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Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FDT) are progressive neurodegenerative disorders that, in several cases, overlap in clinical presentation, and genetic and pathological disease mechanisms. About 10-15% of ALS cases and up to 40% of FTD are familial, usually with dominant traits. ALS and FTD, in several cases, share common gene mutations, such as in C9ORF72 , TARDBP , SQSTM-1 , FUS , VCP , CHCHD10 , and TBK-1 . Also, several mechanisms are involved in ALS and FTD pathogenesis, such as protein misfolding, oxidative stress, and impaired axonal transport. In addition, neuroinflammation and neuroinflammatory cells, such as astrocytes, oligodendrocytes, microglia, and lymphocytes and, overall, the cellular microenvironment, have been proposed as pivotal players in the pathogenesis the ALS-FTD spectrum disorders. This review overviews the current evidence regarding neuroinflammatory markers in the ALS/FTD continuum, focusing on the neuroinflammatory pathways involved in the genetic cases, moving from post-mortem reports to in vivo biofluid and neuroimaging data. We further discuss the potential link between genetic and autoimmune disorders and potential therapeutic implications.

Myasthenia gravis (MG) is a rare autoimmune disease that is potentially threatening for patient life. Auto-antibodies targeting structures of the neuromuscular junction, particularly the acetylcholine receptor (AchR), are often found in the serum of MG patients. New-onset MG after SARS-CoV-2 vaccination has rarely been reported since the introduction of vaccination. Infections and COVID-19 infection have also been reported as possible triggers for a myasthenic crisis. We report a case of new-onset MG after receiving the mRNA COVID-19 vaccination. The patient was a 73-year-old male initially presenting with ocular symptoms and a rapid generalization. We also performed a literature revision of 26 described cases of MG after SARS-CoV-2 immunization. The patients were a majority of males with generalized late-onset MG occurring after the first dose of vaccine, similar to our patient. Only our patient showed a thymoma. Thymic mass and the positivity of AchR antibodies suggest that vaccination might have triggered a subclinical pre-existing MG with symptoms flaring. Clinicians should be aware of possible new-onset MG after COVID-19 vaccination, particularly in at-risk patients. Even though COVID-19 vaccination should be recommended in MG patients, particularly in well-compensated patients. However, more studies need to be performed in the future.

(1) Background: To limit the COVID-19 outbreak, the Italian government implemented social restrictions that may have had psychological and cognitive repercussions on people with dementia. We aimed to analyze cognitive decline during the pandemic year in people evaluated in a memory clinic in northern Italy, the epicenter of COVID-19 spread. (2) Methods: A single-center retrospective study was carried out, including individuals with annual follow-up evaluated in three different years (2020-GROUP, 2019-GROUP, 2018-GROUP). We performed an intergroup comparison of cognitive decline over a one-year follow-up, and an intragroup comparison in the 2020-GROUP to analyze the five-year cognitive decline trajectory, as measured by the MMSE. (3) Results: The 2020-GROUP showed a significant loss of MMSE points per year in the considered follow-up period compared with the 2019-GROUP and 2018-GROUP ( p = 0.021). Demographics, clinical features, and the other analyzed variables, including rate of diagnosis, therapy, and comorbidities, did not significantly differ between groups. The five-year cognitive decline trajectory confirmed a significant worsening of cognitive decline between 2019 and 2020 ( p < 0.001), while the decrease in MMSE scores was not statistically significant between previous time points. (4) Conclusions: COVID-19 pandemic measures have induced a significant worsening of cognitive decline in people with dementia, needing more careful assistance to minimize the adverse effects of social isolation in case of future lockdowns.

Positron emission tomography (PET) allows for the in vivo assessment of early brain functional and molecular changes in neurodegenerative conditions, representing a unique tool in the diagnostic workup. The increased use of multivariate PET imaging analysis approaches has provided the chance to investigate regional molecular processes and long-distance brain circuit functional interactions in the last decade. PET metabolic and neurotransmission connectome can reveal brain region interactions. This review is an overview of concepts and methods for PET molecular and metabolic covariance assessment with evidence in neurodegenerative conditions, including Alzheimer's disease and Lewy bodies disease spectrum. We highlight the effects of environmental and biological factors on brain network organization. All of the above might contribute to innovative diagnostic tools and potential disease-modifying interventions.