS based on both OCT and IR-SLO can be reliably integrated into routine clinical practice.
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Esclerose Múltipla , Redes Neurais de Computação , Oftalmoscopia , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Esclerose Múltipla/diagnóstico , Feminino , Oftalmoscopia/métodos , Adulto , Masculino , Curva ROC , Pessoa de Meia-Idade , Aprendizado de Máquina , Raios InfravermelhosRESUMO
BACKGROUND: There has been no recent comprehensive epidemiological study on a large and stable population of multiple sclerosis (MS) in Isfahan. Therefore, we conducted this study to estimate the incidence and prevalence of MS in Isfahan province from 1996 to 2021. METHOD: In this population-based study, we utilized the dataset from the Vice-Chancellor's Office of Isfahan University of Medical Sciences, which registers all people diagnosed with MS (PDWM) in Isfahan province, excluding those residing in Kashan city. We measured crude incidence and prevalence of MS, separated by sex, and based on age of MS onset, as well as changes in age of MS onset during observation. RESULTS: A total of 9,909 PDWM were included in our study. The incidence during the time period of 1996-2000 was 5.4/100,000 (1.1/100,000 per year), which subsequently increased to 14.1 (2.8/100,000 per years) and 31.1 per 100,000 (6.2/100,000 per year) during 2001-2005 and 2006-2010, respectively. There was a further increase to 70.9/100,000 (14.2/100,000 per year) in 2011-2015, but it remained stable at 71.8/100,000 (12/100,000 per year) during the period of 2016-2021. In 2016, the age-standardized incidence rates of pediatric-onset, adult-onset, and late-onset MS were 1.8/100,000, 31.4/100,000, and 17.5/100,000, respectively. The prevalence of MS in 2021 was 183.9/100,000. The female/male new case ratio was 4.5 during 1996-2000, decreasing to 4.0, 3.9, 3.9, and 2.9 in the subsequent four five-year periods. The mean age of RRMS onset was 26.3 ± 8.1 between 1990 and 1999, 28.5 ± 8.3 during 2000-2009, and increased to 32.8 ± 9.6 in 2010-2019. CONCLUSION: This study shows that Isfahan has one of the highest incidence rate and prevalence ratio of MS in the region. We observed an increase in the incidence rate during the first decade, followed by stability in the last two five- and six-year periods. Further studies are needed to identify the reasons behind the change in incidence of MS in Iran.
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Esclerose Múltipla , Adulto , Criança , Humanos , Masculino , Feminino , Incidência , Esclerose Múltipla/epidemiologia , Irã (Geográfico)/epidemiologia , PrevalênciaRESUMO
OBJECTIVE: The relationship between MS and ethnicity has been understudied in the Middle East compared to the United States and Europe. As Iran as the highest prevalence of MS in the Middle East, we decided to investigate the demographic and clinical differences in people with MS (pwMS) from major ethnicities Iran. METHODS: In a cross-sectional study using data from National Multiple Sclerosis Registry in Iran. PwMS from six provinces were chosen and interviewed for determining their ethnicity. Persians (Fars), Kurds, Lurs, Azeris and Arabs with a clear ethnic background were included. Recorded data from the registry was used to compare the demographic and clinical features. RESULTS: A total of 4015 pwMS (74.2% female) were included in the study with an average age of 36.76 ± 9.68 years. Persians and Kurds had the highest percentage of pwMS in youngest and oldest age groups, respectively, with 2.9% and 5.7% (p<0.01). The highest average age of onset was seen in Persians (29.47 ± 8.89) and the lowest observed in Mazandaranis (26.82 ± 7.68, p<0.01). Azeris and Kurds had the highest proportions of pwMS diagnosed <18 and >55, at rates of 12% and 1.6%, respectively (p<0.01). There were statistically significant differences in distribution of phenotypes (p<0.01) and time to progression to secondary progressive MS (p<0.01) such that Persians had the highest rate of clinically isolated syndrome (CIS) at 19.3% and Arabs had highest rates of relapsing-remitting MS (86.2%) and secondary progressive MS (16.4%). Lurs, Azeris and Mazandaranis had significantly more patients progressing to secondary-progressive MS <5 years from diagnosis (p<0.01). There was a significant difference in number of relapses between the ethnicities (p<0.01) with Lurs having the highest proportion of participants reporting >4 relapses with 23.0% and Azeris having the highest percentage of pwMS reporting no relapse (53.0%). Kurds had the highest Expanded Disability Status Scale (EDSS) average at 2.93 ± 1.99 and Lurs had the lowest with 1.28 ± 1.25 (p<0.01). The differences in prevalence of positive family history for the whole cohort between ethnicities were significant (P=0.02), ranging from 12.8% in Kurds to 19.6% in Persians. CONCLUSION: We found Persians to have higher rates of pediatric MS and higher rates of CIS. Kurds and Lurs had higher and lower EDSS scores, respectively. Lurs and Persian had higher annual relapse rates. We also found lower rates of SPMS among Arabs and earlier progression to SPMS in Lurs, Azeris and Mazandaranis. Such differences highlight the importance of the potential role of ethnicities in diagnosis and prognosis of MS, especially considering their observation within the geographical limits of a single country.
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População do Oriente Médio , Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Progressão da Doença , Irã (Geográfico)/epidemiologia , Esclerose Múltipla/epidemiologia , Esclerose Múltipla Crônica Progressiva/epidemiologia , Recidiva Local de Neoplasia , Recidiva , Sistema de Registros , ÁrabesRESUMO
BACKGROUND: Multiple sclerosis (MS) is a prevalent, disabling, inflammatory, neurodegenerative disease that typically manifests during a highly productive stage of life. Interferon beta-1a was among the first approved disease-modifying therapies for MS and remains among the first-line treatment options. Pegylation of the interferon beta-1a molecule prolongs its half-life while maintaining its efficacy and safety profile. In PEGINTEGRITY study, we aimed to compare peginterferon beta-1a with interferon beta-1a in terms of efficacy and safety in relapsing-remitting multiple sclerosis (RRMS) patients. METHODS: This study was a randomized, active-controlled, parallel-group, multi-center Phase 3 trial conducted in Iran in participants with RRMS. Participants received 125 µg of subcutaneous peginterferon beta-1a every two weeks or 30 µg of intramuscular interferon beta-1a once a week for up to 96 weeks. The primary outcome was the non-inferiority of peginterferon beta-1a to interferon beta-1a in reducing annualized relapse rate (ARR). Other outcomes included the number of patients with 12-week confirmed disability progression, the number of new or newly-enlarging T2 hyperintense lesions, the number of gadolinium-enhancing lesions, the number of new T1 hypointense lesions, the volume of new or newly-enlarging T2 hyperintense lesions, changes in brain volume, immunogenicity, and safety assessments. RESULTS: A total of 168 patients who met the eligibility criteria were enrolled and assigned to two arms of the study, each consisting of 84 participants. Totally, 41 participants (24 patients in the peginterferon beta-1a group and 17 patients in the interferon beta-1a group) were withdrawn from the study. The withdrawn patients were included in the per-protocol analysis for the period of time they were in the study. In 96 weeks, in the per-protocol population, the ARR was 0.05 in the peginterferon beta-1a group versus 0.11 in the interferon beta-1a group, which does not reflect a statistically significant difference (p=0.09; 95 % CI, 0.18-1.14). Considering the upper limit of the one-sided 95 % CI of the rate ratio of peginterferon beta-1a compared to interferon beta-1a, as well as the non-inferiority margin, it can be concluded that the primary outcome was met. The results were also comparable for other efficacy and safety outcomes. CONCLUSION: The results demonstrate the non-inferiority of peginterferon beta-1a to interferon beta-1a with similar efficacy in 96-week ARR in RRMS patients. Both arms were also comparable in other efficacy outcomes and safety profiles with no statistically significant differences. These findings support considering peginterferon beta-1a as a safe and efficient option in patients with RRMS. This study was registered on Iranian Registry of Clinical Trials (IRCT201612306135N8) and clinicaltrials.gov (NCT05242133).