Core Clinical Features Research Articles

Chinese patients with hereditary spastic paraplegias (HSPs): a protocol for a hospital-based cohort study

IntroductionHereditary spastic paraplegias (HSPs) are uncommon but not rare neurodegenerative diseases. More than 100 pathogenic genes and loci related to spastic paraplegia symptoms have been reported. HSPs have the same...

18F-FDG PET/CT and 99mTc-TRODAT Scan Findings in the Variants of Progressive Supranuclear Palsy and Correlation With Clinical Findings.

The aim of this study is to elucidate the patterns of characteristic hypometabolism on 18F-Fluoro Deoxy-glucose (18F-FDG) Positron Emission Tomography/Computed Tomography (PET/CT) in the variants of Progressive supranuclear palsy (PSP) and its correlation with their core clinical features. A retrospective analysis of 88 subjects with clinically suspected PSP was done. An institutional informed consent to participate in the study was taken from all the subjects. All the subjects had undergone a prior 99mTechnetium labeled Tropane derivative of dopamine transporter Single Photon Emission Computed Tomography (99mTc TRODAT-1 SPECT) study and had abnormal scans to confirm degenerative parkinsonism. The subjects were clinically examined by the neurologists using the Progressive Supranuclear Palsy Rating Scale proposed by the Movement Disorder Society and were further clinically segregated into eight subtypes. All the included subjects further underwent a detailed clinical analysis to obtain their individual Schwab and England activities of daily living scale and Modified Hoehn and Yahr staging by a neurologist. All the subjects underwent 18F-FDG PET/CT scan after adequate preparation. The scans were analyzed both qualitatively (visually) and quantitatively using Statistical Parametric Mapping. The frontal, limbic, and sensorimotor cortices represented the common areas of hypometabolism among all the subtypes of PSP. The subcortical regions showing the most significant hypometabolism were the thalami, mid-brain, nucleus accumbens, caudate, globus pallidus, and putamen in descending order. Multiple cortical and subcortical regions of hypometabolism were identified in different subtypes of PSP. The characteristic patterns of hypometabolism observed in the different subgroups were more apparent on quantification and based on visual analysis alone, it may not be possible to differentiate the different subtypes of PSP. A good correlation was seen between some of the core clinical features and hypometabolic clusters.

Pediatric Autoimmune encephalitis: Experience from a Tertiary Care Hospital in Bangladesh

Background: Autoimmune encephalitis (AIE) are distinct group of encephalitis where production of autoimmune antibody causes neuroinflammation. The core clinical features are encephalopathy, psychiatric disorder, movement disorder and seizure. The investigation and treatment modalities are different from that of infectious encephalitis. There are limited studies in pediatric population in particularly in developing country like Bangladesh. Thus this study has been done to describe patients with AIE from a tertiary care hospital.
 Method: This is a retrospective study done in children of 1-16 year from January 2018 to December 2019. AIE was diagnosed on the basis of clinical, electrographic and neuroimaging features and was confirmed with detection of autoantibody in CSF. Treatment was given according to the published literature with immunotherapy mainly.
 Results: Total 15 children were studied, 14 patients were antiNMDAR encephalitis and 1 was antiMOG antibody syndrome. Mean age was 5.98 and 4.5 year respectively. Seizure was the most common clinical feature, mostly focal in nature. Other manifestations were movement disorder, psychiatric disorder, loss of consciousness etc. Most of the patients had abnormal EE, focal epileptic discharge being the commonest. Eight out of 15 had abnormal MRI of brain. Cortical hyperintensity was important feature located mostly in temporal region. In the case of antiMOG antibody syndrome there was demyelinating lesion in multiple areas. Cornerstone of the treatment was mostly combination immunotherapy with IV methylprednisolone and IV immunoglobulin followed by oral steroid. Majority of the patients showed improvement however 3 patients had complete recovery. Complications observed were epilepsy, speech disorder, cognitive disorder, behavioural disorder, ataxia and visual impairment.
 Conclusion: Timely diagnosis and prompt treatment of AIE is very important as proper treatment can cause significant improvement.

Survey outcomes on neuropsychological testing in posterior cortical atrophy

AbstractBackgroundPosterior cortical atrophy (PCA) is a clinico‐radiological syndrome mostly commonly underpinned by Alzheimer’s disease (AD) pathology and has been referred to as the most common atypical AD clinical phenotype. PCA consensus classification criteria emphasize core clinical and cognitive features comprising visual and other posterior features in contrast to relatively spared episodic memory, language, executive functions and behavior (Crutch et al., Alzheimers Dement., 2017). However, posterior features are less commonly evaluated in standard neuropsychological batteries compared to other domains, possibly contributing towards common diagnostic delays, and memory and executive function tests that have visual or numerical demands are particularly challenging in the evaluation of relatively spared functions. Standardization of the neuropsychological assessment of PCA is vital for multi‐center research collaborations, the development of outcome measures for future clinical trials, and better characterization of the extent of overlap with related neurodegenerative syndromes. Experts were surveyed regarding their practice preferences in the assessment of the PCA syndrome.MethodThe membership of the ISTAART Atypical Alzheimer’s Disease Professional Interest Area was invited to participate in a survey examining preferences for measures employed in the assessment of the visual and core cognitive features of PCA, as defined by the 2017 PCA consensus criteria.ResultAtypical AD PIA members included those with backgrounds in neurology, neuropsychology, psychiatry, geriatric medicine and clinical research (respondents N=55). Most commonly assessed features were space perception deficits, simultanagnosia and constructional apraxia, followed by dominant parietal features and alexia. Object perception deficits and early visual functions were less frequently assessed. A subset of respondents included preferred tests to evaluate global functioning and relatively spared features, including example measures less susceptible to visual dysfunction.ConclusionVariations in assessing PCA features are considered with implications for characterizing the extent of AD phenotypic heterogeneity, including proposed ventral and caudal PCA presentations. Results will inform future work to develop consensus recommendations for a short clinical PCA battery and an extended, formal PCA battery, in order to promote capacity for multi‐center studies and advance the development of appropriate outcome measures in trials enrolling patients with PCA and/or prominent posterior dysfunction.

Superiority of the Dépistage Cognitif de Québec (DCQ) over the Montreal Cognitive Assessment in differentiating dementia with Lewy bodies from Alzheimer's disease

AbstractBackgroundRecent criteria for dementia with Lewy bodies (DLB) are available but early diagnosis remains a challenge since few cases display all core clinical features. Discriminating Alzheimer’s disease (AD) from DLB is also complex given the overlap in cognitive dysfunctions between the two conditions. We aimed to study their differential neurocognitive profile using the Dépistage Cognitif de Québec (DCQ), a newly developed screening tool for atypical dementias. Moreover, we explored whether the DCQ was superior to the Montreal Cognitive Assessment (MoCA) in identifying DLB.MethodsWe compared the performance of 15 patients with DLB to 72 patients with the amnestic variant of AD on the five indexes of the DCQ (Memory, Visuospatial, Executive, Language and Behavioral) as well as the MoCA test, administered in random order. Participants were recruited prospectively in a tertiary memory clinic and diagnosed according to current clinical criteria for AD and DLB.ResultsThere were no significant differences between the groups in age (AD: 72.97; DCL: 72.13) or level of education (AD: 12.88; DCL: 12.40). Mean Total MoCA score was similar across conditions (19.01 vs 20.00, p = .54) whereas the Total DCQ score revealed a significant difference between AD and DLB (66.39 vs 72.60, p < .05) (Fig. 2). Further analyses showed superior Area Under the Curve for the DCQ (69.23%; moderately strong) over the MoCA (55.26%; weak) in discriminating DCL from AD (Fig. 1). Bivariate analyses on the DCQ and MOCA indexes were performed using Wilcoxon‐Mann‐Whitney tests. When compared to AD, DLB participants performed worse on the Visuospatial Index (5.04 vs 4.10, p < .05) (Fig. 4), particularly the visuospatial construction task (1.33 vs 0.67 p < .05) while AD participants were significantly more affected on the Memory Index (recall and recognition) (16.13 vs 24.73, p < .0001) (Fig. 3). The remaining DCQ indexes (Executive, Language and Behavioral) were similar between groups.ConclusionsOur data suggests that the DCQ may be a superior tool than the MoCA in distinguishing AD from DLB. The DCQ allowed better characterization of the neurocognitive profile between AD and DLB, where DLB preferentially affects visuospatial skills while AD targets memory abilities.

It Is Time to Study Overlapping Molecular and Circuit Pathophysiologies in Alzheimer's and Lewy Body Disease Spectra.

Alzheimer’s disease (AD) is the leading cause of dementia due to neurodegeneration and is characterized by extracellular senile plaques composed of amyloid β1–42 (Aβ) as well as intracellular neurofibrillary tangles consisting of phosphorylated tau (p-tau). Dementia with Lewy bodies constitutes a continuous spectrum with Parkinson’s disease, collectively termed Lewy body disease (LBD). LBD is characterized by intracellular Lewy bodies containing α-synuclein (α-syn). The core clinical features of AD and LBD spectra are distinct, but the two spectra share common cognitive and behavioral symptoms. The accumulation of pathological proteins, which acquire pathogenicity through conformational changes, has long been investigated on a protein-by-protein basis. However, recent evidence suggests that interactions among these molecules may be critical to pathogenesis. For example, Aβ/tau promotes α-syn pathology, and α-syn modulates p-tau pathology. Furthermore, clinical evidence suggests that these interactions may explain the overlapping pathology between AD and LBD in molecular imaging and post-mortem studies. Additionally, a recent hypothesis points to a common mechanism of prion-like progression of these pathological proteins, via neural circuits, in both AD and LBD. This suggests a need for understanding connectomics and their alterations in AD and LBD from both pathological and functional perspectives. In AD, reduced connectivity in the default mode network is considered a hallmark of the disease. In LBD, previous studies have emphasized abnormalities in the basal ganglia and sensorimotor networks; however, these account for movement disorders only. Knowledge about network abnormalities common to AD and LBD is scarce because few previous neuroimaging studies investigated AD and LBD as a comprehensive cohort. In this paper, we review research on the distribution and interactions of pathological proteins in the brain in AD and LBD, after briefly summarizing their clinical and neuropsychological manifestations. We also describe the brain functional and connectivity changes following abnormal protein accumulation in AD and LBD. Finally, we argue for the necessity of neuroimaging studies that examine AD and LBD cases as a continuous spectrum especially from the proteinopathy and neurocircuitopathy viewpoints. The findings from such a unified AD and Parkinson’s disease (PD) cohort study should provide a new comprehensive perspective and key data for guiding disease modification therapies targeting the pathological proteins in AD and LBD.

Area postrema syndrome in neuromyelitis optica spectrum disorder: diagnostic challenges and descriptive patterns

BackgroundAlthough area postrema syndrome (APS) is one of the core clinical features of neuromyelitis optic spectrum disorder (NMOSD), it is frequently misdiagnosed as gastrointestinal or systemic disorders. In this study, we describe the diagnostic challenges in NMOSD patients with APS and their characteristic clinical and radiological features. All patients who attended our university hospitals during the period from March 2019 to August 2020 with a diagnosis of NMOSD according to the latest diagnostic criteria were admitted and evaluated clinically, radiologically with gadolinium-enhanced brain and spinal MRI, measures of serum Anti-Aquaporin 4 (Anti-AQP4) and clinical status using the Expanded Disability Status Scale (EDSS) scores. APS was diagnosed if there was a history of intractable nausea, vomiting, or hiccups (INVH) that had lasted longer than 1 week with the exclusion of other etiologies, or less than 48 h if associated with a lesion in the dorsal medulla on MRI scan.ResultsTwenty out of 90 (22.2%) identified patients with a diagnosis of NMOSD had a history of unexplained intractable nausea, vomiting or hiccoughs lasting an average of 20 days. Seventeen patients were anti-Aquaporin 4 seropositive. Seven patients (35%) presented initially with isolated clinical features of APS and were diagnosed only after subsequent relapse. Patients with APS preceding other core clinical presentations (13 cases, 65%) were diagnosed after development of motor manifestations. All patients developed acute myelitis during the course of illness. Brain and spinal MRI scans showed that 13 had a linear lesion in the dorsal tegmentum of the medulla oblongata adjacent to the fourth ventricle. Otherwise, longitudinally extensive transverse myelitis was found in 80%, while 35% showed extension of the cord lesion to the AP.ConclusionsAPS as a core clinical characteristic of NMOSD is not a rare presentation as was previously thought and can occur in both AQP4-seropositive and seronegative NMOSD.

Reaching people soon after a traumatic event: an exploratory observational feasibility study of recruitment in the emergency department to deliver a brief behavioral intervention via smartphone to prevent intrusive memories of trauma

BackgroundThe current study explored how to recruit patients soon after a traumatic event, to deliver a novel intervention in a new emergency department in Sweden. This brief behavioral intervention aims to prevent intrusive memories and is delivered soon after trauma in the emergency department. In the UK, it has shown promising results. Traumatic events resulting in admission to the emergency department (e.g., road traffic accidents) may result in subsequent mental health problems such as post-traumatic stress disorder, where intrusive memories of the trauma constitute a core clinical feature. Early interventions that prevent intrusive memories after psychological trauma are lacking.Specific aims were to explore identification of eligible patients (aim 1), fitting in with emergency department staff routines to deliver the study protocol (aim 2), and using the patients’ own smartphones to deliver intervention/control task (aim 3). Two changes to the previous study were (i) extending the trauma types included (ii) a new control condition, also by smartphone.MethodsThis is an explorative observational study. Data was both analyzed descriptively and using the Framework method.ResultsWe identified several possible ways to recruit patients, and establish a sense of embeddedness in the Swedish emergency department context and a positive appreciation from staff. The study protocol was tested with 8 participants. Tasks both in the intervention and control condition were readily delivered via patients’ own smartphones.ConclusionRecruitment of patients and smartphone delivery of the intervention indicates initial feasibility. Researcher presence and administration of study procedures was successfully fitted to emergency department routines and well received by staff. Further pilot work is warranted, underscoring the importance of our collaboration between nursing and psychology.

Progression of Clinical Features in Lewy Body Dementia Can Be Detected Over 6 Months.

ObjectiveThis study aimed to quantify the trajectory and magnitude of change of the key clinical features and corresponding symptom domains of dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD), including global cognition, parkinsonism, recurrent visual hallucinations, cognitive fluctuations, and sleep disturbance.MethodsOne hundred sixteen patients with Lewy body dementia (DLB = 72, PDD = 44) underwent assessment at baseline and 3 and 6 months as part of a prospective multicenter randomized controlled trial. Linear mixed models were constructed for core outcome measures using the Mini-Mental State Examination (MMSE), motor section of the Unified Parkinson's Disease Rating Scale (UPDRS-III), Dementia Cognitive Fluctuations Scale (DCFS), and Neuropsychiatric Inventory (NPI).ResultsWithin the time frame of our study (6 months), we were able to identify a significant cognitive decline of 1.3 points on the MMSE (p = 0.002) and significant worsening of motor parkinsonism with an increase in UPDRS-III score of 3.2 points (p = 0.018). Fluctuation severity also increased using the DCFS with a 6-month change in score of 1.3 points (p = 0.001). Uniquely, a signal for increased severity of sleep symptoms of 1.2 points (NPI-sleep) was also detectable (p = 0.04). Significant changes in neuropsychiatric symptoms were not detected. There was no difference in rates of change of scores between DLB and PDD.DiscussionClinically significant rates of change in core clinical features can be detected and quantified in Lewy body dementia over a relatively short period (6 months) using common clinical instruments and thus may be useful as clinical endpoints for therapeutic trials of disease-modifying and symptomatic agents.

Validation of Autism Diagnosis and Clinical Data in the SPARK Cohort.

The SPARK cohort was established to facilitate recruitment in studies of large numbers of participants with autism spectrum disorder (ASD). Online registration requires participants to have received a lifetime professional diagnosis by health or school providers although diagnoses are not independently verified. This study was set to examine the validity of self- and caregiver-reported autism diagnoses. Electronic medical records (EMR) of 254 SPARK participants (77.6% male, age 10.7years) were abstracted. Using two different methods, confirmation of ASD diagnosis in EMRs was obtained in 98.8% of cases. Core clinical features recorded in EMRs were typical of autism samples and showed very good agreement with SPARK cohort data, providing further evidence of the validity of clinical information in the SPARK database.

P-AD003. Autonomic dysfunction in CASPR2 antibody associated neurological disease

Introduction . Contactin-associated protein-like 2 (CASPR2) antibody-associated neurological disease is a rare autoimmune illness with central and peripheral manifestations. The core clinical features are peripheral nerve hyperexcitability, autonomic dysfunction, insomnia, and fluctuating encephalopathy. We aim to describe the autonomic manifestations in a cohort of patients with CASPR2 antibody-associated neurological disease. Methods . This study was a retrospective chart review that included eight patients with CASPR2 antibody-associated neurological illness. Their medical records were reviewed and details regarding clinical manifestations of autonomic dysfunction and cardiac autonomic function testing (AFT) were collected. The response of autonomic manifestations to immunotherapy was also noted on follow up. Results . Clinically, autonomic manifestations were present in 7/8 patients. Most commonly, cardiovascular manifestations (palpitations, postural dizziness, tachycardia, fluctuating blood pressure, and postural hypotension) were noted in six patients while others included gastrointestinal (diarrhea or constipation), genitourinary (urinary frequency, urinary retention), and sudomotor (hyperhidrosis) manifestations in three patients each. One patient developed a hypertensive emergency with posterior reversible encephalopathy syndrome. AFT was carried out in five patients and it showed severe cardiac autonomic dysfunction in three and definite autonomic dysfunction in two patients. All patients had a reduction in total power with sympathetic dominance. On follow-up after treatment with immunotherapy (mean duration 19.71 ± 17.61 months; range, 2–52 months), all patients had improvement in autonomic symptoms and one patient had persistent tachycardia but no symptoms. Conclusion . Autonomic dysfunction is a core feature of CASPR2 antibody-associated neurological disease and is usually multi-organ in nature with varied manifestations. Cardiac AFT shows sympathetic dominance. While the clinical response to treatment is good, cardiac autonomic dysfunction in the acute period can lead to dangerous fluctuations in blood pressure and result in complications.

Diagnostic Value of the CSF α-Synuclein Real-Time Quaking-Induced Conversion Assay at the Prodromal MCI Stage of Dementia With Lewy Bodies.

To investigate whether the CSF α-synuclein (α-syn) real-time quaking-induced conversion (RT-QuIC) assay accurately identifies patients with mild cognitive impairment (MCI) due to probable Lewy body (LB) disease. We applied α-syn RT-QuIC to 289 CSF samples obtained from 2 independent cohorts, including 81 patients with probable MCI-LB (age 70.7 ± 6.6 years, 13.6% female, Mini-Mental State Examination [MMSE] score 26.1 ± 2.4), 120 with probable MCI due to Alzheimer disease (AD) (age 68.6 ± 7.4 years, 45.8% female, MMSE score 25.5 ± 2.8), and 30 with unspecified MCI (age 65.4 ± 9.3 years, 30.0% female, MMSE score 27.0 ± 3.0). Fifty-eight individuals with no cognitive decline or evidence of neurodegenerative disease and 121 individuals lacking brain α-syn deposits at the neuropathologic examination were used as controls. RT-QuIC identified patients with MCI-LB against cognitively unimpaired controls with 95% sensitivity, 97% specificity, and 96% accuracy and showed 98% specificity in neuropathologic controls. The accuracy of the test for MCI-LB was consistent between the 2 cohorts (97.3% vs 93.7%). Thirteen percent of patients with MCI-AD also had a positive test; of note, 44% of them developed 1 core or supportive clinical feature of dementia with Lewy bodies (DLB) at follow-up, suggesting an underlying LB copathology. These findings indicate that CSF α-syn RT-QuIC is a robust biomarker for prodromal DLB. Further studies are needed to fully explore the added value of the assay to the current research criteria for MCI-LB. This study provides Class III evidence that CSF α-syn RT-QuIC accurately identifies patients with MCI-LB.

Contribution of the Cognitive Approach to Language Assessment to the Differential Diagnosis of Primary Progressive Aphasia

Diagnosis of primary progressive aphasia (PPA) is essentially based on the identification of progressive impairment of language abilities while other cognitive functions are preserved. The three variants of PPA are characterized by core and supportive clinical features related to the presence or absence of language impairment in different linguistic domains. In this article, we review the cognitive neuropsychological approach to the assessment of PPA and its contribution to the differential diagnosis of the three variants. The main advantage of this assessment approach is that it goes beyond the mere description and classification of clinical syndromes and identifies impaired and preserved cognitive and linguistic components and processes. The article is structured according to the main language domains: spoken production, language comprehension, and written language. Each section includes a brief description of the cognitive processes involved in the assessment tasks, followed by a discussion of typical characteristics for each PPA variant and common pitfalls in the interpretation of the results. In addition, the clinical benefit of the cognitive neuropsychological approach for the behavioral management of PPA is briefly sketched out in the conclusion.

FDG-PET patterns associated with ideomotor apraxia and imitation apraxia in patients with corticobasal syndrome

IntroductionApraxia is a core clinical feature of corticobasal syndrome (CBS). Among the subtypes of apraxia, ideomotor and imitation apraxia are frequently found in CBS. However, little is known about the brain networks that are characteristic of each apraxia subtype or their clinical implication. In this study, we used 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to explore the specific patterns of glucose hypometabolism that are characteristic of apraxia subtypes by focusing on ideomotor and imitation apraxia. MethodsWe compared the areas of glucose hypometabolism in the brains of 52 patients with CBS and 13 healthy controls, both as a whole and according to apraxia subtypes. In addition, we investigated the relationship between the apraxia subtypes and the clinical phenotype of CBS. ResultsIn patients with CBS, common hypometabolism was observed in the frontal gyrus, precentral gyrus and caudate regardless of apraxia subtypes. In particular, ideomotor apraxia was associated with hypometabolism in the angular gyrus, while imitation apraxia was associated with hypometabolism in the posterior part including the postcentral gyrus, precuneus, and posterior cingulate gyrus. Patients who showed both ideomotor and imitation apraxia were more likely to show the typical features of CBS and progressive supranuclear palsy compared with patients showing only one type of apraxia. ConclusionGroup comparison analysis using FDG-PET revealed distinct pathways of ideomotor and imitation apraxia in CBS. These findings add to our understanding of the brain networks underlying apraxia in association with the clinical features of CBS.

Prodromal Dementia With Lewy Bodies: Evolution of Symptoms and Predictors of Dementia Onset.

Research criteria for prodromal dementia with Lewy bodies (DLB) were published in 2020, but little is known regarding prodromal DLB in clinical settings. We identified non-demented participants without neurodegenerative disease from the National Alzheimer's Coordinating Center Uniform Data Set who converted to DLB at a subsequent visit. Prevalence of neuropsychiatric and motor symptoms were examined up to 5 years prior to DLB diagnosis. The sample included 116 participants clinically diagnosed with DLB and 348 age and sex-matched (1:3) Healthy Controls. Motor slowing was present in approximately 70% of participants 3 years prior to DLB diagnosis. In the prodromal phase, 50% of DLB participants demonstrated gait disorder, 70% had rigidity, 20% endorsed visual hallucinations, and over 50% of participants endorsed REM sleep behavior disorder. Apathy, depression, and anxiety were common prodromal neuropsychiatric symptoms. The presence of 1+ core clinical features of DLB in combination with apathy, depression, or anxiety resulted in the greatest AUC (0.815; 95% CI: 0.767, 0.865) for distinguishing HC from prodromal DLB 1 year prior to diagnosis. The presence of 2+ core clinical features was also accurate in differentiating between groups (AUC = 0.806; 95% CI: 0.756, 0.855). A wide range of motor, neuropsychiatric and other core clinical symptoms are common in prodromal DLB. A combination of core clinical features, neuropsychiatric symptoms and cognitive impairment can accurately differentiate DLB from normal aging prior to dementia onset.

849 REM Behavioral Disorder as a Predictor of Lewy body Dementia- A Case Report

Abstract Introduction Dementia with Lewy bodies (DLB) is one of the most common types of degenerative dementia after Alzheimer’s dementia. The core clinical features for diagnosis includes cognitive fluctuations, visual hallucinations, rapid eye movement (REM) sleep behavior disorder (RBD), and parkinsonism. Other symptoms include daytime drowsiness, longer daytime naps, prolonged staring spells, and episodes of disorganized speech. REM behavioral disorder (RBD) is commonly associated with DLB, occurring in 85 percent of individuals, often early in the course of the disease. It can precede the clinical diagnosis of DLB by up to 20 years. Report of case(s) A seventy-six-year-old female with a history of well controlled obstructive sleep apnea was diagnosed with REM behavioral disorder in 2012. She had presented with episodes of screaming, attempt to ambulate during sleep, resulting in injury. Her polysomnogram revealed evidence of REM without atonia and a screaming episode during REM. Her RBD symptoms were controlled with clonazepam and melatonin with less frequency of the RBD episodes. The patient gradually started noticing memory issues and by January 2020 she was diagnosed with dementia and was initiated on Aricept. Within 7 months of diagnosis of dementia, she started reporting vivid hallucinations that were not threatening or violent compared to her violent content of RBD. Physical exam revealed impaired cognitive function and mild intermittent resting tremor of the right hand. The neurological exam was normal including normal tone, strength, and gait. She also reported repeated falls and fractures. The diagnosis of Lewy body dementia was made based on the presence of 2 core clinical features. Conclusion The current management of these conditions is mainly symptomatic. In the evolution of neurodegenerative disorder, RBD precedes other conditions like LBD, parkinsonism, etc. Research suggests that alpha-synuclein neurodegeneration is the common pathology behind these conditions. The understanding that RBD presents at the beginning of the evolution, provides us with a unique opportunity for preemptive treatment to prevent further degeneration in turn preventing the debilitation consequence like dementia, parkinsonism, neuroleptic sensitivity, and dysautonomia. Further research is needed for developing these early interventional strategies. Support (if any) NOne

Functional Brain Connectivity Patterns Associated with Visual Hallucinations in Dementia with Lewy Bodies.

Background:The presence of recurrent, complex visual hallucinations (VH) is among the core clinical features of dementia with Lewy bodies (DLB). It has been proposed that VH arise from a disrupted organization of functional brain networks. However, studies are still limited, especially investigating the resting-state functional brain features underpinning VH in patients with dementia.Objective:The aim of the present pilot study was to investigate whether there were any alterations in functional connectivity associated with VH in DLB.Methods:Seed-based analyses and independent component analysis (ICA) of resting-state fMRI scans were carried out to explore differences in functional connectivity between DLB patients with and without VH.Results:Seed-based analyses reported decreased connectivity of the lateral geniculate nucleus, the superior parietal lobule and the putamen with the medial frontal gyrus in DLB patients with VH. Visual areas showed a pattern of both decreased and increased functional connectivity. ICA revealed between-group differences in the default mode network (DMN).Conclusion:Functional connectivity analyses suggest dysfunctional top-down and bottom-up processes and DMN-related alterations in DLB patients with VH. This impairment might foster the generation of false visual images that are misinterpreted, ultimately resulting in VH.

Progression to Dementia in Mild Cognitive Impairment With Lewy Bodies or Alzheimer Disease.

ObjectiveTo determine whether mild cognitive impairment with Lewy bodies or mild cognitive impairment with Alzheimer disease differ in their rates of clinical progression to dementia, we undertook longitudinal observation of mild cognitive impairment cases with detailed clinical assessment of Lewy body diagnostic characteristics.MethodsTwo prospective longitudinal cohorts including 111 individuals ≥60 years of age with mild cognitive impairment were assessed annually to track cognitive and clinical progression, including the presence or absence of core clinical features and proposed biomarkers of dementia with Lewy bodies. Multistate modeling was used to assess the associations of diagnostic characteristics of dementia with Lewy bodies with clinical progression from mild cognitive impairment to dementia, with death as a competing outcome.ResultsAfter a mean follow-up of 2.2 years (range 1–6.7 years), 38 of the 111 (34%) participants progressed to dementia: 10 with AD, 3 with possible dementia with Lewy bodies, and 25 with probable dementia with Lewy bodies. The presence of any Lewy body disease characteristic was associated with an increased hazard of transition to dementia; this risk further increased as more diagnostic characteristics were observed (hazard ratio 1.33 per characteristic, 95% confidence interval [CI] 1.11–1.60) and was especially high for those experiencing complex visual hallucinations (hazard ratio 1.98, 95% CI 0.92–4.29) or cognitive fluctuations (hazard ratio 3.99, 95% CI 2.03–7.84).ConclusionsDiagnostic characteristics of Lewy body disease are associated with an increased risk of transition from mild cognitive impairment to dementia.

Cognitive conversion disorder (functional cognitive disorder) – what’s new?

IntroductionSome patients present with significant subjective cognitive symptoms, sometimes interfering with day-to-day live, that are not compatible with any recognizable psychiatric, neurodegenerative or systemic condition. Recent studies have proposed that these patients can be diagnosed with Conversion Disorder (Subtype Cognitive), also known as Functional Cognitive Disorder (FCD). This is a relatively recent concept, that still lacks consensus.ObjectivesReview the current state of knowledge regarding prevalence, diagnosis criteria, core clinical features and proposed treatment of Functional Cognitive Disorder.MethodsBibliographic review of the literature published in English in the last 5 years, in the databases Pubmed, PsycINFO and Cochrane. The keywords used were: Functional Cognitive Disorder; Cognition; Conversion Disorder. A review of the titles and abstracts of the resulting articles was made, and selected according to their relevance to the study.ResultsTen articles related to prevalence, diagnosis, clinical associations and treatment of Functional Cognitive Disorder were selected, of which two were systematic reviews, three descriptive studies, three cross sectional clinical studies of memory clinics attendants, one cohort prospective study and one article was a case series report.ConclusionsThe prevalence of FCD is estimated between 11.6% and 56% of patients presenting to memory clinics. However, the prevalence of FCD is hindered by the lack of consensus regarding its definition. Recently, Ball et al proposed a definition in line with the DSM-5 definition of Conversion Disorder with emphasis on positive criteria with the identification of positive evidence of internal inconsistency. Treatment discussion is still limited, and the approach is similar to other conversion disorders.

Long-term Safety and Efficacy of Mexiletine in Myotonic Dystrophy Types 1 and 2.

Myotonic dystrophy types 1 and 2 are progressive multisystem genetic disorders whose core clinical feature is myotonia. Mexiletine, an antagonist of voltage-gated sodium channels, is a recommended antimyotonic agent in the nondystrophic myotonias, but its use in myotonic dystrophy is limited because of lack of data regarding its long-term efficacy and safety profile. To address this issue, this study retrospectively evaluated patients with myotonic dystrophy receiving mexiletine over a mean time period of 32.9 months (range 0.1-216 months). This study demonstrated that 96% of patients reported some improvement in myotonia symptoms with mexiletine treatment. No clinically relevant cardiac adverse events were associated with the long-term use of mexiletine. These findings support that mexiletine is both safe and effective when used long-term in myotonic dystrophy. This study provides Class IV evidence that mexiletine is a well-tolerated and effective treatment for myotonic dystrophy types 1 and 2.