Neurophysiological aspects in SARS-CoV-2–induced acute respiratory distress syndrome

Patients with coronavirus disease 2019 (COVID-19) often develop acute respiratory failure and acute respiratory distress syndrome (ARDS) that requires intensive care unit (ICU) hospitalization and invasive mechanical ventilation, associated with a high mortality rate. In addition, many patients fail early weaning attempts, further increasing ICU length of stay and mortality. COVID-19 related ARDS can be complicated by neurological involvement with mechanisms of direct central nervous system (CNS) infection and with overlapping para-infective mechanisms of the peripheral nervous system (PNS). We aimed to evaluate the possible involvement of the brainstem and PNS in patients with COVID-19 related ARDS and difficulty in weaning from mechanical ventilation. We evaluated electroencephalogram (EEG), brainstem auditory evoked potentials (BAEPs), electroneurography of the four limbs and the phrenic nerve in 10 patients with respiratory insufficiency due to SARS-CoV-2. All were admitted to intensive care unit and were facing prolonged weaning from mechanical ventilation. All ten patients showed a mild diffuse non-specific slowing of brain electrical activity on the EEG. Four patients had an acute motor axonal neuropathy with absent or reduced amplitude phrenic nerve CMAP while four patients showed impairment of the BAEPs. A patient with peripheral nerve impairment suggestive of Guillain-Barré syndrome (GBS) underwent an intravenous immunoglobulin (IVIg) cycle that led to an improvement in the weaning process and progressive motor improvement. The inclusion of a comprehensive neurological evaluation in COVID-19 patients in ICU facilitated the early identification and effective management of Nervous System involvement

Role of DNA Methylation Profile in Diagnosing Astroblastoma: A Case Report and Literature Review

Astroblastoma is a rare tumor of the central nervous system (CNS) with uncertain clinical behavior. Recently, DNA methylation profiling has been shown to provide a highly robust and reproducible approach for the classification of all CNS tumors across different age groups. By using DNA methylation profiling, a subset of CNS high-grade tumors with astroblastoma-like morphology characterized by the meningioma 1 gene (MN1) rearrangements, has been identified; they were termed “CNS high-grade neuroepithelial tumors with MN1 alteration” (CNS-HGNET-MN1). Here, we describe a case of CNS-HGNET-MN1 diagnosed by DNA methylation profiling, using Illumina Infinium HumanMethylationEPIC BeadChip (EPIC), that offers the opportunity to conduct a brief literature review. The patient presented with an episode of partial seizures involving the right hemisoma. A gross total resection was performed. No other treatment was proposed in light of the histological and molecular findings. After 21 months, the patient is disease-free in good clinical conditions. Also in view of this case, we recommend DNA-methylation profiling as an important tool for diagnosis and more effective patient stratification and management

Vemurafenib Treatment of Pleomorphic Xanthoastrocytoma in a Child With Down Syndrome

Brain tumors are the most common solid neoplasms of childhood, but they are very rarely reported in children with Down Syndrome (DS), who develop more commonly different types of malignancies. In particular, we hereby report the case of an 8-years-old child with DS that presented to our attention for neurological and endocrinological issues. Brain imaging revealed the presence of a mass that was partially resected revealing a histological diagnosis of Pleomorphic Xanthoastrocytoma (PXA), a rare WHO grade II tumor extending from the diencephalic region into the surrounding brain tissue. These tumors can harbor the BRAF mutation p.V600E, targetable by the specific inhibitor Vemurafenib. After confirming the presence of the mutation in the tumor, the patient was treated with Vemurafenib. The treatment proved to be effective, leading to a partial response and a stabilization of the disease. Usually, in patients with DS a reduction of the dose of chemotherapeutic drugs is necessary. Vemurafenib was instead well-tolerated as the only observed adverse effect was grade I skin toxicity. This is, to our knowledge, the first case of a PXA reported in a child with DS and the first DS patient treated with Vemurafenib

Ulnar Goniometer: a simple device for better neurophysiological evaluation of the Motor Conduction Velocity of the Ulnar Nerve.

OBJECTIVE The use of the Ulnar Goniometer standardizes the method of detecting the Motor Conduction Velocity (MCV) of the Ulnar nerve by keeping the elbow flexed at a fixed angle, thus enabling an easier and more precise measurement. MATERIALS AND METHODS The stimulations were performed by two independent operators. We evaluated 30 participants of both genders with paresthetic symptoms of the upper limbs and 30 healthy and asymptomatic volunteers. Each operator performed the examination without and with the use of the Ulnar Goniometer, detecting the velocity of motor conduction wrist-below elbow and the speed above-elbow (AE) below-elbow (BE). Agreement between the measurements was assessed with intraclass correlation coefficient (ICC). RESULTS The repeatability of the measurements between operators was modest without the use of the support (ICC = 0.152) while a good agreement was found when the operators used the support (ICC = 0.499). DISCUSSION AND CONCLUSIONS The most obvious results of the study were the reduction of the difference between operators using the Ulnar goniometer, the increase in the repeatability of the measurements and the specificity of the test

Goniometro Ulnare: un semplice dispositivo per una migliore valutazione neurofisiologica della velocità di conduzione motoria del nervo ulnare.

OBIETTIVO L’utilizzo del Goniometro Ulnare ha l’obiettivo standardizzare il metodo di rilevazione della Velocità di Conduzione Motoria (VCM) del nervo Ulnare mantenendo il gomito flesso ad un’angolazione standardizzata, favorendo così una più agevole e precisa misurazione. MATERIALI E METODI Le stimolazioni sono state eseguite da due diversi operatori; ogni operatore ha eseguito l'esame senza e con l'uso del Goniometro Ulnare, rilevando la Velocità di conduzione motoria polso-sotto gomito e la velocità sovragomito (above-elbow AE) sottogomito (below-elbow, BE). Abbiamo calcolato il grado di omogeneità tra le misurazioni e il coefficiente di correlazione intraclasse. RISULTATI Valutando 30 partecipanti di ambo i sessi con sintomi parestetici degli arti superiori e 30 volontari sani e asintomatici, la ripetibilità delle misurazioni tra operatori è stata modesta senza l'uso del supporto (ICC = 0,152) mentre si è riscontrato un buon accordo quando gli operatori hanno utilizzato il supporto (ICC = 0,499).. CONCLUSIONI I risultati più evidenti dello studio sono stati la riduzione della differenza tra operatori utilizzando il goniometro Ulnare, l’aumento della riproducibilità della misurazione e della specificità del test

Central conduction abnormalities in patients receiving levodopa-carbidopa intestinal gel infusion

In recent years, several studies have reported a relatively high frequency of polyneuropathy in patients with Parkinson\u2019s disease (PD), in particular, in patients receiving levodopa-carbidopa intestinal gel (LCIG) infusion. In spite of the several patients investigated with nerve conduction studies, no study has prospectively explored a possible central nervous system involvement of patients receiving LCIG infusion. We prospectively evaluated eight PD patients receiving LCIG infusion, who underwent neurophysiological evaluations with nerve conduction studies, visual, somatosensory and motor evoked potentials before LCIG infusion, and 1 and 6\ua0months after. At 6\ua0months follow-up, we found significant reduction in sural nerve SNAP amplitude, increase of central sensory conduction time N22-P40, and increases of central motor conduction time recorded from I dorsal interosseous and tibialis anterior. In PD patients with LCIG infusion, we found a subclinical neurophysiological impairment of both peripheral and central nervous system

The Role of Allogeneic Transplantation in Chronic Myeloid Leukemia in 2023: A Case-Based Concise Review

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML), granting patients a life expectancy close to that of the normal population and, in a subset of patients, the possibility to discontinue therapy. Nonetheless, for a not negligible minority of patients, TKIs are not able to control CML. Allogeneic hematopoietic cell transplantation (HCT) has long been a pivotal therapy for CML. At present, allogeneic HCT is considered an option in CML patients diagnosed or progressing to blast phase (BP), for those in chronic phase (CP) resistant to multiple lines of TKI therapy or for those experiencing severe toxicity, mostly hematologic, under TKIs. Moving from real-world cases, we reviewed the results of allogeneic HCT in the setting of advanced-phase CML or failure of TKIs, with a focus on the progresses in transplant technology that has extended transplant options in elderly CML patients and in those lacking a sibling donor, and on the post-HCT strategies for prevention and treatment of disease relapse

Impact of Cryopreservation of Peripheral Blood Stem Cells (PBSC) in Transplantation from Matched Unrelated Donor (MUD)

Background: Cryopreservation of PBSC for allogenic hematopoietic stem cell transplantation (allo-HSCT) was implemented due to the current Coronavirus 2019 pandemic. The impact of match unrelated donor (MUD) graft freezing on the outcome of allo-HSCT in terms of hematological recovery, graft versus host disease (GVHD), and survival are still controversial. Methods: In this study, we compared graft composition, clinical characteristics, and outcome of 31 allo-HSCT from MUD cryopreserved PBSC (Cryo Group) with 23 matched-pair allo-HSCT from fresh MUD PBSC (Fresh Group) performed in our center between January 2020 and July 2021. Results: No significant differences were recognized in clinical characteristics of patients, donors, and transplants between the Cryo and Fresh groups except for a better prognostic comorbidity index (HCT-CI) of the Cryo group. In the Cryo Group, the median time from apheresis to cryopreservation was 46.0 h (range 23.8–53.5), while the median time from cells collection and reinfusion was 13.9 days (range 5.8–28.1). In the Fresh Group, median time from apheresis to reinfusion was 35.6 h (range 21.4–51.2). The number of viable (7-AAD negative) CD34+ cells per kg patient infused was significantly lower in the Cryo Group (5.2 ± 1.9 × 106/kg vs. 7.0 ± 1.3 × 106/kg; p < 0.001). Indeed, there was a 36% (11–70) median loss of viable CD34+/kg cells after freezing. All patients engrafted: median time to neutrophil engraftment (>0.5 × 109/L) was 13.5 days (range 12–15) for Cryo Group and 14 days (range 13–16) days for Fresh Group (p = 0.522), while the median time to platelet engraftment (>20 × 109/L) was, respectively, 14 (range 12–18) and 15 (range 12–17) days (p = 0.904). The incidence of grade ≥ 2 acute GVHD was similar in the two groups (56.5% Cryo Group vs. 60.0% Fresh Group; p = 0.832) and no differences in terms of OS (p = 0.090), PFS (p = 0.200) and TRM (p = 0.970) were observed between the Cryo and Fresh groups. Conclusions: In our series, no differences between the Cryo and Fresh groups were found in engraftment, grade ≥ 2 acute GVHD incidence, OS, PFS, and TRM despite a lower CD34+ infused dose in the Cryo Group. Frozen PBSCs could be considered a safe option also for allo-HSCT from MUD but a higher amount of PBSC should be collected to warrant an adequate viable CD34+ post-thawing

Prediction of Breast Cancer Histological Outcome by Radiomics and Artificial Intelligence Analysis in Contrast-Enhanced Mammography

Purpose: To evaluate radiomics features in order to: differentiate malignant versus benign lesions; predict low versus moderate and high grading; identify positive or negative hormone receptors; and discriminate positive versus negative human epidermal growth factor receptor 2 related to breast cancer. Methods: A total of 182 patients with known breast lesions and that underwent Contrast-Enhanced Mammography were enrolled in this retrospective study. The reference standard was pathology (118 malignant lesions and 64 benign lesions). A total of 837 textural metrics were extracted by manually segmenting the region of interest from both craniocaudally (CC) and mediolateral oblique (MLO) views. Non-parametric Wilcoxon–Mann–Whitney test, receiver operating characteristic, logistic regression and tree-based machine learning algorithms were used. The Adaptive Synthetic Sampling balancing approach was used and a feature selection process was implemented. Results: In univariate analysis, the classification of malignant versus benign lesions achieved the best performance when considering the original_gldm_DependenceNonUniformity feature extracted on CC view (accuracy of 88.98%). An accuracy of 83.65% was reached in the classification of grading, whereas a slightly lower value of accuracy (81.65%) was found in the classification of the presence of the hormone receptor; the features extracted were the original_glrlm_RunEntropy and the original_gldm_DependenceNonUniformity, respectively. The results of multivariate analysis achieved the best performances when using two or more features as predictors for classifying malignant versus benign lesions from CC view images (max test accuracy of 95.83% with a non-regularized logistic regression). Considering the features extracted from MLO view images, the best test accuracy (91.67%) was obtained when predicting the grading using a classification-tree algorithm. Combinations of only two features, extracted from both CC and MLO views, always showed test accuracy values greater than or equal to 90.00%, with the only exception being the prediction of the human epidermal growth factor receptor 2, where the best performance (test accuracy of 89.29%) was obtained with the random forest algorithm. Conclusions: The results confirm that the identification of malignant breast lesions and the differentiation of histological outcomes and some molecular subtypes of tumors (mainly positive hormone receptor tumors) can be obtained with satisfactory accuracy through both univariate and multivariate analysis of textural features extracted from Contrast-Enhanced Mammography images