Identifying Red Flags in Myasthenia Gravis Diagnosis, Reassessment, and Myasthenic Crisis: An Italian Delphi-Based Position Paper Francesco Habetswallner, Luca Bello, Fiammetta Biasini, Bernardo Maria De Martino, Fiammetta Vanoli, Paolo E. Alboini, Giovanni Antonini, Carlo Antozzi, Valentina Damato, Vincenzo Di Stefano, Amelia Evoli, Matteo Gastaldi, Raffaele Iorio, Michelangelo Maestri, Renato Mantegazza, Roberto Massa, Rita Rinaldi, Francesco Saccà, Carmelo Rodolico Acta Neurologica Scandinavica, 2026 Background and Purpose Myasthenia gravis (MG) is a complex autoimmune disorder affecting neuromuscular transmission, often leading to diagnostic and therapeutic challenges. Timely identification of “red flags” in diagnosis, therapeutic reassessment, and myasthenic crisis is crucial to optimizing patient outcomes. This Delphi‐based consensus is aimed at synthesizing expert recommendations for improving clinical practice in Italy. Methods A scientific board of 19 MG specialists and an extended panel of 47 neuromuscular experts participated in a structured Delphi methodology. Over an 11‐month period, consensus was developed across four areas: diagnostic red flags, confirmatory instrumental examinations, therapeutic reassessment, and the continuum from exacerbation to impending myasthenic crisis or to crisis. The threshold for achieving consensus was set at ≥ 75% agreement. Results Globally, 68 statements reached consensus. Key findings include the identification of “red flags” for suspecting MG, with fluctuating and fatigable muscle weakness serving as primary diagnostic indicators, often involving ocular, bulbar, and respiratory muscles. Instrumental tests, such as repetitive nerve stimulation and antibody assays, were deemed essential for diagnostic confirmation. Therapeutic reassessment in MG is warranted for unsatisfactory symptom control, clinically significant adverse events, new or worsening comorbidities, planning pregnancy, or neoplastic disease. Persistent fluctuations, exacerbations, or triggers like infections should prompt adjustments, aiming to optimize treatment while minimizing risks. High‐risk factors and triggers for myasthenic crises, including thymoma and infections, were identified, with arterial blood gas analysis highlighted as critical for crisis management. Conclusions This consensus provides actionable recommendations to enhance the identification and management of MG, addressing diagnostic delays, therapy optimization, and crisis prevention. These findings aim to guide clinical practice and foster a systematic approach to managing this heterogeneous disorder.
Early real-life experience on Zilucoplan for generalized myasthenia gravis: ZILU25 multicenter observational study Vincenzo Di Stefano, Nicasio Rini, Carlo Antozzi, Paolo Emilio Alboini, Paolo Alonge, Liliana Bevilacqua, Fiammetta Biasini, Alvino Bisecco, Silvia Bonanno, Filippo Brighina, Luca Codeluppi, Giulia D'Alvano, Valentina Damato, Carmen Erra, Laura Fionda, Lucia Florio, Melania Guida, Francesco Habetswallner, Raffaele Iorio, Pietro Luppino, Michelangelo Maestri Tassoni, Lorenzo Maggi, Martina Marini, Sofia Marini, Stefania Morino, Alessia Pugliese, Elena Rossini, Francesco Saccà, Alessio Sarnataro, Francesco Tuccillo, Fiammetta Vanoli, Massimiliano Ugo Verza, Claudia Vinciguerra, Rita Frangiamore Journal of the Neurological Sciences, 2025 BACKGROUND AND OBJECTIVES: Generalized Myasthenia gravis (gMG) is a rare chronic autoimmune disease affecting the postsynaptic membrane of the neuromuscular junction. New treatment options, such as the C5 inhibitors, are growing with promising results. In this study we investigated the real-world use of Zilucoplan for AChR-positive gMG in Italy. MATERIALS AND METHODS: Zilucoplan was self-administered by daily subcutaneous injections. Efficacy was assessed by Myasthenia Gravis Foundation of America Post-intervention status (MGFA-PIS), Myasthenia Gravis Activity of Daily Living (MG-ADL), Myasthenia Gravis Composite (MGC), Myasthenia Gravis quantitative (QMG) scales and 15-items Myasthenia Gravis Quality of Life (MG-QOL-15) questionnaire at baseline and after 1, 4, 12, 24 and 48 weeks. RESULTS: 54 patients (37 females, aged 57.3) received zilucoplan with a mean follow-up of 26.4 weeks. We observed a clinical meaningful and significant reduction of MG-ADL, QMG, MGC and MG-QOL-15 scores from W4 to W12 and sustained at W24 of follow-up. The MG-ADL responder rate was 75.6 % at W12 and 82.9 % at W24. Minimal symptoms expression (MSE) was obtained in 55.6 % of patients at W48 with a mean reduction of the daily prednisone dose of 8.3 mg at W24. Chronic IVIg was associated to a better response to MG-ADL at W12 at multivariate analysis. DISCUSSION AND CONCLUSIONS: Zilucoplan was well-tolerated and effective in most patients with AChR-positive gMG. A clinical meaningful effect was reported since the first week and was sustained after 24 weeks. Further studies are needed to confirm these preliminary real-life data.
Focal myositis: a literature review of clinical and immunopathological aspects Alessia Pugliese, Alba Migliorato, Adele Barbaccia, Fiammetta Biasini, Olimpia Musumeci, et al. Acta Myologica, 2024 Objectives: Focal myositis (FM) is a rare and restricted skeletal muscle inflammation, presenting as a solid mass with a typical lower leg localization and benign prognosis. In most cases the process solves spontaneously or after immunosuppressant therapy, but sometimes it recurs or progresses to a systemic inflammation. The basis of the disease are mostly unknown. Methods: Hence, we provide an update of histopathological features of FM, in order to better define the underlying pathomechanisms of this disorder. A PubMed literature search was focused on the case reports published in English from July 1977 to December 2023. Results: FM and other myositis may show similar morphological features. Emerging studies on MMP molecules and future eventual research on microRNAs (miRNAs) could help in differential diagnosis. Conclusions: Clinical, laboratory, neurophysiological and imaging findings can allow a correct diagnosis. However, muscle biopsy seems to be the only diagnostic tool to differentiate among FM and other localized soft tissue masses.
Neurological Presentation of Giant Pituitary Tumour Apoplexy: Case Report and Literature Review of a Rare but Life-Threatening Condition Valentina Puglisi, Elisabetta Morini, Fiammetta Biasini, Luisa Vinciguerra, Giuseppe Lanza, Placido Bramanti Journal of Clinical Medicine, 2022 Background: Giant pituitary adenomas are benign intracranial tumours with a diameter ≥4 cm. Even if hormonally non-functional, they may still cause local extension, leading to symptoms that include mostly gland dysfunction, mass effects, and, much less frequently, apoplexy due to haemorrhage or infarction. Neurological presentation of giant pituitary tumour apoplexy is even more rare and has not been systematically reviewed. Case Presentation: An 81-year-old woman was admitted to the Emergency Department because of acute onset headache, bilateral visual deficit, and altered consciousness. Computed tomography showed a giant mass lesion (>5.5 cm diameter) expanding upward to the suprasellar cistern, optic chiasm, and third ventricle, over-running the sphenoid sinus, and with lateral invasion of the cavernous sinus. Laboratory investigations revealed central adrenal and hypothyroidism insufficiency, while magnetic resonance imaging confirmed a voluminous suprasellar tumour (~6 cm diameter), with signs of pituitary tumour apoplexy. Neurological manifestations and gland-related deficits improved after hormonal replacement therapy with a high dose of intravenous hydrocortisone, followed by oral hydrocortisone and levo-thyroxine. The patient declined surgical treatment and follow-up visit. Conclusions: Giant pituitary tumour apoplexy is a rare but potentially life-threatening condition. Prompt diagnosis and multidisciplinary management may allow a remarkable clinical improvement, as seen in this case.
Chronic inflammatory demyelinating polyradiculoneuropathy relapse after mexiletine withdrawal in a patient with concomitant myotonia congenita: A case report on a potential treatment option Simona Portaro, Fiammetta Biasini, Placido Bramanti, Antonino Naro, Rocco Salvatore Calabrò Medicine United States, 2020 INTRODUCTION: we report on the first case of a woman affected by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and recessive myotonia congenita (MC), treated with mexiletine. We aimed at describing the possible role of mexiletine in CIDP management. PATIENT CONCERNS: A 44-year-old female affected by CIDP and MC, gained beneficial effects for CIDP symptoms (muscle weakness, cramps, and fatigue) and relapses, after mexiletine intake (200 mg twice a day). The patient presented with detrimental effects after mexiletine drop out, with a worsening of CIDP symptoms. INTERVENTIONS: The patient reported a nearly complete remission of muscle stiffness and weakness up to 3 years since mexiletine intake. Then, she developed an allergic reaction with glottis edema, maybe related to mexiletine intake, as per emergency room doctors' evaluation, who suggested withdrawing the drug. OUTCOMES: The patient significantly worsened after the medication drop out concerning both CIDP and MC symptoms. CONCLUSION: This is the first report on the association of CIDP and MC in the same patient. Such diseases may share some clinical symptoms related to a persistent sodium currents increase, which maybe due either to the over-expression of sodium channels following axonal damage due to demyelination or to the chloride channel genes mutations. This is the possible reason why mexiletine maybe promising to treat CIDP symptoms.
Myasthenia Gravis: Unusual Presentations and Diagnostic Pitfalls Carmelo Rodolico, Daniela Parisi, Simona Portaro, Fiammetta Biasini, Stefano Sinicropi, Annamaria Ciranni, Antonio Toscano, Sonia Messina, Olimpia Musumeci, Giuseppe Vita, Paolo Girlanda Journal of Neuromuscular Diseases, 2016 BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder presenting with fluctuating, fatigable muscle weakness. Initial symptoms classically involve ocular and proximal limb muscles. Rarely, MG may onset with unusual features, so it can be misdiagnosed with other neuromuscular diseases. OBJECTIVE: To describe unusual and atypical presentations of MG in a large cohort of patients, considering and discussing diagnostic difficulties and pitfalls. METHODS: We report on 21 out of 508 MG patients, coming to our department in the last 27 years and presenting with atypical or unusual features. The diagnosis was achieved performing a careful clinical examination, a proper neurophysiological assessment, the neostigmine test, the AChR and MuSK antibodies assay and chest CT-scan. RESULTS: Patients with atypical/unusual MG onset were the 4.4% of all MG patients population. We describe seven different clinical categories: asymmetric distal upper limbs weakness, foot drop, isolated triceps brachii weakness and foot drop, post exertional axial weakness with dropped head, acute facial dyplegia, limb-girdle MG and MG with sudden lower limbs weakness and recurrent falls. CONCLUSIONS: Atypical and unusual presentations may increase the risk to misdiagnose or delay MG diagnosis. Isolated limb-girdle presentation is the most frequent atypical form in our series.
Preliminary study on sarcoglycan sub-complex in rat cerebral and cerebellar cortex Italian Journal of Anatomy and Embryology, 2012
