Journal of Neurology Research Reviews & Reports

Introduction

Due to the COVID-19 pandemic infection, on March 2020 Italy entered a lockdown that lasted until the summer.

During that period, all non-essential elective medical and surgical procedures were stopped. Consequently, patients with multiple sclerosis (MS) discontinued their outpatient activities such as neurological consultations, physiotherapy, occupational therapy, and radiological follow-ups. Also, patients with MS had to face alone a number of difficulties such as shopping, looking after loved ones, going to work, organize remote teaching for their children. Neurologists had to weigh up the need to start or continue disease-modifying treatments against the risk of infection and MS activity. Being an unprecedented situation, most decisions were made based on a theoretical approach.

As a consequence, a moderate to severe psychological impact of the outbreak has been reported. Being a female, a student, or having specific physical symptoms (including coughs, myalgia, chills, and poor self-rated health status) were factors associated with the pandemic’s psychological impact, anxiety, and depression [1]. Patients with MS were found to be specifically vulnerable to the neuropsychiatric impacts of the COVID-19 pandemic. Besides, people with MS are known to undertake maladaptive coping strategies, which will make them even more susceptible to the detrimental neuropsychiatric effects of the outbreak [2]. To investigate quarantine’s impact due to the COVID-19 pandemic on patients with MS, we developed a 36 items self- report questionnaire divided into five domains.

Materials and Methods

From March 15 to May 4 2020, 120 questionnaires were emailed to the patients with MS most recently visited at the MS Center of the Policlinico Umberto I, Sapienza University of Rome. As a control group, the same questionnaire was emailed to 100 patients with chronic migraine (CM) visited at the same hospital’s headache center, matched for age, sex, and education. We chose patients with CM as it is a very disabling neurologic condition. In terms of associated disability expressed with “years lived with disability,”

Migraine ranked first in the subgroup of people under the age of 50, the age group deeply involved in family and work duties. In addition, among people with frequent migraine, the chronic form causes the highest degree of disability and costs, both direct and indirect [3, 4].

Patients diagnosed with psychiatric comorbidity or taking antidepressants (i.e., amitriptyline as prophylactic medication for migraine or SSRI for fatigue) were excluded.

The questionnaire consisted of 36-items self-reported, divided into five domains. Each item was scored on a Likert scale ranging from 0-4: 0= never, 1= rarely, 2= sometimes, 3= often, 4= almost always. In the first domain, we evaluated any concerns about MS and therapy in relation to the COVID-19 pandemic (score 0-28); in the second, we asked about personal and family caregiving (score 0-16); in the third, we investigated working activities (score 0-16); in the fourth, we evaluated general (4G score 0-32) and disease-related (4 DR, score 0-32) emotions during the lockdown; in the fifth, we assessed future expectations concerning health status, social life, and working activity (score 0-20). We evaluated both the total score (0-144) and the impact on patients of each domain (none, mild, and high impact) using cut-off values (table 1). For each dimension the cut-offs were calculated on the basis of the scores obtained for the individual answers. In particular, three levels have been identified:

0-1: low frequency

2-4: medium-high frequency

-No impact: given by the sum of the maximum number of answers never/rarely with a score of 0/1.

-Medium impact: given by the sum of the maximum number of answers sometimes with a score of 2.

-High impact: given by the sum of the maximum number of answers often/always with a score of 3/4.

Taking the first dimension (disease management) as an example: it consists of 7 questions for which the maximum score of the “no impact” level is given by multiplying the number of questions by the maximum value attributed to the answers never/rarely: 7 x 1 = All scores between 0 and 7 for this dimension will fall into the “non-impact” category.

Similarly, the “medium impact” level is given by multiplying the number of questions by the maximum of the value attributed to the answers “sometimes”: 7 x 2 = 14. All scores between 8 and 14 for this dimension will fall into the “medium impact” category; finally, the “high impact” level is given by multiplying the number of questions by the maximum of the value attributed to the “often/ always” answers: 7 x 4 = 28. All scores between 15 and 28 for this dimension will fall into the “high impact” category.

The same questionnaire applied in patients with CM had already been published elsewhere [5].

The questionnaire was completed voluntarily, all patients gave their written informed consent, and all subjects’ privacy rights were observed. The work has been carried out following The Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans and was approved by our local ethical committee.

Statistical Analysis

All statistical analyses were performed using the software SPSS, v 25.0 (IBM Co., Armonk, NY). Data were analyzed for normality of distribution using the Kolmogorov-Smirnov test and were expressed as mean (± standard deviation (SD)) for continuous variables or as frequencies (n, %) for categorical variables. Group comparisons (MS vs. CM) were performed using the Fisher test or χ2 test when appropriate for categorical variables. Any 2-sided P< .05 was considered statistically significant.

Results

Out of 120 questionnaires emailed to patients with MS, 104 replied (87%) (68 F, mean age 45 years, ± 12, education 15 years ± 3). Conversely, out of the 100 sent to people with CM, only 68 answered (45 F, age years 46, ± 13 years, education 14 ± 4 years). In the total sample (172 patients) 85 were employed as clerks, 38 were white-collar workers, 44 were unemployed or homemaker, and 5 were students; 83 were married, 69 were unmarried, and 20 were divorced or widowed (Table 2).

Twenty-two patients spent the lockdown alone, 40 with another person, and 110 with two or more people. We found no differences between people with MS and CM concerning demographic and general variables (education, marital status, employment, and the number of cohabitants).

Among patients with MS, 71 had a relapsing-remitting 20 a secondary progressive, and 13 a primary progressive form of MS. Mean EDSS was 2.0 ±1.5 (table 2).

Considering the degree of impact for each domain, the highest frequencies of “high-impact” scores were detected in domains 4 and 5, investigating respectively general and disease-related emotions and future expectations. In particular, about 37% and 45% of patients with MS manifested problems in the emotional sphere. They were worried about future health status, social life, and working activities compared to patients with CM (p= 0.05 and 0.02, respectively). About half of the people with MS expressed some concerns about MS and therapy in relation to the COVID-19 pandemic (p= 0.0002, see table 3). The frequency of response and the degree of impact for each area in people with MS and CM is showed in figure 1.

Domain 1: Concerns about MS and drug therapy.

Domain 2: Concerns about family and personal caregiving.

Domain 3: Concerns about the working activity.

Domain 4: G and DR: Both general and disease-related emotions during the lockdown.

Domain 5: Future expectations concerning health status, social life, and working activity.

Figure 1: Frequency of response and the degree of impact for each area in patients with MS (in bold) and CM (light shades).

Domain 1: Concerns about MS and drug therapy

Domain 2: Concerns about family and personal caregiving

Domain 3: Concerns about the working activity

Domain 4: G and DR: Both general and disease-related emotions during the lockdown

Domain 5: Future expectations concerning health status, social life, and working activity

Discussion

In this study, we developed a self-report questionnaire to evaluate the clinical and emotional impact of lockdown on people with MS. At the beginning of the pandemic, neurologists were confronted with how to advise their patients regarding immunosuppressive treatment. National professional bodies (e.g., Italian Society of Neurology and Association of British Neurologists) and patient organizations have responded by issuing guidelines for the COVID-19 pandemic, primarily focused on MS disease-modifying therapies (DMTs) [6-8]. The MS International Federation published global advice to the MS community addressing measures to reduce infection risk and general implications related to DMTs use [7]. The National MS Society endorsed the MS International Federation global advice and published broad DMT guidelines on its COVID-19 web page [8].

Our questionnaire was sent in February 2020 when Europe was at the beginning of the pandemic, and many uncertainties existed concerning DMTs exposure. People were scared (still they are), and the media gave (and give) conflicting information. In this scenario, it is not surprising that about half of the people with MS expressed some concerns about MS and therapy during the COVID-19 pandemic. A recent multicenter observational study describing the clinical characteristics and outcomes in patients with MS and COVID-19 found that age, EDSS, and obesity were independent risk factors for severe COVID-19; no association was evident between DMTs exposure and COVID-19 severity [9]. These data are in line with other recent reports, but, in the beginning, we were not aware of it [10]. An Australian survey, evaluating the perspective of people with MS on their DMT about the COVID-19 pandemic, found that a large proportion of patients had some concern regarding the impact of their DMT on COVID-19, whether the overall level of concern on their risk of contracting COVID-19 or on a theoretical risk for more severe disease in most cases was at most mild [11].

Patients appeared to be concerned about the emotional side of the pandemic also. About 30% of patients with MS stated that quarantine has a strong impact on general and disease-related emotions, and about 40% were worried about the future. People with chronic migraines also complained of emotional distress but to a lesser extent.

Many studies reported negative psychological effects during quarantine, including post-traumatic stress symptoms, confusion, and anger [2]. Stressors included longer quarantine duration, infection fears, frustration, boredom, inadequate supplies, inadequate information, financial loss, and stigma [2]. Therefore, quarantine’s potential benefits need to be weighed against the possible psychological costs [12-14].

Our patients had no psychiatric comorbidity, but they still showed anxiety and concern about the pandemic and future expectations. In a recent study, patients with MS were more anxious, stressed, and depressed during the COVID-19 pandemic than their caregivers and people without MS [15]. Given that our patients were not assessed for psychiatric symptoms with the formal psychometric test, adjustments for level of anxiety and depression were not performed. Therefore, we can only identify the presence of symptoms suggestive of emotional distress. Moreover, since we excluded individuals with pre-existing psychiatric difficulties, our results may underestimate the psychological impact of the pandemic on the MS population, given that those already suffering from depression/anxiety are likely more vulnerable to additional pandemic-related distress.

Very few patients with MS and CM were worried about personal and family caregiving and work activities. It is possible that the prolongation of the pandemic, and the consequent quarantine, could lead to greater repercussions also on these two aspects. There is evidence that the effect on the psychological and everyday life of quarantine can still be detected months or years later, suggesting the need to carry out effective mitigation measures as part of the quarantine planning process [16]. In this regard, we have planned a longer follow-up of these patients to evaluate any new problems arising after the end of the lockdown.

In conclusion, the lockdown’s emotional impact has been particularly meaningful in patients with MS, even higher than that observed in patients with other chronic diseases, such as CM.

Author Contributions

Conceptualization: Dr Altieri and Dr Fratino, methodology: Dr Fratino, formal analysis: Dr Altieri, investigations: Dr Altieri, Pauri, Conte, Frontoni, Dr Merluzzo and Dr Criusafulli, writing— original draft preparation: Dr Altieri, writing—review and editing: Dr Altieri, Conte, Di Piero.

All authors have read and agreed to the published version of the manuscript.

Founding: this research received no external founding

Declarations of Interest: none

Acknowledgements: Editorial assistance was provided by Francesca Cappellini

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