Background and Aims:

Gait abnormality is one of the most invalidating features of subjects with Parkinson’s disease (PD) which leads to a high risk of falls, impairs patients’ autonomy and decreases quality of life. The aims of this study were: (i) to assess the ability of 16 gait stability indexes to identify gait instability and recurrent fallers in persons with Parkinson’s Disease (pwPDs) irrespective of age and gait speed and (ii) to investigate their correlation with clinical and kinematic variables.

Methods:

Fifty-five walking trials from subjects with PD and 55 age-and-speed matched healthy subjects (HS) acquired with an inertial sensor system and included in the study. Based on the acceleration patterns provided by the inertial measurement unit, we calculated the harmonic ratios (HR), percent recurrence and percent determinism (RQAdet), coefficient of variation, normalized jerk score and the longest Lyapunov exponent.

Results:

A value ≤ 1.50 at the HR in the antero-posterior direction (HR_AP) discriminated between pwPDs subjects at Hoehn & Yahr stage (HY) 3 and HS with a 67% probability, between pwPDS at HY 3 and pwPDs at lower HY stages with a probability of 73% and it identified recurrent fallers with a probability of 77%. HR_AP correlated with pelvic obliquity and rotation. RQAdet in the AP direction discriminated between pwPDs and HS with a 67% probability, irrespective of the HY stage and was correlated with stride duration and cadence.

Conclusions:

HR_AP and RQAdet in the AP direction can be used as age- and speed-independent markers of gait instability.

Background and Aims:

OnabotulinumtoxinA (BoNT-A) proved effective in the prevention of chronic migraine in large pivotal trials.

In this exploratory, open label, single-arm trial (NCT 04578782 clinicaltrials.gov) we evaluated the efficacy and safety of BoNT-A (Allergan-AbbVie) in the prevention of high-frequency episodic migraine (HFEM, 8-14 migraine days/month in the previous 3 months).

Methods:

We enrolled 32 HFEM subjects (age 44.8±11.9 yrs, 11.0±2.2 migraine days,11.5±2.1 headache days, 7 females). After a 28-day baseline period, subjects underwent 4 subsequent BoNT-A treatments according to the PREEMPT paradigm, delivered 12 weeks apart. The primary outcome measure was the monthly migraine days (MMD) reduction in the 12-week period after the last BoNT-A treatment as compared to baseline.

Results:

BoNT-A reduced the number of MMD by 3.68 days (-33.1%, p<0.01). Thirthy-nine % of the patients experienced a >50% reduction in MMD. BoNT-A significantly reduced also the number of headache days (-33.9%, p<0.01) and the intake of acute medications (-22.9%, p=0.03). Disability and QoL scores improved markedly (MIDAS -41.7%, p<0.01 and MSQ -31.7%, p<0.01). Adverse events were transient and mild-to-moderate in severity. Only one patient discontinued the study due to a cutaneous adverse reaction.

Conclusions:

BoNT-A administered according to the PREMPT paradigm proved effective in the preventive treatment of HFEM. This observation may have important clinical implications since HFEM subjects are a population at high risk of chronification and/or medication overuse.

Financial support

This study is an investigator-initiated research study partially supported by Allergan – Abbvie

Background and Aims:

Evaluating the efficacy of one-year treatment with erenumab in a cohort of patients with chronic migraine, with and without medication overuse headache, who previously failed at least 3 preventive therapies.

Methods:

We analyzed 82 patients (F59, M23, mean age:49.5+9.8, chronic migraine history: 12.9+10.7yrs). The most represented comorbidities (59%) were psychiatric conditions (e.g. depression and anxiety). Erenumab (70-140mg) was administered monthly for 13 treatments (T1 through T13). Our primary outcome measure was the pattern reversal of migraine from chronic to episodic. Thirteen patients(16%) interrupted treatment, 11 subjects for poor efficacy, after a mean of 7.3 months. We collected clinical data on headache features (diaries), disability (MIDAS, HIT-6), allodynia, anxiety and depression scales (questionnaires) at baseline and quarterly.

Results:

Patients with a pattern reversal from chronic to episodic migraine (i.e.>50%responders) were 33.3% at T1, rising to 71% at T13(Fig.1). Super-responders (i.e.>75%responders) were 9.7% at T1 reaching 34.3% at T13. A significant improvement in migraine days and symptomatic intake was detected already at T1 and persisted over the one-year treatment(Fig.2). An improvement in MIDAS and HIT-6 scores was detected from T3(p<0.001), while allodynia intensity decreased significantly from T6(p<0.001)(Fig.3) and anxiety and depression scores after T9 (HADS-A p=0.03,HADS-D p=0.01). Mild side effects were reported by 50% of patients (predominantly constipation, cutaneous reactions and fatigue).

Conclusions:

Erenumab induced a high percentage of pattern reversal in difficult-to-treat patients with chronic migraine. Reduction of monthly migraine days was already significant after the 1^st month of treatment, other clinical parameters improved significantly over time. Erenumab benefit persisted for the entire treatment period.

Background and Aims:

Migraine subjects experience a derangement of the nociceptive system control as the disease progresses. The endocannabinoid system may modulate the nociceptive pathways. We evaluated the nociceptive spinal modulation together with anandamide (AEA) and palmitoylethanolamide (PEA) circulating levels in patients with episodic migraine exposed to nitroglycerin (NTG - 0.9 mg, sublingual).

Methods:

We enrolled 24 patients (MiG - 33.0±8.1 years, 22 female) and 19 healthy controls (HC - 29.5±9.3, 15 female). Nociceptive withdrawal reflex and plasma AEA and PEA levels were recorded at baseline and at 30 (T30), 60 (T-60) and 120 (T-120) minutes after NTG administration. In subjects with a positive provocation test (NTG+) during the hospital observation period (180 minutes), the evaluations were repeated at migraine onset (T-MIG) and after 1 hour (T-MIG-1h).

Results:

Sixteen MiG patients (66.7%) and 0 HCs had an NTG+ response. NTG induced spinal sensitization in both NTG+ and NTG- patients, detectable as a decrease in temporal summation threshold (p=0.001 and 0.016, respectively). AEA levels significantly increased in all subjects until T-120 (p=0.035), without differences between MiG and HC groups. PEA levels significantly increased only in MiG patients at T-120 (p=0.001).

In 13 patients with NTG+ response before 180 minutes, we detected spinal nociceptive facilitation at T-MIG and at T-MIG-1h (p=0.001), and PEA increase at T-MIG-1h (p=0.031).

We did not find any correlations between neurophysiological parameters and levels of endocannabinoid mediators.

Conclusions:

NTG facilitates spinal nociceptive modulation and is associated to increased circulating PEA levels in subjects who develop a migraine. This response likely represents a compensatory anti-inflammatory/analgesic mechanism.

Abstract Body

Migraine is a highly disabling neurological disorder that affects more than 1 billion individuals worldwide. For decades, migraine has been thought to be a complex and indecipherable condition, poorly understood with regards to pathogenesis. Migraine is caused by the interaction of genetic and environmental factors on the functioning of multiple brain areas. Because of major progress in the understanding of its pathogenesis, novel mechanism-based drugs for preventing the debilitating attacks or for acutely treat them have recently emerged, thus enriching the armamentarium of treatments. In addition, neuromodulation and digital therapeutics are progressively gaining space in the migraine arena, which was entered in the last few years by monoclonal antibodies targeting CGRP, CGRP antagonists, 5HT1F agonists (ditans), peripheral nerve stimulation device and a more widespread and conscious use of electronic systems to identify and control attack triggers.

Migraine management is presently undergoing a positive revolution where the paradigm is slowly, but progressively switching from the trial-and-error or comorbidity-driven approach to an informed clinical management built on the combination of evidence-based data and a panel of individual features: frequency and severity of attacks, previous treatment failures and patient's preferences.

The availability of mechanism-specific drugs will hopefully facilitate the identification of biomarkers of response, which the scientific community is vigorously searching. Such an achievement will allow the final transition to the next level of migraine treatment, tailored therapies to individuals, thus granting the maximum effectiveness of treatments with the least possible amount of side effects.

Abstract Body

Migraine is a highly disabling neurological disorder that affects more than 1 billion individuals worldwide. For decades, migraine has been thought to be a complex and indecipherable condition, poorly understood with regards to pathogenesis. Migraine is caused by the interaction of genetic and environmental factors on the functioning of multiple brain areas. Because of major progress in the understanding of its pathogenesis, novel mechanism-based drugs for preventing the debilitating attacks or for acutely treat them have recently emerged, thus enriching the armamentarium of treatments. In addition, neuromodulation and digital therapeutics are progressively gaining space in the migraine arena, which was entered in the last few years by monoclonal antibodies targeting CGRP, CGRP antagonists, 5HT1F agonists (ditans), peripheral nerve stimulation device and a more widespread and conscious use of electronic systems to identify and control attack triggers.

Migraine management is presently undergoing a positive revolution where the paradigm is slowly, but progressively switching from the trial-and-error or comorbidity-driven approach to an informed clinical management built on the combination of evidence-based data and a panel of individual features: frequency and severity of attacks, previous treatment failures and patient's preferences.

The availability of mechanism-specific drugs will hopefully facilitate the identification of biomarkers of response, which the scientific community is vigorously searching. Such an achievement will allow the final transition to the next level of migraine treatment, tailored therapies to individuals, thus granting the maximum effectiveness of treatments with the least possible amount of side effects.