Journal of the Neurological Sciences issue 446 now available

Neuro-immune deconvolution analysis of OAS3 as a transcriptomic central node in HIV-associated neurocognitive disorders

Sanfilippo et al.

Published online: January 19, 2023

Neurological complications of AIDS (NeuroAIDS) include primary HIV-associated neurocognitive disorder (HAND). OAS3 is an enzyme belonging to the 2′, 5′ oligoadenylate synthase family induced by type I interferons and involved in the degradation of both viral and endogenous RNA.

Here, we used microarray datasets from NCBI of brain samples of non-demented HIV-negative controls (NDC), HIV, deceased patients with HAND and encephalitis (HIVE) (treated and untreated with antiretroviral therapy, ART), and with HAND without HIVE. The HAND/HIVE patients were stratified according to the OAS3 gene expression.

The genes positively and negatively correlated to the OAS3 gene expression were used to perform a genomic deconvolution analysis using neuroimmune signatures (NIS) belonging to sixteen signatures. Expression analysis revealed significantly higher OAS3 expression in HAND/HIVE and HAND/HIVE/ART compared with NDC. OAS3 expressed an excellent diagnostic ability to discriminate NDC from HAND/HIVE, HAND from HAND/HIVE, HAND from HAND/HIVE/ART, and HIV from HAND/HIVE. Noteworthy, OAS3 expression levels in the brains of HAND/HIVE patients were positively correlated with viral load in both peripheral blood and cerebrospinal fluid (CSF). Furthermore, deconvolution analysis revealed that the genes positively correlated to OAS3 expression were associated with inflammatory signatures. Neuronal activation profiles were significantly activated by the genes negatively correlated to OAS3 expression levels. Moreover, gene ontology analysis performed on genes characterizing the microglia signature highlighted an immune response as a main biological process.

According to our results, genes positively correlated to OAS3 gene expression in the brains of HAND/HIVE patients are associated with inflammatory transcriptomic signatures and likely worse cognitive impairment.

Epilepsy and brain tumors: Two sides of the same coin

Published online: February 13, 2023

Epilepsy is the most common symptom in patients with brain tumors. The shared genetic, molecular, and cellular mechanisms between tumorigenesis and epileptogenesis represent 'two sides of the same coin'. These include augmented neuronal excitatory transmission, impaired inhibitory transmission, genetic mutations in the BRAF, IDH, and PIK3CA genes, inflammation, hemodynamic impairments, and astrocyte dysfunction, which are still largely unknown. Low-grade developmental brain tumors are those most commonly associated with epilepsy.

Given this strict relationship, drugs able to target both seizures and tumors would be of extreme clinical usefulness. In this regard, anti-seizure medications (ASMs) are optimal candidates as they have well-characterized effects and safety profiles, do not increase the risk of developing cancer, and already offer well-defined seizure control. The most important ASMs showing preclinical and clinical efficacy are brivaracetam, lacosamide, perampanel, and especially valproic acid and levetiracetam. However, the data quality is low or limited to preclinical studies, and results are sometimes conflicting. Future trials with a prospective, randomized, and controlled design accounting for different prognostic factors will help clarify the role of these ASMs and the clinical setting in which they might be used.

In conclusion, brain tumor-related epilepsies are clear examples of how close, multidisciplinary collaborations among investigators with different expertise are warranted for pursuing scientific knowledge and, more importantly, for the well-being of patients needing targeted and effective therapies.

The Benson Complex Figure Test detects deficits in visuoconstruction and visual memory in symptomatic familial frontotemporal dementia: A GENFI study

Published online: February 15, 2023

Sensitive cognitive markers are still needed for frontotemporal dementia (FTD). The Benson Complex Figure Test (BCFT) is an interesting candidate test, as it assesses visuospatial, visual memory, and executive abilities, allowing the detection of multiple mechanisms of cognitive impairment. To investigate differences in BCFT Copy, Recall and Recognition in presymptomatic and symptomatic FTD mutation carriers, and to explore its cognitive and neuroimaging correlates.

In the symptomatic stage, the BCFT identifies differential mechanisms of cognitive impairment depending on the genetic mutation, corroborated by gene-specific cognitive and neuroimaging correlates. Our findings suggest that impaired performance on the BCFT occurs relatively late in the genetic FTD disease process. Therefore its potential as cognitive biomarker for upcoming clinical trials in presymptomatic to early-stage FTD is most likely limited.

Determining the value of early measurement of interleukin-10 in predicting the absence of brain lesions in CT scans of patients with mild traumatic brain injury

Published online: January 21, 2023

Blood-based biomarkers were recently proposed as predictors of traumatic brain injury (TBI) outcomes. This would be a critical step forward since the majority of TBI events are mild and structural brain damage in this group may be missed by current brain imaging methods.

We sought to determine the performance of early measurement of interleukin-10 (IL-10) to distinguish computed tomography (CT)-positive from negative patients with mild TBI. For mild TBI patients between 36 and 66 years, classification performance increased significantly at the 100% sensitivity level with a specificity of 93%.

Our results suggest that IL-10 may be an easily accessible clinically useful diagnostic biomarker that can distinguish between mild TBI patients with and without structural brain damage with higher effectiveness when lower times of blood sampling are employed and patients are between 36 and 66 years of age.