Using diffusion tensor (DT) magnetic resonance imaging (MRI), damage to brain intrahemispheric and interhemispheric connections was assessed in 26 sporadic primary lateral sclerosis (PLS) patients compared with 28 sporadic amyotrophic lateral sclerosis (ALS) patients with similar disability and 35 healthy controls. DT MRI diagnostic accuracy in distinguishing the two motor neuron disease (MND) variants was tested. PLS and ALS patients showed a distributed pattern of abnormalities of the motor system, including the corticospinal tracts and corpus callosum (CC). PLS versus ALS patients showed a more severe damage to the motor CC fibers and subcortical white matter (WM) underlying the primary motor cortices. Both patient groups showed an extra-motor damage, which was more severe in PLS. This did not appear to be driven by longer disease duration in PLS. In PLS patients, damage to the CC mid-body correlated with the severity of upper motor neuron clinical burden. CC fractional anisotropy values had the highest accuracy in distinguishing PLS from controls and ALS. PLS and ALS share an overlapped pattern of WM abnormalities. This underscores that PLS, despite its distinct clinical phenotype and long survival, still lies within the wider MND spectrum. Whether CC diffusivity may be a novel marker to increase confidence in an early diagnostic separation of PLS from ALS still needs to be investigated.

Background and objectives The identification of predictors of response to antiCGRP mAbs could favor tailored therapies and personalized treatment plans. This study is aimed at investigating predictors of ≥ 50%, ≥ 75% and 100% response at 24 weeks in patients with high-frequency episodic (HFEM: 8–14 days/month) or chronic migraine (CM). Methods This is a large, multicenter, cohort, real-life study. We considered all consecutive adult patients affected by HFEM or CM who were prescribed antiCGRP mAbs for ≥ 24 weeks in 20 headache centers. Patients were interviewed face-to-face using a shared semi-structured questionnaire carefully exploring socio-demographic and clinical characteristics. Patients received subcutaneous erenumab (70 mg or140 mg, monthly), galcanezumab (120 mg monthly, following a 240 mg loading dose), or fremanezumab (225 mg, monthly or 675 mg, quarterly) according to drug market availability, physician’s choice, or patient’s preference. The primary endpoint of the study was the assessment of ≥ 50% response predictors at 24 weeks. Secondary endpoints included ≥ 75% and 100% response predictors at 24 weeks. Results Eight hundred sixty-four migraine patients had been treated with antiCGRP mAbs for ≥ 24 weeks (erenumab: 639 pts; galcanezumab: 173 pts; fremanezumab: 55 pts). The ≥50% response (primary endpoint) in HFEM was positively associated with unilateral pain (UP) + unilateral cranial autonomic symptoms (UAs) (OR:4.23, 95%CI:1.57–11.4; p = 0.004), while in CM was positively associated with UAs (OR:1.49, 95%CI:1.05–2.11; p = 0.026), UP + UAs (OR:1.90, 95%CI:1.15–3.16; p = 0.012), UP + allodynia (OR:1.71, 95%CI:1.04–2.83; p = 0.034), and negatively associated with obesity (OR:0.21, 95%CI:0.07–0.64; p = 0.006). The 75% response (secondary endpoint) was positively associated with UP + UAs in HFEM (OR:3.44, 95%CI:1.42–8.31; p = 0.006) and with UP + UAs (OR:1.78, 95%CI:1.14–2.80; p = 0.012) and UP + allodynia (OR:1.92, 95%CI:1.22–3.06; p = 0.005) in CM. No predictor of 100% response emerged in patients with HFEM or CM. Conclusions A critical evaluation of headache characteristics indicating peripheral or central sensitization may help in predicting responsiveness to antiCGRP mAbs in HFEM and CM. A more precise pain profiling may represent a steppingstone for a mechanism-based approach and personalized treatment of migraine with compounds targeting specific molecular mechanisms.

Resting state functional connectivity of the sensorimotor and extramotor brain networks was studied in 24 patients with primary lateral sclerosis (PLS) relative to 26 healthy controls. The relationships of RS functional connectivity with patient clinical and cognitive status and white matter tract damage (i.e., corticospinal tracts, corpus callosum, and superior longitudinal fasciculus) were investigated. Compared with controls, PLS patients showed an increased functional connectivity within the sensorimotor, frontal, and left frontoparietal networks spanning the pre- and postcentral, medial and dorsal frontal, insular, and superior temporal regions. Patients with more severe physical disability and a more rapid rate of disease progression had increased sensorimotor connectivity values. The increased functional connectivity within the frontal network was associated with executive dysfunction. In addition, higher functional connectivity correlated with greater structural damage to network-specific white matter tracts. This study shows clinically meaningful increased resting state functional connectivity in PLS.