Payam Tabaee Damavandi

Background and ObjectivesIatrogenic cerebral amyloid angiopathy (iCAA), likely caused by transmission of amyloid-beta by medical procedures, is a rare but distinct cerebral amyloid angiopathy (CAA)...

Status epilepticus (SE) is a life-threatening persistent epileptic seizure that can arise from various brain structures, leaving its brain circuit unknown. In this study, we utilize brain imaging changes during SE to reveal the brain architecture and circuit of persistent seizures. Multimodal lesion mapping identified that brain imaging changes during SE localize to a specific predisposed brain architecture characterized by increased metabolic rate, high synaptic and mitochondrial density, glutamate (mGLUR5 and NMDA) and GABA receptors. Gene expression patterns within lesion locations revealed a transcriptomic profile enriched for epilepsy pathologies (including SE), neuronal and synaptic processes, and glutamate signaling. Lesion network mapping demonstrated these same lesions map to a common brain circuit, unifying a traditionally heterogeneous patient population. Findings were validated in an independent cohort and the identified SE circuit distinguished brain imaging changes during SE from other lesion etiologies with excellent accuracy (91%), significantly outperforming all other tested maps. With this SE circuit, we identify therapeutic targets for precision therapy that could modulate this circuit. This study demonstrates brain imaging changes in SE converge on a unified brain circuit that could help diagnostic workup of patients in critical care and guide clinical trials of precision therapy for persistent seizures.

Objective: Crossed cerebellar diaschisis is a neuroimaging phenomenon observed in various neurological conditions, including status epilepticus. This systematic review aims to summarize the clinical and radiological characteristics of patients developing crossed cerebellar diaschisis following status epilepticus and to discuss potential pathophysiological mechanisms. Methods: A systematic literature search was conducted using MEDLINE/PubMed, Embase, Web of Science, and CENTRAL from inception to October 2025. Studies reporting crossed cerebellar diaschisis in patients with status epilepticus, confirmed by neuroimaging (MRI, PET, or SPECT), were included. Data on demographics, semiology, etiology, imaging findings, EEG, and outcomes were extracted and synthesized. A spatial analysis of supratentorial MRI abnormalities associated with crossed cerebellar diaschisis was performed in 18 cases with suitable imaging. Results: Sixty patients from 50 studies were included. Mean age was 46.1 years; 50% were female. Convulsive status epilepticus was present in 62% of cases. Etiology was acute in 40%, unknown in 45%. Crossed cerebellar diaschisis was most frequently detected via DWI hyperintensity (55%) and FLAIR/T2 changes (52%). Arterial spin labelling and SPECT often showed hyperperfusion in the acute phase. Spatial mapping of supratentorial MRI abnormalities revealed a predominant involvement of cortical temporo‐occipital regions, with minimal subcortical involvement, aligning with known cerebro‐cerebellar connectivity patterns. Cerebellar symptoms were rare (5%), but cerebellar atrophy was reported in 7% of cases. Mortality was 10%; 30% recovered completely, while 33% had neurological deficits at discharge. Significance: Crossed cerebellar diaschisis is a dynamic phenomenon, presenting with both hyper‐ and hypoperfusion or metabolism, based on the timing and severity of status epilepticus. It may result from increased inhibitory cerebellar activity during seizures, followed by metabolic exhaustion and Purkinje cell loss. Although often clinically silent, it might lead to long‐term cerebellar atrophy and neurological sequelae.

Variants of cerebral amyloid angiopathy (CAA) have been increasingly reported. Iatrogenic CAA (iCAA) is a subtype arising in patients with a history of neurosurgery. Current etiopathogenetic hypotheses focus on previous exposure to contaminated materials, such as cadaveric dura, followed by a prion-like mechanism. CAA-related inflammation (CAA-ri) represents the inflammatory variant of CAA, usually with a good response to immunosuppressive therapy. To date, the association between iCAA and CAA-ri has not been clarified yet. This study reports cases of iCAA evolving into CAA-ri, emphasizing the clinical and radiologic overlaps between these conditions. This retrospective observational study included patients with clinical and radiologic features of CAA-ri and a history of neurosurgical intervention, observed at 2 Italian neurologic centers. Patients were identified from CAA databases and screened for neurosurgical history before 1990. Eligible cases met diagnostic criteria for CAA-ri. Clinical data were anonymized and included surgical details, evidence of amyloid-β in the CNS (amyloid-PET, CSF biomarkers, genetic screening), and CAA-ri features (symptoms, imaging findings, treatment, and outcomes). We identified 6 patients with iCAA who developed clinical and instrumental features of CAA-ri during their follow-up. The mean age at neurosurgery was 17.2 years (range: <1-43) while the onset of CAA-ri occurred at 61.8 years (range: 48-79), with an average latency of 44.7 years (range: 36-59). Despite immunosuppressive treatment, 2 patients experienced a rapid decline in their clinical condition and deceased within a few months from CAA-ri onset. This study increases awareness about the potential occurrence of CAA-ri in patients with iCAA, confirming its aggressive nature and highlighting the importance of neuroinflammation in the pathogenesis of the disease. In these patients, CAA-ri seems to be associated with a severe clinical course and a poor response to steroid treatment, often resulting in a fatal outcome in the short term.

Background: Sex differences play a significant role in the epidemiology, biology, and outcomes of many cancers, including glioblastoma (GB), the most common and aggressive primary brain tumor. GB is more frequent in males, while females tend to have longer survival, though the underlying reasons for these differences remain poorly understood. Potential contributors include hormonal influences, sex-specific risk factors, and treatment disparities. Understanding these differences is critical for optimizing personalized treatment strategies. Methods: We conducted a retrospective analysis of patients with gliomas from a neuro-oncological database, with a primary focus on GB cases. Variables collected included sex, age, tumor type, molecular biomarker, and treatment modalities. The primary objective was to assess sex-based differences in tumor characteristics and outcomes, while the secondary objective was to identify predictors of time to progression and mortality. Results: The cohort comprised 125 GB, 48 astrocytomas, and 16 oligodendrogliomas, with no significant sex-based differences in age or tumor type distribution. Among GB patients, multifocality was more prevalent in females (14% vs. 8%; p = 0.01); also, EGFR amplification was more frequent in females (25.5% vs. 52.5%; p = 0.007). Males received chemotherapy (80% vs. 63%; p = 0.04) and radiotherapy (84% vs. 67%; p = 0.03) more frequently than females. Survival was positively associated with MGMT methylation (p = 0.002) and negatively associated with TERT mutation (p = 0.01). Multivariable analysis identified TERT mutation as a predictor of increased mortality (HR = 4.1; 95% CI: 1.2–14; p = 0.025), while multifocality predicted both mortality (HR = 2.3; 95% CI: 1.3–3.9; p = 0.003) and reduced time to progression (HR = 3.3; 95% CI: 1.02–10.6; p = 0.04). Conclusions: This study underscores the importance of sex and molecular profiling in GB management, revealing distinct patterns in tumor characteristics and treatment administration between males and females. Our findings advocate for the integration of sex-specific considerations and molecular profiling into clinical decision-making to improve outcomes for GB patients.

Recently, a subset of patients affected by cerebral amyloid angiopathy (CAA) distinguished by atypical juvenile onset and a hypothesized iatrogenic origin (iatrogenic CAA, iCAA) has emerged. β-Amyloid (Aβ) accumulation evidenced by amyloid PET positivity or CSF Aβ decrease was included in the iCAA diagnostic criteria. Conversely, diagnostic criteria for sporadic CAA (sCAA) do not involve biomarker analysis. The aim of this study was to assess CSF and plasma levels of Aβ and tau in iCAA and sCAA cohorts. Patients affected by probable or possible CAA according to established criteria (Boston 2.0) were prospectively recruited at Fondazione IRCCS Carlo Besta and San Gerardo dei Tintori from May 2021 to January 2024. Patients with probable and possible iCAA or sCAA with available plasma and/or CSF samples were included. Clinical and neurologic data were collected, and levels of Aβ40, Aβ42, total tau, and phospho-tau (p-tau) were assessed in CSF and plasma by SiMoA and Lumipulse. 21 patients with iCAA (72% male, mean age at symptom onset 50 years [36-74]) and 32 patients with sCAA (44% male, mean age at symptom onset 68 years [52-80]) were identified. Cognitive impairment and cardiovascular risk factors in the sCAA cohort were more common compared with the iCAA cohort. Patients with sCAA and iCAA showed similar CSF levels for Aβ40 (p = 0.5 [sCAA, 95% CI 2,604-4,228; iCAA, 95% CI 1,958-3,736]), Aβ42 (p = 0.7 [sCAA, 95% CI 88-157; iCAA, 95% CI 83-155]), and total tau (p = 0.08 [sCAA, 95% CI 80-134; iCAA, 95% CI 37-99]). Plasma levels of Aβ40 (p = 0.08, 95% CI 181-222), Aβ42 (p = 0.3, 95% CI 6-8), and total tau (p = 0.4, 95% CI 3-6) were not statistically different in patients with sCAA compared with iCAA ones (Aβ40, 95% CI 153-193; Aβ42, 95% CI 6-7 and total tau, 95% CI 2-4). Despite presenting with a younger age at onset, fewer cardiovascular risk factors, and lower cognitive impairment, patients with iCAA demonstrated Aβ and tau levels comparable with elderly patients with sCAA, supporting a common molecular paradigm between the 2 CAA forms.

Both the role and the importance of magnesium in clinical practice have grown considerably in recent years. Emerging evidence suggests an association between loss of magnesium homeostasis and increased mortality in the critical care setting. The underlying mechanism is still unclear, but an increasing number of in vivo and in vitro studies on magnesium’s immunomodulating capabilities may shed some light on the matter. This review aims to discuss the evidence behind magnesium homeostasis in critically ill patients, and its link with intensive care unit mortality via a likely magnesium-induced dysregulation of the immune response. The underlying pathogenetic mechanisms, and their implications for clinical outcomes, are discussed. The available evidence strongly supports the crucial role of magnesium in immune system regulation and inflammatory response. The loss of magnesium homeostasis has been associated with an elevated risk of bacterial infections, exacerbated sepsis progression, and detrimental effects on the cardiac, respiratory, neurological, and renal systems, ultimately leading to increased mortality. However, magnesium supplementation has been shown to be beneficial in these conditions, highlighting the importance of maintaining adequate magnesium levels in the intensive care setting.

Brain tumor-related epilepsy (BTRE) is a common comorbidity in patients with brain neoplasms and it may be either the first symptom or develop after the tumor diagnosis. Increasing evidence suggests that brain tumors and BTRE share common pathophysiological mechanisms. Glutamatergic mechanisms can play a central role in promoting both primary brain tumor growth and epileptogenesis. Perampanel (PER), which acts as a selective antagonist of glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, may play a role both in the reduction in tumor growth and the control of epileptiform activity. This systematic review aimed to summarize the pre-clinical and clinical evidence about the antitumor properties, antiseizure effects and tolerability of PER in BTRE. Eight pre-clinical and eight clinical studies were identified. The currently available evidence suggests that PER can be an effective and generally well-tolerated therapeutic option in patients with BTRE. In vitro studies demonstrated promising antitumor activity of PER, while no role in slowing tumor progression has been demonstrated in rat models; clinical data on the potential antitumor activity of PER are scarce. Additional studies are needed to explore further the effects of PER on tumor progression and fully characterize its potentialities in patients with BTRE.