Association of cerebral microbleeds with cerebrospinal fluid Alzheimer-biomarkers and clinical symptoms in early dementia with Lewy bodies.

OBJECTIVES: To determine the prevalence, localization and associations of cerebral microbleeds (CMB) in dementia with Lewy bodies (DLB) with its core clinical symptoms and cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD). We hypothesize DLB patients with CMB have increased amyloid burden compared to those without CMB, which could also translate into clinical differences. METHODS: Retrospective cross-sectional analysis from the AlphaLewyMA study (https://clinicaltrials.gov/ct2/show/NCT01876459). Patients underwent a standardized protocol of brain MRI including 3D T1, 3D FLAIR and T2* sequences, and CSF analysis of AD biomarkers. CMB and white matter hyperintensities (WMHs) were visually assessed in prodromal and mild demented (DLB, N = 91) and AD (AD, N = 67) patients. RESULTS: CMB prevalence did not differ among DLB and AD (24.2% vs. 37.3%; p = 0.081). CMB were mainly distributed in lobar topographies in both DLB (74%) and AD (89%). CMB in DLB was not associated with global cognitive performance, executive functioning, speed of information processing, or AD CSF biomarkers. Similarly, there was no difference regarding specific clinical symptoms: fluctuations, psychotic phenomena, sleep behavior disorder and Parkinsonism between DLB patients with and without CMB. AD patients with CMB had increased burden of WMH compared to those without (2.1 ± 0.86 vs. 1.4 ± 0.89; p = 0.005), according to Fazekas scale, whereas no significant difference was observed in DLB patients (1.68 ± 0.95 vs. 1.42 ± 0.91; p = 0.25). CONCLUSION: CMB were equally prevalent with similar topographic distribution in both DLB and AD patients. CMB was not associated with CSF AD biomarkers or core clinical symptoms in DLB.

Dementia with Lewy bodies and gait neural basis: a cross-sectional study.

BACKGROUND: Dementia with Lewy Bodies (DLB) is responsible for cognitive-behavioural disorders but also for gait disorders. The latter are thought to be related to parkinsonism, but the neural bases of these disorders are not well known, especially in the early stages. The aim of this study was to investigate by volumetric Magnetic Resonance Imaging the neuronal basis of gait disorders in DLB patients, compared to Healthy Elderly Controls and Alzheimer's Disease patients. METHODS: Clinical examination with motor assessment including 10-meter walking speed, one-leg balance and Timed Up and Go test, a comprehensive neuropsychological evaluation and 3D brain Magnetic Resonance Imaging were performed on 84 DLB patients, 39 Alzheimer's Disease patients and 22 Healthy Elderly Controls. We used Statistical Parametric Mapping 12 to perform a one-sample t-test to investigate the correlation between each gait score and gray matter volume (P ≤ 0.05 corrected for family-wise error). RESULTS: We found a correlation for DLB patients between walking speed and gray matter decrease (P < 0.05, corrected for family-wise error) in caudate nuclei, anterior cingulate cortex, mid-cingulate cortex, hippocampi, supplementary motor area, right cerebellar cortex and left parietal operculum. We found no correlation with Timed Up and Go test and one-leg balance. CONCLUSION: Gait disorders are underpinned by certain classical regions such as the cerebellum and the supplementary motor area. Our results suggest there may be a motivational and emotional component of voluntary gait in DLB subjects, underpinned by the cingulate cortex, a spatial orientation component, underpinned by hippocampi and suggest the involvement of brain processing speed and parkinsonism, underpinned by the caudate nuclei. TRIAL REGISTRATION: The study protocol has been registered on ClinicalTrials.gov. (NCT01876459) on June 12, 2013.

Therapeutic trials and Dementia with Lewy bodies: a systematic review of the literature.

BACKGROUND: Cognitive diseases with Lewy bodies occur in two forms: dementia with Lewy bodies (DLB) and Parkinsonian dementia (PD), which follows the evolution of Parkinson disease. There is currently no curative treatment for these cognitive diseases with Lewy bodies. Therapeutic trials in DLB are rare, due to the fact that the disease has only recently been described and the first international diagnostic criteria have only recently been published (1996). METHOD: This article proposes a synthesis of the therapeutic trials carried out into DLB in the last five years, including PD patients, using the Clinicaltrials.gov and Pubmed.gov databases. RESULTS: We identified 35 therapeutic trials on ClinicalTrials.gov and 14 on PubMed. In line with our temporal criteria, 21 trials were analysed. Of the 11 completed trials with reported results, two drugs showed positive results: two trials with zonisamide (phases 2 and 3) showed improvements in Parkinsonian syndrome and one trial with neflamapimod (phase 2) showed improvements in cognition and walking. CONCLUSION: In recent years, there has been an increase in therapeutic research into DLB, which is consistent with the prevalence of this disease - approximately 200,000 patients in France. Compared to other cognitive neurodegenerative diseases, therapeutic research is largely insufficient, although the proportion of positive trials is significant. Effective treatment to modify the course of the disease would have significant consequences for patients and their relatives.

[Therapeutic trials in dementia with Lewy bodies: a systematic review of the literature]. / Les essais thérapeutiques dans la maladie à corps de Lewy : revue systématique de la littérature.

BACKGROUND: Cognitive diseases with Lewy bodies occur in two forms: dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), which follows the progression of Parkinson's disease. There is currently no curative treatment for these cognitive diseases with Lewy bodies. Therapeutic trials in DLB are rare, due to the recent description of the disease as well as its first international diagnostic criteria (1996). METHOD: This article proposes a synthesis of the therapeutic trials carried out in DLB in the last 5 years, including PDD patients with DLB patients, using the Clinicaltrials.gov and Pubmed.gov databases. RESULTS: We identified 35 therapeutic trials on Clinical Trials and 14 on PubMed. According to our temporal criteria, 21 trials were analyzed. Among the 11 completed trials with reported results, two molecules showed positive results: two trials with zonisamide (phase 2 and 3) showed a gain on parkinsonism and one trial with neflamapimod (phase 2) a gain on cognition and walking. CONCLUSION: In recent years, there has been an increase in the therapeutic research effort in DLB, which is consistent with the prevalence of this disease - approximately 200,000 patients in France. Compared to other cognitive neurodegenerative diseases, therapeutic research is largely insufficient, whereas the proportion of positive trials is important. An effective disease modifying would have strong consequences for the patient and the relatives.

Differential diagnostic value of total alpha-synuclein assay in the cerebrospinal fluid between Alzheimer's disease and dementia with Lewy bodies from the prodromal stage.

BACKGROUND: Several studies have investigated the value of alpha-synuclein assay in the cerebrospinal fluid (CSF) of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) patients in the differential diagnosis of these two pathologies. However, very few studies have focused on this assay in AD and DLB patients at the MCI stage. METHODS: All patients were enrolled under a hospital clinical research protocol from the tertiary Memory Clinic (CM2R) of Alsace, France, by an experienced team of clinicians. A total of 166 patients were included in this study: 21 control subjects (CS), 51 patients with DLB at the prodromal stage (pro-DLB), 16 patients with DLB at the demented stage (DLB-d), 33 AD patients at the prodromal stage (pro-AD), 32 AD patients at the demented stage (AD-d), and 13 patients with mixed pathology (AD+DLB). CSF levels of total alpha-synuclein were assessed using a commercial enzyme-linked immunosorbent assay (ELISA) for alpha-synuclein (AJ Roboscreen). Alzheimer's biomarkers (t-Tau, P-Tau, Aß42, and Aß40) were also measured. RESULTS: The alpha-synuclein assays showed a significant difference between the AD and DLB groups. Total alpha-synuclein levels were significantly higher in AD patients than in DLB patients. However, the ROC curves show a moderate discriminating power between AD and DLB (AUC = 0.78) which does not improve the discriminating power of the combination of Alzheimer biomarkers (AUC = 0.95 with or without alpha-synuclein). Interestingly, the levels appeared to be altered from the prodromal stage in both AD and DLB. CONCLUSIONS: The modification of total alpha-synuclein levels in the CSF of patients occurs early, from the prodromal stage. The adding of alpha-synuclein total to the combination of Alzheimer's biomarker does not improve the differential diagnosis between AD and DLB. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01876459 (AlphaLewyMa).

Impaired contrast sensitivity at low spatial frequency in cannabis users with early onset.

The regular use of cannabis generates pronounced cognitive disorders, especially in users who begin before the age of 15-16. However, less is known about the impact of regular cannabis on visual function, especially in the case of early onset. Cannabinoid receptors (CB1) are expressed in areas of the visual system, like the thalamus and primary cortex, which might originate sensory disorders. Hence, we measured contrast sensitivity (CS) in three groups, i.e. cannabis users with late onset of cannabis use (after 16 years old), cannabis users with early onset". We used a constant method which allowed us to control for biased responses. Stimuli were presented at high and low spatial frequencies and in both static and dynamic conditions (8Hz). As contrast sensitivity is measured behaviorally based on an explicit response and could thus be impacted by attentional or vigilance disorders, participants' attention and vigilance were carefully monitored by means of the D2 test, CPT-AX for attention and pupillography for vigilance. Cannabis users with early onset were significantly impaired only at low spatial frequency. This effect was independent of response bias, vigilance and attention. These results show for the first time that early cannabis use impacts contrast sensitivity at low spatial frequency.

Botulinum toxin A: successful décolleté rejuvenation.

BACKGROUND: Décolleté wrinkles develop with age. In women more than 35 years of age these wrinkles are still transient, but become permanent at about age 50. In a substantial number of women décolleté wrinkles, seem to be associated with an insertion of platysma exceeding the second intercostal space. We report botulinum A toxin therapy of these wrinkles in five patients. OBJECTIVE: To show the effect of botulinum A toxin on décolleté wrinkles. METHODS: All five women with décolleté lines treated with botulinum A had different varieties of the platysma muscle inserting deep down beneath the fourth intercostal space. During platysma contraction injection points were marked and a certain dosage of toxin was applied. RESULTS: Two weeks after therapy a significant improvement of the treated décolleté region was observed. CONCLUSION: These observations indicated that botulinum A toxin can be an effective and safe method in the temporary management of décolleté wrinkles. It should therefore be considered as a new adjuvant treatment in cosmetic décolleté rejuvenation.

Treatment of cutaneous leishmaniasis by photodynamic therapy.

BACKGROUND: Cutaneous leishmaniasis represents a common health problem and standard treatments are often ineffective or yield poor cosmetic results. OBJECTIVE: We compared the efficacy of photodynamic therapy (PDT) with paromomycin sulfate in 10 lesions of cutaneous leishmaniasis. METHODS: Five lesions were treated by PDT with Metvix (Photocure, Oslo, Norway) and 75 J/cm(2) red light. PDT was performed twice weekly and, after 12 weeks, once weekly. The other 5 lesions were treated with paromomycin sulfate once daily. All nonresponding lesions of the paromomycin-treated plaques finally also underwent PDT. RESULTS: All 5 lesions treated by PDT and 2 of the paromomycin sulfate-treated plaques were clinically and histologically Leishmania free. Three lesions with poor response to paromomycin sulfate finally responded to subsequent PDT. Ten months after therapy there was no recurrence, and cosmetic outcome after PDT was excellent. CONCLUSION: PDT may be an effective therapeutic alternative in cutaneous leishmaniasis.