Covid-19 in Parkinson's Disease treated by drugs or brain stimulation / COVID-19 en la enfermedad de Parkinson tratada con fármacos o estimulación cerebral

Purpose: Covid-19 has affected all people, especially those with chronic diseases, including Parkinson's Disease (PD). Covid-19 may affect both motor and neuropsychiatric symptoms of PD patients. We intend to evaluate different aspects of Covid-19 impact on PD patients. Methods: 647 PD patients were evaluated in terms of PD-related and Covid-19-related clinical presentations in addition to past medical history during the pandemic through an online questioner. They were compared with an age-matched control group consist of 673 individuals and a sample of the normal population consist of 1215 individuals. Results: The prevalence of Covid-19 in PD patients was 11.28%. The mortality was 1.23% among PD patients. The prevalence of Covid-19 in PD patients who undergone Deep Brain Stimulation (DBS) was 18.18%. No significant association was found between the duration of disease and the prevalence of Covid-19. A statistically significant higher prevalence of Covid-19 in PD patients who had direct contact with SARS-CoV-19 infected individuals was found. No statistically significant association has been found between the worsening of motor symptoms and Covid-19. PD patients and the normal population may differ in the prevalence of some psychological disorders, including anxiety and sleeping disorders, and Covid-19 may affect the psychological status. Conclusion: PD patients possibly follow tighter preventive protocols, which lead to lower prevalence and severity of Covid-19 and its consequences in these patients. Although it seems Covid-19 does not affect motor and psychological aspects of PD as much as it was expected, more accurate evaluations are suggested in order to clarify such effects.(AU)

Objetivo: La COVID-19 ha afectado a toda la población, especialmente a aquellos con enfermedades crónicas, incluyendo a los pacientes con enfermedad de Parkinson (EP). La COVID-19 puede empeorar tanto los signos motores como los síntomas neuropsiquiátricos de los pacientes con EP. El objetivo de este estudio es evaluar diferentes aspectos del impacto de la COVID-19 en los pacientes con EP. Métodos: A través de un cuestionario virtual se evaluó a 647 pacientes con EP de acuerdo con sus presentaciones clínicas relacionadas con la EP y con la COVID-19, además de la historia médica previa durante la pandemia. Se compararon con un grupo de controles sanos de la misma edad que constaba de 673 individuos y una muestra de la población general de 1.215 individuos. Resultados: La prevalencia de la COVID-19 en pacientes con EP fue del 11,28%. La mortalidad fue del 1,23% entre los pacientes con EP. La prevalencia de COVID-19 en pacientes con EP con estimulación cerebral profunda fue del 18,18%. No se encontró una asociación significativa entre la duración de la enfermedad y la prevalencia de COVID-19. Se halló una prevalencia mayor de COVID-19 que fue estadísticamente significativa en pacientes con EP que tuvieron contacto directo con personas infectadas con SARS-CoV-2. No se encontró una asociación estadísticamente significativa entre el empeoramiento de los signos motores y la COVID-19. Los pacientes con EP y la población general podrían diferir en la prevalencia de algunos trastornos psicológicos, incluidos los trastornos de ansiedad y del sueño, y la COVID-19 podría afectar al estado psicológico. Conclusión: Los pacientes con EP posiblemente sigan protocolos preventivos más estrictos, lo que conduce a una menor prevalencia y gravedad de COVID-19 y de sus consecuencias en estos pacientes.(AU)

Covid-19 in Parkinson's Disease treated by drugs or brain stimulation.

PURPOSE: Covid-19 has affected all people, especially those with chronic diseases, including Parkinson's Disease (PD). Covid-19 may affect both motor and neuropsychiatric symptoms of PD patients. We intend to evaluate different aspects of Covid-19 impact on PD patients. METHODS: 647 PD patients were evaluated in terms of PD-related and Covid-19-related clinical presentations in addition to past medical history during the pandemic through an online questioner. They were compared with an age-matched control group consist of 673 individuals and a sample of the normal population consist of 1215 individuals. RESULTS: The prevalence of Covid-19 in PD patients was 11.28%. The mortality was 1.23% among PD patients. The prevalence of Covid-19 in PD patients who undergone Deep Brain Stimulation (DBS) was 18.18%. No significant association was found between the duration of disease and the prevalence of Covid-19. A statistically significant higher prevalence of Covid-19 in PD patients who had direct contact with SARS-CoV-19 infected individuals was found. No statistically significant association has been found between the worsening of motor symptoms and Covid-19. PD patients and the normal population may differ in the prevalence of some psychological disorders, including anxiety and sleeping disorders, and Covid-19 may affect the psychological status. CONCLUSION: PD patients possibly follow tighter preventive protocols, which lead to lower prevalence and severity of Covid-19 and its consequences in these patients. Although it seems Covid-19 does not affect motor and psychological aspects of PD as much as it was expected, more accurate evaluations are suggested in order to clarify such effects.

Non-infectious meningitis and CNS demyelinating diseases: A conceptual review.

Many cases of aseptic meningitis or meningoencephalitis, unresponsive to antimicrobial treatments, have been reported recently in patients with established/new-onset central nervous system (CNS) inflammatory demyelinating diseases (CNSIDDs). Given the higher probability of infectious etiologies, CNSIDDs are rarely considered among the differentials in meningitis or meningoencephalitis cases. We gathered and tabulated cases of non-infectious, steroid-responsive meningitis or meningoencephalitis associated with neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-associated disease (MOGAD). This conceptual review highlights the need to bolster routine infectious workups with immunological workups in cases of meningoencephalitis or meningitis where potential autoimmune etiologies can be suspected. Although differentiating CNSIDDs with meningeal involvement from infectious meningitis may not substantially affect acute treatment strategies, long-term management and follow-up of the two are entirely different. We also discuss future research directions and hypotheses on how CNSIDDs may be associated with meningitis-like presentations, e.g. overlapping glial fibrillary acidic protein astrocytopathy or autoimmune encephalitis, alterations in regulatory T-helper cells function, and undetected viral agents.

Risk factors of severe COVID-19 in people with multiple sclerosis : A systematic review and meta-analysis.

OBJECTIVES: To gather, synthesize, and meta-analyze data regarding the risk factors associated with a severe course of COVID-19 among patients with multiple sclerosis (pwMS). METHODS: MEDLINE, Embase, Scopus, and WoS were searched in May 2021. Briefly, the eligibility criteria included: 1) studies assessing COVID-19 severity among adult pwMS; 2) definitive diagnoses or high clinical suspicion of COVID-19; 3) a categorization of COVID-19 severity into at least two categories; 4) quantitative effect size and precision measurements; and 5) English language; and 6) clear effect size/precision measures. internal validity of studies was assessed using the NIH Quality Assessment Tools. A list of possible risk factors was created based on the search results and was later used in extraction, synthesis, and meta-analysis of the data. RESULTS: Thirteen studies were included in the syntheses. Outcome measures were either extracted from the papers, obtained from the primary researchers or calculated manually. The meta-analyses showed a significantly (P<0.05) increased odds of a severe COVID-19 in pwMS with all of the assessed risk factors, except smoking and most DMTs. CONCLUSION: This study facilitates evidence-based risk/benefit assessments in practice. Older men with progressive MS on anti-CD20 therapies are more at risk of an unfortunate COVID-19 outcome.

Covid-19 in Parkinson's Disease treated by drugs or brain stimulation.

PURPOSE: Covid-19 has affected all people, especially those with chronic diseases, including Parkinson's Disease (PD). Covid-19 may affect both motor and neuropsychiatric symptoms of PD patients. We intend to evaluate different aspects of Covid-19 impact on PD patients. METHODS: 647 PD patients were evaluated in terms of PD-related and Covid-19-related clinical presentations in addition to past medical history during the pandemic through an online questioner. They were compared with an age-matched control group consist of 673 individuals and a sample of the normal population consist of 1215 individuals. RESULTS: The prevalence of Covid-19 in PD patients was 11.28%. The mortality was 1.23% among PD patients. The prevalence of Covid-19 in PD patients who undergone Deep Brain Stimulation (DBS) was 18.18%. No significant association was found between the duration of disease and the prevalence of Covid-19. A statistically significant higher prevalence of Covid-19 in PD patients who had direct contact with SARS-CoV-19 infected individuals was found. No statistically significant association has been found between the worsening of motor symptoms and Covid-19. PD patients and the normal population may differ in the prevalence of some psychological disorders, including anxiety and sleeping disorders, and Covid-19 may affect the psychological status. CONCLUSION: PD patients possibly follow tighter preventive protocols, which lead to lower prevalence and severity of Covid-19 and its consequences in these patients. Although it seems Covid-19 does not affect motor and psychological aspects of PD as much as it was expected, more accurate evaluations are suggested in order to clarify such effects.

Seizure incidence among neuromyelitis optica spectrum disorder patients.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSDs) are a group of neuroinflammatory diseases, which mainly affect the optic nerve and spinal cord. NMOSD is an astrocytic channelopathy involving the aquaporin-4 (AQP4) water channels in the central nervous system. Patients can present with seizure attacks as a first manifestation or relapse. However, compared with multiple sclerosis (MS) or myelin oligodendrocyte glycoprotein encephalomyelitis (MOG-EM), seizure attacks are less frequent in NMOSD. METHODS: In this study, we aimed to find out the incidence of seizure attacks during the disease course of 137 NMOSD patients who were registered in our centre from January 2011 till January 2020. Furthermore, we reviewed the literature for NMOSD cases with seizure attacks during their follow-up, in order to investigate the reason for this low incidence of seizures. RESULTS: Only one of our patients (0.72%) experienced an episode of generalised tonic-clonic seizure during his follow-up. CONCLUSION: Reviewing the literature revealed that although seizures are rare in NMOSD, AQP4 disruption possibly increases the risk of seizure attacks. We therefore concluded that the role of AQP4 in seizures is controversial and needs more investigation.

WITHDRAWN: Incidence and mortality of COVID-19 in Iranian multiple sclerosis patients treated with disease-modifying therapies.

This article has been withdrawn at the request of the authors and editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

The higher prevalence of multiple sclerosis among Iranian Georgians; new clues to the role of genetic factors.

BACKGROUND: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) with varied prevalence rates among populations with different ethnic backgrounds. Therefore, studies done on minorities have shed more light on the risk factors. OBJECTIVE: Comparing MS prevalence in Georgian-based population immigrated to Iran and other Iranians. METHODS: All records of MS patients enrolled in the two biggest registry systems were investigated. All of the patients born in Fereydunshahr and Buin va Miandasht (2 biggest cities with Georgian immigrants) were interviewed and their baseline characteristics were obtained. Patients' ethnic background information were obtained from the Iran National organization for civil registration. RESULTS: Forty-one patients from Fereydunshahr and Buin va Miandasht were identified. The population of the two cities combined and the estimated number of Georgian-based patients in both cities were reported 59817 and 12000, respectively. The estimated ethnicity-adjusted prevalence among the Georgian-based individuals was 2.3 times higher than the non-Georgian ones. Baseline characteristics were also compared. CONCLUSION: There was a higher prevalence of multiple sclerosis among the Georgian minority of Isfahan. Due to the ethnic background of the Georgian minority, genetic risk factors should be considered more as a risk factor.

Soil heavy metals are associated with the distribution of multiple sclerosis in Isfahan, Iran.

BACKGROUND: Few epidemiological studies have explored the effects of soil pollution on multiple sclerosis (MS) risk in Asia. METHOD: Based on catchment areas, Isfahan province is divided into five regions (Central, North, East, West, and South), and Soil sampling performed in catchment area with the highest range of MS prevalence and incidence. Samples were analyzed for cobalt (Co), lead (Pb), cadmium (Cd), copper (Cu), zinc (Zn), and absorbable forms of Pb, Cd, and Co. Linear regression is used to examine the association of soil heavy metals with prevalence of MS in central part of Isfahan province. RESULT: Multiple sclerosis prevalence ranged from 5.62 to 156.65 in different townships. Based on regression analysis, in case of considering fixed amounts for the rest of elements, a one (SD) increase of absorbable Pb and absorbable Cd are associated with 0.385 (SD) (P < 0.0001) increase and 0.209 (SD) (P < 0.007) decrease in MS prevalence, respectively. CONCLUSION: This study documented a significant association between exposure to absorbable Pb and Cd in soil with prevalence of MS in Isfahan. Further work is warranted to confirm this association and if validated, to understand the mechanisms behind the association.

Association of TIM-1 5383-5397ins/del and TIM-3 -1541C>T polymorphisms with multiple sclerosis in Isfahan population.

Multiple sclerosis (MS) is an organ-specific autoimmune disease in central nervous system, affecting about 2.5 million people around the world. Probable involvement of two newly identified immunoregulator molecules, TIM-1 and TIM-3, has been reported in autoimmune diseases. In this study, for the first time, the association of TIM-1 5383-5397ins/del and TIM-3 -1541C>T polymorphisms with MS in an Iranian population was considered. The results of our study showed that there is no significant association between TIM-1 5383-5397ins/del and MS (P = 0.38); however, the frequency of CT genotype of TIM-3 -1541C>T in patient group was significantly higher than the control group, and there was a significant association between CT genotype and MS (P = 0.009, OR = 4.08).

Necrotizing external otitis: a case series.

OBJECTIVES: Necrotizing (malignant) external otitis (NEO) is a life-threatening progressive infection of the external auditory canal, mastoid, and skull base. Here, we review the clinical findings for a series of NEO patients. METHODOLOGY: This case review study includes 18 patients with NEO (males: 11 (61.11%), females: 7 (38.88%), with a mean age of 65.11 years (range: 40-79)), hospitalized at Al-Zahra hospital in Isfahan province, Iran, during 2007-2011. RESULTS: The most common presentations were otalgia 18 (100%), otorrhea 15 (83.33%), edema and erythema of the external ear canal 14 (77.77%), and hearing loss 11 (61.11%). We found osteomyelitis of the skull base that involved cranial nerves (most commonly the facial nerve) in 8 patients (44.44%), which seemed to be a higher incidence than reported in previous studies. Pseudomonas aeruginosa was found in ear specimen cultures in only 7 cases (38.88%), which could be attributed to inappropriate topical and oral use of antipseudomonal agents before proper diagnosis. Nine patients underwent surgical debridement. All cases responded to systemic antipseudomonal antibiotics with no mortality. However, recurrence occurred during the follow-up period in two cases; yet, the patients responded to retreatment. CONCLUSION: The life expectancy is increasing for diabetic and immunocompromised patients; thus, it is necessary to identify those who have a high risk for NEO, especially older diabetic patients who complain of otalgia and otorrhea that are resistant to routine treatment. Immediate diagnosis and proper treatment is crucial to prevent complications and mortality.

Interferon-beta-1beta protects against multiple sclerosis-induced endothelial cells apoptosis.

Disruption of the blood-brain-barrier (BBB) due to endothelial cell (EC) injury is an essential step in formation of multiple sclerosis (MS) lesions. We investigated the role of endothelial cell (EC) apoptosis in the pathophysiology of MS, studying the therapeutic effect of IFN-beta-1b against MS sera-induced endothelial apoptosis. Human umbilical vein endothelial cells were treated with sera from patients with active MS (in relapse), MS in remission, or sera from healthy volunteers (each n = 5). Apoptosis was assessed by annexin V-propidium iodide staining. Effects of IFN-beta-1b on EC apoptosis were tested at increasing doses (10, 100, and 1000 U/ml). Nitrite (NO2-⁻) levels were determined in culture supernatants. EC apoptosis was increased by sera from exacerbating MS patients, but not remission, compared to healthy individuals (p less than 0.001). Effects were blocked by IFN-beta-1b at 10 U/ml (p less than 0.05), but not higher doses, and was associated with increased NO/NO2- production (less than 0.05). EC apoptosis leading to disruption of the BBB may play a role in MS etiology and represents a novel therapeutic mechanism of action for IFN-beta-1b in MS therapy.

Dalfampridine: review of its efficacy in improving gait in patients with multiple sclerosis.

Multiple sclerosis (MS) is a progressive immune-mediated neurodegenerative disease of human central nervous system (CNS), which causes irreversible disability in young adults. The cause and cure for MS remain unknown. Pathophysiology of MS includes two arms: inflammatory demyelination and neurodegeneration. The inflammatory demyelination of MS which is mainly promoted by a massive activation of the immune system against putative CNS antigen(s) leads to loss of oligodendrocyte/myelin complex which slows down or halts impulse conduction in denuded axons. Practically, loss of myelin significantly reduces signal conduction along the demyelinated axons through alterations in the distribution of axonal ion channels. Dalfampridine (4-aminopyridine or 4-AP) is an oral potassium channel blocker, which was recently approved by FDA for symptomatic treatment of MS. Dalfampridine, which acts at the central and peripheral nervous systems, enhances conduction in demyelinated axons and improves walking ability of MS patients. A number of clinical trials have evaluated the safety and efficacy of fampridine in MS patients with the degree of gait improvement as the main outcome. The objective of this manuscript is to provide an overview of the pharmacology, pharmacokinetics, clinical trials, side effects and interactions of dalfampridine used in treatment of MS patients.

Epidemiology of amyotrophic lateral sclerosis in Isfahan, Iran.

BACKGROUND: Few studies are carried out on the epidemiology of amyotrophic lateral sclerosis (ALS) in Middle East with no reports from Iran. OBJECTIVE: To determine the epidemiological and clinical features of ALS amongst the Iranian population living in Isfahan, Iran. METHODS: Medical records of all hospitals with a neurology department and outpatient neurology clinics in Isfahan province from 2002 to 2006 were reviewed, and all patients with the diagnosis of ALS according to El Escorial diagnostic criteria were extracted and related demographic and clinical data were gathered and analyzed. RESULTS: We found 98 new patients (66 men and 32 women) with definite, probable, or possible ALS. The average annual incidence was 0.42/100,000, with the highest incidence rate amongst those aged 70-74. On 21 March 2006, the crude prevalence was 1.57/100,000. Median survival from onset was 48 months (95% confidence interval 34-61) and survival rates for 1, 3,and 5 years after the onset were 94%, 66%, and 32%, respectively. CONCLUSIONS: The incidence and prevalence of ALS in the Iranian population seems to be lower compared to other populations and the survival of patients was longer than previously reported.

Increasing female preponderance of multiple sclerosis in Isfahan, Iran: a population-based study.

There is an overall increase in the worldwide prevalence and incidence of multiple sclerosis (MS). Studies from several countries also demonstrated an increase of female/male ratio over time denoting an increase in the incidence of MS particularly in women. In this study we sought to assess the trends in MS incidence and prevalence in males and females over recent decades in Isfahan, Iran, which differs from other regions in terms of environmental and lifestyle changes. We determined female/male ratio by year of birth (YOB) in 1584 patients with MS registered with Isfahan Multiple Sclerosis Society (IMSS) from April 2003 to August 2007. A comparison of sex ratio of MS patients by YOB showed a significant, progressive, gradual increase, with an apparent interruption in the late 1960s. In this study year of birth is a significant predictor for sex ratio (p < 0.001, chi(2) = 17.130, Spearman's rank correlation r = 0.893). Our findings show that there is a significant increase in the incidence of MS among females for the the last decades in the Isfahan province of Iran. This rapid increase may be related to changes in environmental interactions rather than genetic factors, and among them vitamin D insufficiency, enhanced diagnosis, and lifestyle changes appear to be more plausible causative factors.

Recognition of the kind of stress coping in patients of multiple sclerosis.

BACKGROUND: Investigations have shown that some factors like stress can increase the recurrence and severity of multiple sclerosis (MS). Considering the direct influences of depression and anxiety on our body immunity system, and also the relation between stress and factors, such as Insulin Growth Factor (IGF-1), involved in neurogenesis and myelin repairing, it is an essential issue to identify the most common method used in relieving stress by such patients. OBJECTIVE: To identify the type of common coping methods for stressful situation. MATERIALS AND METHODS: This case-control study was performed on 50 patients of both the genders with MS in Esfahan (Esfahan MS Association). The data were collected and then analyzed using analysis of variance (ANOVA) method with the help of SPSS software version 15. P value less than 0.05 was considered as statistically significant. RESULTS: In our study, coping method for stressful situation was significantly different in MS patients versus the healthy group (P=0.02). Descriptive indices showed that these patients use avoidant method more commonly than the control group (mean=45.01, SD=8.9 vs. mean=40.8, SD=11.8, respectively). CONCLUSION: Due to the different methods used by MS patients to cope with stressful situation in comparison with the healthy ones, more appropriate techniques can be introduced to modify them, and hence, less stress-induced side effects could be expected in this population.

Multiple sclerosis and neurofibromatosis type 1: report of seven patients from Iran.

INTRODUCTION: Co-occurrence of multiple sclerosis (MS) and neurofibromatosis type 1 (NF1) is rare. CASE REPORTS: In this study, we describe the clinical and neuroimaging features of seven patients with NF1 and MS. In our patients, six patients with MS were women, in all of them history of NF1 existed. Three of our patients had primary progressive, one had secondary progressive MS, and three relapsing-remitting MS. Optic neuritis as presenting symptoms was seen in three patients, and motor manifestation as presenting symptom was observed in three patients. The risk of having both NF1 and MS seemed to be higher than would be expected based on the prevalence rates of the two diseases in the general population. CONCLUSION: The findings of this study suggest a possible casual relationship between MS and NF1, indicating higher risk of MS among patients with NF1.

Efficacy of gabapentin in the treatment of SUNCT syndrome.

This study was designed to evaluate the efficacy of gabapentin (GBP) in the treatment of SUNCT syndrome on a relatively large sample of Persian patients. Eight patients with SUNCT syndrome underwent a 4-week, open-label, daily treatment of 600-900 mg GBP. The frequency, intensity and duration of attacks were compared before and after the trial. After 4 weeks of treatment, intensity, duration and frequency of headaches were significantly (P < 0.05) reduced. In addition, five patients (62.5%) were completely relieved from headaches, and in the other three patients the mean intensity, frequency and duration of headaches were decreased notably. In this study, GBP was well tolerated and no unfavourable side-effects were reported. After the end of the trial all patients continued the medication, and after 3 months none reported undesired side-effects or return of the headaches to the pre-treatment status. Our patients had a significant response to GBP, and considering other case reports on the effectiveness of GBP in the treatment of SUNCT syndrome, we propose that, taking into account the good side-effect profile and lack of interactions of GBP, this drug could be considered as an option for the treatment of SUNCT.

Comparison of interferon beta products and azathioprine in the treatment of relapsing-remitting multiple sclerosis.

We compared the relative efficacy of interferon beta (IFNbeta) products and azathioprine (AZA) in the treatment of relapsing- remitting multiple sclerosis (RRMS). Ninety-four previously untreated patients of short duration with RRMS were randomly allocated to the two treatment groups. The first group received IFNbeta products (Betaferon,Avonex or Rebif); the second group received AZA for 12 months. Response to treatment was assessed at 3, 6, and 12 months after starting therapy. The mean number of relapse during one year of the study was lower in the AZA group than in the IFNbeta products group (0.28 vs. 0.64, P < 0.05). After 12 months, 57.4% of patients receiving IFNbeta products remained relapse free compared with 76.6% of those given AZA. The Expanded Disability Status Scale (EDSS) decreased by 0.30 units in IFNbeta-treated patients (P < 0.05) and 0.46 in AZAtreated patients (P < 0.001). Treatment with IFNbeta products and AZA significantly reduces the relapse rate and EDSS score in patients with RRMS, while AZA is more effective than the IFNbeta formulations.

Conjugal multiple sclerosis in Isfahan, Iran: a population-based study.

Conjugal multiple sclerosis (MS) is a rare form of MS in which both spouses are affected, and at least one is affected after marriage. Among 1606 definite MS patients, 1076 were in marital relationship, among whom we identified six conjugal pairs, giving the conjugal rate of 0.5%. This rate is 12.5 times higher than the estimated risk of MS for the general population (0.04%). The observed conjugal rate suggests an increased risk of developing MS for MS patients' spouses, this could be due to transmission or, more likely, to the same environmental factors shared in adult life.