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Background: Anosognosia, or unawareness of symptoms, is common in Huntington's disease (HD), but the neuroanatomical basis of this is unknown. Objective: To identify neuroanatomical correlates of HD anosognosia using structural MRI data. Methods: We leveraged a pre-processed dataset of 570 HD participants across the well-characterized PREDICT-HD and TRACK-HD cohort studies. Anosognosia index was operationalized as the score discrepancies between HD participants and their caregivers on the Frontal Systems Behavior Scale (FrSBe). Results: Univariate correlation analyses identified volumes of globus pallidus, putamen, caudate, basal forebrain, substantia nigra, angular gyrus, and cingulate cortex as significant correlates of anosognosia after correction for multiple comparisons. A multivariable model constructed with stepwise regression that included volumetric data showed globus pallidus volume alone explained more variance in anosognosia severity than motor impairment or CAP score alone. Conclusions: Anosognosia appears to be related to degeneration affecting both cortical and subcortical areas. Globus pallidus neurodegeneration in particular appears to be a key process of importance.

Asunto(s)

Agnosia , Enfermedad de Huntington , Imagen por Resonancia Magnética , Humanos , Enfermedad de Huntington/diagnóstico por imagen , Enfermedad de Huntington/patología , Masculino , Femenino , Agnosia/diagnóstico por imagen , Agnosia/etiología , Agnosia/patología , Persona de Mediana Edad , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Globo Pálido/diagnóstico por imagen , Globo Pálido/patología

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BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) is an accepted therapy for Parkinson's disease (PD) with disabling motor complications. For elderly patients with poorer cognition and postural instability, GPi has been proposed as the preferable DBS target based on expert opinion, arguing GPi-DBS may be less complicated by depression, apathy, worsened verbal fluency, and executive dysfunction, resulting in greater improvement in quality of life (QoL). However, data supporting such patient-tailored approach are lacking. OBJECTIVES: The aims were to analyze whether the DBS target influences QoL in a PD cohort and a matched subgroup of frail patients with poor cognitive status and reduced postural stability, and whether other factors affect the QoL outcomes. METHODS: In this retrospective study, we analyzed a single-center cohort of 138 PD patients who received bilateral STN-DBS (117) or GPi-DBS (21) using the mentioned approach for target selection. All patients underwent standardized clinical evaluations of motor- and nonmotor signs as well as QoL before and 1 year after surgery. RESULTS: DBS of both targets improved motor signs, dyskinesias, and pain. QoL improved without significant difference between the targets, but with a trend for greater improvement across all QoL domains in favor of the STN, even in an STN subgroup matched to the GPi group. CONCLUSION: Our results contradict the prevailing belief that GPi-DBS is superior in frail PD patients with cognitive decline and postural instability, questioning the proposed patient-tailored approach of DBS target selection. Further studies are needed for a data-driven approach.

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The globus pallidus externus (GPe) is a central component of the basal ganglia circuit that acts as a gatekeeper of cocaine-induced behavioral plasticity. However, the molecular and circuit mechanisms underlying this function are unknown. Here, we show that GPe parvalbumin-positive (GPePV) cells mediate cocaine responses by selectively modulating ventral tegmental area dopamine (VTADA) cells projecting to the dorsomedial striatum (DMS). Interestingly, GPePV cell activity in cocaine-naive mice is correlated with behavioral responses following cocaine, effectively predicting cocaine sensitivity. Expression of the voltage-gated potassium channels KCNQ3 and KCNQ5 that control intrinsic cellular excitability following cocaine was downregulated, contributing to the elevation in GPePV cell excitability. Acutely activating channels containing KCNQ3 and/or KCNQ5 using the small molecule carnosic acid, a key psychoactive component of Salvia rosmarinus (rosemary) extract, reduced GPePV cell excitability and impaired cocaine reward, sensitization, and volitional cocaine intake, indicating its therapeutic potential to counteract psychostimulant use disorder.

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Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) can markedly reduce muscle rigidity in people with Parkinson's disease (PD); however, the mechanisms mediating this effect are poorly understood. Computational modeling of DBS provides a method to estimate the relative contributions of neural pathway activations to changes in outcomes. In this study, we generated subject-specific biophysical models of GPi DBS (derived from individual 7-T MRI), including pallidal efferent, putamenal efferent, and internal capsule pathways, to investigate how activation of neural pathways contributed to changes in forearm rigidity in PD. Ten individuals (17 arms) were tested off medication under four conditions: off stimulation, on clinically optimized stimulation, and on stimulation specifically targeting the dorsal GPi or ventral GPi. Quantitative measures of forearm rigidity, with and without a contralateral activation maneuver, were obtained with a robotic manipulandum. Clinically optimized GPi DBS settings significantly reduced forearm rigidity (P < 0.001), which aligned with GPi efferent fiber activation. The model demonstrated that GPi efferent axons could be activated at any location along the GPi dorsal-ventral axis. These results provide evidence that rigidity reduction produced by GPi DBS is mediated by preferential activation of GPi efferents to the thalamus, likely leading to a reduction in excitability of the muscle stretch reflex via overdriving pallidofugal output.NEW & NOTEWORTHY Subject-specific computational models of pallidal deep brain stimulation, in conjunction with quantitative measures of forearm rigidity, were used to examine the neural pathways mediating stimulation-induced changes in rigidity in people with Parkinson's disease. The model uniquely included internal, efferent and adjacent pathways of the basal ganglia. The results demonstrate that reductions in rigidity evoked by deep brain stimulation were principally mediated by the activation of globus pallidus internus efferent pathways.

Asunto(s)

Estimulación Encefálica Profunda , Globo Pálido , Rigidez Muscular , Enfermedad de Parkinson , Humanos , Globo Pálido/fisiopatología , Globo Pálido/fisiología , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/fisiopatología , Rigidez Muscular/fisiopatología , Rigidez Muscular/terapia , Masculino , Femenino , Persona de Mediana Edad , Anciano , Vías Nerviosas/fisiopatología , Vías Nerviosas/fisiología , Modelos Neurológicos

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BACKGROUND: The complexities of unilateral dystonia have led to exploring simultaneous (dual) globus pallidus internus (GPi) and motor ventral thalamus (Vim/Vop) deep brain stimulation (DBS), yet detailed assessments are lacking. OBJECTIVES: To assess the efficacy of GPi, Vim/Vop, and dual DBS in unilateral dystonia. METHODS: Three patients with unilateral dystonia (two idiopathic, one acquired), implanted with two DBS electrodes targeting ipsilateral Vim/Vop and GPi, were included. Three stimulation modalities were assessed. First, one electrode was activated, then the other, and finally, both electrodes were activated simultaneously. RESULTS: DBS yielded substantial symptomatic reductions in all three evaluated stimulation modalities. Patients exhibited varying responses regarding quality-of-life and depressive symptoms. Treatment satisfaction didn't align with clinical improvements, potentially affected by unrealistic expectations. CONCLUSIONS: This study contributes critical insights into GPi, Vim/Vop and simultaneous stimulation for unilateral dystonia. The safety of the procedure underscores the promise of this approach.

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There is evidence that the subthalamic nucleus (STN) and globus pallidus pars externa (GPe) involve in the development of Parkinson's disease, a neurodegenerative disorder characterized by motor and non-motor symptoms and loss of dopaminergic neurons in which the error index (EI) in firing patterns is widely used to address the related issues. Whether and how this interaction mechanism of STN and GPe affects EI in Parkinson's disease is uncertain. To account for this, we propose a kind of basal ganglia-thalamic network model associated with Parkinson's disease coupled with neurons, and investigate the effect of synaptic conductance of STN and GPe on EI in this network, as well as their internal relationship under EI as an index. The results show a relationship like a piecewise function between the error index and the slope of the state transition function of synaptic conductance from STN to GPe ( g snge ) and from GPe to STN ( g gesn ). And there is an approximate negative correlation between EI and g gesn . Increasing g snge and decreasing g gesn can improve the fidelity of thalamus information transmission and alleviate Parkinson's disease effectively. These obtained results can give some theoretical evidence that the abnormal synaptic releases of STN and GPe may be the symptoms of the development of Parkinson's disease, and further enrich the understanding of the pathogenesis and treatment mechanism of Parkinson's disease.

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Chorea-acanthocytosis (ChAc) is a rare, neurodegenerative disorder caused by mutations in the VPS13A gene. In this article, we report on a 32-year-old man diagnosed with ChAc, with involuntary movements of the mouth and trunk, drooling of the mouth, slurred speech, and abnormal vocalizations as the main clinical manifestations. Three weeks after implantation of globus pallidus internal (GPi)-deep brain stimulation (DBS), the patient's symptoms improved significantly. For example, articulation is clear, involuntary trunk movements and salivation have largely disappeared, and abnormal vocalizations have been significantly reduced. After 1 year of follow-up, the improvement in involuntary movement symptoms is essentially the same as before. As far as we know, we are the first to report the relief of involuntary vocalizations in a patient with GPi-DBS treatment, and that salivation and involuntary trunk movements have almost disappeared, and all other symptoms are significantly relieved, which is rare in previous cases. All of the above proves that the treatment of our case with DBS was very successful and that longer term follow-up is critical. We also hope that our case will provide new references and therapeutic ideas for the future treatment of patients with ChAc.

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Parkinson's disease (PD) ranks as the second most prevalent and rapidly growing neurodegenerative disorder. As a primary output nucleus within the basal ganglia (BG), the globus pallidus interna (GPi) is a key structure in BG information processing. It is also a key target for deep brain stimulation (DBS) to alleviate motor symptoms of PD. Previous studies have identifiedPD patients exhibiting abnormal neuronal activity in the GPi. On the other hand, various types of dopamine receptor (DR)-positive neurons have been identified within the GPi. However, the electrophysiological properties of specific DR-positive neurons within the GPi and their alterations in PD have not been addressed. In the present study, we used whole-cell patch-clamp recordings to identify two neuronal subpopulations within the GPi, dopamine D1 receptor (D1R)-positive, and dopamine D2 receptor (D2R)-positive neurons, which exhibited distinct electrophysiological properties. Additionally, significant alterations of electrophysiological properties of D2R-positive neurons within the GPi were observed in 6-hydroxydopamine (6-OHDA)-lesioned mice. These data suggest that the distinct electrophysiological properties of specific DR-positive neurons and their abnormal alteration in the GPi may be associated with PD's pathogenesis.

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BACKGROUND: Invasive deep brain stimulation (DBS) has been shown to be effective in treating patients with Parkinson's disease (PD), yet its clinical use is limited to patients at the advanced stage of the disease. Transcranial temporal interference stimulation (tTIS) may be a novel nonneurosurgical and safer alternative, yet its therapeutic potential remains unexplored. OBJECTIVE: This pilot study aims to examine the feasibility and safety of tTIS targeting the right globus pallidus internus (GPi) for motor symptoms in patients with PD. METHODS: Twelve participants with mild PD completed this randomized, double-blind, and sham-controlled experiment. Each of them received either 20-minute or sham tTIS of the right GPi. Before and immediately after the stimulation, participants completed the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS-III) in the "medication-on" state to assess the motor symptoms. The blinding efficacy and side effects were also assessed. RESULTS: tTIS was well tolerated by participants, with only mild, transient adverse effects reported. tTIS significantly reduced MDS-UPDRS-III scores by 6.64 points (14.7%), particularly in bradykinesia (23.5%) and tremor (15.3%). The left side showed more significant alleviation in motor symptoms, particularly bradykinesia, compared to the right side. Participants with severer bradykinesia and tremor before stimulation experienced greater improvement after tTIS. CONCLUSION: This pilot study suggests that the tTIS, as a novel noninvasive DBS approach, is feasible and safe for alleviating motor symptoms in mild PD, especially bradykinesia and tremor. Future larger-scale and more definitive studies are needed to confirm the benefits. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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OBJECTIVE: The aim of this study is to investigate the clinical efficacy of the empathy-based attribution analysis-cognitive restructuring-pharmacological treatment model for the management of globus syndrome. METHOD: Sixty-nine newly diagnosed patients with globus syndrome at the Wenzhou People's Hospital Department of Gastroenterology outpatient clinic were enrolled in this study. After obtaining informed consent, patients were randomly assigned to either the observation group (attribution analysis-cognitive restructuring-classical pharmacotherapy; n = 35) or the control group (pharmacotherapy alone; n = 34), with a treatment course of 4 weeks. Efficacy assessments were conducted before and during treatment using the 9-item Patient Health Questionnaire-9 (PHQ-9), the 7-item Generalized Anxiety Disorder-7 (GAD-7), and the Patient Health Questionnaire-15 (PHQ-15). RESULTS: After four weeks of treatment, the total efficacy rate was 100 % in the observation group and 27.6 % in the control group, with a statistically significant difference between the groups (P < 0.05). Scores on the PHQ-9, GAD-7, and PHQ-15 significantly improved in the observation group compared to before treatment and were better than those in the control group, with statistically significant differences (P < 0.05). CONCLUSION: The empathy-based attribution analysis-cognitive restructuring-pharmacological treatment model for the management of globus syndrome demonstrated good clinical efficacy, providing strong evidence for further clinical promotion.

Asunto(s)

Terapia Cognitivo-Conductual , Empatía , Humanos , Femenino , Masculino , Adulto , Resultado del Tratamiento , Persona de Mediana Edad , Terapia Cognitivo-Conductual/métodos , Síndrome

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OBJECTIVE: Deep brain stimulation (DBS) targeting the globus pallidus interna (GPi) has been shown to significantly improve motor symptoms for the treatment of medication-refractory Parkinson's disease. Yet, heterogeneity in clinical outcomes persists, possibly due to suboptimal target identification within the GPi. By leveraging robust sampling of the GPi and 6-month postsurgical outcomes, this study aims to determine optimal symptom-specific GPi DBS targets. METHODS: In this study, the authors analyzed the anatomical lead location and 6-month postsurgical, double-blinded outcome measures of 86 patients who underwent bilateral GPi DBS. These patients were selected from the multicenter Veterans Affairs (VA)/National Institutes of Neurological Disorders and Stroke (NINDS) Cooperative Studies Program (CSP) 468 study to identify the optimal target zones ("sweet spots") for the control of overall motor (United Parkinson's Disease Rating Scale [UPDRS]-III), axial, tremor, rigidity, and bradykinesia symptoms. Lead coordinates were normalized to Montreal Neurological Institute space and the optimal target zones were identified and validated using a leave-one-patient-out approach. RESULTS: The authors' findings revealed statistically significant optimal target zones for UPDRS-III (R = 0.37, p < 0.001), axial (R = 0.22, p = 0.042), rigidity (R = 0.20, p = 0.021), and bradykinesia (R = 0.23, p = 0.004) symptoms. These zones were localized within the primary motor and premotor subdivisions of the GPi. Interestingly, these zones extended beyond the GPi lateral border into the GPi-globus pallidus externa (GPe) lamina and into the GPe, but they did not reach the GPi ventral border, challenging traditional surgical approaches based on pallidotomies. CONCLUSIONS: Drawing upon a robust dataset, this research effectively delineates specific optimal target zones for not only overall motor improvement but also symptom subscores. These insights hold the potential to enhance the precision of targeting in subsequent bilateral GPi DBS surgical procedures.

RESUMEN

OBJECTIVES: Target localization for deep brain stimulation (DBS) is a crucial step that influences the clinical benefit of the DBS procedure together with the reduction of side effects. In this work, we address the feasibility of DBS target localization in the globus pallidus internus (GPi) aided by intraoperative motor evoked potentials (MEP) with emphasis on the reduction of capsular side effects. MATERIAL AND METHODS: Micro-macroelectrode recordings were performed intraoperatively on 20 patients that underwent DBS treatment of the GPi (GPi-DBS). MEP were elicited intraoperatively by microelectrode stimulation during stereotactic DBS surgery. We studied the relationship between MEP thresholds and the internal capsule (IC) proximity. RESULTS: We found a significant correlation between intraoperative MEP thresholds and IC proximity. CONCLUSIONS: We provide further evidence of the role of MEPs for DBS target localization in the GPi, which extends and confirms the usefulness of MEPs as previously reported by DBS target localization studies dealing with the subthalamic and thalamic nuclei. Our approach is advantageous in that it provides criteria to determine the DBS target without the need to rely on a patient's response while avoiding capsular effects.

Asunto(s)

Estimulación Encefálica Profunda , Potenciales Evocados Motores , Globo Pálido , Humanos , Estimulación Encefálica Profunda/métodos , Globo Pálido/fisiología , Masculino , Femenino , Persona de Mediana Edad , Potenciales Evocados Motores/fisiología , Anciano , Monitorización Neurofisiológica Intraoperatoria/métodos , Adulto , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/fisiopatología

RESUMEN

Pyruvate Dehydrogenase (PDH) E2 deficiency due to Dihydrolipoamide acetyltransferase (DLAT) mutations is a very rare condition with only nine reported cases to date. We describe a 15-year-old girl with mild intellectual disability, paroxysmal dystonia and bilateral basal ganglia signal abnormalities on brain magnetic resonance imaging (MRI). Additionally, neurophysiological, imaging, metabolic and exome sequencing studies were performed. Routine metabolite testing, and GLUT1 and PRRT2 mutation analysis were negative. A repeat brain MRI revealed 'Eye-of-the-tiger-sign'. Exome sequencing identified homozygous valine to glycine alteration at amino acid position 157 in the DLAT gene. Bioinformatic and family analyses indicated that the alteration was likely pathogenic. Patient's dystonia was responsive to low-dose carbamazepine. On weaning carbamazepine, patient developed hallucinations which resolved after carbamazepine was restarted. PDH E2 deficiency due to DLAT mutation has a more benign course compared to common forms of PDH E1 deficiency due to X-linked PDHA1 mutations. All known cases of PDH E2 deficiency due to DLAT mutations share the features of episodic dystonia and intellectual disability. Our patient's dystonia and hallucinations responded well to low-dose carbamazepine.

Asunto(s)

Carbamazepina , Distonía , Alucinaciones , Humanos , Femenino , Adolescente , Distonía/genética , Distonía/tratamiento farmacológico , Carbamazepina/uso terapéutico , Alucinaciones/genética , Alucinaciones/tratamiento farmacológico , Mutación , Acetiltransferasa de Residuos Dihidrolipoil-Lisina/genética , Discapacidad Intelectual/genética , Discapacidad Intelectual/tratamiento farmacológico , Anticonvulsivantes/uso terapéutico

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Convenient and effective biomarkers are essential for the early diagnosis and treatment of Alzheimer's disease (AD). In the cross-sectional study, 103 patients with AD, 82 patients with aMCI and 508 normal controls (NC) were enrolled. The single-molecule array (Simoa) technique was used to assess the levels of plasma proteins, including NfL, T-tau, P-tau-181, Aß40, Aß42. Montreal Cognitive Assessment (MoCA) was used to assess the overall cognitive function of all subjects. Moreover, Amyloid PET and structural head MRI were also performed in a subset of the population. In the follow-up, the previous 508 normal older adults were followed up for two years, then COX regression analysis was used to investigate the association between baseline plasma proteins and future cognitive outcomes. NfL, T-tau, P-tau-181, Aß40, Aß42 and Aß42/40 were altered in AD dementia, and NfL, Aß42 and Aß42/40 significantly outperformed all plasma proteins in differentiating AD dementia from NC, while NfL and Aß42/40 could effectively distinguish between aMCI and NC. However, only plasma NfL was associated with future cognitive decline, and it was negatively correlated with MoCA (r = - 0.298, p < 0.001) and the volume of the left globus pallidus (r = - 0.278, p = 0.033). Plasma NfL can help distinguish between cognitively normal and cognitively impaired individuals (MCI/dementia) at the syndrome level. However, since we have not introduced other biomarkers for AD, such as PET CT or cerebrospinal fluid, and have not verified in other neurodegenerative diseases, whether plasma NFL can be used as a biomarker for AD needs to be further studied and explored.

Asunto(s)

Enfermedad de Alzheimer , Péptidos beta-Amiloides , Biomarcadores , Proteínas Sanguíneas , Proteínas tau , Humanos , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/diagnóstico , Masculino , Femenino , Anciano , Estudios Transversales , Estudios Longitudinales , Biomarcadores/sangre , China , Proteínas Sanguíneas/análisis , Proteínas Sanguíneas/metabolismo , Proteínas tau/sangre , Proteínas tau/líquido cefalorraquídeo , Péptidos beta-Amiloides/sangre , Persona de Mediana Edad , Disfunción Cognitiva/sangre , Disfunción Cognitiva/diagnóstico , Tomografía de Emisión de Positrones , Imagen por Resonancia Magnética , Proteínas de Neurofilamentos/sangre , Anciano de 80 o más Años , Fragmentos de Péptidos/sangre , Fragmentos de Péptidos/líquido cefalorraquídeo

RESUMEN

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) is a standard treatment for Parkinson's disease (PD), with both regions exhibiting similar treatment effectiveness. However, posttreatment neuropsychiatric side effects, such as severe depression, are common, primarily due to the loss of serotonergic cells. Identifying a region with fewer serotonergic neurons could potentially reduce these side effects. This study aimed to quantify the number of serotonergic neurons in the STN and GPi. Both regions were analyzed using hematoxylin and eosin staining and immunohistochemistry. The GPi exhibited a significantly lower number and H-score of serotonergic neurons than the STN. Within the STN, the number and H-score of serotonergic neurons were higher in the medial aspect than in the lateral aspect. Three different types of neurons, large and small, were observed. In STN, large neurons were concentrated in the center and small neurons in the periphery. This distribution was not observed in GPi. In addition, the concentration of the serotonergic neurons is less in GPi. These findings suggest that the GPi may be a safer target region, potentially reducing the incidence of post-DBS depression.

RESUMEN

Agyrophilic grains (AGs) are age-related limbic-predominant lesions in which four-repeat tau is selectively accumulated. Because previous methodologically heterogeneous studies have demonstrated inconsistent findings on the relationship between AGs and dementia, whether AGs affect cognitive function remains unclear. To address this question, we first comprehensively evaluated the distribution and quantity of Gallyas-positive AGs and the severity of neuronal loss in the limbic, neocortical, and subcortical regions in 30 cases of pure argyrophilic grain disease (pAGD) in Braak stages I-IV and without other degenerative diseases, and 34 control cases that had only neurofibrillary tangles with Braak stages I-IV and no or minimal Aß deposits. Then, we examined whether AGs have independent effects on neuronal loss and dementia by employing multivariate ordered logistic regression and binomial logistic regression. Of 30 pAGD cases, three were classified in diffuse form pAGD, which had evident neuronal loss not only in the limbic region but also in the neocortex and subcortical nuclei. In all 30 pAGD cases, neuronal loss developed first in the amygdala, followed by temporo-frontal cortex, hippocampal CA1, substantia nigra, and finally, the striatum and globus pallidus with the progression of Saito AG stage. In multivariate analyses of 30 pAGD and 34 control cases, the Saito AG stage affected neuronal loss in the amygdala, hippocampal CA1, temporo-frontal cortex, striatum, globus pallidus, and substantia nigra independent of the age, Braak stage, and limbic-predominant age-related TDP-43 encephalopathy (LATE-NC) stage. In multivariate analyses of 23 pAGD and 28 control cases that lacked two or more lacunae and/or one or more large infarctions, 100 or more AGs per × 400 visual field in the amygdala (OR 10.02, 95% CI 1.12-89.43) and hippocampal CA1 (OR 12.22, 95% CI 1.70-87.81), and the presence of AGs in the inferior temporal cortex (OR 8.18, 95% CI 1.03-65.13) affected dementia independent of age, moderate Braak stages (III-IV), and LATE-NC. Given these findings, the high density of limbic AGs and the increase of AGs in the inferior temporal gyrus may contribute to the occurrence of dementia through neuronal loss, at least in cases in a low to moderate Braak stage.

Asunto(s)

Demencia , Neocórtex , Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Demencia/patología , Neocórtex/patología , Sistema Límbico/patología , Persona de Mediana Edad , Ovillos Neurofibrilares/patología , Sustancia Negra/patología , Globo Pálido/patología , Enfermedades Neurodegenerativas/patología

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Background: Dysphagia can involve any structure from the mouth to the lower esophageal sphincter. The etiologies vary from benign causes to malignant lesions. There is dearth of data regarding dysphagia in our population. Methods: A total of 208 patients with complaints of dysphagia were screened for the study. After ruling out neurological/local oropharyngeal causes of dysphagia, 200 patients with suspected esophageal dysphagia (ED) were recruited in the study. Dysphagia was graded as per the dysphagia scoring system. All patients underwent upper gastro-intestinal endoscopy and were evaluated for the presence of mechanical and non-mechanical causes of ED. Results: The mean age of patients with dysphagia was 53.8 ± 15.4 years. with males and females being 82 and 118, respectively. The mean duration of the symptom was 7.2 ± 10.6 months (median 3 months). Ninety-eight patients (49%) having dysphagia were in the age group of 56-65 years. The dysphagia score was 0 among 58, and 4 among 26 subjects. Foreign body sensation was the most frequent chief complaint in 90 (45%) patients. Ninety-six (48%) and 104 (52%) patients had mechanical and non-mechanical causes of dysphagia, respectively. Among mechanical causes of dysphagia, 68 patients (70.8%) had esophageal growth and 28 (29.2%) had esophageal stricture. Sixty-seven patients had squamous cell carcinoma. Among non-mechanical causes, 50 (48.1%) had globus sensation, 24 (23.1%) had hiatus hernia, and 16 (15.4%) functional dysphagia. Conclusion: Dysphagia is a common problem with varied etiologies. The esophageal growth and globus sensation are among the predominant causes of ED. We stress that all patients of dysphagia must be meticulously investigated.

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Keratan sulfate (KS) is a proteoglycan secreted in the fetal brain astrocytes and radial glia into extracellular parenchyma as granulofilamentous deposits. KS surrounds neurons except dendritic spines, repelling glutamatergic and facilitating GABAergic axons. The same genes are expressed in both neuroblast migration and axonal growth. This study examines timing of KS during morphogenesis of some normally developing human fetal forebrain structures. Twenty normal human fetal brains from 9-41 weeks gestational age were studied at autopsy. KS was examined by immunoreactivity in formalin-fixed paraffin sections, plus other markers including synaptophysin, S-100ß protein, vimentin and nestin. Radial and tangential neuroblast migratory pathways from subventricular zone to cortical plate were marked by KS deposits as early as 9wk GA, shortly after neuroblast migration initiated. During later gestation this reactivity gradually diminished and disappeared by term. Long axonal fascicles of the internal capsule and short fascicles of intrinsic bundles of globus pallidus and corpus striatum also appeared as early as 9-12wk, as fascicular sleeves before axons even entered. Intense KS occurs in astrocytic cytoplasm and extracellular parenchyma at 9wk in globus pallidus, 15wk thalamus, 18wk corpus striatum, 22wk cortical plate, and hippocampus postnatally. Corpus callosum and anterior commissure do not exhibit KS at any age. Optic chiasm shows reactivity at the periphery but not around intrinsic subfasciculi. We postulate that KS forms a chemical template for many long and short axonal fascicles before axons enter and neuroblast migratory pathways at initiation of migration. Cross-immunoreactivity with aggrecan may render difficult molecular distinction.

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Carbon monoxide poisoning is one of the leading causes of mortality and morbidity by poisoning in the world. Signs and symptoms are nonspecific and related to impaired oxygen delivery to tissues, with the brain being the most affected organ due to its high oxygen demand. CO-Hb is a poor indicator of severity and long-term outcome, with clinicians relying more on clinical features such as level of consciousness and need for intubation, organ dysfunction and shock and also pH level. A 45-year-old female was found unconscious in her home with the fireplace lit and smoke all over the house. She was last seen well 18 hours before. She was brought to the emergency department and was admitted to the ICU in coma and cardiogenic shock, with a metabolic acidosis with hyperlactacidemia and a CO-Hb level of 15.5%. Laboratorial investigation revealed hepatic cytolysis, acute renal failure, rhabdomyolysis and a troponin I level of 338 ng/L. ECG showed no acute myocardial ischemia. Echocardiogram revealed diffuse hypokinesia with an ejection fraction of 25%. Head CT scan showed bilateral and symmetrical hypodensities of the globus pallidus. The patient underwent hyperbaric oxygen treatment with full neurological and cardiac recovery, allowing extubation 48 hours after admission. This rare severe case of coma due to carbon monoxide intoxication with globus pallidus injury and cardiogenic shock was successfully treated with hyperbaric oxygen, showing that it can be the right treatment choice in these cases, with an excellent impact on neurological and cardiac outcome.

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L'intoxication au CO est une des causes principales de décès par empoisonnement dans le monde. Les signes, non spécifiques, sont dus à l'hypoxie cellulaire et le cerveau est le plus souvent atteint en raison de sa consommation d'oxygène élevée. Le taux d'HbCO est un indice peu fiable de la gravité initiale et du risque de séquelles si bien que l'on préfère se baser sur la clinique (conscience, nécessité d'intubation, dysfonctions d'organe, choc) et le pH sanguin. Une femme de 45 ans a été trouvée inconsciente à son domicile entièrement enfumé, cheminée allumée. Le dernier contact remontait à 18 heures. Elle a été hospitalisée en réanimation en coma et choc cardiogénique, avec une acidose lactique et une HbCO à 15,5%. La biologie retrouvait une cytolyse hépatique, une insuffisance rénale aiguë, une rhabdomyolyse et une troponine I à 338 ng/L. L'ECG ne trouvait pas d'ischémie, l'échocardiographie objectivait une hypokinésie globale et évaluait la fraction d'éjection à 25%. La TDM cérébrale montrait une hypodensité pallidale bilatérale. L'oxygénothérapie hyperbare (OHB) a permis une récupération neurologique et cardiaque complètes, permettant l'extubation à h48. Cette récupération complète après OHB confirme qu'il peut s'agir du traitement idoine des intoxications graves au CO, avec un excellent impact sur les devenirs cardiaque et neurologique.