Indirect functional connectivity does not predict overall survival in glioblastoma.

BACKGROUND: Lesion network mapping (LNM) is a popular framework to assess clinical syndromes following brain injury. The classical approach involves embedding lesions from patients into a normative functional connectome and using the corresponding functional maps as proxies for disconnections. However, previous studies indicated limited predictive power of this approach in behavioral deficits. We hypothesized similarly low predictiveness for overall survival (OS) in glioblastoma (GBM). METHODS: A retrospective dataset of patients with GBM was included (n = 99). Lesion masks were registered in the normative space to compute disconnectivity maps. The brain functional normative connectome consisted in data from 173 healthy subjects obtained from the Human Connectome Project. A modified version of the LNM was then applied to core regions of GBM masks. Linear regression, classification, and principal component (PCA) analyses were conducted to explore the relationship between disconnectivity and OS. OS was considered both as continuous and categorical (low, intermediate, and high survival) variable. RESULTS: The results revealed no significant associations between OS and network disconnection strength when analyzed at both voxel-wise and classification levels. Moreover, patients stratified into different OS groups did not exhibit significant differences in network connectivity patterns. The spatial similarity among the first PCA of network maps for each OS group suggested a lack of distinctive network patterns associated with survival duration. CONCLUSIONS: Compared with indirect structural measures, functional indirect mapping does not provide significant predictive power for OS in patients with GBM. These findings are consistent with previous research that demonstrated the limitations of indirect functional measures in predicting clinical outcomes, underscoring the need for more comprehensive methodologies and a deeper understanding of the factors influencing clinical outcomes in this challenging disease.

Impact of 2021 European Academy of Neurology/Peripheral Nerve Society diagnostic criteria on diagnosis and therapy of chronic inflammatory demyelinating polyradiculoneuropathy variants.

BACKGROUND AND PURPOSE: There are different criteria for the diagnosis of different variants of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guidelines provide specific clinical criteria for each CIDP variant even if their therapeutical impact has not been investigated. METHODS: We applied the clinical criteria for CIDP variants of the 2021 EAN/PNS guidelines to 369 patients included in the Italian CIDP database who fulfilled the 2021 EAN/PNS electrodiagnostic criteria for CIDP. RESULTS: According to the 2021 EAN/PNS clinical criteria, 245 patients achieved a clinical diagnosis of typical CIDP or CIDP variant (66%). We identified 106 patients with typical CIDP (29%), 62 distal CIDP (17%), 28 multifocal or focal CIDP (7%), four sensory CIDP (1%), 27 sensory-predominant CIDP (7%), 10 motor CIDP (3%), and eight motor-predominant CIDP (2%). Patients with multifocal, distal, and sensory CIDP had milder impairment and symptoms. Patients with multifocal CIDP had less frequently reduced conduction velocity and prolonged F-wave latency and had lower levels of cerebrospinal fluid protein. Patients with distal CIDP more frequently had reduced distal compound muscle action potentials. Patients with motor CIDP did not improve after steroid therapy, whereas those with motor-predominant CIDP did. None of the patients with sensory CIDP responded to steroids, whereas most of those with sensory-predominant CIDP did. CONCLUSIONS: The 2021 EAN/PNS criteria for CIDP allow a better characterization of CIDP variants, permitting their distinction from typical CIDP and more appropriate treatment for patients.

Long-term treatment of hereditary transthyretin amyloidosis with patisiran: multicentre, real-world experience in Italy.

BACKGROUND: Hereditary transthyretin (ATTRv, v for variant) amyloidosis with polyneuropathy is a rare disease caused by mutations in the transthyretin gene. In ATTRv amyloidosis, multisystem extracellular deposits of amyloid cause tissue and organ dysfunction. Patisiran is a small interfering RNA molecule drug that reduces circulating levels of mutant and wild-type TTR proteins. Prior to its regulatory approval, patisiran was available in Italy through a compassionate use programme (CUP). The aim of this study was to analyse the long-term outcomes of patients who entered into the CUP. METHODS: This was a multicentre, observational, retrospective study of patients with ATTRv amyloidosis treated with patisiran. The analysis included change from baseline to 12, 24, 36 and 48 months in familial amyloid polyneuropathy (FAP) stage, polyneuropathy disability (PND) class, neuropathy impairment score (NIS), modified body mass index (mBMI), Compound Autonomic Dysfunction Test (CADT), Karnofsky Performance Status (KPS) scale and Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) questionnaire. Safety data were also analysed. RESULTS: Forty patients from 11 Italian centres were enrolled: 23 in FAP 1 (6 in PND 1 and 17 in PND 2) and 17 in FAP 2 (8 in PND 3a and 9 in PND 3b) stage. In this population, the mean NIS at baseline was 71.4 (± 27.8); mBMI, 917.1 (± 207) kg/m2; KPS, 67.1 (± 14.0); Norfolk QoL-DN, 62.2 (± 25.2); and CADT, 13.2 (± 3.3). Statistical analysis showed few significant differences from baseline denoting disease stability. No new safety signals emerged. CONCLUSIONS: Patisiran largely stabilised disease in patients with ATTRv amyloidosis.

Glioblastoma and brain connectivity: the need for a paradigm shift.

Despite substantial advances in cancer treatment, for patients with glioblastoma prognosis remains bleak. The emerging field of cancer neuroscience reveals intricate functional interplays between glioblastoma and the cellular architecture of the brain, encompassing neurons, glia, and vessels. New findings underscore the role of structural and functional connections within hierarchical networks, known as the connectome. These connections contribute to the location, spread, and recurrence of a glioblastoma, and a patient's overall survival, revealing a complex interplay between the tumour and the CNS. This mounting evidence prompts a paradigm shift, challenging the perception of glioblastomas as mere foreign bodies within the brain. Instead, these tumours are intricately woven into the structural and functional fabric of the brain. This radical change in thinking holds profound implications for the understanding and treatment of glioblastomas, which could unveil new prognostic factors and surgical strategies and optimise radiotherapy. Additionally, a connectivity approach suggests that non-invasive brain stimulation could disrupt pathological neuron-glioma interactions within specific networks.

Hospitalization-based epidemiology of systemic and cardiac amyloidosis in the Veneto Region, Italy.

AIM: Defining the epidemiology of systemic and cardiac amyloidosis (CA) is a contemporary challenge. The present study aimed to estimate incidence and time trends in amyloidosis-related hospitalizations (AH) in Veneto Region (5 million inhabitants, Northeastern Italy). METHODS: International Classification of Diseases (ICD-9) codes were used to identify AH in Veneto from 2010 to 2020. AH were defined as any hospitalization with a discharge summary reporting an ICD-9 code for systemic amyloidosis. Hospitalization for CA was defined as records with ICD-9 code for systemic amyloidosis and ICD-9 code for heart failure,cardiomyopathy or arrhythmia. Hospital/outpatient encounters for carpal tunnel syndrome (CTS) surgeries also were extracted. AH incidence was estimated using a buffer of 5 years. RESULTS: In the time range 2015-2020, the incidence rate of AH was 23.5 cases per 106 (95% confidence interval, CI, 21.8; 25.3), mainly affecting patients>65 years (76.2%) and males (63.5%), with a progressively increasing trend (percent annual increase 17%, 95% CI 12; 22%). The 10 year prevalence of AH in 2020 was 124.5 per 106 (95% CI 114.9; 134.8). In 2020, annual hospitalized prevalent cases of CA were about 70% of all cases (159/228), mainly patients >65 years and males. Among patients with multiple CTS surgeries, a subsequent code for cardiac disease was found in 913 after a median of 3.9 years, more frequently in men than in women (463/6.526 7.1% versus 450/11.406 3.9%). CONCLUSIONS: In Veneto, we recorded a significantly increasing trend in the incidence of AH, with concordant increasing prevalence estimates.