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20 febbraio 2023




“Neural stem cell transplantation in patients with progressive multiple sclerosis: an open-label, phase 1 study”


Angela Genchi, Elena Brambilla, Francesca Sangalli, Marta Radaelli, Marco Bacigaluppi, Roberto Furlan, Annapaola Andolfo, Denise Drago, Cinzia Magagnotti, Giulia Maria Scotti, Raffaella Greco, Paolo Vezzulli, Linda Ottoboni, Marco Bonopane, Daniela Capilupo, Francesca Ruffini, Daniela Belotti, Benedetta Cabiati, Stefania Cesana, Giada Matera, Letizia Leocani, Vittorio Martinelli, Lucia Moiola, Luca Vago, Paola Panina-Bordignon, Andrea Falini, Fabio Ciceri, Anna Uglietti, Maria Pia Sormani, Giancarlo Comi, Mario Alberto Battaglia, Maria A. Rocca, Loredana Storelli, Elisabetta Pagani, Giuseppe Gaipa & Gianvito Martino


Nature medicine -   Published online: 9 January 2023

Selezionato dal lettore: Dott.ssa Susanna Ratti

MOTIVATION: Neural stem cells represent a potential therapeutic approach for several neurologic disorders. In the last decade several preclinical studies have demonstrated that their mechanism of action goes beyond the replacement of cells lost or damaged outlining a role in immunomodulation, neurogenesis and brain plasticity. These mechanisms could represent an effective and innovative therapeutic approach for patients with progressive multiple sclerosis (PMS) for whom an effective therapy preventing neurodegeneration has not yet been developed. Indeed, studies on animal models of multiple sclerosis have shown that the transplantation of neuronal precursors cells (NPC) promotes the release of neurotrophic factors that support neuronal plasticity and remyelination. Clinical trials are necessary to evaluate the safety and efficacy of NPC transplantation in patients with PMS. This phase one trial represents the first one to explore safety and tolerability of intrathecally transplanted human fetal NPCs (hfNPCs) in patients with PMS. Patients enrolled were divide in four treatment cohorts due to test safety and tolerability of increasing treatment dose and underwent to two years of follow-up. The study met his primary endpoint proving safety and tolerability of the treatment with no remarkable acute procedural complications and no dose-limiting toxicities. Adverse events at short and mid-time were considered mild with no differences between the treatment cohorts. The secondary endpoints aim at assess the potential treatment effect and were evaluated by analysing neurologic and neurophysiological outcomes, CSF and plasma biomarkers analysis, inflammatory, proteomic and metabolomic CSF profiling and MRI assessment. The authors found increased levels of CSF neuroprotective proteins and a significantly reduced rate of the whole brain and grey matter volume loss, which correlated with the number of injected hfNPCs. Despite the small sample size (12 patients) and the uncontrolled design (non-randomized study), this study can be considered pioneering in terms of the innovative nature of the used techniques and the importance of the results obtained and paves the way for future trials with larger samples and possibly higher dose of transplanted cells.




“Autoimmune Encephalitis Misdiagnosis in Adults” 


Eoin P. Flanagan, MD; Michael D. Geschwind, MD, PhD; A. Sebastian Lopez-Chiriboga, MD; Kyle M. Blackburn, MD; Sanchit Turaga, MD; Sophie Binks, MD; Jennifer Zitser, MD; JeffreyM. Gelfand, MD; Gregory S. Day, MD; S. Richard Dunham, MD; Stefanie J. Rodenbeck, MD; Stacey L. Clardy,MD, PhD; Andrew J. Solomon, MD; Sean J. Pittock, MD; Andrew McKeon, MD; Divyanshu Dubey, MD; Anastasia Zekeridou, MD, PhD; Michel Toledano, MD; Lindsey E. Turner; Steven Vernino,MD, PhD; Sarosh R. Irani, MD, DPhil


JAMA Neurol. 2023;80(1):30-39. doi:10.1001/jamaneurol.2022.4251


Selezionato dal lettore: Dott. Riccardo Tiberi


MOTIVATION: Autoimmune encephalitis are a growing group of autoimmune neurological illnesses which mainly affect the medial temporal lobes. Anti-NMDAR, anti-LGI1 and anti-CASPR2 antibodies are among the most well-known, but other antibodies are infrequent and less well-known. Apart from the typical encephalitis symptoms of altered awareness, fever and focal neurological abnormalities, limbic encephalitis can also cause neuropsychiatric signs and seizures. 
This study aimed to identify which diseases are most often misdiagnosed as autoimmune encephalitis, since there is a potential for false positive autoantibody results in patients with other diseases and this can lead to diagnostic delays and useless or even harmful therapies. 
Retrospective analysis was performed on 107 patients from 6 specialized facilities who had been misdiagnosed with autoimmune encephalitis. Inadequate adherence to diagnostic criteria was the most frequent reason for misinterpretation; specifically, a gradual onset of symptoms and the absence of suggestive MRI and CSF abnormalities should raise suspicion for a different diagnosis. Moreover, care should be taken when interpreting a specific antibody, especially serum anti-thyroid peroxidase, low-titer anti-GAD65 and anti-CASPR2 antibodies, isolated serum anti-NMDAr antibodies. The most common alternative diagnosis were functional neurologic or psychiatric disorders, neurodegenerative, infectious or neoplastic disorders. 
This study highlights that a thorough knowledge of autoimmune encephalitis is mandatory, but also that, being a relatively new classified group of neurological diseases, caution is needed when interpreting laboratoristic findings in the absence of suggestive clinical features.



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