RESUMEN

There is a clear need for experts with the requisite knowledge and experience to offer medicolegal opinions pertaining to various neuropsychiatric conditions. There is also an important distinction between clinical and medicolegal roles, and the need for training and expertise applicable to forensic assessment. But there remain few available experts with credentials spanning neuropsychiatry and forensic assessment. This creates a dilemma whereby parties involved in litigation featuring neuropsychiatric illness or injury are frequently forced to choose between experts with either knowledge and skills applicable to neuropsychiatric conditions or experts with skills and experience applicable to forensic assessment. Either choice introduces risk. Whether flawed medicolegal opinions are a consequence of deficient medical knowledge or an inadequate forensic evaluation process, the result remains the same, with triers of fact potentially being exposed to problematic testimony. There is, however, a more fundamental problem that implicates patient care more broadly: spurious dichotomies created by the historical segregation of psychiatry and neurology. Optimizing clinical care for patients with neuropsychiatric conditions, improving medical education in support of such care, and enabling forensic neuropsychiatric assessment must then start with more proactive efforts to reintegrate psychiatry and neurology.

Asunto(s)

RESUMEN

This study investigates audiogenic epilepsy in Krushinsky-Molodkina (KM) rats, questioning the efficacy of conventional EEG techniques in capturing seizures during animal restraint. Using a wireless EEG system that allows unrestricted movement, our aim was to gather ecologically valid data. Nine male KM rats, prone to audiogenic seizures, received implants of wireless EEG transmitters that target specific seizure-related brain regions. These regions included the inferior colliculus (IC), pontine reticular nucleus, oral part (PnO), ventrolateral periaqueductal gray (VLPAG), dorsal area of the secondary auditory cortex (AuD), and motor cortex (M1), facilitating seizure observation without movement constraints. Our findings indicate that targeted neural intervention via electrode implantation significantly reduced convulsive seizures in approximately half of the subjects, suggesting therapeutic potential. Furthermore, the amplitude of brain activity in the IC, PnO, and AuD upon audiogenic stimulus onset significantly influenced seizure severity and nature, highlighting these areas as pivotal for epileptic propagation. Severe cases exhibited dual waves of seizure generalization, indicative of intricate neural network interactions. Distinctive interplay between specific brain regions, disrupted during convulsive activity, suggests neural circuit reconfiguration in response to escalating seizure intensity. These discoveries challenge conventional methodologies, opening avenues for novel approaches in epilepsy research and therapeutic interventions.

Asunto(s)

Asunto(s)

RESUMEN

Behavioral neurology & neuropsychiatry (BNNP) fellowships are accredited by the United Council for Neurologic Subspecialties (UCNS). Programs cover the UCNS-recommended topics differently. A curriculum accessible to all fellowships would standardize education and identify gaps in topics that are less well covered across programs. The purpose of the present needs assessment was to inform the development of the Online Core Curriculum and Mastery: BNNP (OCCAM-BNNP), a website for all UCNS-accredited BNNP programs. Program directors and fellows were surveyed to learn how well topics are covered and identify educational gaps, or specific topics on the UCNS website that are less well represented among programs. Thirty-seven fellowship program directors listed on the UCNS website were invited to take the survey and forward it to both current fellows (graduating in 2021) and recent graduates (graduated from 2015 to 2020). There were 29 responses from 37 programs. Of the 34 topics that respondents rated on a 1-5 Likert scale (from "not covered" to "completely covered"), 15 of 34 (44%) were identified as having >40% of responses as mostly "not covered," "incompletely covered," or "partially covered." Ninety-seven percent of respondents affirmed that it would be useful to have a free web-based resource for BNNP education. Slightly under one-half of all BNNP topics were not well covered. A survey was undertaken to identify and fill the educational gaps indicated by fellowship directors and fellows, and the OCCAM-BNNP website was developed as a repository for relevant content, providing a resource that many BNNP clinicians would find useful.

Asunto(s)

RESUMEN

Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a neuropathologically-defined disease that affects 40% of persons in advanced age, but its associated neurological syndrome is not defined. LATE neuropathological changes (LATE-NC) are frequently comorbid with Alzheimer's disease neuropathologic changes (ADNC). When seen in isolation, LATE-NC have been associated with a predominantly amnestic profile and slow clinical progression. We propose a set of clinical criteria for a limbic-predominant amnestic neurodegenerative syndrome (LANS) that is highly associated with LATE-NC but also other pathologic entities. The LANS criteria incorporate core, standard and advanced features that are measurable in vivo, including older age at evaluation, mild clinical syndrome, disproportionate hippocampal atrophy, impaired semantic memory, limbic hypometabolism, absence of neocortical degenerative patterns and low likelihood of neocortical tau, with degrees of certainty (highest, high, moderate, low). We operationalized this set of criteria using clinical, imaging and biomarker data to validate its associations with clinical and pathologic outcomes. We screened autopsied patients from Mayo Clinic (n = 922) and ADNI (n = 93) cohorts and applied the LANS criteria to those with an antemortem predominant amnestic syndrome (Mayo, n = 165; ADNI, n = 53). ADNC, ADNC/LATE-NC and LATE-NC accounted for 35%, 37% and 4% of cases in the Mayo cohort, respectively, and 30%, 22%, and 9% of cases in the ADNI cohort, respectively. The LANS criteria effectively categorized these cases, with ADNC having the lowest LANS likelihoods, LATE-NC patients having the highest likelihoods, and ADNC/LATE-NC patients having intermediate likelihoods. A logistic regression model using the LANS features as predictors of LATE-NC achieved a balanced accuracy of 74.6% in the Mayo cohort, and out-of-sample predictions in the ADNI cohort achieved a balanced accuracy of 73.3%. Patients with high LANS likelihoods had a milder and slower clinical course and more severe temporo-limbic degeneration compared to those with low likelihoods. Stratifying ADNC/LATE-NC patients from the Mayo cohort according to their LANS likelihood revealed that those with higher likelihoods had more temporo-limbic degeneration and a slower rate of cognitive decline, and those with lower likelihoods had more lateral temporo-parietal degeneration and a faster rate of cognitive decline. The implementation of LANS criteria has implications to disambiguate the different driving etiologies of progressive amnestic presentations in older age and guide prognosis, treatment, and clinical trials. The development of in vivo biomarkers specific to TDP-43 pathology are needed to refine molecular associations between LANS and LATE-NC and precise antemortem diagnoses of LATE.

RESUMEN

Mindfulness is a state of awareness characterized by open and non-judgmental recognition of thoughts and sensations and an ability to resist the usual wandering of an individual's attention. Usually achieved by meditation, mindfulness is recognized as a treatment for chronic pain. Evidence, thus far, has been characterized by poor quality trials and mixed results, but a growing body of research is further investigating its effectiveness. Despite inconclusive evidence, the inherent difficulties of mindfulness research, and problems of accessibility in rural settings, mindfulness meditation is an emerging treatment strategy for many chronic pain patients. This report presents the case of a patient admitted to a rural hospital in New South Wales, whose quality of life was severely impacted by chronic pain.

RESUMEN

In this systematic review, we evaluate the safety, tolerability, and immunogenicity of vaccination efforts against Alzheimer's disease (AD) in human subjects from both ongoing and completed vaccination trials. Databases like PubMed, Embase, and Scopus were used to identify relevant articles on completed vaccination trials whereas the clinicaltrials.gov database was used for identifying ongoing clinical trials for vaccination against AD in humans until January 2022. Only interventional randomized or non-randomized clinical trials which reported on the safety and immunogenicity of vaccine against AD in humans were included. Cochrane risk of bias tool-2 (RoB-2) or risk of bias in non-randomized studies- of intervention (ROBINS-I) was used for risk of bias assessment as appropriate. A narrative descriptive synthesis of the findings was done. Sixteen randomized/non-randomized clinical trials (phase I: six and phase II: 10) for seven different types of vaccines against AD were identified comprising a total of 2080 participants. Apart from the development of meningoencephalitis in 6% of patients receiving AN1792 in an interrupted phase II trial, the rest of the trial reported promising results on the safety and immunogenicity of vaccines. While only a subset of reported adverse events was treatment related, none of the fatalities reported during the trial were considered related to vaccine administration. The serological response rate ranged from 100% (4/16 trials) to 19.7% in an interrupted trial. Although current trials show promising results, adequately powered phase III studies are needed to conclusively establish the safety, immunogenicity and therapeutic efficacy of vaccines.

RESUMEN

Dysexecutive Alzheimer's disease (dAD) manifests as a progressive dysexecutive syndrome without prominent behavioral features, and previous studies suggest clinico-radiological heterogeneity within this syndrome. We uncovered this heterogeneity using unsupervised machine learning in 52 dAD patients with multimodal imaging and cognitive data. A spectral decomposition of covariance between FDG-PET images yielded six latent factors ("eigenbrains") accounting for 48% of variance in patterns of hypometabolism. These eigenbrains differentially related to age at onset, clinical severity, and cognitive performance. A hierarchical clustering on the eigenvalues of these eigenbrains yielded four dAD subtypes, i.e. "left-dominant," "right-dominant," "bi-parietal-dominant," and "heteromodal-diffuse." Patterns of FDG-PET hypometabolism overlapped with those of tau-PET distribution and MRI neurodegeneration for each subtype, whereas patterns of amyloid deposition were similar across subtypes. Subtypes differed in age at onset and clinical severity where the heteromodal-diffuse exhibited a worse clinical picture, and the bi-parietal had a milder clinical presentation. We propose a conceptual framework of executive components based on the clinico-radiological associations observed in dAD. We demonstrate that patients with dAD, despite sharing core clinical features, are diagnosed with variability in their clinical and neuroimaging profiles. Our findings support the use of data-driven approaches to delineate brain-behavior relationships relevant to clinical practice and disease physiology.

Asunto(s)

RESUMEN

Neurobehavioral and neuropsychiatric symptoms are highly prevalent among individuals diagnosed with cognitive impairment or dementia and impact the quality of life for patients and caregivers alike. Diagnosis and management of these conditions (including primarily depression, anxiety, apathy, psychosis, agitation, and aggression) is crucial to optimal patient care outcomes in clinical practice. The present article provides a practical review of diagnostic approaches and management strategies for behavioral and neuropsychiatric disorders arising in patients with cognitive impairment, up to and including dementia.

Asunto(s)

RESUMEN

Creutzfeldt-Jakob disease (CJD) is a rare, uniformly fatal prion disease. Although CJD commonly presents with rapidly progressive dementia, ataxia, and myoclonus, substantial clinicopathological heterogeneity is observed in clinical practice. Unusual and predominantly cognitive clinical manifestations of CJD mimicking common dementia syndromes are known to pose as an obstacle to early diagnosis and prognosis. We report a series of three patients with probable or definite CJD (one male and two females, ages 52, 58 and 68) who presented to our tertiary behavioral neurology clinic at Mayo Clinic Rochester that met criteria for a newly defined progressive dysexecutive syndrome. Glucose hypometabolism patterns assessed by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) strongly resembled those of dysexecutive variant of Alzheimer's disease (dAD). However, magnetic resonance imaging (MRI) demonstrated restricted diffusion in neocortical areas and deep nuclei, while cerebrospinal fluid biomarkers indicated abnormal levels of 14-3-3, total-tau, and prion seeding activity (RT-QuIC), establishing the diagnosis of CJD. Electroencephalogram (EEG) additionally revealed features previously documented in atypical cases of CJD. This series of clinical cases demonstrates that CJD can present with a predominantly dysexecutive syndrome and FDG-PET hypometabolism typically seen in dAD. This prompts for the need to integrate information on clinical course with multimodal imaging and fluid biomarkers to provide a precise etiology for dementia syndromes. This has important clinical implications for the diagnosis and prognosis of CJD in the context of emerging clinical characterization of progressive dysexecutive syndromes in neurodegenerative diseases like dAD.

Asunto(s)

RESUMEN

INTRODUCTION: Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers are promising tools to help identify the underlying pathology of neurocognitive disorders. In this manuscript, we report our experience with AD CSF biomarkers in 262 consecutive patients in a tertiary care memory clinic. METHODS: We retrospectively reviewed 262 consecutive patients who underwent lumbar puncture (LP) and CSF measurement of AD biomarkers (Aß1-42, total tau or t-tau, and p-tau181). We studied the safety of the procedure and its impact on patient's diagnosis and management. RESULTS: The LP allowed to identify underlying AD pathology in 72 of the 121 patients (59%) with early onset amnestic mild cognitive impairment (aMCI) with a high probability of progression to AD; to distinguish the behavioral/dysexecutive variant of AD from the behavioral variant of frontotemporal dementia (bvFTD) in 25 of the 45 patients (55%) with an atypical neurobehavioral profile; to identify AD as the underlying pathology in 15 of the 27 patients (55%) with atypical or unclassifiable primary progressive aphasia (PPA); and to distinguish AD from other disorders in 9 of the 29 patients (31%) with psychiatric differential diagnoses and 19 of the 40 patients (47%) with lesional differential diagnoses (normal pressure hydrocephalus, encephalitis, prion disease, etc.). No major complications occurred following the LP. INTERPRETATION: Our results suggest that CSF analysis is a safe and effective diagnostic tool in select patients with neurocognitive disorders. We advocate for a wider use of this biomarker in tertiary care memory clinics in Canada.

Asunto(s)

RESUMEN

PURPOSE: We aimed to investigate: (1) the clinical, diagnostic value of a written discourse task, and (2) the relationship between executive functions and written discourse within the spectrum of individuals with mild cognitive impairment (MCI). METHOD: To determine whether written discourse performance predicts clinical course among individuals with MCI, we retrospectively classified individuals with MCI as converters (N = 26) who were later diagnosed with dementia or as a stable MCI group (N = 45). We quantified core word measures from written discourse samples obtained from the Cookie Theft picture description task. RESULT: Written discourse measures differentiated converters from the stable MCI group. Converters produced a fewer number of core words than the stable MCI group. A measure of executive function significantly predicted performance on the production of core words in written discourse for the converters. In a multivariable regression, production of core words remained the only explanatory variable closely associated with the progression to dementia in MCI. CONCLUSION: Written discourse tasks can predict the likelihood of MCI progressing to dementia, independently of recall and an executive function measure. Correlational results suggest that written discourse performance was associated with executive function as measured by the Trail Making Test. Our findings emphasize the usefulness of including written discourse tasks in language assessment batteries targeting preclinical dementia populations.

Asunto(s)

RESUMEN

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been associated with neuropsychiatric complications ranging from new-onset psychosis to delirium, dysexecutive syndromes, catatonia, and akinetic mutism (AM). AM can be conceptualized as a disorder of motivation wherein patients exhibit a loss of speech and spontaneous movement, owing to disruption of underlying frontal-subcortical circuits. OBJECTIVES: The objectives of this study were to review the concept and differential diagnosis of AM, as well as the clinical literature on AM in COVID-19 and discuss potential implications for underlying functional neuroanatomy and mechanistic pathways, as well as clinical management. METHODS: A narrative literature review was performed using PubMed querying published articles for topics associated with AM and its occurrence in COVID-19. RESULTS: AM has been described in case reports and a prospective cohort study of patients with COVID with neurological complaints. Three COVID-19 AM subgroups can be distinguished, including individuals with severe respiratory illness, those with meningoencephalitis, and those with delirium and pre-existing neuropsychiatric illness. Electrophysiology and functional imaging suggest COVID-19 AM may result from underlying frontal lobe dysfunction and disruption of associated distributed circuits subserving goal-directed behavior. Distinctive combinations of pathophysiological mechanisms may be at play in the different subgroups of COVID-19 AM cases. CONCLUSION: AM has been described in association with COVID-19 and may manifest in clinically heterogenous subgroups with distinct underlying mechanisms. The diagnosis of AM and evaluation of potential etiologies can be complex. The occurrence of AM contributes evidence to the hypothesis of frontal lobe dysfunction in COVID-19.

Asunto(s)

RESUMEN

A patient diagnosed with developmental delay, intellectual disability, and autistic and obsessive-compulsive symptoms was found to have a posterior fossa arachnoid cyst (PFAC) compressing the cerebellum. The patient was referred to our Ataxia Unit for consideration of surgical drainage of the cyst to improve his clinical constellation. This scenario led to an in-depth analysis including a literature review, functional resting-state MRI analysis of our patient compared to a group of controls, and genetic testing. While it is reasonable to consider that there may be a causal relationship between PFAC and neurodevelopmental or psychiatric symptoms in some patients, there is also a nontrivial prevalence of PFAC in the asymptomatic population and a significant possibility that many PFAC are incidental findings in the context of primary cognitive or psychiatric symptoms. Our functional MRI analysis is the first to examine brain function, and to report cerebellar dysfunction, in a patient presenting with cognitive/psychiatric symptoms found to have a structural abnormality compressing the cerebellum. These neuroimaging findings are inherently limited due to their correlational nature but provide unprecedented evidence suggesting that cerebellar compression may be associated with cerebellar dysfunction. Exome gene sequencing revealed additional etiological possibilities, highlighting the complexity of this field of cerebellar clinical and scientific practice. Our findings and discussion may guide future investigations addressing an important knowledge gap-namely, is there a link between cerebellar compression (including arachnoid cysts and possibly other forms of cerebellar compression such as Chiari malformation), cerebellar dysfunction (including fMRI abnormalities reported here), and neuropsychiatric symptoms?

Asunto(s)

RESUMEN

A 62-year-old male presented to hospital with acute aphasia. His past medical history was significant for a previous left middle cerebral artery stroke, from which he fully recovered, hypertension, dyslipidemia, coronary artery disease, one episode of atrial fibrillation postoperatively, and thalidomide exposure in utero. Although initially he was thought to be aphasic, on further examination, he demonstrated significant abulia. His level of consciousness was normal, and neurological examination was otherwise unremarkable. A CT angiogram of the head and neck was performed. The patient was not a candidate for acute therapy, as he had established stroke on imaging, and the time of onset was unclear.

Asunto(s)

RESUMEN

For British neurologists, one case was considered to represent significant evidence regarding the organization of language in the brain in the second half of the 19th century. The interpretation of its significance was based on repeated standard clinical assessment of behavioral deficits, the use of a psychological model of processing, and lesion localization to inform understanding of clinic-pathological correlation. The aphasic deficits experienced by a single case were observed and recorded by London neurologist Henry Charlton Bastian (1837-1915) over a period of 18 years and used as a demonstration of clinico-pathological reasoning regarding language function. This case was well documented in many of Bastian's publications; presented in teaching demonstrations; included in discussions at medical society meetings and public lectures; and reported widely in the medical press. When this patient died, the autopsy findings were added to the extensive record of his language deficits. Some aspects of the size and site of the lesion were consistent with Bastian's clinical predictions arising from his model of language processing, while others presented more of a paradox. This single case was a significant source of discussion and reflection in the medical community throughout the second half of the 19th century. Examination of various interpretations of this case reveal the assumptions regarding the functional architecture of language processing and more general theoretical considerations of how evidence from cases of acquired neurogenic aphasia can be employed in developing such models. This long view into a historical case sheds light on the challenges of clinic-pathological correlation methods in the understanding of localization of language functions which remain today.

RESUMEN

Neurology and psychiatry share common historical origins and rely on similar tools to study brain disorders. Yet the practical integration of medical and scientific approaches across these clinical neurosciences remains elusive. Although much has been written about the need to incorporate emerging systems-level, cellular-molecular, and genetic-epigenetic advances into a science of mind for psychiatric disorders, less attention has been given to applying clinical neuroscience principles to conceptualize neurologic conditions with an integrated neurobio-psycho-social approach. In this perspective article, the authors briefly outline the historically interwoven and complicated relationship between neurology and psychiatry. Through a series of vignettes, the authors then illustrate how some traditional psychiatric conditions are being reconceptualized in part as disorders of neurodevelopment and awareness. They emphasize the intersection of neurology and psychiatry by highlighting conditions that cut across traditional diagnostic boundaries. The authors argue that the divide between neurology and psychiatry can be narrowed by moving from lesion-based toward circuit-based understandings of neuropsychiatric disorders, from unidirectional toward bidirectional models of brain-behavior relationships, from exclusive reliance on categorical diagnoses toward transdiagnostic dimensional perspectives, and from silo-based research and treatments toward interdisciplinary approaches. The time is ripe for neurologists and psychiatrists to implement an integrated clinical neuroscience approach to the assessment and management of brain disorders. The subspecialty of behavioral neurology & neuropsychiatry is poised to lead the next generation of clinicians to merge brain science with psychological and social-cultural factors. These efforts will catalyze translational research, revitalize training programs, and advance the development of impactful patient-centered treatments.

Asunto(s)

RESUMEN

The behavioral variant of frontotemporal dementia is usually a sporadic and progressive neurodegenerative disorder. Here, we report the subacute onset of a frontotemporal dementia phenotype with a treatable etiology. The patient has a history of rheumatoid arthritis, episcleritis, and thyroid eye disease on immunosuppressive therapy. He experienced a rapid personality change, including inappropriate behavior, which suggested frontotemporal dementia. Results of imaging and neuropsychological testing also suggested frontotemporal dementia. Because of his autoimmune diseases and unusually short onset of symptoms, serum paraneoplastic panel and cerebrospinal fluid were analyzed and revealed elevated P/Q- and N-type calcium channel antibodies. Treatment with therapeutic plasma exchange resulted in a rapid improvement of his behavior and cognition. This case suggests that there may be some treatable causes of frontotemporal dementia symptomatology, that is, paraneoplastic antibodies. In the context of atypical features of frontotemporal dementia, practitioners should maintain a high index of suspicion.