Search

Francesca Anzellotti, Raffaella Franciotti, Holta Zhuzhuni, Aurelio D'Amico, Astrid Thomas, Marco Onofrj Department of Neuroscience and Imaging, Aging Research Centre, Gabriele d'Annunzio University Foundation, Gabriele d'Annunzio University, Chieti, Italy Abstract: Nonepileptic seizures (NES) apparently look like epileptic seizures, but are not associated with ictal electrical discharges in the brain. NES constitute one of the most important differential diagnoses of epilepsy. They have been recognized as a distinctive clinical phenomenon for centuries, and video/electroencephalogram monitoring has allowed clinicians to make near-certain diagnoses. NES are supposedly unrelated to organic brain lesions, and despite the preponderance of a psychiatric/psychological context, they may have an iatrogenic origin. We report a patient with NES precipitated by levetiracetam therapy; in this case, NES was observed during the disappearance of epileptiform discharges from the routine video/electroencephalogram. We discuss the possible mechanisms underlying NES with regard to alternative psychoses associated with the phenomenon of the forced normalization process. Keywords: nonepileptic seizures, forced normalization, levetiracetam, behavioral side effects

Background and Purpose: Dementia with Lewy bodies (DLB) is characterised by neuroleptic hypersensitivity. It is unclear, however, whether the neuroleptic hypersensitivity implies an increased incidence of neuroleptic malignant syndrome (NMS) or of akinetic crisis (AC), which are expressions of the same possibly lethal clinical event, and whether AC in DLB can appear independently of neuroleptic treatment. In our prospective study, we assessed the incidence of AC in a cohort of DLB as compared with that in patients with Parkinson disease (PD).Methods: In total, 614 patients with PD and 236 DLB were recruited and followed during 2005-2013. AC was diagnosed as sudden akinetic state unresponsive to dopaminergic rescue drugs, dysphagia and serological alterations without recovery for 48 h or more requiring hospital admission. Exposure to neuroleptics was specifically evaluated, because of the high implicit risk in DLB.Results: 24 patients with PD (3.9%) and 16 patients with DLB (6.8%) developed AC. 77 (32.6%) DLB and 32 (5.2%) PD were exposed to typical neuroleptics, but only 8 DLB and 3 PD presented with AC. Disease duration before AC was lower in DLB than in PD group (p<0.01). Outcome was fatal in 8 patients with (50%) DLB and 3 (12.5%) PD (p=0.05). When age and use of neuroleptics were adjusted for into a Cox proportional hazards model predicting time to AC, the HR of patients with DLB was 13.0 (95% CI 4.23 to 39.9; p<0.001).Conclusions: AC in DLB can appear independently of neuroleptic treatment, occurs earlier and is more frequently fatal than in PD. [ABSTRACT FROM AUTHOR]

BACKGROUND: Progressive supranuclear palsy (PSP) is an atypical parkinsonism clinically characterized by prominent axial extrapyramidal motor symptoms with frequent falls. The clinical response to L-dopa is poor and there is strong need for alternative treatment strategies. METHODS: We tested the efficacy of a rehabilitative program combining a dynamic antigravity postural system (SPAD) and a vibration sound system (ViSS) on postural instability of 10 patients affected by PSP. The patients underwent SPAD and VISS treatments with a 3 sessions/week schedule for 2 months. Patients were clinically examined at baseline, every week during the 2-months treatment, and at 1 month after the end of treatment for the following parameters: baropodometry static, baropodometry dynamic and stabilometry. PSP rating scale and PD36 quality of life scale were also administered. RESULTS: The combined rehabilitative program produced improvement of all the parameters explored (p = 0.01-0.05) at the end of treatment as compared to baseline. Baropodometric dynamics improvement lasted until the end of follow-up. CONCLUSION: Our results suggest that a specific rehabilitation program could improve postural instability in PSP patients. A more continuous treatment protocol would allow stabilizations of results. [ABSTRACT FROM AUTHOR]

Abstract: Multisensory processing involving visual and auditory inputs is modulated by their relative temporal offsets. In order to assess whether multisensory integration alters the activation timing of primary visual and auditory cortices as a function of the temporal offsets between auditory and visual stimuli, a task was designed in which subjects had to judge the perceptual simultaneity of the onset of visual stimuli and brief acoustic tones. These were presented repeatedly with three different inter-stimulus intervals that were chosen to meet three perceptual conditions: (1) physical synchrony perceived as synchrony by subjects (SYNC); (2) physical asynchrony perceived as asynchrony (ASYNC); (3) physical asynchrony perceived ambiguously (AMB, i.e. 50% perceived as synchrony, 50% as asynchrony). Magnetoencephalographic activity was recorded during crossmodal sessions and unimodal control sessions. The activation of primary visual and auditory cortices peaked at a longer latency for the crossmodal conditions as compared to the unimodal conditions. Moreover, the latency in the auditory cortex was longer in the SYNC than in the ASYNC condition, whereas in the visual cortex the latency in the AMB condition was longer than in the ASYNC condition. These findings suggest that multisensory processing affects temporal dynamics already in primary cortices, that such activity can differ regionally and can be sensitive to the temporal offsets of multisensory inputs. In addition, in the AMB condition the conscious awareness of asynchrony might be associated to a later activation of the primary auditory cortex. [Copyright &y& Elsevier]

Abstract: Persistent Genital Arousal Disorder (PGAD) refers to the experience of persistent sensations of genital arousal that are felt to be unprovoked, intrusive and unrelieved by one or several orgasms. It is often mistaken for hypersexuality since PGAD often results in a high frequency of sexual behaviour. At present little is known with certainty about the etiology of this condition. We described a woman with typical PGAD symptoms and orgasmic seizures that we found to be related to a specific epileptic focus. We performed a EEG/MEG and fMRI spontaneous activity study during genital arousal symptoms and after the chronic administration of 300 mg/day of topiramate. From MEG data an epileptic focus was localized in the left posterior insular gyrus (LPIG). FMRI data evidenced that sexual excitation symptoms with PGAD could be correlated with an increased functional connectivity (FC) between different brain areas: LPIG (epileptic focus), left middle frontal gyrus, left inferior and superior temporal gyrus and left inferior parietal lobe. The reduction of the FC observed after antiepileptic therapy was more marked in the left than in the right hemisphere in agreement with the lateralization identified by MEG results. Treatment completely abolished PGAD symptoms and functional hyperconnectivity. The functional hyperconnectivity found in the neuronal network including the epileptic focus could suggest a possible central mechanism for PGAD. [Copyright &y& Elsevier]

Abstract Background Autoscopic phenomena are psychic illusory visual experiences consisting of the perception of the image of one's own body or face within space, either from an internal point of view, as in a mirror or from an external point of view. Descriptions based on phenomenological criteria distinguish six types of autoscopic experiences: autoscopic hallucination, he-autoscopy or heautoscopic proper, feeling of a presence, out of body experience, negative and inner forms of autoscopy. Methods and results We report a case of a patient with he-autoscopic seizures. EEG recordings during the autoscopic experience showed a right parietal epileptic focus. This finding confirms the involvement of the temporo-parietal junction in the abnormal body perception during autoscopic phenomena. We discuss and review previous literature on the topic, as different localization of cortical areas are reported suggesting that out of body experience is generated in the right hemisphere while he-autoscopy involves left hemisphere structures.

In this MEG study, we investigated cortical alpha/sigma and beta ERD/ERS induced by median nerve stimulation to extend previous evidence on different resonant and oscillatory behavior of SI and SII (NeuroImage 13 [2001] 662). Here, we tested whether simple somatosensory stimulation could induce a distinctive sequence of alpha/sigma and beta ERD/ERS over SII compared to SI. We found that for both alpha/sigma (around 10 Hz) and beta (around 20 Hz) rhythms, the latencies of ERD and ERS were larger in bilateral SII than in contralateral SI. In addition, the peak amplitude of alpha/sigma and beta ERS was smaller in bilateral SII than in contralateral SI. These results indicate a delayed and prolonged activation of SII responses, reflecting a protracted information elaboration possibly related to SII higher order role in the processing of somatosensory information. This temporal dynamics of alpha/sigma and beta rhythms may be related to a sequential activation scheme of SI and SII during the somatosensory information processes. Future studies should evaluate in SII the possible different functional significance of alpha/sigma with respect to beta rhythms during somatosensory processing. [Copyright &y& Elsevier]

Magnetoencephalography (MEG) has been applied for more than 20 years to the localization of the epileptic focus in partial epilepsies, but correlation with electroencephalographic (EEG) data in homogeneous groups of patients is scarce.Objective. – The aim of our work was to use EEG and MEG for the study of a group of adults and children affected by cryptogenetic partial epilepsy.Methods. – We analyzed the traces obtained from electroencephalographic and magnetoencephalographic recordings of 10 patients of ages ranging from 7 to 38 years affected by cryptogenetic partial epilepsy. We evaluated the presence of commonly detected or uniquely detected spikes, and, whenever possible, we used MEG for localization of the epileptic focus.Results. – Three patients showed no epileptic activity during the EEG and MEG sessions. Overall agreement between EEG and MEG (presence of concordant spikes with the same localization shown by both techniques) was obtained in five patients. In one patient the spikes detected by EEG and MEG were different, and in another patient interictal activity was demonstrated exclusively by EEG.Conclusions. – EEG in this series was not inferior to MEG in terms of spike detection. Combination of EEG and MEG is feasible, better than each technique alone, and may be useful for non-invasive diagnosis and monitoring of pediatric and adult patients with partial epilepsies. [Copyright &y& Elsevier]

Background: Marinesco-Sjögren syndrome (MSS) is an autosomal recessive neuromuscular disorder that arises in early childhood and is characterized by congenital cataracts, myopathy associated with muscle weakness, and degeneration of Purkinje neurons leading to ataxia. About 60% of MSS patients have loss-of-function mutations in the SIL1 gene. Sil1 is an endoplasmic reticulum (ER) protein required for the release of ADP from the master chaperone Bip, which in turn will release the folded proteins. The expression of non-functional Sil1 leads to the accumulation of unfolded proteins in the ER and this triggers the unfolded protein response (UPR). A dysfunctional UPR could be a key element in the pathogenesis of MSS, although our knowledge of the molecular pathology of MSS is still incomplete., Methods: RNA-Seq transcriptomics was analysed using the String database and the Ingenuity Pathway Analysis platform. Fluorescence confocal microscopy was used to study the remodelling of the extracellular matrix (ECM). Transmission electron microscopy (TEM) was used to reveal the morphology of the ECM in vitro and in mouse tendon., Results: Our transcriptomic analysis, performed on patient-derived fibroblasts, revealed 664 differentially expressed (DE) transcripts. Enrichment analysis of DE genes confirmed that the patient fibroblasts have a membrane trafficking issue. Furthermore, this analysis indicated that the extracellular space/ECM and the cell adhesion machinery, which together account for around 300 transcripts, could be affected in MSS. Functional assays showed that patient fibroblasts have a reduced capacity of ECM remodelling, reduced motility, and slower spreading during adhesion to Petri dishes. TEM micrographs of negative-stained ECM samples from these fibroblasts show differences of filaments in terms of morphology and size. Finally, structural analysis of the myotendinous junction of the soleus muscle and surrounding regions of the Achilles tendon revealed a disorganization of collagen fibres in the mouse model of MSS (woozy)., Conclusions: ECM alterations can affect the proper functioning of several organs, including those damaged in MSS such as the central nervous system, skeletal muscle, bone and lens. On this basis, we propose that aberrant ECM is a key pathological feature of MSS and may help explain most of its clinical manifestations., (© 2024. The Author(s).)

Previous studies have reported an association between oral microbial dysbiosis and the development and progression of pathologies in the central nervous system. Porphyromonas gingivalis ( Pg ), the keystone pathogen of the oral cavity, can induce a systemic antibody response measured in patients' sera using enzyme-linked immunosorbent assays. The present case-control study quantified the immune system's response to Pg abundance in the oral cavities of patients affected by different central nervous system pathologies. The study cohort included 87 participants: 23 healthy controls (HC), 17 patients with an acute neurological condition (N-AC), 19 patients with a chronic neurological condition (N-CH), and 28 patients with neurodegenerative disease (N-DEG). The results showed that the Pg abundance in the oral cavity was higher in the N-DEG patients than in the HC ( p = 0.0001) and N-AC patients ( p = 0.01). In addition, the Pg abundance was higher in the N-CH patients than the HCs ( p = 0.005). Only the N-CH patients had more serum anti- Pg antibodies than the HC ( p = 0.012). The inadequate response of the immune system of the N-DEG group in producing anti- Pg antibodies was also clearly indicated by an analysis of the ratio between the anti- Pg antibodies quantity and the Pg abundance. Indeed, this ratio was significantly lower between the N-DEG group than all other groups ( p = 0.0001, p = 0.002, and p = 0.03 for HC, N-AC, and N-CH, respectively). The immune system's response to Pg abundance in the oral cavity showed a stepwise model: the response diminished progressively from the patients affected with an acute condition to the patients suffering from chronic nervous system disorders and finally to the patients affected by neurodegenerative diseases.

In Mild Cognitive Impairment (MCI), identifying a high risk of conversion to Alzheimer's Disease Dementia (AD) is a primary goal for patient management. Machine Learning (ML) algorithms are widely employed to pursue data-driven diagnostic and prognostic goals. An agreement on the stability of these algorithms -when applied to different biomarkers and other conditions- is far from being reached. In this study, we compared the different prognostic performances of three supervised ML algorithms fed with multimodal biomarkers of MCI subjects obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Random Forest, Gradient Boosting, and eXtreme Gradient Boosting algorithms predict MCI conversion to AD. They can also be simultaneously employed -with the voting procedure- to improve predictivity. AD prediction accuracy is influenced by the nature of the data (i.e., neuropsychological test scores, cerebrospinal fluid AD-related proteins and APOE ε4, cerebral structural MRI (sMRI) data). In our study, independent of the applied ML algorithms, sMRI data showed the lowest accuracy (0.79) compared to other classes. Multimodal data were helpful in the algorithms' performances by combining clinical and biological measures. Accordingly, using the three ML algorithms, the highest accuracy (0.90) was reached by employing neuropsychological and AD-related biomarkers. Finally, the feature selection procedure indicated that the most critical variables in the respective classes were the ADAS-Cog-13 scale, the medial temporal lobe and hippocampus atrophy, and the ratio between phosphorylated Tau and Aβ42 proteins. In conclusion, our data support the notion that using multiple ML algorithms and multimodal biomarkers helps make more accurate and solid predictions., (Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: The high co-occurrence of somatic symptom disorder (SSD) in Parkinson's disease (PD) patients suggests overlapping pathophysiology. However, little is known about the neural correlates of SSD and their possible interactions with PD. Existing studies have shown that SSD is associated with reduced task-evoked activity in the medial prefrontal cortex (mPFC), a central node of the default-mode network (DMN). SSD is also associated with abnormal γ-aminobutyric acid (GABA) content, a marker of local inhibitory tone and regional hypoactivity, in the same area when SSD co-occurs with PD., Objectives: To disentangle the individual and shared effects of SSD and PD on mPFC neurotransmission and connectivity patterns and help disclose the neural mechanisms of comorbidity in the PD population., Methods: The study cohort included 18 PD patients with SSD (PD + SSD), 18 PD patients, 13 SSD patients who did not exhibit neurologic disorders, and 17 healthy subjects (HC). Proton magnetic resonance (MR) spectroscopy evaluated GABA levels within a volume of interest centered on the mPFC. Resting-state functional MR imaging investigated the region's functional connectivity patterns., Results: Compared to HC or PD groups, the mPFC of SSD subjects exhibited higher GABA levels and connectivity. Higher mPFC connectivity involved DMN regions in SSD patients without PD and regions of the executive and attentional networks (EAN) in patients with PD comorbidity., Conclusions: Aberrant reconfigurations of connectivity patterns between the mPFC and the EAN are distinct features of the PD + SSD comorbidity. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Swallowing is a complex but stereotyped motor activity aimed at serving two vital purposes: alimentary function and the protection of upper airways. Therefore, any impairment of the swallowing act can represent a significant clinical and personal problem that needs an accurate diagnosis by means of reliable and non-invasive techniques. Thus, a systematic review and meta-analysis was performed to investigate the reliability of the Iowa Oral Pressure Instrument (IOPI) in distinguishing healthy controls (HC) from patients affected by swallowing disorders or pathologies and conditions that imply dysphagia. A comprehensive search was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and using PubMed, Scopus, Web of Science, Cochrane, and Lilacs databases. Overall, 271 articles were identified and, after a three-step screening, 33 case-control and interventional studies reporting IOPI measurements were included. The methodological quality of the retrieved studies resulted in being at a low risk of bias. The meta-analysis on case-control studies showed that maximum tongue pressure (MIP) values were always higher in HC than in patients, with an overall effect of the MIP difference of 18.2 KPa (17.7-18.7 KPa CI). This result was also confirmed when the sample was split into adults and children, although the MIP difference between HC and patients was greater in children than in adults (21.0 vs. 15.4 KPa in the MIP mean difference overall effect, respectively). Tongue endurance (TE) showed conflicting results among studies, with an overall effect among studies near zero (0.7 s, 0.2-1.1 s CI) and a slight tendency toward higher TE values in HC than in patients. Among the intervention studies, MIP values were higher after treatment than before, with a better outcome after the experimental tongue training exercise than traditional treatments (the MIP mean difference overall effect was 10.8 and 2.3 KPa, respectively). In conclusion, MIP values can be considered as a reliable measure of swallowing function in adults and in children, with a more marked MIP difference between HC and patients for the children population. MIP measures in patients are also able to detect the best outcome on the tongue function after the training exercise compared to traditional training.

Cortical network modularity underpins cognitive functions, so we hypothesized its progressive derangement along the course of frontotemporal (FTD) and Alzheimer's (AD) dementing diseases. EEG was recorded in 18 FTD, 18 AD, and 20 healthy controls (HC). In the FTD and AD patients, the EEG recordings were performed at the prodromal stage of dementia, at the onset of dementia, and three years after the onset of dementia. HC underwent three EEG recordings at 2-3-year time interval. Information flows underlying EEG activity recorded at electrode pairs were estimated by means of Mutual Information (MI) analysis. The functional organization of the cortical network was modelled by means of the Graph theory analysis on MI adjacency matrices. Graph theory analysis showed that the main hub of HC (Parietal area) was lost in FTD patients at onset of dementia, substituted by provincial hubs in frontal leads. No changes in global network organization were found in AD. Despite a progressive cognitive impairment during the FTD and AD progression, only the FTD patients showed a derangement in the cortical network modularity, possibly due to dysfunctions in frontal functional connectivity., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: Temporal lobe epilepsy (TLE) is the most frequent focal epilepsy in adulthood. Catamenial C1-type TLE, is characterized by a cyclic seizure exacerbation during the menstrual phase. The heart rate variability (HRV) analysis assesses cardiac autonomic control and may represent a biomarker for Sudden Unexpected Death in Epilepsy (SUDEP). It is plausible that female sex hormones can influence HRV. These changes might be more pronounced in patients suffering from catamenial C1-type TLE where hormonal changes also increase seizure susceptibility. To that aim, we evaluated HRV changes during the menstrual phase of women suffering from catamenial C1-type TLE., Methods: We enrolled 12 adults with a diagnosis of catamenial C1-type TLE (Catamenial Group) and 12 age-, and seizure-frequency-matched controls with TLE (Non-Catamenial Group). Each patient underwent a 20-minute EEG + EKG recording in resting state during the menstrual phase. HRV parameters were calculated with a short-lasting analysis of EKG records. Time domain-related, frequency domain-related, as well as non-linear analysis parameters, were compared between the two groups., Result: Compared to the Non-Catamenial Group, the Catamenial Group showed significant reductions in SDNN (p-value = 0.01), RMSSD (p-value = 0.04), pNN50 (p-value = 0.001), LnLF ms 2 (p-value = 0.05), LnHF ms 2 (p-value = 0.007), SD1 (p-value = 0.02), and SD2 (p-value = 0.01). These results were independent from age, disease duration, numbers of ASM, and seizure etiology., Conclusion: Our data provide experimental evidence that vagal output is reduced during the menstrual phase in patients with catamenial C1-type TLE. These results indicate that, during the menstrual phase, patients with catamenial C1-type TLE may be at a higher risk of developing cardiac dysfunctions and SUDEP., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Alzheimer's disease (AD) is a neurodegenerative condition driven by multifactorial etiology. Mild cognitive impairment (MCI) is a transitional condition between healthy aging and dementia. No reliable biomarkers are available to predict the conversion from MCI to AD., Objective: To evaluate the use of machine learning (ML) on a wealth of data offered by the Alzheimer's Disease Neuroimaging Initiative (ADNI) and Alzheimer's Disease Metabolomics Consortium (ADMC) database in the prediction of the MCI to AD conversion., Methods: We implemented an ML-based Random Forest (RF) algorithm to predict conversion from MCI to AD. Data related to the study population (587 MCI subjects) were analyzed by RF as separate or combined features and assessed for classification power. Four classes of variables were considered: neuropsychological test scores, AD-related cerebrospinal fluid (CSF) biomarkers, peripheral biomarkers, and structural magnetic resonance imaging (MRI) variables., Results: The ML-based algorithm exhibited 86% accuracy in predicting the AD conversion of MCI subjects. When assessing the features that helped the most, neuropsychological test scores, MRI data, and CSF biomarkers were the most relevant in the MCI to AD prediction. Peripheral parameters were effective when employed in association with neuropsychological test scores. Age and sex differences modulated the prediction accuracy. AD conversion was more effectively predicted in females and younger subjects., Conclusion: Our findings support the notion that AD-related neurodegenerative processes result from the concerted activity of multiple pathological mechanisms and factors that act inside and outside the brain and are dynamically affected by age and sex.

Background: Patients with bipolar spectrum disorders (BSDs) exhibit an increased risk of Parkinson's disease (PD)., Objective: The aim is to investigate whether a previous diagnosis of BSDs influences the phenotype of PD., Methods: Of 2660 PD patients followed for at least 6 years (6-27), 250 (BSD-PD) had BSDs, 6-20 years before PD diagnosis; 48%-43% had a PD or BSD family history, and 34 carried glucocerebrosidase (GBA) and Parkin (PRKN) mutations. The cohort was split into a subset of 213 BSD-PD patients, compared with 426 matched PD patients without BSDs, and a subset of 34 BSD-PD and 79 PD patients carrying GBA or PRKN mutations. Carriers of mutations absent in BSD-PD patients and of synuclein triplication were excluded. Structured clinical interviews and mood disorder questionnaires assessed BSDs. Linear mixed models evaluated the assessment scales over time. Thirteen BSD-PD patients underwent subthalamic nucleus deep brain stimulation (STN-DBS) and were compared with 27 matched STN-DBS-treated PD patients., Results: Compared to PD patients, BSD-PD showed (1) higher frequency of family history of PD (odds ratio [OR] 3.31; 2.32-4.71) and BSDs (OR 6.20; 4.11-9.35) 5); (2) higher incidence of impulse control disorders (hazard ratio [HR] 5.95, 3.89-9.09); (3) higher frequency of functional disorders occurring before PD therapy (HR, 5.67, 3.95-8.15); (4) earlier occurrence of delusions or mild dementia (HR, 7.70, 5.55-10.69; HR, 1.43, 1.16-1.75); and (5) earlier mortality (1.48; 1.11-1.97). Genetic BSD-PD subjects exhibited clinical features indistinguishable from nongenetic BSD-PD subjects. STN-DBS-treated BSD-PD patients showed no improvements in quality of life compared to the control group., Conclusions: BSDs as a prodrome to PD unfavorably shape their course and are associated with detrimental neuropsychiatric features and treatment outcomes. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Objectives: Visuo-perceptual deficits and visual hallucinations (VHs) are common disturbances in patients with dementia with Lewy bodies (DLB) and those with Parkinson's disease (PD). In particular, delays in visual evoked potential (VEP), reversed by l-dopa administration, have previously been observed in PD patients. Impairment in metabolic functions of dopaminergic amacrine cells within the inner plexiform layer of the retina has been largely documented and has been posited as the underlying cause of visual and retinal alterations in PD. The aims of the present study were to investigate the presence of VEP abnormalities in DLB patients, as compared to a PD control group, and to assess the presence of significant correlations between neurophysiological measures and clinical symptoms (i.e., presence of visuospatial deficits and/or visual hallucinations)., Methods: Fifteen DLB patients and fifteen matched PD patients underwent pattern reversal before and after l-dopa administration, and a short neuropsychological assessment., Results: In DLB patients, we observed delay of the P100 latency to foveal stimuli in both eyes compared to normative values. Compared to PD, DLB patients showed higher values of the P100 latency for foveal stimulation from the right eye prior to l-dopa administration (p = 0.018). No correlations between VEP alterations, visuo-spatial deficit and visual hallucinations were found., Discussion: Our findings demonstrated a longer P100 delay in DLB than in PD patients, especially along the right visual pathway. In contrast to previous studies, which focused on a dopaminergic pre-geniculate impairment of visual pathways, our evidence suggests that other mechanisms, possibly relying on thalamic involvement, which is known to be dysfunctional in DLB, can interfere with VEP abnormalities., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Consensus criteria on corticobasal degeneration (CBD) include alien limb (AL) phenomena. However, the gist of the behavioral features of AL is still "a matter of debate." CBD-related AL has so far included the description of involuntary movements, frontal release phenomena (frontal AL), or asomatognosia (posterior or "real" AL). In this context, the most frequent symptoms are language and praxis deficits and cortical sensory misperception. However, asomatognosia requires, by definition, intact perception and cognition. Thus, to make a proper diagnosis of AL in the context of CBD, cognitive and language dysfunctions must be carefully verified and objectively assessed. We reviewed the current literature on AL in CBD and now propose that the generic use of the term AL should be avoided. This catchall AL term should instead be deconstructed. We propose that the term AL is appropriate to describe clinical features associated with specific brain lesions. More discrete sets of regionally bound clinical signs that depend on dysfunctions of specific brain areas need to be assessed and presented when posing the diagnosis. Thus, in our opinion, the AL term should be employed in association with precise descriptions of the accompanying involuntary movements, sensory misperceptions, agnosia-asomatognosia contents, and the presence of utilization behavior. The review also offers an overview of functional magnetic resonance imaging-based studies evaluating AL-related phenomena. In addition, we provide a complementary set of video clips depicting CBD-related involuntary movements that should not mistakenly be interpreted as signs of AL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Di Pietro, Russo, Dono, Carrarini, Thomas, Di Stefano, Telese, Bonanni, Sensi, Onofrj and Franciotti.)

Recent studies support the hypothesis that microbes can seed some Alzheimer's disease (AD) cases, leading to inflammation and overproduction of amyloid peptides. Porphyromonas gingivalis (Pg) is a keystone pathogen of chronic periodontitis and has been identified as risk factor for the development and progression of AD. The present preliminary study aimed to quantify Pg abundance in neurodegenerative disease (ND) patients compared with neurologic patients without neurodegenerative disorders (no-ND) and healthy controls (HC) to determine possible association between Pg abundance and neurodegenerative process. Pg was quantified on DNA extracted from the oral samples of 49 patients and 29 HC by quantitative polymerase chain reaction (qPCR). Anti-Pg antibodies were also detected on patient serum samples by enzyme-linked immunosorbent assays (ELISA). The Pg abundance in the oral cavity was significantly different among groups ( p = 0.004). It was higher in ND than no-ND ( p = 0.010) and HC ( p = 0.008). The Pg abundance was correlated with the antibodies ( p = 0.001) with different slopes between ND and no-ND ( p = 0.037). Pg abundance was not correlated with oral indices and comorbidities. These results extend our understanding of the association between oral pathogens and AD to other neurodegenerative processes, confirming the hypothesis that oral pathogens can induce an antibody systemic response, influencing the progression of the disease.

We investigated in a longitudinal multicenter cohort study functional cortical connectivity changes along the course of frontotemporal dementia (FTD) and Alzheimer's disease (AD) from the prodromal stage of the diseases. Electroencephalography (EEG) was recorded in 18 FTD and 18 AD patients at the prodromal stage of dementia, at dementia onset, and 3 years after dementia onset. Twenty healthy controls (HC) underwent EEG recordings at the same time interval as the patients. Mutual information (MI) analysis measured the strength of functional network connectivity. FTD and AD patients showed greater MI at the prodromal stage of dementia (FTD vs. HC P = 2 × 10-8; AD vs. HC P = 4 × 10-3). Local connectivity was higher in left and right frontal areas of FTD (P = 7 × 10-5 and 0.03) and in left and right posterior areas in AD (P = 3 × 10-5 and 5 × 10-5) versus HC. We showed cortical hyperconnectivity at the prodromal stage of dementia in areas involved in the specific pathological process of FTD (frontal regions) and AD (posterior regions). Hyperconnectivity disappeared during follow-up, thus suggesting that it is an early electrophysiological feature of dementia, potentially useful to identify prodromal FTD and AD., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)