Diagnostic Utility of Measuring Cerebral Atrophy in the Behavioral Variant of Frontotemporal Dementia and Association With Clinical Deterioration

Can widely available measures of atrophy on magnetic resonance imaging increase diagnostic certainty of underlying frontotemporal lobar degeneration (FTLD) and estimate clinical deterioration in the behavioral variant of frontotemporal dementia (bvFTD)? This diagnostic/prognostic study investigated the clinical utility of 5 validated visual atrophy scales (VAS) and the Magnetic Resonance Parkinsonism Index. When combined, VAS showed excellent diagnostic performance for differentiating between bvFTD with high and low confidence of FTLD and for the estimation of longitudinal clinical deterioration, whereas the Magnetic Resonance Parkinsonism Index was increased in bvFTD with underlying 4-repeat tauopathies. These findings suggest that, in bvFTD, VAS can be used to increase diagnostic certainty of underlying FTLD and estimate longitudinal clinical deterioration. This diagnostic/prognostic study assesses the utility of 6 visual atrophy scales and the Magnetic Resonance Parkinsonism Index in patients with behavioral variant frontotemporal dementia to distinguish those with high vs low confidence of frontotemporal lobar degeneration. The presence of atrophy on magnetic resonance imaging can support the diagnosis of the behavioral variant of frontotemporal dementia (bvFTD), but reproducible measurements are lacking. To assess the diagnostic and prognostic utility of 6 visual atrophy scales (VAS) and the Magnetic Resonance Parkinsonism Index (MRPI). In this diagnostic/prognostic study, data from 235 patients with bvFTD and 225 age- and magnetic resonance imaging-matched control individuals from 3 centers were collected from December 1, 1998, to September 30, 2019. One hundred twenty-one participants with bvFTD had high confidence of frontotemporal lobar degeneration (FTLD) (bvFTD-HC), and 19 had low confidence of FTLD (bvFTD-LC). Blinded clinicians applied 6 previously validated VAS, and the MRPI was calculated with a fully automated approach. Cortical thickness and subcortical volumes were also measured for comparison. Data were analyzed from February 1 to June 30, 2020. The main outcomes of this study were bvFTD-HC or a neuropathological diagnosis of 4-repeat (4R) tauopathy and the clinical deterioration rate (assessed by longitudinal measurements of Clinical Dementia Rating Sum of Boxes). Measures of cerebral atrophy included VAS scores, the bvFTD atrophy score (sum of VAS scores in orbitofrontal, anterior cingulate, anterior temporal, medial temporal lobe, and frontal insula regions), the MRPI, and other computerized quantifications of cortical and subcortical volumes. The areas under the receiver operating characteristic curve (AUROC) were calculated for the differentiation of participants with bvFTD-HC and bvFTD-LC and controls. Linear mixed models were used to evaluate the ability of atrophy measures to estimate longitudinal clinical deterioration. Of the 460 included participants, 296 (64.3%) were men, and the mean (SD) age was 62.6 (11.4) years. The accuracy of the bvFTD atrophy score for the differentiation of bvFTD-HC from controls (AUROC, 0.930; 95% CI, 0.903-0.957) and bvFTD-HC from bvFTD-LC (AUROC, 0.880; 95% CI, 0.787-0.972) was comparable to computerized measures (AUROC, 0.973 [95% CI, 0.954-0.993] and 0.898 [95% CI, 0.834-0.962], respectively). The MRPI was increased in patients with bvFTD and underlying 4R tauopathies compared with other FTLD subtypes (14.1 [2.0] vs 11.2 [2.6] points; P < .001). Higher bvFTD atrophy scores were associated with faster clinical deterioration in bvFTD (1.86-point change in Clinical Dementia Rating Sum of Boxes score per bvFTD atrophy score increase per year; 95% CI, 0.99-2.73; P < .001). Based on these study findings, in bvFTD, VAS increased the diagnostic certainty of underlying FTLD, and the MRPI showed potential for the detection of participants with underlying 4R tauopathies. These widely available measures of atrophy can also be useful to estimate longitudinal clinical deterioration

Behavioral Variant Frontotemporal Dementia

Frontotemporal dementia (FTD) is a sporadic or genetic neurodegenerative disease in which frontotemporal involvement is typically encountered. According to clinical features, three groups are distinguished as behavioral (bvFTD) and progressive aphasia variants; semantic dementia and progressive non-fluent aphasia. The most common type is bvFTD mimicking as disinhibition, apathy, loss of empathy, perseverative / compulsive behaviors, hyperorality, executive dysfunction and diagnosed with imaging, pathogenic mutation and histopathological evidence as well as clinical diagnosis. Brain magnetic resonance imaging (MRI) studies show atrophy especially in ventromedial frontal cortex, posterior orbital frontal regions, insula, anterior cingulate cortex and subcortical structures; the degeneration of these structures, known as the salience network, is held responsible for deterioration of the executive functions. In the early period, the presence of frontotemporal hypometabolism in positron emission tomography is more sensitive than MRI, parietal hypometabolism and amyloid deposition are not seen. Tau levels in cerebrospinal fluid may be low or high in FTD, but the tau / amyloid-beta ratio is found to be highly specific. More than 40% of bvFTD cases have family history and most autosomal dominant inheritance patterns are present. In FTD, cholinergic system is protected, cell loss in serotoninergic receptor and raphe nucleus is evident. Dopaminergic and cholinergic therapy has not been found to be useful and even worsening of behavioral symptoms with cholinesterase inhibitors has been reported. Selective serotonin reuptake inhibitors and trazodone are effective on behavioral symptoms and sleep problems. Pharmacological and non-pharmacological interventions, training and counseling services are important for the relatives of patients

Normalized Theta but Increased Gamma Activity after Acetylcholinesterase Inhibitor Treatment in Alzheimer's Disease: Preliminary qEEG Study

Acetylcholinesterase inhibitors (AChE-I) are the core treatment of mild to severe Alzheimer's disease (AD). However, the efficacy of AChE-I treatment on electroencephalography (EEG) and cognition remains unclear. We aimed to investigate the EEG power and coherence changes, in addition to neuropsychological performance, following a one-year treatment. Nine de-novo AD patients and demographically-matched healthy controls (HC) were included. After baseline assessments, all AD participants started cholinergic therapy. We found that baseline and follow-up gamma power analyzes were similar between groups. Yet, within the AD group after AChE-I intake, individuals with AD displayed higher gamma power compared to their baselines (P < .039). Also, baseline gamma coherence analysis showed lower values in the AD than in HC (P < .048), while these differences disappeared with increased gamma values of AD patients at the follow-up. Within the AD group after AChE-I intake, individuals with AD displayed higher theta and alpha coherence compared to their baselines (all, P < .039). These increased results within the AD group may result from a subclinical epileptiform activity. Even though AChE-I is associated with lower mortality, our results showed a significant effect on EEG power yet can increase the subclinical epileptiform activity. It is essential to be conscious of the seizure risk that treatment may cause

Comparative Assessment Of Induction Efficacy Of Propofol Preparations

Objectives: 10 compare the hypnotic effects (using Bispectral Index [BIS]), hemodynamic parameters, injection pain and quality of anesthesia during induction of anesthesia of the 3 commercial propofol preparations (Abbott Propofol, Abbott Laboratories), Pofol (Dongkook Pharm. Co. Ltd.), and Propofol 1% Fresenius (Fresenius Kabi). Methods: After Ethics Committee Approval, a prospective, randomized, double-blind study was designed in Hacettepe University Hospitals Operating Theaters in 2005. The patients aged 18-65 years, American Society of Anesthesiologists (ASA) grades I and 11 scheduled for elective surgery under general anesthesia with orotracheal intubation. Ninety patients were randomized into 3 groups with 30 patients in each group. Propofol infusion rate was 2.5 mg. seconds(-1). Induction time and doses to reach BIS level of 50 10, injection pain, BIS values and hemodynamic parameters were recorded every minutes for the first 7 minutes and than every 2 minutes for 15 minutes. We used a special chart to assess the induction quality. Results: Demographical parameters and ASA Physical status were similar in all groups. There were no significant differences in induction quality, induction time and doses, injection pain, BIS values and hemodynamic parameters. Conclusion: Abbott Propofol, Pofol and Propofol 1% Fresenius have similar effects on anesthesia induction quality and the cost should be taken into consideration when choosing the type of commercial formulation propofol emulsions.Wo

Auditory brain oscillatory responses in drug-naive patients with Parkinson's disease

Parkinson's Disease (PD) is a common neurodegenerative disorder affecting the function of dopaminergic cells in basal ganglia. Besides the motor symptoms, tremor, and dysfunction of sensory systems. In the literature, there was limited studies which investigates the basic sensorial processing in PD. Therefore, we aimed to establish the sensorial processing of simple auditory stimulations in naive PD comparing to healthy controls (HC) via delta, theta, and alpha brain oscillatory responses. 12 naive PD and 12 HC participated to the study. Brain responses recorded via the 64-channel electroencephalography (EEG) system in an electromagnetically and acoustically isolated room. The auditory stimuli (1500 Hz, 60 dB SPL, 500 ms) were delivered to the subjects via a head-phone. The inter-stimulus interval was ranged between 2.5-4.5 s. The peak-to-peak maximum amplitudes were measured in the delta, theta and alpha frequency bands on 11 electrodes (including the frontal, central and parietal areas) for the statistical analysis in which one-way ANOVA test was employed for the comparisons between PD and HC. For the delta oscillatory responses, PD group has bigger amplitudes in frontal, central and parietal areas in comparison with HC. For the theta and alpha oscillatory responses, PD group has bigger amplitudes in parietal areas in comparison with HC. As a result, amplitudes of brain oscillatory responses in PD group were significantly bigger than the HC. In this context, decreased inhibitory mechanisms of cortical auditory processing due to the dysfunction of the dopaminergic activity may lead the increased evoked responses in PD group

Management of free-floating thrombus within the arcus aorta and supra-aortic arteries

Introduction: Clinical management strategy and the best treatment option of free floating thrombus (FFT), detected in patients with acute ischemic cerebrovascular diseases is still uncertain due to the rarity of these conditions. Recent studies emphasize that FFT within cerebral vessels may not be a surgical emergency since complete dissolution without any further neurologic progression occurred in 86% of patients treated medically

Monthly methylprednisolone in combination with interferon beta or glatiramer acetate for relapsing-remitting multiple sclerosis: A multicentre, single-blind, prospective trial

Objectives: Multiple sclerosis is usually clinically characterized by repeated subacute relapses followed by remissions. Corticosteroids are used for relapses, and this treatment has been shown to increase the speed of recovery from these. We aimed to evaluate the efficacy and safety of pulsed methylprednisolone given every month as an add-on therapy to interferon beta or glatiramer acetate in patients with relapsing-remitting multiple sclerosis

Monthly Pulse Methylprednisolone Therapy is Effective in Preventing Permanent Disease Progression in Secondary Progressive Multiple Sclerosis

Introduction: Secondary progressive multiple sclerosis (SPMS) is the phase in which disability continues to worsen with or without accompanying attacks. Monthly methylprednisolone pulse therapy can be used in the secondary progressive phase. The purpose of the present study was to evaluate the effects of methylprednisolone pulse therapy on the basis of clinical and MRI parameters in patients with SPMS

Paced auditory serial addition test: National normative data

Objectives: The presence and monitoring of cognitive impairment is frequently overlooked in a disease such as multiple sclerosis (MS), which has the potential to affect the physical, social, and socioeconomic lives of individuals in early adulthood. The purpose of this study was to establish Paced Auditory Serial Addition Test (PASAT) normative data for the healthy Turkish population

Primary central nervous system lymphoma in immunocompetent individuals: a single center experience

Primary central nervous system lymphoma (PCNSL) is defined as the involvement of brain, leptomeninges, eyes or spinal cord by non-Hodgkin lymphoma. The role of various prognostic markers in predicting adverse outcome is debated. Objectives: To investigate the clinical and immunohistochemical findings of immunocompetent PCNSL cases (39 cases) diagnosed at the study center, and evaluate the influence of potential prognostic factors on overall survival (OS) of patients. Methods: Data regarding patient characteristics, neuroimaging, pathological and immunohistochemical features and follow-up were obtained from patient records. The influence of potential prognostic parameters on OS was investigated by log-rank test and Cox regression analysis. Results: Patients who received combined chemotherapy and radiotherapy had a significantly better OS when compared to chemotherapy alone. Other variables included in this study were not associated with a significant survival advantage. Conclusion: In this study, we failed to demonstrate a relationship between different clinicopathological variables and OS of patients. Prospective studies with large patient series are needed to investigate other potential prognostic factors