The cardiac Mg²⁺-sensitive, TRPM6, and TRPM7-like channels remain undefined, especially with the uncertainty regarding TRPM6 expression in cardiomyocytes. Additionally, their contribution to the cardiac action potential (AP) profile is unclear. Immunofluorescence assays showed the expression of the TRPM6 and TRPM7 proteins in isolated pig atrial and ventricular cardiomyocytes, of which the expression was modulated by incubation in extracellular divalent cation-free conditions. In patch clamp studies of cells dialyzed with solutions containing zero intracellular Mg²⁺ concentration ([Mg²⁺]_i) to activate the Mg²⁺-sensitive channels, raising extracellular [Mg²⁺] ([Mg²⁺]_o) from the 0.9-mM baseline to 7.2 mM prolonged the AP duration (APD). In contrast, no such effect was observed in cells dialyzed with physiological [Mg²⁺]_i. Under voltage clamp, in cells dialyzed with zero [Mg²⁺]_i, depolarizing ramps induced an outward-rectifying current, which was suppressed by raising [Mg²⁺]_o and was absent in cells dialyzed with physiological [Mg²⁺]_i. In cells dialyzed with physiological [Mg²⁺]_i, raising [Mg²⁺]_o decreased the L-type Ca²⁺ current and the total delayed-rectifier current but had no effect on the APD. These results suggest a co-expression of the TRPM6 and TRPM7 proteins in cardiomyocytes, which are therefore the molecular candidates for the native cardiac Mg²⁺-sensitive channels, and also suggest that the cardiac Mg²⁺-sensitive current shortens the APD, with potential implications in arrhythmogenesis.

Background and Objectives: Ravulizumab, a long-acting C5 complement inhibitor, was approved in the US and Europe in 2022 as an add-on therapy for the standard treatment of AChR-positive generalized MG (gMG). We share our real-world experience with adult patients receiving this therapy in Romania. Materials and Methods: Six AChR-positive gMG patients received ravulizumab through an Early Access Program (January 2023–October 2024). Patient outcomes were assessed at the therapy start and q8w using Quantitative MG (QMG), MG Activities of Daily Living (MG-ADL), and MG Quality of Life 15-item revised (MG-QoL15r) scales. Results: Age at disease onset ranged from 15 to 35 years. Four of the six patients were women. Two patients had gMG severity level of IIa, and four patients of IIb according to the Myasthenia Gravis Foundation of America (MGFA) classification. Five patients experienced rapid and sustained improvements in MG symptoms with MG-ADL score reductions ranged from −3 to −5 at 26 weeks post-ravulizumab start (except for those with a low baseline score: three and one). QMG score dropped in three patients (−2 to 12) during the treatment period, increased in two (+2 and +8), and remained stable in one (zero). Three patients showed sustained improvement in MG symptoms after ≥60 weeks. MG-QoL15r significantly dropped (−22 to −10) throughout the treatment period. One patient experienced ravulizumab-associated adverse events (vomiting, diarrhea, chills) that resolved within 24 h following symptomatic management, two to three episodes of myasthenic exacerbations during treatment, and discontinued it. Conclusions: All cases presented here had early-onset AChR antibody-positive, non-thymomatous MG. Despite differences in disease duration and underlying conditions, clinically meaningful and sustained improvements in gMG symptoms, and reduced corticosteroid doses were observed in all patients except one after adding ravulizumab to the treatment plan.

Amyloidosis may be associated with blood cancers like mul­ti­ple myeloma, if it is not a cancer itself. Instead, it re­sults from the buildup of an abnormal protein called amy­loid, which accumulates in tissues and organs. This amy­loid accumulation can lead to various symptoms and cause or­gan damage, impacting the functioning of the heart, kid­neys, liver, spleen, nervous system, and gastrointestinal tract. The extent and severity of the damage vary based on which organs are affected, contributing to the complexity of the disease. Peripheral neuropathies are a specific ma­ni­fes­ta­tion of systemic amyloidosis, primarily seen in trans­thy­retin amyloidosis (ATTR) and immunoglobulin light chain (AL) amyloidosis. This article highlights some cellular and molecular mechanisms involved in the nervous system im­pair­ment in these forms of amyloidosis. These conditions da­mage the nervous system due to the deposition of in­so­luble β-folded amyloid sheets in the peripheral nervous sys­tem. In AL amyloidosis, a clonal disorder of plasma cells, light or heavy chain immunoglobulin fragments are de­po­sited in tissues. In hereditary transthyretin amyloidosis, caused by auto­so­mal-dominant mutations of the TTR gene, mu­tant pro­teins misfold, initiating the disease process. Amy­loid fi­brils accumulate in the endonerve of peripheral nerves, af­fec­ting the dorsal root and sympathetic ganglia, lead­ing to Schwann cell atrophy and disrupting the blood-nerve bar­rier. This article focuses on the cellular and mo­le­cu­lar me­cha­nisms involved in nervous system da­mage, but it does not cover therapeutic approaches, which can be found in spe­cia­lized publications.

Hemiplegic migraine (HM) is a rare subtype of migraine cha­rac­te­rized by temporary motor weakness or paralysis on one side of the body, often accompanied by other aura symp­toms such as visual disturbances, speech difficulties or sensory changes. In pediatric patients, HM poses a diag­nostic challenge due to its variable presentation and over­lap with other neurological disorders such as stroke, epi­lep­sy or functional disorders. This overview summarizes the current understanding of pediatric hemiplegic mi­graine, including clinical features, diagnostic criteria, ge­ne­tic background, differential diagnosis and available treat­ment options. Early recognition and appropriate ma­nage­ment are crucial to reduce the risk of misdiagnosis and un­ne­ces­sary interventions in afflicted children.

Encephalitis with anti-NMDA receptor antibodies is one of the most common autoimmune encephalitis, after acute de­myelinating encephalitis. Recent data from the spe­cia­lized literature bring attention to a series of hypo­the­ti­cal me­cha­nisms regarding the causes of the symptoms of en­ce­pha­litis with anti-NMDA receptor antibodies. Beyond these, the acute psychosis that can occur is associated with the presence in the blood and cerebrospinal fluid of antibodies directed at the NR1a subunit of the NMDA re­cep­tor, which causes a slowing of the activity of neurons at this level. Behavioral, mood and cognitive disorders can be the cause of reversible atrophy predominantly in the fron­to­temporal area, where NMDA receptors are densely distri­buted.