•Neurophysiological techniques offer insights into the physiopathology of brain aging.•They provide information on brain activity, connectivity, and network dynamics.•They may enable the prediction ...of MCI progression to dementia.•They may allow the differential diagnosis among neurodegenerative diseases.
Brain aging is associated with a decline in cognitive performance, motor function and sensory perception, even in the absence of neurodegeneration. The underlying pathophysiological mechanisms remain incompletely understood, though alterations in neurogenesis, neuronal senescence and synaptic plasticity are implicated. Recent years have seen advancements in neurophysiological techniques such as electroencephalography (EEG), magnetoencephalography (MEG), event-related potentials (ERP) and transcranial magnetic stimulation (TMS), offering insights into physiological and pathological brain aging. These methods provide real-time information on brain activity, connectivity and network dynamics. Integration of Artificial Intelligence (AI) techniques promise as a tool enhancing the diagnosis and prognosis of age-related cognitive decline. Our review highlights recent advances in these electrophysiological techniques (focusing on EEG, ERP, TMS and TMS–EEG methodologies) and their application in physiological and pathological brain aging. Physiological aging is characterized by changes in EEG spectral power and connectivity, ERP and TMS parameters, indicating alterations in neural activity and network function. Pathological aging, such as in Alzheimer's disease, is associated with further disruptions in EEG rhythms, ERP components and TMS measures, reflecting underlying neurodegenerative processes. Machine learning approaches show promise in classifying cognitive impairment and predicting disease progression. Standardization of neurophysiological methods and integration with other modalities are crucial for a comprehensive understanding of brain aging and neurodegenerative disorders. Advanced network analysis techniques and AI methods hold potential for enhancing diagnostic accuracy and deepening insights into age-related brain changes.
Objective
To evaluate the long‐term effectiveness, safety, and tolerability of erenumab in a real‐world migraine population, looking for putative predictors of responsiveness.
Background
Erenumab ...proved to be effective, safe, and well tolerated in the prevention of episodic migraine (EM) and chronic migraine (CM) in long‐term extension studies of double‐blind, placebo‐controlled trials in patients with no more than two (EM) or three (CM) prior preventive treatment failures.
Methods
A 48‐week, multicenter, longitudinal cohort real‐life study was conducted at 15 headache centers across eight Italian regions between December 20, 2018 and July 31, 2020. We considered all consecutive patients with high‐frequency episodic migraine (HFEM) or CM aged 18–65 years. Each patient was treated with erenumab 70 mg, administered monthly. The dose was switched to 140 mg in nonresponders and in responders who had become nonresponders for at least 4 weeks. Change in monthly migraine days (MMDs) or monthly headache days (MHDs) at Weeks 45–48 compared with baseline was the primary efficacy endpoint. Secondary endpoints encompassed variation in monthly analgesic intake, achievement of a ≥50%, ≥75%, or 100% reduction in migraine or headache days, and any change in the Visual Analogue Scale (VAS) and Headache Impact Test‐6 scores (HIT‐6) during the same time interval.
Results
A total of 242 patients with migraine received at least one dose of erenumab 70 mg and were considered for safety analysis, whereas 221 received a monthly erenumab dose for ≥48 weeks and were included in the effectiveness and safety analysis set. All patients had previously been treated unsuccessfully with ≥3 migraine‐preventive medication classes. From baseline to Weeks 45–48, erenumab treatment reduced MMD by 4.3 ± 5.3 (mean ± SD) in patients with HFEM, and MHD by 12.8 ± 8.9 (mean ± SD) in subjects with CM. VAS and HIT‐6 scores were decreased by 1.8 ± 1.9 (mean ± SD) and 12.3 ± 11 (mean ± SD) in HFEM, and by 3.0 ± 2.2 (mean ± SD) and 13.1 ± 11.2 (mean ± SD) in CM. Median monthly analgesic intake passed from 11.0 (interquartile range IQR 10.0–13.0) to 5 (IQR 2.0–8.0) in HFEM and from 20.0 (IQR 15.0–30.0) to 6.0 (IQR 3.8–10.0) in CM. The ≥50% responders were 56.1% (32/57) in HFEM and 75.6% (124/164) in CM; ≥75% responders were 31.6% (18/57) and 44.5% (73/164); and 100% responders were 8.8% (5/57) and 1.2% (2/164), respectively. At Week 48, 83.6% (137/164) of patients with CM had reverted to EM. Erenumab was safe and well tolerated. Responsiveness to erenumab was positively associated with cutaneous allodynia (OR: 5.44, 95% CI: 1.52–19.41; p = 0.009) in HFEM. In patients with CM, ≥50% responsiveness was positively associated with male sex (OR: 2.99, 95% CI: 1.03–8.7; p = 0.044) and baseline migraine frequency (OR: 1.12, 95% CI: 1.05–1.20; p = 0.001) and negatively associated with psychiatric comorbidities (OR: 0.37, 95% CI: 0.15–0.87; p = 0.023) and prior treatment failures (OR: 0.77, 95% CI: 0.64–0.92; p = 0.004).
Conclusions
Long‐term (48‐week) erenumab treatment provides sustained effectiveness, safety, and tolerability in real‐life patients with HFEM or CM with ≥3 prior preventive treatment failures. The dose of 140 mg was required in most patients along the study and should be taken into consideration as the starting dose. Allodynia (in HFEM), male sex, and baseline migraine frequency (in CM) might represent positive responsiveness predictors. Conversely, psychiatric comorbidities and multiple prior preventive treatment failures could be negative predictors in patients with CM.
Disease-modifying therapies (DMTs) can affect vaccine responses in individuals with multiple sclerosis (MS). We assessed the humoral and T-cell responses following SARS-CoV-2 mRNA vaccination in MS ...patients receiving various DMTs. We prospectively enrolled 243 participants, including 113 healthy control subjects and 130 MS patients. Blood samples for detecting SARS-CoV-2 antibodies were collected at three time points: T0, before the first vaccine dose; T1, before the second dose; and T2, one month after the second dose. In a subgroup of 51 patients and 20 controls, samples were collected at T0 and T2 to assess the T-cell immune response to the Spike antigen of SARS-CoV-2 using ELISPOT-IFNγ. The IgG levels in patients treated with fingolimod and ocrelizumab (159.1 AU/ml and 467.1 AU/ml, respectively) were significantly lower than those in healthy controls and patients on other DMTs (P < 0.0001). The mean Ig titers were higher in patients with an absolute lymphocyte count ≥1000 cells/mm3 compared to those with a count between 500 and 1000 and with a count <500 (mean ± SD:7205.6 ± 7339.2, 2413.1 ± 4515.4 and 165.9 ± 152.2, respectively; p = 0.008). We found correlations between antibody levels and age (r = 0.233, p = 0.008). A positive Spike-specific T-cell response was detectable in 100 % of vaccinated healthy controls and patients treated with teriflunomide, dimethyl-fumarate, and natalizumab, in 90.5 % of fingolimod patients, and in 63.8 % of ocrelizumab patients. There is a correlation between IgG-specific titer after SARS-CoV-2 vaccination and clinical variables (age, lymphocyte count). Notably, a T-cell–specific response to SARS-CoV-2 developed in patients treated with fingolimod and ocrelizumab, even with lower rates of humoral response.
Background
Many patients treated with Natalizumab experience wearing-off symptoms (WoS) towards the end of the administration cycle. During the pandemic we advised and asked patients undergoing ...treatment with Natalizumab if they wanted to be shifted from a standard interval dosing (StID of 4 weeks) to an extended interval dosing (ExID of 5–6 weeks), regardless of their JCV index. Our main objective was to study prevalence and incidence of WoS when ExID was adopted.
Methods
We enrolled 86 patients, from May 2020 to January 2021, evaluated at baseline and during a 6 months follow-up with a survey focused on WoS, Fatigue Severity Scale (FSS), Expanded Disability Status Scale (EDSS) and MRI.
Results
Among the 86 patients, 32 (37.2%) reported WoS. Most common one was fatigue (93.7%). Mean EDSS was higher in the group reporting WoS (3.8 WoS vs 3.1 non-WoS,
p
< 0.05).
Sphincterial function
was the EDSS item that significantly differed between the WoS group and the non-WoS group (1.4 WoS vs 0.6 non-WoS,
p
< 0.001). WoS correlate with the FSS scale (
p
< 0.001).
Conclusion
Adopting an extended interval dosing does not result in significantly different occurrence of WoS between the ExID and the StID populations, in our cohort of patients. Interestingly, there is a strong correlation between WoS and a higher EDSS and FSS. Safety and efficacy of Natalizumab with ExID are relatively preserved in our study.
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