Olfactory Loss and Brain Connectivity after COVID-19: Structural Follow-Up at One Year.

The structural connectivity from the primary olfactory cortex to the main secondary olfactory areas was previously reported as relatively increased in the medial orbitofrontal cortex in a cohort of 27 recently SARS-CoV-2-infected (COV+) subjects, of which 23/27 had clinically confirmed olfactory loss, compared to 18 control (COV-) normosmic subjects, who were not previously infected. To complement this finding, here we report the outcome of an identical high angular resolution diffusion MRI analysis on follow-up data sets collected in 18/27 COV+ subjects (10 males, mean age ± SD: 38.7 ± 8.1 years) and 10/18 COV- subjects (5 males, mean age ± SD: 33.1 ± 3.6 years) from the previous samples who repeated both the olfactory functional assessment and the MRI examination after ~1 year. By comparing the newly derived subgroups, we observed that the increase in the structural connectivity index of the medial orbitofrontal cortex was not significant at follow-up, despite 10/18 COV+ subjects were still found hyposmic after ~1 year from SARS-CoV-2 infection. We concluded that the relative hyperconnectivity of the olfactory cortex to the medial orbitofrontal cortex could be, at least in some cases, an acute or reversible phenomenon linked to the recent SARS-CoV-2 infection with associated olfactory loss.

Olfactory loss and brain connectivity after COVID-19.

To address the impact of COVID-19 olfactory loss on the brain, we analyzed the neural connectivity of the central olfactory system in recently SARS-CoV-2 infected subjects with persisting olfactory impairment (hyposmia). Twenty-seven previously SARS-CoV-2 infected subjects (10 males, mean age ± SD 40.0 ± 7.6 years) with clinically confirmed COVID-19 related hyposmia, and eighteen healthy, never SARS-CoV-2 infected, normosmic subjects (6 males, mean age ± SD 36.0 ± 7.1 years), were recruited in a 3 Tesla MRI study including high angular resolution diffusion and resting-state functional MRI acquisitions. Specialized metrics of structural and functional connectivity were derived from a standard parcellation of olfactory brain areas and a previously validated graph-theoretic model of the human olfactory functional network. These metrics were compared between groups and correlated to a clinical index of olfactory impairment. On the scanning day, all subjects were virus-free and cognitively unimpaired. Compared to control, both structural and functional connectivity metrics were found significantly increased in previously SARS-CoV-2 infected subjects. Greater residual olfactory impairment was associated with more segregated processing within regions more functionally connected to the anterior piriform cortex. An increased neural connectivity within the olfactory cortex was associated with a recent SARS-CoV-2 infection when the olfactory loss was a residual COVID-19 symptom. The functional connectivity of the anterior piriform cortex, the largest cortical recipient of afferent fibers from the olfactory bulb, accounted for the inter-individual variability in the sensory impairment. Albeit preliminary, these findings could feature a characteristic brain connectivity response in the presence of COVID-19 related residual hyposmia.

Headache Worsening after COVID-19 Vaccination: An Online Questionnaire-Based Study on 841 Patients with Migraine.

Vaccines have represented the breakthrough in the fight against COVID-19. Based on reported headache attacks after vaccination in randomized controlled trials, we focused on the effects of COVID-19 vaccine administration on the migraine population, using an online questionnaire published on Italian Facebook groups oriented to headache patients. We collected data about the demographics and clinical parameters of migraine severity, COVID-19 infection, vaccination, and characteristics of headaches following vaccination. Out of 841 migraine patients filling in the questionnaire, 66.47% and 60.15% patients experienced a headache attack (from 1 hour to 7 days) after the first and the second vaccine dose, respectively. The main finding concerns headaches perceived by 57.60% of patients: attacks following vaccination were referred to as more severe (50.62% of patients), long-lasting (52.80% of patients) and hardwearing (49.69% of patients) compared to the usually experienced migraine attacks. This could be related to the production of inflammatory mediators such as type Iß interferon. Considering the high prevalence of migraine in the general population, awareness of the possibility of headaches worsening following COVID-19 vaccination in these patients may allow both patients and clinicians to face this clinical entity with conscious serenity, and to reduce the waste of resources towards inappropriate health-care.

Correlates of psychological distress in epileptic patients during the COVID-19 outbreak.

INTRODUCTION: Following the severe consequences of the coronavirus disease 2019 (COVID-19) outbreak, on March 9th, 2020 the Italian Government implemented extraordinary measures to limit viral transmission, including restrictive quarantine measures. Psychological distress represents the seizure-precipitating factor most often reported by patients with epilepsy. To date, no studies have analyzed the role played by the different dimensions of psychological distress quarantine-induced in patients with epilepsy. MATERIALS AND METHODS: We included a total of 40 patients, 18 suffered from generalized, and 22 from focal epilepsy. The patients previously seen in the outpatient clinic during the pre-lockdown period between January and February 2020 were reevaluated after the lockdown period. Psychological distress was evaluated by using the three subscales of Impact of Event Scale-Revised (IES-R). Finally, we employed logistic regression analyses to explore the demographic and clinical features associated to high scores on IES-R. RESULTS: Patients with higher scores on IES-R Intrusion and IES-R Avoidance subscales demonstrated an increased number of epileptic attacks compared to prelockdown period. Multivariate logistic regression analyses showed that a specific subgroup of patients (i.e., older, female with more anxious symptoms) are at higher risk of increased seizure frequency. CONCLUSIONS: Our study confirmed that the frequency of epileptic seizures increased during lockdown when compared to pre-lockdown period. The early identification of patients more vulnerable to worsening is crucial to limit the risk of requiring hospital or clinical treatment during the COVID-19 outbreak.

Correlates of Psychological Distress in Patients with Parkinson's Disease During the COVID-19 Outbreak.

BACKGROUND: Following the severe consequences of the COVID-19 outbreak, on March 9, 2020, the Italian government implemented extraordinary measures to limit viral transmission, including restrictive quarantine measures. This resulted in a rapid and profound change of people's daily lives. OBJECTIVE: We assessed the psychological impact of the 40-day quarantine in a large cohort of patients with Parkinson's disease (PD) and caregivers. Moreover, we analyzed whether prelockdown clinical features may be associated with subjective response of patients with PD to this traumatic event. METHODS: A total of 94 patients with PD were enrolled in the study. The Impact of Event Scale-Revised, the Kessler Psychological Distress Scale, and the 12-item Zarit Burden Inventory were obtained from patients and caregivers by email. A multivariate regression analysis was performed to determine whether prelockdown clinical motor and nonmotor features were associated with the psychological impact of lockdown. RESULTS: Regression analyses showed that prelockdown levels of anxiety, treatment-related motor complications, patients' quality of life, and lockdown hours per day were significantly associated with psychological impact measures of the 40-day quarantine. In addition, we showed that caregiver burden was correlated with overall patient autonomy and attention/memory impairment. CONCLUSIONS: We identified specific PD motor and nonmotor features potentially predisposing to higher psychological impact of stressful situations, such as quarantine. This may help guide postpandemic interventions and preventive strategies to avoid further impairment of psychological well-being in patients with PD.