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Abstract We investigated the potential of machine learning for diagnostic classification in late-life major depression based on an advanced whole brain white matter segmentation framework. Twenty-six late-life depression and 12 never depressed individuals aged > 55 years, matched for age, MMSE, and education underwent brain diffusion tensor imaging and a multi-contrast, multi-atlas segmentation in MRIcloud. Fractional anisotropy volume, mean fractional anisotropy, trace, axial and radial diffusivity (RD) extracted from 146 white matter parcels for each subject were used to train and test the AdaBoost classifier using stratified 12-fold cross validation. Performance was evaluated using various measures. The statistical power of the classifier was assessed using label permutation test. Statistical analysis did not yield significant differences in DTI measures between the groups. The classifier achieved a balanced accuracy of 71% and an Area Under the Receiver Operator Characteristic Curve (ROC-AUC) of 0.81 by trace, and a balanced accuracy of 70% and a ROC-AUC of 0.80 by RD, in limbic, cortico-basal ganglia-thalamo-cortical loop, brainstem, external and internal capsules, callosal and cerebellar structures. Both indices shared important structures for classification, while fornix was the most important structure for classification by both indices. The classifier proved statistically significant, as trace and RD ROC-AUC scores after permutation were lower than those obtained with the actual data (P = 0.022 and P = 0.024, respectively). Similar results were obtained with the Gradient Boosting classifier, whereas the RBF-kernel Support Vector Machine with k-best feature selection did not exceed the chance level. Finally, AdaBoost significantly predicted the class using all features together. Limitations are discussed. The results encourage further investigation of the implemented methods for computer aided diagnostics and anatomically informed therapeutics.

Abstract Bi‐allelic variants in peroxiredoxin 3 (PRDX3) have only recently been associated with autosomal recessive spinocerebellar ataxia characterized by early onset slowly progressive cerebellar ataxia, variably associated with hyperkinetic and hypokinetic features, accompanied by cerebellar atrophy and occasional olivary and brainstem involvement. Herein, we describe a further simplex case carrying a reported PRDX3 variant as well as two additional cases with novel variants. We report the first Brazilian patient with SCAR32, replicating the pathogenic status of a known variant. All presented cases from the Brazilian and Indian populations expand the phenotypic spectrum of the disease by displaying prominent neuroradiological findings. SCAR32, although rare, should be included in the differential diagnosis of sporadic or recessive childhood and adolescent‐onset pure and complex cerebellar ataxia.

Background: Sleep patterns often shift as people age, a phenomenon frequently associated with the onset of neurodegenerative conditions. Additionally, distinct alterations occur in brain structure as individuals grow older, particularly within the hippocampus, a region known for its role in cognition and sleep regulation. Yet, how exactly do changes in sleep relate to specific subfields within the hippocampus is still unclear. Methods: We conducted a study involving non-demented healthy adults from the Aiginition Longitudinal Biomarker Investigation Of Neurodegeneration (ALBION) cohort. Participants underwent objective sleep measurements using wrist Actiwatch and WatchPAT devices. Further, all participants underwent the same Magnetic Resonance Imaging (MRI) protocol, including a 3D high resolution T1-weighted sequence, on the same 3.0 Tesla MRI scanner using an eight-channel head coil. The study aimed to examine the relationship between objectively measured sleep metrics and the morphology of twenty-two distinct hippocampal subregions. Results: In total, 75 non-demented participants with 63 mean years of age were included in the study. Results indicated that a higher frequency of awakenings during sleep was associated with increased volume in the right presubiculum body (beta = 0.630, p False Discovery Rate (FDR)

(1) Background: Many studies link food intake with clinical cognitive outcomes, but evidence for brain biomarkers, such as memory-related limbic white matter (WM) tracts, is limited. We examined the association between food groups, limbic WM tracts integrity, and memory performance in community-dwelling individuals. (2) Methods: We included 117 non-demented individuals (ALBION study). Verbal and visual episodic memory tests were administered, and a composite z-score was calculated. Diffusion tensor imaging tractography was applied for limbic WM tracts (fornix-FX, cingulum bundle-CB, uncinate fasciculus-UF, hippocampal perforant pathway zone-hPPZ). Food intake was evaluated through four 24-h recalls. We applied linear regression models adjusted for demographics and energy intake. (3) Results: We found significant associations between (a) higher low-to-moderate alcohol intake and higher FX fractional anisotropy (FA), (b) higher full-fat dairy intake and lower hPPZ FA, and (c) higher red meat and cold cuts intake and lower hPPZ FA. None of the food groups was associated with memory performance. (4) Conclusions: Despite non-significant associations between food groups and memory, possibly due to participants’ cognitive profile and/or compensatory mechanisms, the study documented a possible beneficial role of low-to-moderate alcohol and a harmful role of full-fat dairy and red meat and cold cuts on limbic WM tracts.

Background: Outcome data regarding the administration of tenecteplase (TNK) to acute ischemic stroke (AIS) patients presenting in the extended time window are limited. Objectives: We aimed to assess the current evidence regarding the efficacy and safety of TNK at a dose of 0.25 mg/kg for AIS treatment in the extended time window. Design: A systematic review and meta-analysis was conducted including all available randomized-controlled clinical trials (RCTs) that compared TNK 0.25 mg/kg versus no thrombolysis in AIS patients presenting in the extended time window (>4.5 h after last-seen-well or witnessed onset). Data sources and methods: Eligible studies were identified by searching Medline, Scopus, and international conference abstracts. The predefined efficacy outcomes of interest were 3-month excellent functional outcome [defined as the modified Rankin Scale (mRS) score ⩽1; primary outcome], 3-month good functional outcome (mRS ⩽ 2), 3-month reduced disability (⩾1-point reduction across all mRS scores). We determined symptomatic intracranial hemorrhage (sICH), any ICH and 3-month mortality as safety endpoints. A random-effects model was used to calculate risk ratios (RRs) and common odds ratios (cORs) with corresponding 95% confidence intervals (CIs). Results: Three RCTs were included comprising 556 patients treated with TNK versus 560 controls. TNK 0.25 mg/kg was associated with a higher likelihood of 3-month excellent functional outcome compared to controls (RR = 1.17; 95% CI = 1.01–1.36; I 2 = 0%), whereas there was no difference regarding good functional outcome (RR = 1.05; 95% CI = 0.94–1.17; I 2 = 0%) and reduced disability (adjusted cOR = 1.14; 95% CI = 0.92–1.40; I 2 = 0%) at 3 months. The risks of sICH (RR = 1.67; 95% CI = 0.70–4.00; I 2 = 0%), any ICH (RR = 1.08; 95% CI = 0.90–1.29; I 2 = 0%) and 3-month mortality (RR = 1.10; 95% CI = 0.81–1.49; I 2 = 0%) were similar between the groups. Conclusion: Based on data from three RCTs showing increased efficacy and a favorable safety profile of TNK in the treatment of AIS in the extended time window, continuing efforts of ongoing RCTs in the field are clearly supported. Trial registration: PROSPERO registration ID: CRD42023448707.

Although magnetic resonance spectroscopy (MRS) has provided in vivo measurements of brain chemical profiles in bipolar disorder (BD), there are no data on clinically and therapeutically important onset polarity (OP) and predominant polarity (PP). We conducted a proton MRS study in BD polarity subphenotypes, focusing on emotion regulation brain regions. Forty-one euthymic BD patients stratified according to OP and PP and sixteen healthy controls (HC) were compared. 1H-MRS spectra of the anterior and posterior cingulate cortex (ACC, PCC), left and right hippocampus (LHIPPO, RHIPPO) were acquired at 3.0T to determine metabolite concentrations. We found significant main effects of OP in ACC mI, mI/tNAA, mI/tCr, mI/tCho, PCC tCho, and RHIPPO tNAA/tCho and tCho/tCr. Although PP had no significant main effects, several medium and large effect sizes emerged. Compared to HC, manic subphenotypes (i.e., manic-OP, manic-PP) showed greater differences in RHIPPO and PCC, whereas depressive suphenotypes (i.e., depressive-OP, depressive-PP) in ACC. Effect sizes were consistent between OP and PP as high intraclass correlation coefficients (ICC) were confirmed. Our findings support the utility of MRS in the study of the neurobiological underpinnings of OP and PP, highlighting that the regional specificity of metabolite changes within the emotion regulation network consistently marks both polarity subphenotypes.

Neuropsychological profiling and clinical DTI of three stroke patients highlight the importance of the ventral language system in normal language comprehension and cognition.

Post-stroke language recovery remains one of the main unresolved topics in the field of aphasia. In recent years, there have been efforts to identify specific factors that could potentially lead to improved language recovery. However, the exact relationship between the recovery of particular language functions and possible predictors, such as demographic or lesion variables, is yet to be fully understood. In the present study, we attempted to investigate such relationships in 42 patients with aphasia after left hemisphere stroke, focusing on three language domains: auditory comprehension, naming and speech fluency. Structural imaging data were also obtained for the identification of the lesion sites. According to our findings, patients demonstrated an overall improvement in all three language domains, while no demographic factor significantly contributed to aphasia recovery. Interestingly, specific lesion loci seemed to have a differential effect on language performance, depending on the time of testing (i.e., acute/subacute vs. chronic phase). We argue that this variability concerning lesion–deficit associations reflects the dynamic nature of aphasia and further discuss possible explanations in the framework of neuroplastic changes during aphasia recovery.

Current understanding of Multiple Sclerosis (MS) pathophysiology implicates perturbations in adaptive cellular immune responses, predominantly T cells, in Relapsing-Remitting forms (RRMS). Nevertheless, from a clinical perspective MS is a heterogeneous disease reflecting the heterogeneity of involved biological systems. This complexity requires advanced analysis tools at the single-cell level to discover biomarkers for better patient-group stratification. We designed a novel 44-parameter mass cytometry panel to interrogate predominantly the role of effector and regulatory subpopulations of peripheral blood myeloid subsets along with B and T-cells (excluding granulocytes) in MS, assessing three different patient cohorts: RRMS, PPMS (Primary Progressive) and Tumefactive MS patients (TMS) (n=10, 8, 14 respectively). We further subgrouped our cohort into inactive or active disease stages to capture the early underlying events in disease pathophysiology. Peripheral blood analysis showed that TMS cases belonged to the spectrum of RRMS, whereas PPMS cases displayed different features. In particular, TMS patients during a relapse stage were characterized by a specific subset of CD11c+CD14+ CD33+, CD192+, CD172+-myeloid cells with an alternative phenotype of monocyte-derived macrophages (high arginase-1, CD38, HLA-DR-low and endogenous TNF-a production). Moreover, TMS patients in relapse displayed a selective CD4 T-cell lymphopenia of cells with a Th2-like polarised phenotype. PPMS patients did not display substantial differences from healthy controls, apart from a trend toward higher expansion of NK cell subsets. Importantly, we found that myeloid cell populations are reshaped under effective disease-modifying therapy predominantly with glatiramer acetate and to a lesser extent with anti-CD20, suggesting that the identified cell signature represents a specific therapeutic target in TMS. The expanded myeloid signature in TMS patients was also confirmed by flow cytometry. Serum neurofilament light-chain levels confirmed the correlation of this myeloid cell signature with indices of axonal injury. More in-depth analysis of myeloid subsets revealed an increase of a subset of highly cytolytic and terminally differentiated NK cells in PPMS patients with leptomeningeal enhancement (active-PPMS), compared to those without (inactive-PPMS). We have identified previously uncharacterized subsets of circulating myeloid cells and shown them to correlate with distinct disease forms of MS as well as with specific disease states (relapse/remission).

The impact of Moyamoya Disease (MMD) on cognition inadult Caucasian patients has not yet been thoroughly investigated. The current study is the first to present detailed neuropsychological data on a series of Greek patients with MMD. A group of eight patients was assessed with an extensive neuropsychological battery, including measures of episodic memory, working memory, executive functions, language, and social cognition. The results indicated that MMD may be characterized by a trichotomous neurocognitive profile, characterized by prominent impairment in working memory, executive functions, and social cognition. Overall, we stress the need for a thorough cognitive evaluation of MMD patients and further highlight the potential importance of social cognition in this particular disease. Possible associations between the three impaired cognitive domains in our group are also discussed.

Research investigating pragmatic deficits in individuals with right hemisphere damage focuses on identifying the potential mechanisms responsible for the nature of these impairments. Nonetheless, the presumed shared cognitive mechanisms that could account for these deficits have not yet been established through data-based evidence from lesion studies. This study aimed to examine the co-occurrence of pragmatic language deficits, Theory of Mind impairments, and executive functions while also exploring their associations with brain lesion sites. Twenty-five patients suffering from unilateral right hemisphere stroke and thirty-seven healthy participants were recruited for this study. The two groups were tested in pragmatics, Theory of Mind, and executive function tasks. Structural imaging data were also obtained for the identification of the lesion sites. The findings of this study suggest a potential convergence among the three aforementioned cognitive mechanisms. Moreover, we postulate a hypothesis for a neural circuitry for communication impairments observed in individuals with right hemisphere damage.

Background and purpose: The aim of our study is to present, for the first time, the clinical, radiological, and neurocognitive characteristics of Greek adult patients with Moyamoya disease (MMD). Methods: We analyzed prospectively collected data of 12 patients referred to our department from 2004 to 2019. All patients underwent a thorough diagnostic work up, including extensive clinical, neuroradiological, and neurocognitive assessment. Results: Our study population consisted of 7 females and the median age at the time of the diagnosis was 43.5 years. No patient had a positive family history of the disease and roughly 50% were hypertensives. Ten patients presented with transient or permanent cerebrovascular ischemia and two patients suffered from hemorrhagic complications. The median NIHSS was 7.5 (0–23) and clinical status remained stable during follow-up with conservative treatment in most of the patients. The majority (83.3%) had bilateral disease confirmed by DSA. All lesions exclusively affected the anterior circulation, with 50% of patients presenting with stenoocclusive changes. No aneurysm or AVM were revealed. The most common neurocognitive deficits were in the executive and language domains. Conclusions: Our MMD patients had a later onset of the disease and an absence of familial occurrence. The most common manifestation was ischemia, transient or permanent, and all lesions affected the anterior circulation, whereas no vascular malformations (AVM, aneurysms) were demonstrated in brain imaging. These findings in Greek patients imply a probable different, Mediterranean phenotype.

Background and purpose: Sporadic cerebral amyloid angiopathy (CAA) is a small vessel disease, resulting from progressive amyloid-β deposition in the media/adventitia of cortical and leptomeningeal arterioles. We sought to assess the prevalence of baseline characteristics, clinical and radiological findings, as well as outcomes among patients with CAA, in the largest study to date conducted in Greece. Methods: Sixty-eight patients fulfilling the Boston Criteria v1.5 for probable/possible CAA were enrolled and followed for at least twelve months. Magnetic Resonance Imaging was used to assess specific neuroimaging markers. Data regarding cerebrospinal fluid biomarker profile and Apolipoprotein-E genotype were collected. Multiple logistic regression analyses were performed to identify predictors of clinical phenotypes. Cox-proportional hazard regression models were used to calculate associations with the risk of recurrent intracerebral hemorrhage (ICH). Results: Focal neurological deficits (75%), cognitive decline (57%), and transient focal neurological episodes (TFNEs; 21%) were the most common clinical manifestations. Hemorrhagic lesions, including lobar cerebral microbleeds (CMBs; 93%), cortical superficial siderosis (cSS; 48%), and lobar ICH (43%) were the most prevalent neuroimaging findings. cSS was independently associated with the likelihood of TFNEs at presentation (OR: 4.504, 95%CI:1.258–19.088), while multiple (>10) lobar CMBs were independently associated with cognitive decline at presentation (OR:5.418, 95%CI:1.316–28.497). cSS emerged as the only risk factor of recurrent ICH (HR:4.238, 95%CI:1.509–11.900) during a median follow-up of 20 months. Conclusions: cSS was independently associated with TFNEs at presentation and ICH recurrence at follow-up, while a higher burden of lobar CMBs with cognitive decline at baseline. These findings highlight the prognostic value of neuroimaging markers, which may influence clinical decision-making.

Introduction: Previous epidemiological evidence has established the co-occurrence of malignant melanoma (MM) and Parkinson’s disease (PD). Shared molecular mechanisms have been proposed to be implicated in this relationship. The aim of the present study was to assess the prevalence of MM in patients with sporadic and genetic types of PD, as well as in asymptomatic carriers of PD-related genes. Methods: Data regarding past medical history and concomitant disease of 1416 patients with PD (including 20 participants with prodromal disease who phenoconverted to PD), 275 healthy controls (HCs) and 670 asymptomatic carriers of PD-related genes were obtained from the database of the Parkinson’s Progression Markers Initiative (PPMI). Focus was placed on information about a medical record of MM. We also retrieved data regarding the genetic status of selected PPMI participants with a positive MM history. Results: In total, 46 patients with PD reported a positive MM history. Concerning the genetic forms of PD, nine of these PD patients (2.47%) carried a Leucine Rich Repeat Kinase 2 (LRRK2) gene mutation (mainly the G2019S), while eight (4.49%) harbored a Glucocerebrosidase (GBA) gene mutation (mainly the N370S). No alpha-synuclein (SNCA) gene mutation was identified in patients with an MM history. The remaining 29 PD patients (3.5%) were genetically undetermined. In total, 18 asymptomatic carriers of PD-related genes had a positive medical history for MM: among them, 10 carried an LRRK2 gene mutation (2.69%) and 10 a GBA gene mutation (3.51%) (2 were dual carriers). MM history was identified for seven HCs (2.5%). Conclusions: We replicated the previously reported association between genetically undetermined PD (GU-PD) and MM. A correlation of LRRK2 mutations with the development of MM could not be verified in either symptomatic PD patients or asymptomatic carriers, implicating distinct pathogenetic mechanisms as compared to GU-PD. Importantly, despite the limited literature evidence on Gaucher disease, this study highlights for the first time the relatively high prevalence of MM among asymptomatic and symptomatic PD GBA mutation carriers, with potential clinical implications.

The purpose of this study was to retrospectively compare efficacy and safety between intradiscal injection of a gelified ethanol product and tubular discectomy in the treatment of intervertebral disk herniation. A bi-central institutional database research identified forty (40) patients suffering from symptomatic contained disc herniation. Nucleolysis Group included 20 patients [mean 50.05 ± 9.27 years-of-age (male/female 14/6–70/30%)] and Surgery Group included 20 patients [mean 48.45 ± 14.53 years-of-age, (male/female 12/8–60/40%)]. Primary outcome was overall 12-month improvement over baseline in leg pain (NVS units). Procedural technical outcomes were recorded, and adverse events were evaluated at all follow-up intervals. CIRSE classification system was used for complications’ reporting. Mean pre-operative pain score in Nucleolysis Group was 7.95 ± 0.94 reduced to 1.25 ± 1.11 at month 1 and 0.45 ± 0.75 NVS units at year 1. Mean pre-operative pain score in Surgery Group was 7.65 ± 1.13 reduced to 1.55 ± 1.79 at month 1 and 0.70 ± 1.38 NVS units at year 1. Pain decrease was statistically significant after both procedures (p < 0.001). There was no statistically significant difference between pain reduction in both groups (p = 0.347). The decrease differences of the pain effect upon general activities, sleeping, socializing, walking, and enjoying life in the follow-up period between the two groups were not statistically significant. No complications were noted in both groups. Results from the current study report that intradiscal injection of a gelified ethanol and tubular discectomy were equally effective on terms of efficacy and safety for the treatment of symptomatic lumbar intervertebral disc herniation regarding the 12-month mean leg pain improvement. Both achieved similar rapid significant clinical improvement persisting throughout follow-up period.

Idiopathic bormal pressure hydrocephalus (iNPH) is a neurological syndrome that clinically presents with Hakim’s triad, namely cognitive impairment, gait disturbances, and urinary incontinence. The fact that iNPH is potentially reversible makes its accurate and early diagnosis of paramount importance. Its main imaging characteristic is the dilation of the brain’s ventricular system and the imaging parameters are also included in its diagnostic criteria along with clinical data. There is a variety of different modalities used and a great number of imaging markers that have been described while assessing iNPH patients. The present literature review attempts to describe the most important of these imaging markers and to shed some light on their role in diagnosis, differential diagnosis, and possibly prognosis of this potentially reversible neurological syndrome.

Abstract Chronic cannabis use and schizophrenia are both thought to affect reward processing. While behavioural and neural effects on reward processing have been investigated in both conditions, their interaction has not been studied, although chronic cannabis use is common among these patients. In the present study eighty-nine participants divided into four groups (control chronic cannabis users and non-users; schizophrenia patient cannabis users and non-users) performed a two-choice decision task, preceded by monetary cues (high/low reward/punishment or neutral), while being scanned using functional magnetic resonance imaging. Reward and punishment anticipation resulted in activation of regions of interest including the thalamus, striatum, amygdala and insula. Chronic cannabis use and schizophrenia had opposing effects on reward anticipation sensitivity. More specifically control users and patient non-users showed faster behavioural responses and increased activity in anterior/posterior insula for high magnitude cues compared to control non-users and patient users. The same interaction pattern was observed in the activation of the right thalamus for reward versus punishment cues. This study provided evidence for interaction of chronic cannabis use and schizophrenia on reward processing and highlights the need for future research addressing the significance of this interaction for the pathophysiology of these conditions and its clinical consequences.

Neurobrucellosis presents in various clinical forms and should always be considered in neurological patients in highly endemic areas such as the Mediterranean basin. Establishing a diagnosis can be challenging since serological testing can sometimes yield negative results. We present a rare case of a seronegative relapse of neurobrucellosis in a patient who had been successfully treated for systemic brucellosis. Oligoclonal bands, an agglutination test, and 16S rRNA sequencing of cerebrospinal fluid proved essential in unmasking a confined central nervous system relapse. This case reinforces the need for establishing diagnostic criteria for neurobrucellosis, which could potentially include oligoclonal bands and an agglutination test on the cerebrospinal fluid.

Introduction: High-quality evidence regarding the use of endovascular treatment (EVT) in patients with acute basilar artery occlusion (BAO) has been provided by recently completed randomized controlled clinical trials (RCTs). Methods: We conducted a systematic review and meta-analysis including all available RCTs that investigated efficacy and safety of EVT in addition to best medical treatment (BMT) versus BMT alone for BAO. The random-effects model was used, while the fragility index (FI) was calculated for dichotomous outcomes of interest. Results: Four RCTs were included comprising a total of 988 patients with acute BAO (mean age: 65.6 years, 70% men, median NIHSS: 24, 39% pretreatment with intravenous thrombolysis). EVT was related to higher likelihood of good functional outcome (RR: 1.54; 95% CI: 1.16–2.05; I2 = 60%), functional independence (RR: 1.83; 95% CI: 1.08–3.08; I2 = 79%) and reduced disability at 3 months (adjusted common OR: 1.96; 95% CI: 1.26–3.05; I2 = 59%) compared to BMT alone. Despite that EVT was associated with a higher risk for symptomatic intracranial hemorrhage (RR: 7.78; 95% CI: 2.36–25.61; I2 = 0%) and any intracranial hemorrhage (RR: 2.85; 95% CI: 1.50–5.44; I2 = 16%), mortality at 3 months was lower among patients that received EVT plus BMT versus BMT alone (RR: 0.76; 95% CI: 0.65–0.89; I2 = 0%). However, sufficient robustness was not evident in any of the reported associations (FI < 10) including the overall effect regarding the primary outcome. The former associations were predominantly driven by RCTs with recruitment limited in China. Conclusions: EVT combined with BMT is associated with a higher likelihood of achieving good functional outcomes and a lower risk of death at 3 months compared to BMT alone, despite the higher risk of sICH. An individual-patient data meta-analysis is warranted to uncover and adjust for potential sources of heterogeneity and to provide further insight.

Sarcomas are heterogenous mesenchymal neoplasms with more than 80 different histologic subtypes. Lung followed by liver and bone are the most common sites of sarcoma metastatic disease. Ablative techniques have been recently added as an additional alternative curative or palliative therapeutic tool in sarcoma metastatic disease. When compared to surgery, ablative techniques are less invasive therapies which can be performed even in non-surgical candidates and are related to decreased recovery time as well as preservation of the treated organ’s long-term function. Literature data upon ablative techniques for sarcoma metastatic disease are quite heterogeneous and variable regarding the size and the number of the treated lesions and the different histologic subtypes of the original soft tissue or bone sarcoma. The present study focuses upon the current role of minimal invasive thermal ablative techniques for the management of metastatic sarcoma disease. The purpose of this review is to present the current minimally invasive ablative techniques in the treatment of metastatic soft tissue and bone sarcoma, including local control and survival rates.

Background: Magnetic resonance spectroscopy (MRS) in amyotrophic lateral sclerosis (ALS) has been overwhelmingly applied to motor regions to date and our understanding of frontotemporal metabolic signatures is relatively limited. The association between metabolic alterations and cognitive performance in also poorly characterised. Material and Methods: In a multimodal, prospective pilot study, the structural, metabolic, and diffusivity profile of the hippocampus was systematically evaluated in patients with ALS. Patients underwent careful clinical and neurocognitive assessments. All patients were non-demented and exhibited normal memory performance. 1H-MRS spectra of the right and left hippocampi were acquired at 3.0T to determine the concentration of a panel of metabolites. The imaging protocol also included high-resolution T1-weighted structural imaging for subsequent hippocampal grey matter (GM) analyses and diffusion tensor imaging (DTI) for the tractographic evaluation of the integrity of the hippocampal perforant pathway zone (PPZ). Results: ALS patients exhibited higher hippocampal tNAA, tNAA/tCr and tCho bilaterally, despite the absence of volumetric and PPZ diffusivity differences between the two groups. Furthermore, superior memory performance was associated with higher hippocampal tNAA/tCr bilaterally. Both longer symptom duration and greater functional disability correlated with higher tCho levels. Conclusion: Hippocampal 1H-MRS may not only contribute to a better academic understanding of extra-motor disease burden in ALS, but given its sensitive correlations with validated clinical metrics, it may serve as practical biomarker for future clinical and clinical trial applications. Neuroimaging protocols in ALS should incorporate MRS in addition to standard structural, functional, and diffusion sequences.

Multiple sclerosis (MS) and its various comorbidities that may be observed are of great interest due to the complexity of MS pathophysiology and all of the immunological changes that follow. The incidence of cancer in MS has been investigated for several years, as not only does it affect ongoing therapeutical decisions, but also, certain disease-modifying treatments (DMTs) may increase the risk of tumorigenesis. For the first time, we present a case of a female patient with pediatric-onset MS (POMS) and multiple endocrine neoplasia 2B (MEN2B) and analyze the immunological impact of these diseases on the therapeutical choice, under the umbrella of her COVID-19 infection and the SARS-CoV-2 pandemic as a whole. We also review the existing literature regarding the immunogenetic and immunological correlations between these two extremely rare diseases and discuss the most suitable treatment for our case, which seems to be an anti-CD20 agent due to a better outcome in putative MS worsening and tumor progression, when killer immunoglobulin-like receptors’ (KIR) expression is reduced in natural killer (NK) cells. We also broaden our concerns on this comorbidity issue, at the same time focusing on the future research needed in this unexplored field of the comorbidity of MS and cancers.

The involvement of the right hemisphere (RH) in language, and especially after aphasia resulting from left hemisphere (LH) lesions, has been recently highlighted. The present study investigates white matter structure in the right hemisphere of 25 chronic post-stroke aphasic patients after LH lesions in comparison with 24 healthy controls, focusing on the four cortico-cortical tracts that link posterior parietal and temporal language-related areas with Broca’s region in the inferior frontal gyrus of the LH: the Superior Longitudinal Fasciculi II and III (SLF II and SLF III), the Arcuate Fasciculus (AF), and the Temporo-Frontal extreme capsule Fasciculus (TFexcF). Additionally, the relationship of these RH white matter tracts to language performance was examined. The patients with post-stroke aphasia in the chronic phase and the healthy control participants underwent diffusion tensor imaging (DTI) examination. The aphasic patients were assessed with standard aphasia tests. The results demonstrated increased axial diffusivity in the RH tracts of the aphasic patients. Patients were then divided according to the extent of the left hemisphere white matter loss. Correlations of language performance with radial diffusivity (RD) in the right hemisphere homologs of the tracts examined were demonstrated for the TFexcF, SLF III, and AF in the subgroup with limited damage to the LH language networks and only with the TFexcF in the subgroup with extensive damage. The results argue in favor of compensatory roles of the right hemisphere tracts in language functions when the LH networks are disrupted.

Aims: Our goal was to expand the spectrum of clinico-radiologic characteristics and the possible therapeutic choices in patients with tumefactive demyelinating lesions (TDLs). Methods: A retrospective analysis of 50 patients with at least one TDL was performed at an academic neurology center (2008–2020). Results: Our cohort comprised mostly women (33/50) with a mean age of 38 years at TDL onset. The mean follow-up time was 76 months. The mean Expanded Disability Status Scale score at TDL onset and at the latest neurological evaluation was 3.7 and 2.3, respectively. We subcategorized the patients into seven groups based mainly on the clinical/radiological findings and disease course. Group A included patients presenting with a Marburg-like TDL ( n = 4). Groups B and C comprised patients presenting with monophasic ( n = 7) and recurrent TDLs ( n = 12), respectively. Multiple sclerosis (MS) patients who subsequently developed TDL ( n = 16) during the disease course were categorized as Group D. Group E comprised patients who initially presented with TDL and subsequently developed a classical relapsing–remitting MS without further evidence of TDL ( n = 5). Groups F ( n = 2) and G ( n = 4) involved MS patients who developed TDL during drug initiation (natalizumab, fingolimod) and cessation (interferon, fingolimod), respectively. Regarding long-term treatments applied after corticosteroid administration in the acute phase, B-cell-directed therapies were shown to be highly effective especially in cases with recurrent TDLs. Cyclophosphamide was spared for more aggressive disease indicated by a poor response to corticosteroids and plasma exchange failure. Conclusion: Tumefactive central nervous system demyelination is an heterogenous disease; its stratification into distinct groups according to different phenotypes can establish more efficient treatment strategies, thus improving clinical outcomes in the future.

The aim of the present study was the implementation of the composite imaging “Radscale” in patients with idiopathic normal pressure hydrocephalus (iNPH) and the evaluation of its score, as well as absolute stroke volume and peak flow velocity of cerebrospinal fluid (CSF) in aqueduct as indicators of a positive response following a tap test. Forty-five patients with iNPH were included. Clinical evaluation involved the 10 m timed walk test before and every 24 h for 3 consecutive days after evacuative lumbar puncture (LP). Neuropsychological evaluation comprised a mini mental state examination (MMSE), frontal assessment battery (FAB), 5-word test (5WT) and CLOX drawing test 1 and 2, which were carried out before and 48 h after LP. The tap test’s response was defined as a ≥20% improvement in gait and/or a ≥10% improvement in neuropsychological tests. All scores of neuropsychological and clinical variables, except for immediate 5WT and CLOX-1, differed significantly before and 48 h after LP. Improvement in time and steps of a 10 m timed walk test differed significantly between female and male patients. Out of 45 total patients, 19 were tap test responders and 26 non-responders. The total score of Radscale and CSF flow parameters did not differ between responders and non-responders. However, “Callosal angle” sub-score differed significantly between these two groups. A greater “callosal angle” sub-score, meaning more acute callosal angle, was associated with a positive tap test response, rendering it a useful measurement in the stratification of iNPH patients that will potentially respond to CSF shunting.

Magnetic resonance spectroscopy (MRS) has contributed important academic insights in motor neuron diseases (MNDs), particularly in amyotrophic lateral sclerosis (ALS). Over the past three decades momentous methodological advances took place, including the emergence of high-field magnetic resonance imaging (MRI) platforms, multi-voxel techniques, whole-brain protocols, novel head-coil designs, and a multitude of open-source imaging suites. Technological advances in MRS are complemented by important conceptual developments in MND, such as the recognition of the importance of extra-motor brain regions, multi-timepoint longitudinal study designs, assessment of asymptomatic mutation carriers, description of genotype-associated signatures, and the gradual characterisation of non-ALS MND phenotypes. We have conducted a systematic review of published MRS studies in MND to identify important emerging research trends, key lessons from pioneering studies, and stereotyped shortcomings. We also sought to highlight notable gaps in the current literature so that research priorities for future studies can be outlined. While MRS remains relatively underutilised in MND compared to other structural, diffusivity and functional imaging modalities, our review suggests that MRS can not only advance our academic understanding of MND biology, but has a multitude of practical benefits for clinical and pharmaceutical trial applications.

Atypical forms of demyelinating diseases with tumor-like lesions and aggressive course represent a diagnostic and therapeutic challenge for neurologists. Herein, we describe a 50-year-old woman presenting with subacute onset of left hemiparesis, memory difficulties and headache. Brain MRI revealed a tumefactive right frontal-parietal lesion with perilesional edema, mass effect and homogenous post-contrast enhancement, along with other small atypical lesions in the white-matter. Brain biopsy of cerebral lesion ruled out lymphoma or any other neoplastic process and patient placed on corticosteroids with complete clinical/radiological remission. Two years after disease initiation, there was disease exacerbation with reappearance of the tumor-like mass. The patient initially responded to high doses of corticosteroids but soon became resistant. Plasma-exchange sessions were not able to limit disease burden. Resistance to therapeutic efforts led to a second biopsy that showed perivascular demyelination, predominantly consisting of macrophages, with a small number of T and B lymphocytes, and the presence of reactive astrocytes, typical of Creutzfeldt-Peters cells. The patient received high doses of cyclophosphamide with substantial clinical/radiological response but relapsed after 7-intensive cycles. She received 4-weekly doses of rituximab with disease exacerbation and brainstem involvement. She eventually died with complicated pneumonia. We present a very rare case of recurrent tumefactive demyelinating lesions, with atypical tumor-like characteristics, with initial response to corticosteroids and cyclophosphamide, but subsequent development of drug-resistance and unexpected exacerbation upon rituximab administration. Our clinical case raises therapeutic dilemmas and points to the need for immediate and appropriate immunosuppression in difficult to treat tumefactive CNS lesions with Marburg-like features.

Background and Objectives: The aim of the present study was to report the safety and efficacy of percutaneous navigation under local anesthesia for computed tomography-guided microwave ablation of malignant liver lesions located in the hepatic dome. Patients with primary and secondary malignant liver lesions located in the hepatic dome who underwent percutaneous computed tomography-guided microwave ablation using a computer-assisted navigation system under local anesthesia were prospectively evaluated. The primary objective was technical success. Materials and Methods: The sample consisted of 10 participants (16 lesions) with a mean age of 60.60 years (SD = 9.25 years) and a mean size of 20.37 ± 7.29 cm, and the mean follow-up time was 3.4 months (SD = 1.41) months. Results: Primary technical success was 93.75%. Tumor remnant was noticed at one month follow-up in a single metastatic lesion, which was re-treated with an ablation session, and no tumor remnant was depicted in the subsequent imaging follow-up (secondary technical success 100%). Grade I self-limited complications (according to the CIRSE classification system) included small pleural effusion (n = 1) and minor bleeding post antenna removal (n = 1) requiring nothing but observation. Conclusions: the findings of the present study indicate that percutaneous navigation under local anesthesia is a safe and efficacious approach for computed tomography-guided microwave ablation of malignant liver lesions located in the hepatic dome. Large randomized controlled studies are warranted to observe treatment effectiveness and compare the results with those of other options.

To compare different parameters of the sphericity index of the ablation zone following microwave ablation (MWA) on cirrhotic- and healthy-liver parenchyma in a series of patients treated with the same MWA system. Institutional database research identified 46 patients (77 lesions) who underwent MWA. “Cirrhotic liver group” (CLG) included 35 hepatocellular carcinoma lesions; “healthy liver group” (HLG) included 42 metastatic lesions. The long axis (LAD), short axis 1 (SAD-1) and 2 (SAD-2), the mean SAD-1 and SAD-2 (mSAD) diameter (in mm) and the mean sphericity (mSPH) index of the ablation zones were evaluated for each treated lesion in both groups from baseline to follow-up. A mixed model analysis of variance reported significant main effect of group on SAD-1 (p = 0.023), SAD-2 (p = 0.010) and mSAD (p = 0.010), with HLG showing lower values compared to CLG. No differences were detected on the LAD (pFDR = 0.089; d = 0.45), and mSPH (pFDR = 0.148, d = 0.40) between the two groups. However, a significant main effect of time was found on LAD (p < 0.001), SAD-1 (p < 0.001), SAD-2 (p < 0.001) and mSAD (p < 0.001), with decreased values in all indices at follow-up compared to baseline. A significant group by time interaction was observed on mSPH (p = 0.044); HLG had significantly lower mSPH at follow-up where CLG did not show any significant change. Our findings indicate that although in cirrhotic liver short axis diameter of the MWA zone seems to be significantly longer, this has no effect on the sphericity index which showed no significant difference between cirrhotic vs. healthy liver lesions. On the contrary, on one month follow-up ablation zones tend to become significant more ellipsoid in healthy whilst remains stable in cirrhotic liver.

Introduction. A wide range of medical conditions may mimic multiple sclerosis. Among them, cerebrovascular diseases, including moyamoya disease, need to be excluded since they share common clinical features and radiographic findings with multiple sclerosis. Case Report. A 44-year-old woman experienced transient numbness of her right sided face and arm and was referred to our unit due to small brain lesions in magnetic resonance imaging, with a possible diagnosis of multiple sclerosis. Neurological examination was unremarkable except for plantar reflexes and jerky deep tendon reflexes. Brain magnetic resonance angiography revealed findings typically seen in moyamoya disease, confirmed with digital subtraction angiography. Antiplatelet therapy started, but few days later, she developed suddenly global aphasia and right hemiparesis (National Institutes of Health Stroke Scale/NIHSS 6). Brain magnetic resonance imaging revealed acute infarct in the distribution of the left middle cerebral artery. At her discharge, she was significantly improved (NIHSS 3). Conclusion. Diagnosis of multiple sclerosis is often challenging. In particular, in young patients with transient neurological symptoms and atypical white matter lesions in magnetic resonance imaging, cerebrovascular disorders such as moyamoya disease should be considered in the differential diagnosis. Detailed clinical and neuroimaging evaluation are mandatory for the correct diagnosis.

Approximately 50% of colorectal cancer patients will develop metastases during the course of the disease. Local or locoregional therapies for the treatment of liver metastases are used in the management of oligometastatic colorectal liver disease, especially in nonsurgical candidates. Thermal ablation (TA) is recommended in the treatment of limited liver metastases as free-standing therapy or in combination with surgery as long as all visible disease can be eradicated. Percutaneous TA has been proven as a safe and efficacious therapy offering sustained local tumor control and improved patient survival. Continuous technological advances in diagnostic imaging and guidance tools, the evolution of devices allowing for optimization of ablation parameters, as well as the ability to perform margin assessment have improved the efficacy of ablation. This allows resectable small volume diseases to be cured with percutaneous ablation. The ongoing detailed information and increasing understanding of tumor biology, genetics, and tissue biomarkers that impact oncologic outcomes as well as their implications on the results of ablation have further allowed for treatment customization and improved oncologic outcomes even in those with more aggressive tumor biology. The purpose of this review is to present the most common indications for image-guided percutaneous ablation in colorectal cancer liver metastases, to describe technical considerations, and to discuss relevant peer-reviewed evidence on this topic. The growing role of imaging and image-guidance as well as controversies regarding several devices are addressed.

Hippocampal pathology in Amyotrophic Lateral Sclerosis (ALS) remains surprisingly under recognized despite compelling evidence from neuropsychology, neuroimaging and neuropathology studies. Hippocampal dysfunction contributes significantly to the clinical heterogeneity of ALS and requires structure-specific cognitive and neuroimaging tools for accurate in vivo evaluation. Recent imaging studies have generated unprecedented insights into the presymptomatic and longitudinal processes affecting this structure and have contributed to the characterisation of both focal and network-level changes. Emerging neuropsychology data suggest that memory deficits in ALS may be independent from executive dysfunction. In the era of precision medicine, where the development of individualized care strategies and patient stratification for clinical trials are key priorities, the comprehensive review of hippocampal dysfunction in ALS is particularly timely.