Impaired cholinergic integrity of the colon and pancreas in dementia with Lewy bodies.

Dementia with Lewy bodies is characterized by a high burden of autonomic dysfunction and Lewy pathology in peripheral organs and components of the sympathetic and parasympathetic nervous system. Parasympathetic terminals may be quantified with 18F-fluoroetoxybenzovesamicol, a PET tracer that binds to the vesicular acetylcholine transporter in cholinergic presynaptic terminals. Parasympathetic imaging may be useful for diagnostics, improving our understanding of autonomic dysfunction and for clarifying the spatiotemporal relationship of neuronal degeneration in prodromal disease. Therefore, we aimed to investigate the cholinergic parasympathetic integrity in peripheral organs and central autonomic regions of subjects with dementia with Lewy bodies and its association with subjective and objective measures of autonomic dysfunction. We hypothesized that organs with known parasympathetic innervation, especially the pancreas and colon, would have impaired cholinergic integrity. To achieve these aims, we conducted a cross-sectional comparison study including 23 newly diagnosed non-diabetic subjects with dementia with Lewy bodies (74 ± 6 years, 83% male) and 21 elderly control subjects (74 ± 6 years, 67% male). We obtained whole-body images to quantify PET uptake in peripheral organs and brain images to quantify PET uptake in regions of the brainstem and hypothalamus. Autonomic dysfunction was assessed with questionnaires and measurements of orthostatic blood pressure. Subjects with dementia with Lewy bodies displayed reduced cholinergic tracer uptake in the pancreas (32% reduction, P = 0.0003) and colon (19% reduction, P = 0.0048), but not in organs with little or no parasympathetic innervation. Tracer uptake in a region of the medulla oblongata overlapping the dorsal motor nucleus of the vagus correlated with autonomic symptoms (rs = -0.54, P = 0.0077) and changes in orthostatic blood pressure (rs = 0.76, P < 0.0001). Tracer uptake in the pedunculopontine region correlated with autonomic symptoms (rs = -0.52, P = 0.0104) and a measure of non-motor symptoms (rs = -0.47, P = 0.0230). In conclusion, our findings provide the first imaging-based evidence of impaired cholinergic integrity of the pancreas and colon in dementia with Lewy bodies. The observed changes may reflect parasympathetic denervation, implying that this process is initiated well before the point of diagnosis. The findings also support that cholinergic denervation in the brainstem contributes to dysautonomia.

Synaptic Density and Glucose Consumption in Patients with Lewy Body Diseases: An [11 C]UCB-J and [18 F]FDG PET Study.

BACKGROUND: Patients with Lewy body diseases exhibit variable degrees of cortical and subcortical hypometabolism. However, the underlying causes behind this progressive hypometabolism remain unresolved. Generalized synaptic degeneration may be one key contributor. OBJECTIVE: The objective of this study was to investigate whether local cortical synaptic loss is proportionally linked to the magnitude of hypometabolism in Lewy body disease. METHOD: Using in vivo positron emission tomography (PET) we investigated cerebral glucose metabolism and quantified the density of cerebral synapses, as measured with [18 F]fluorodeoxyglucose ([18 F]FDG) PET and [11 C]UCB-J, respectively. Volumes-of-interest were defined on magnetic resonance T1 scans and regional standard uptake value ratios-1 values were obtained for 14 pre-selected brain regions. Between-group comparisons were conducted at voxel-level. RESULTS: We observed regional differences in both synaptic density and cerebral glucose consumption in our cohorts of non-demented and demented patients with Parkinson's disease or dementia with Lewy bodies compared to healthy subjects. Additionally, voxel-wise comparisons showed a clear difference in cortical regions between demented patients and controls for both tracers. Importantly, our findings strongly suggested that the magnitude of reduced glucose uptake exceeded the magnitude of reduced cortical synaptic density. CONCLUSION: Here, we investigated the relationship between in vivo glucose uptake and the magnitude of synaptic density as measured using [18 F]FDG PET and [11 C]UCB-J PET in Lewy body patients. The magnitude of reduced [18 F]FDG uptake was greater than the corresponding decline in [11 C]UCB-J binding. Therefore, the progressive hypometabolism seen in Lewy body disorders cannot be fully explained by generalized synaptic degeneration. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Reduced Synaptic Density in Patients with Lewy Body Dementia: An [11 C]UCB-J PET Imaging Study.

BACKGROUND: Patients with Parkinson's disease (PD) often develop dementia, but the underlying substrate is incompletely understood. Generalized synaptic degeneration may contribute to dysfunction and cognitive decline in Lewy body dementias, but in vivo evidence is lacking. OBJECTIVE: The objective of this study was to assess the density of synapses in non-demented PD (nPD) subjects (N = 21), patients with PD-dementia or Dementia with Lewy bodies (DLB) (N = 13), and age-matched healthy controls (N = 15). METHOD: Using in vivo PET imaging and the novel synaptic-vesicle-glycoprotein 2A (SV2A) radioligand [11C]UCB-J, SUVR-1 values were obtained for 12 pre-defined regions. Volumes-of-interest were defined on MRI T1 scans. Voxel-level between-group comparisons of [11C]UCB-J SUVR-1 were performed. All subjects underwent neuropsychological assessment. Correlations between [11C]UCB- J PET and domain-specific cognitive functioning were examined. RESULTS: nPD patients only demonstrated significantly reduced SUVR-1 values in the substantia nigra (SN) compared to HC. DLB/PDD patients demonstrated reduced SUVR-1 values in SN and all cortical VOIs except for the hippocampus and amygdala. The voxel-based analysis supported the VOI results. Significant correlation was seen between middle frontal gyrus [11C]UCB-J SUVR-1 and performance on tests of executive function. CONCLUSION: Widespread cortical reduction of synaptic density was documented in a cohort of DLB/PDD subjects using in vivo [11C]UCB-J PET. Our study confirms previously reported synaptic loss in SN of nPD patients. [11C]UCB-J binding in selected cortical VOIs of the DLB/PDD patients correlated with their levels of cognitive function across relevant neuropsychological domains. These findings suggest that the loss of synaptic density contributes to cognitive impairment in nPD and DLB/PDD. © 2021 International Parkinson and Movement Disorder Society.

Development of persistent headache following stroke: a 3-year follow-up.

BACKGROUND: Headache following stroke has been described in previous studies with an incidence of 23%-54%, but a clear description of headache developing after stroke onset is still lacking. The aim of this study was to determine the incidence and characteristics of persistent novel headache after stroke and to describe the use of medication, including dipyridamole. METHODS: As a follow-up to a prospective study, a standardized questionnaire about characteristics of novel headache and medication use was sent out to surviving patients three years after their stroke. RESULTS: The questionnaire was sent to 256 patients and returned by 222, of whom 12% (26/222) of patients reported persistent novel headache. Dipyridamole had no significant influence on the incidence. Stroke-attributed headache according to predefined criteria was reported in 7.2% (16/222) of patients, with tension-type-like headache in 50.0%, migraine-like in 31.3% and medication overuse in 6.25% of patients. More than half of patients experienced moderate to severe pain and had a score of 55 or above on the Headache Impact Test-6 scale. CONCLUSION: Novel headache after stroke affects one in 10 patients and seems to be unrelated to dipyridamole use. Persistent headache attributed to stroke is similar to tension-type headache for half of patients.

Tube feeding in dementia.

The number of people with dementia is expected to increase both in Denmark and globally. As dementia progresses dyphagia often develop, and increase risk of aspiration. Enteral nutrition via nasogatric and percutaneus feeding tube have several complications, and does not reduce the risk of pneumonia, hospital readmission, or decrease mortality. Neither does it have any positive effects on quality of life. On a national and international scale, a multidisciplinary team approach is recommended, but no international guidelines concerning this subject exist.

Diagnostic Cut-offs for CSF ß-amyloid and tau proteins in a Danish dementia clinic.

BACKGROUND: Analysis of beta-amyloid 1-42 (Aß42), total tau (t-tau) and phosphorylated-tau 181 (p-tau) in the cerebrospinal fluid (CSF) is often performed as a part of the diagnostic work-up in case of suspected Alzheimer's dementia (AD). Unfortunately, studies on optimal CSF biomarker cut-offs in a real-world clinical setting are scarce. METHODS: We retrospectively evaluated the biomarker levels of 264 consecutive patients referred to our dementia clinic. The biomarkers were analysed with the Elecsys(R) assays. Diagnoses were based on all available clinical information, including FDG-PET scans. RESULTS: In total, we identified 233 patients diagnosed with dementia. The median MMSE score was 22 (IQR 18-25). AD pathophysiology was suspected in 156 patients, and the corresponding cut-offs based on the Youden index were: Aß42: 903 ng/L (ROC-AUC 0.78); t-tau: 272 ng/L (ROC-AUC 0.78); p-tau: 24 ng/L (ROC-AUC 0.85); t-tau/Aß42 ratio: 0.34 (ROC-AUC 0.91); p-tau/Aß42 ratio: 0.029 (ROC-AUC 0.92). CONCLUSIONS: We found the tau/Aß42 ratios to possess the best diagnostic performance, but our estimated cut-off values for the ratios were somewhat higher than previously reported. Consequently, if the CSF analyses are used to support a diagnosis of AD in a heterogeneous high-prevalence cohort, adjustment of the cut-offs may be warranted.

Central post-stroke pain: clinical characteristics, pathophysiology, and management.

Central post-stroke pain (CPSP) is a neuropathic pain syndrome that can occur after a cerebrovascular accident. This syndrome is characterised by pain and sensory abnormalities in the body parts that correspond to the brain territory that has been injured by the cerebrovascular lesion. The presence of sensory loss and signs of hypersensitivity in the painful area in patients with CPSP might indicate the dual combination of deafferentation and the subsequent development of neuronal hyperexcitability. The exact prevalence of CPSP is not known, partly owing to the difficulty in distinguishing this syndrome from other pain types that can occur after stroke (such as shoulder pain, painful spasticity, persistent headache, and other musculoskeletal pain conditions). Future prospective studies with clear diagnostic criteria are essential for the proper collection and processing of epidemiological data. Although treatment of CPSP is difficult, the most effective approaches are those that target the increased neuronal hyperexcitability.

[Phenotypic variability in a family with genetically verified familial hemiplegic migraine type 2]. / Fænotypisk variation i en familie med genetisk verificeret familiær hemiplegisk migræne type 2.

After playing handball, a 13-year-old girl developed a comatose condition during 7-10 days with hemiparesis and aphasia. From age three to nine she was treated for partial epilepsy. She never had symptoms of migraine. Her father had childhood epilepsy and at the age of 40 and 44 he experienced two attacks with prolonged coma, fever, seizures, hemiparesis and aphasia. His mother had symptoms of severe hemiplegic migraine. Father and daughter were genetically tested and an earlier described mutation in ATP1A2 gene was found. These cases illustrate the phenotypic variability in familial hemiplegic migraine type 2.

[Child neglect in the county of Copenhagen. Changing incidence?]. / Omsorgssvigt mod børn i Københavns Amt. Aendrer hyppigheden sig?

INTRODUCTION: The aim of the study was to evaluate the incidence of physical violence, neglect, and sexual abuse of children as reported to the local authorities in the County of Copenhagen during the year 1998, and compare it with a similar study conducted in 1993. MATERIAL AND METHODS: A questionnaire was posted to the local authorities of the 18 districts in the county. They were asked how many new, verified, and suspected cases of physical, emotional, and sexual abuse had come to their attention in 1998. RESULTS: A total number of 182 cases were identified, corresponding to a total incidence of 2.1 cases per 1000 children aged 0-17 years (2.1@1000), with 0.6@1000 for physical abuse, 0.8@1000 for emotional neglect, and 0.7@1000 for sexual abuse. More than one-third of the cases were considered verified. We found a slight fall in the incidence of abuse of children, as compared to our study from 1993 (2.1@1000 as compared to 2.7@1000 in 1993). The incidence of physical neglect, which the authors' assess to be the most reliable parameter, was found to be unchanged (0.8@1000). DISCUSSION: The authors recommend a common, uniform, centralised registration of cases of child abuse in the counties. We suggest that such registration should contain information about the age of the child, initials, type of abuse, verified or suspected, and who reported the case.

Early evoked pain or dysesthesia is a predictor of central poststroke pain.

Central poststroke pain (CPSP) is a central neuropathic pain condition caused by a cerebrovascular lesion affecting the central somatosensory nervous system. Once developed, CPSP is difficult to treat, so there is an interest in identifying stroke patients at risk for the development of CPSP. This study examined if sensory abnormalities, including evoked dysesthesia, allodynia, or hyperalgesia to static and dynamic touch, cold, and pinprick, at stroke onset are a predictor for the development of CPSP. Consecutive stroke patients were recruited from a large prospective study of poststroke pain in Aarhus, Denmark, between 2007 and 2008. Patients underwent a structured pain interview and a standardized sensory examination within 4 days of admission, and a structured telephone interview was conducted after 3 and 6months. Patients who developed poststroke pain in the affected side without any other plausible cause were classified as having possible CPSP. A total of 275 stroke patients completed the study, and 29 patients (10.5%) were classified as having possible CPSP. The diagnosis was confirmed by a clinical examination in 15 of 17 patients, corresponding to a prevalence of 8.3%. The presence of allodynia, hyperalgesia, or dysesthesia in response to the sensory examination at stroke onset increased the odds for CPSP at 6months by 4.6 (odds ratio; 95% confidence interval 1.5-13.9). The combination of reduced or absent sensation to pinprick or cold and early evoked pain or dysesthesia at onset increased odds by 8.0 (odds ratio; 95% confidence interval 2.6-24.8). In conclusion, early evoked pain or dysesthesia is a predictor for CPSP.

Central poststroke pain: a population-based study.

Central poststroke pain (CPSP) is a specific pain condition arising as a direct consequence of a cerebrovascular lesion. There is limited knowledge about the epidemiology and clinical characteristics of this often neglected but important consequence of stroke. In this population-based study, a questionnaire was sent out to all (n=964) stroke patients identified through the Danish National Indicator Project Stroke Database in Aarhus County, Denmark, between March 2004 and February 2005. All surviving patients who fulfilled 4 questionnaire criteria for possible CPSP (n=51) were selected for further clinical examination, and their pain was classified by using stringent and well-defined criteria and a detailed, standardized clinical examination. The minimum prevalence of definite or probable CPSP in this population is 7.3% and the prevalence of CPSP-like dysesthesia or pain is 8.6%. Pinprick hyperalgesia was present in 57%, cold allodynia in 40%, and brush-evoked dysesthesia in 51% of patients with CPSP. Because of its negative impact on quality of life and rehabilitation, pain is an important symptom to assess in stroke survivors.

Pain following stroke: a population-based follow-up study.

BACKGROUND AND PURPOSE: Chronic pain is increasingly recognized as a consequence of stroke. This study aimed to describe the prevalence and pain types of new onset chronic pain ("novel pain") in patients with stroke compared with a randomly selected reference group from the general population and to identify factors associated with pain development in stroke patients. METHODS: In a population-based follow-up design, development of chronic pain after stroke was assessed by a questionnaire sent to consecutive stroke patients, registered in a Danish national stroke database, two years after their stroke. A randomly selected sex- and age-matched reference group from the same catchment area received a similar questionnaire about development of new types of chronic pain in the same time period. A total of 608 stroke patients and 519 reference subjects were included in the study. RESULTS: Development of novel pain was reported by 39.0% of stroke patients and 28.9% of reference subjects (OR 1.57, CI 1.21-2.04), and was associated with low age and depression in a multivariate model. Daily intake of pain medication for novel pain was reported by 15.3% and 9.4% of the stroke and reference population, respectively. Novel headache, shoulder pain, pain from increased muscle stiffness, and other types of novel pain were more common in stroke patients, whereas joint pain was equally common in the two groups. CONCLUSIONS: Development of chronic pain is more common in stroke patients compared with sex- and age-matched reference subjects. Evaluation of post-stroke pain should be part of stroke follow-up.

[Poststroke pain]. / Smerter efter apopleksi.

Pain following stroke is a common but often neglected problem. Headache is present in about one fourth of patients in the acute phase. Later, chronic musculoskeletal pain including shoulder pain may be present, partly due to muscle weakness, posture and stiffness. Central neuropathic pain is a chronic pain, often described as burning or shooting and in some cases associated with pain evoked by light touch or cold. Central pain usually develops within months after the stroke and is located within the area of sensory abnormality corresponding to the CNS region damaged by the stroke.