Skin innervation across amyotrophic lateral sclerosis clinical stages: new prognostic biomarkers.

Over recent decades, peripheral sensory abnormalities, including the evidence of cutaneous denervation, have been reported among the non-motor manifestations in amyotrophic lateral sclerosis (ALS). However, a correlation between cutaneous innervation and clinical features has not been found. The aims of this study were to assess sensory involvement by applying a morpho-functional approach to a large population of ALS patients stratified according to King's stages and correlate these findings with the severity and prognosis of the disease. We recruited 149 ALS patients and 41 healthy controls. Patients undertook clinical questionnaires for small fibre neuropathy symptoms (Small Fiber Neuropathy Symptoms Inventory Questionnaire) and underwent nerve conductions studies (NCS) and 3-mm punch skin biopsies from leg, thigh and fingertip. We assessed intraepidermal nerve fibre (IENF) and Meissner corpuscle (MC) density by applying an indirect immunofluorescence technique. Moreover, a subset of 65 ALS patients underwent a longitudinal study with repeat biopsies from the thigh at 6- and 12-month follow-ups. Serum NfL levels were measured in 40 patients. Sensory symptoms and sensory NCS abnormalities were present in 32.2% and 24% of patients, respectively, and increased across clinical stages. Analogously, we observed a progressive reduction in amplitude of the sensory and motor ulnar nerve potential from stage 1 to stage 4. Skin biopsy showed a significant loss of IENFs and MCs in ALS compared with healthy controls (all P < 0.001). Across the clinical stages, we found a progressive reduction in MCs (P = 0.004) and an increase in IENFs (all P < 0.027). The increase in IENFs was confirmed by the longitudinal study. Interestingly, the MC density inversely correlated with NfL level (r = -0.424, P = 0.012), and survival analysis revealed that low MC density, higher NfL levels and increasing IENF density over time were associated with a poorer prognosis (all P < 0.024). To summarize, in patients with ALS, peripheral sensory involvement worsens in parallel with motor disability. Furthermore, the correlation between skin innervation and disease activity may suggest the use of skin innervation as a putative prognostic biomarker.

Therapeutic choices and disease activity after 2 years of treatment with cladribine: An Italian multicenter study (CladStop).

BACKGROUND AND PURPOSE: Cladribine tablets, a purine analogue antimetabolite, offer a unique treatment regimen, involving short courses at the start of the first and second year, with no further treatment needed in years 3 and 4. However, comprehensive evidence regarding patient outcomes beyond the initial 24 months of cladribine treatment is limited. METHODS: This retrospective, multicenter study enrolled 204 patients with multiple sclerosis who had completed the 2-year course of cladribine treatment. The primary outcomes were therapeutic choices and clinical disease activity assessed by annualized relapse rate after the 2-year treatment course. RESULTS: A total of 204 patients were enrolled; most patients (75.4%) did not initiate new treatments in the 12 months postcladribine. The study found a significant reduction in annualized relapse rate at the 12-month follow-up after cladribine completion compared to the year prior to starting therapy (0.07 ± 0.25 vs. 0.82 ± 0.80, p < 0.001). Furthermore, patients with relapses during cladribine treatment were more likely to start new therapies, whereas older patients were less likely. The safety profile of cladribine was favorable, with lymphopenia being the primary registered adverse event. CONCLUSIONS: This study provides insights into therapeutic choices and disease activity following cladribine treatment. It highlights cladribine's effectiveness in reducing relapse rates and disability progression, reaffirming its favorable safety profile. Real-world data, aligned with previous reports, draw attention to ocrelizumab and natalizumab as common choices after cladribine. However, larger, prospective studies for validation and a more comprehensive understanding of cladribine's long-term impact are necessary.

A Blood Test for the Diagnosis of Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune chronic disease characterized by inflammation and demyelination of the central nervous system (CNS). Despite numerous studies conducted, valid biomarkers enabling a definitive diagnosis of MS are not yet available. The aim of our study was to identify a marker from a blood sample to ease the diagnosis of MS. In this study, since there is evidence connecting the serotonin pathway to MS, we used an ELISA (Enzyme-Linked Immunosorbent Assay) to detect serum MS-specific auto-antibodies (auto-Ab) against the extracellular loop 1 (ECL-1) of the 5-hydroxytryptamine (5-HT) receptor subtype 2A (5-HT2A). We utilized an ELISA format employing poly-D-lysine as a pre-coating agent. The binding of 208 serum samples from controls, both healthy and pathological, and of 104 serum samples from relapsing-remitting MS (RRMS) patients was tested. We observed that the serum-binding activity in control cohort sera, including those with autoimmune and neurological diseases, was ten times lower compared to the RRMS patient cohort (p = 1.2 × 10-47), with a sensitivity and a specificity of 98% and 100%, respectively. These results show that in the serum of patients with MS there are auto-Ab against the serotonin receptor type 2A which can be successfully used in the diagnosis of MS due to their high sensitivity and specificity.

ChatGPT vs. neurologists: a cross-sectional study investigating preference, satisfaction ratings and perceived empathy in responses among people living with multiple sclerosis.

BACKGROUND: ChatGPT is an open-source natural language processing software that replies to users' queries. We conducted a cross-sectional study to assess people living with Multiple Sclerosis' (PwMS) preferences, satisfaction, and empathy toward two alternate responses to four frequently-asked questions, one authored by a group of neurologists, the other by ChatGPT. METHODS: An online form was sent through digital communication platforms. PwMS were blind to the author of each response and were asked to express their preference for each alternate response to the four questions. The overall satisfaction was assessed using a Likert scale (1-5); the Consultation and Relational Empathy scale was employed to assess perceived empathy. RESULTS: We included 1133 PwMS (age, 45.26 ± 11.50 years; females, 68.49%). ChatGPT's responses showed significantly higher empathy scores (Coeff = 1.38; 95% CI = 0.65, 2.11; p > z < 0.01), when compared with neurologists' responses. No association was found between ChatGPT' responses and mean satisfaction (Coeff = 0.03; 95% CI = - 0.01, 0.07; p = 0.157). College graduate, when compared with high school education responder, had significantly lower likelihood to prefer ChatGPT response (IRR = 0.87; 95% CI = 0.79, 0.95; p < 0.01). CONCLUSIONS: ChatGPT-authored responses provided higher empathy than neurologists. Although AI holds potential, physicians should prepare to interact with increasingly digitized patients and guide them on responsible AI use. Future development should consider tailoring AIs' responses to individual characteristics. Within the progressive digitalization of the population, ChatGPT could emerge as a helpful support in healthcare management rather than an alternative.