Multiple sclerosis (MS) is a chronic, inflammatory, and degenerative disease of the central nervous system (CNS). Inflammation is observed in all stages of MS, both within and around the lesions, and can have beneficial and detrimental effects on MS pathogenesis. A possible mechanism for the neuroprotective effect in MS involves the release of brain-derived neurotrophic factor (BDNF) by immune cells in peripheral blood and inflammatory lesions, as well as by microglia and astrocytes within the CNS. BDNF is a neurotrophic factor that plays a key role in neuroplasticity and neuronal survival. This review aims to analyze the current understanding of the role that inflammation plays in MS, including the factors that contribute to both beneficial and detrimental effects. Additionally, it explores the potential role of BDNF in MS, as it may modulate neuroinflammation and provide neuroprotection. By obtaining a deeper understanding of the intricate relationship between inflammation and BDNF, new therapeutic strategies for MS may be developed.

Pathological evidence of amyloid on nerve biopsy has been the gold standard for diagnosis in hereditary transthyretin amyloidosis polyneuropathy (hATTR-PN) for a long time. In this article, we reviewed the pathological findings of a large series of sural nerve biopsies from a cohort of hATTR-PN patients, collected by different Italian referral centers. Patients and Methods: We reviewed clinical and pathological data from hATTR-PN patients, diagnosed and followed in five Italian referral centers for peripheral neuropathies. Diagnosis was formulated after a positive genetic test for transthyretin (TTR) mutations. Sural nerve biopsy was performed according to standard protocols. Results: Sixty-nine sural nerve biopsies from hATTR-PN patients were examined. Congo red positive deposits were found in 73% of cases. Only the Phe64Leu mutation failed to show amyloid deposits in a high percentage of biopsies (54%), as already described. Unusual pathological findings, such as myelin abnormalities or inflammatory infiltrates, were detected in occasional cases. Conclusions: Even if no longer indicated to confirm hATTR-PN clinical suspicion, nerve biopsy remains, in expert hands, a rapid and inexpensive tool to detect amyloid deposition. In Italy, clinicians should be aware that a negative biopsy does not exclude hATTR-PN, particularly for Phe64Leu, one of the most frequent mutations in this country.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system characterized by broad inter- and intraindividual heterogeneity and different prognoses. Multisystem comorbidities are frequent features in people with MS (PwMS) and can affect treatment choices, quality of life, disability and mortality. In this scenario, autoimmune comorbidities play a cardinal role for several reasons, such as the implication on MS pathogenesis, diagnostic delay, disease activity, disability progression, brain atrophy, and treatment choice. However, the impact of an autoimmune comorbid condition on MS is not fully elucidated. This review aims to summarize the currently available data on the incidence and prevalence of autoimmune diseases in PwMS, the possible effect of this association on clinical and neuroradiological MS course and its impact on treatment choice.

Multiple sclerosis (MS) is a chronic inflammatory and degenerative demyelinating disease of the central nervous system of unknown etiology, which affects individuals in their early adulthood. However, nearly 5–10% of people with MS can be diagnosed at ages above 50 years old, referred to as late-onset multiple sclerosis (LOMS). Some studies have reported a distinctive presentation, clinical course, and prognosis for LOMS, implicating a different diagnostic and therapeutic approach for this population. Furthermore, similar manifestations between LOMS and other age-related conditions may lead to potential misdiagnosis and diagnostic delays, and a higher burden of multimorbidity associated with aging can further complicate the clinical picture. This review aims to explore the clinical characteristics, the disease course, and the differential diagnosis of LOMS and addresses therapeutic considerations for this population.

Background and purpose: Hereditary transthyretin (TTR) amyloidosis (ATTRv) is a dominantly inherited, adult‐onset, progressive, and fatal disease caused by mutations in the transthyretin gene. Therapeutic agents approved for this disease include the TTR stabilizer tafamidis and the gene‐silencing drugs patisiran and inotersen. Inotersen is an antisense oligonucleotide that suppresses the hepatic production of transthyretin. After European Medical Agency approval in 2018, an early‐access program was opened in Italy, and in this article, we present the long‐term outcome of a cohort of Italian ATTRv patients who received inotersen within this program.Methods: This is a multicenter, observational, retrospective study of patients affected by ATTRv that started inotersen during the early‐access program. The primary end point was safety. Secondary end points included change from baseline in familial amyloid polyneuropathy (FAP) stage, Polyneuropathy Disability, Neuropathy Impairment Scale, Compound Autonomic Dysfunction Test, Norfolk Quality of Life–Diabetic Neuropathy, troponin, N‐terminal pro–brain natriuretic peptide, interventricular septum thickness, and body mass index.Results: In total, 23 patients were enrolled. No patient permanently discontinued the treatment because of thrombocytopenia, and no cases of severe thrombocytopenia were observed. Five patients discontinued the treatment permanently because of voluntary withdrawal (two patients), renal failure after infective pyelonephritis, not related to inotersen, drug‐related hypotension, and amyloid‐negative crescentic glomerulonephritis. In seven patients, dosing frequency was reduced to every 2 weeks due to recurrent thrombocytopenia. Considering the FAP stage, only two patients worsened, whereas the other 21 patients remained stable until the last follow‐up available.Conclusions: The long‐term safety profile of inotersen is favorable. Neurologic disease severity at baseline is the main factor associated with progression.

Background: Theory of Mind (ToM) is the ability to predict and anticipate others' behaviors through the mental state attribution process. This study aims to investigate the ToM in patients with medication-overuse headache (MOH) and episodic migraine (EM) and to compare it with healthy controls (HC).Methods: This study enrolled patients with MOH, patients with EM, and HC. ToM was assessed through the Theory of Mind Assessment Scale (ThOMAS), which includes four subscales: Scale A, I-Me, Scale B, Other-Self, Scale C, I-Other, and Scale D, Other-Me, through the Reading the Mind in the Eyes test (RMET), which measures complex emotion recognition, and through the Toronto Alexithymia Scale (TAS-20), which measures alexithymia. Concomitant psychiatric disturbances were evaluated through the Hamilton Anxiety Rating Scale, the Hamilton Depression Rating Scale, and the Dissociative Experiences Scale-II.Results: The study involved 21 patients with EM, 22 patients with MOH, and 18 HC. In all the four subscales of the ThOMAS, there was a significant difference between HC, EM, and MOH patients: Scale A (p = 0.009), Scale B (p = 0.004), Scale C (p = 0.039), and Scale D (p = 0.008). In the RMET, MOH patients had worse performances than EM patients and HC (p = 0.039). MOH group exhibited higher levels of alexithymia when compared to the HC (p = 0.033) and higher levels of anxiety than HC (p = 0.001).Conclusion: MOH patients showed a subtle psychopathological pattern characterized by impaired social adaptation.