D. Monaco

Visual hallucinations in PD and Lewy body dementias: old and new hypotheses.

Visual Hallucinations (VH) are a common non-motor symptom of Parkinson’s Disease (PD) and the Lewy body dementias (LBD) of Parkinsons disease with dementia (PDD) and Dementia with Lewy Bodies (DLB). The origin of VH in PD and LBD is debated: earlier studies considered a number of different possible mechanisms underlying VH including visual disorders, Rapid Eye Movement (REM) Sleep Intrusions, dysfunctions of top down or bottom up visual pathways, and neurotransmitter imbalance. More recently newer hypotheses introduce, among the possible mechanisms of VH, the role of attention networks (ventral and dorsal) and of the Default Mode Network (DMN) a network that is inhibited during attentional tasks and becomes active during rest and self referential imagery. Persistent DMN activity during active tasks with dysfunctional imbalance of dorsal and ventral attentional networks represents a new hypothesis on the mechanism of VH. We review the different methods used to classify VH and discuss reports supporting or challenging the different hypothetical mechanisms of VH.

Revisiting P300 cognitive studies for dementia diagnosis: Early dementia with Lewy bodies (DLB) and Alzheimer disease (AD)

AIMS OF THE STUDY Earlier P300 studies were conducted when the prevalence of dementia with Lewy Bodies (DLB) was unknown. Our study aims to examine whether P300 abnormalities are present in DLB and to evidence possible differences between DLB and Alzheimers disease (AD). A second aim of this study is to look for correlations between P300 recordings and EEG, as abnormal EEG variability has been described in DLB. PATIENTS AND METHODS Auditory P300 responses were recorded by a classic oddball paradigm in 50 controls, in 36 DLB patients, and in 40 AD patients with MMSE>20. RESULTS Reliable auditory P300 responses were obtained in 26 DLB (72%), 33 AD (82.5%), and 46 controls (92%). P300 was more delayed and had lower amplitude in DLB compared to AD groups. P300 topography was also different as the anterior-to-posterior scalp amplitude gradient was reversed in DLB. P300 latency correlated with neuropsychological test scores and with EEG variables. Gradient inversion and delayed P300 responses in frontal derivations evidenced differences between DLB and AD patients with a sensitivity of 70% and a specificity of 97%. CONCLUSIONS P300 recordings are abnormal in DLB and can be useful to distinguish DLB from AD.

Updates on Somatoform Disorders (SFMD) in Parkinson's Disease and Dementia with Lewy Bodies and discussion of phenomenology

Somatoform Disorders (SFMD) were recently described in Parkinson Disease (PD) and Dementia with Lewy Bodies (DLB). The present paper updates the observations in our cohort of patients and further details clinical phenomenology. Of 3178 patients consecutively referred to our Institutions from 1999, 1572 subjects had neurodegenerative diseases and 1718 psychiatric disorders. After 2-9 years of follow up, 488 patients were labelled as PD, 415 as Alzheimer Disease, 162 as DLB, 48 as Progressive Supranuclear Palsy, 48 as Multiple System Atrophy and 49 as Fronto-Temporal Dementia. The frequency of SFMD (DSM-IV-TR criteria) was determined in each diagnostic category by direct observation of SFMD symptoms, psychiatric interviews, SCL 90Rss, collection of previous general practitioners and hospital charts. The frequency of SFMD was considerably higher in DLB (29 patients, 18%) and PD (37 patients, 7.5%) than in any other group (0-2%). The frequency of SFMD in psychiatric patients was 2%. SFMD in PD and DLB were characterised by motor and non-motor patterns and were often accompanied by catatonic signs consisting of posturing stereotypies and negativism (55%). SFMD symptoms preceded PD motor signs by 6 months-5 years in 92% of the 29 DLB and 37 PD patients and in 70% SFMD were recurrent at follow-up. In 93% of these patients, hypochondria was a preceding or concomitant background.

Eyelid retraction in dementia with Lewy bodies and Parkinson’s disease

Dear Sirs, Eyelid retraction (ELR), indicates widening of the palpebral opening with white parts of the sclera appearing above and, often, below the limbus. ELR was indicated with different and controversial eponyms including Graefe’s, pseudo-Graefe’s, Stellwag’s, or Dalrymple’s sign [1], which were, however, originally ascribed to endocrinological conditions [1, 2]. Dalrymple’s, Stellwag’s and Graefe’s signs are typical of Grave’s disease: the first indicating retraction of the upper eyelid, causing abnormal wideness of the palpebral fissure, the second infrequent or incomplete blinking, the third tardy or jerky downward movement of the upper eyelids when the gaze is directed downward. Pseudo-Graefe’s (or Fuch’s) sign is characterized by elevation or retraction of the upper eyelid when the eye is looking downwards. Collier’s sign is the only accepted synonymous of neurogenic eyelid retraction [3]: it is defined as unilateral or bilateral lid retraction due to midbrain lesion, occurring at any age. ELR was initially reported as an early sign of typical and atypical parkinsonisms [4, 5]. With the more recent identification of progressive supranuclear palsy (PSP) [6], ELR became a mark sign of the disease or a red flag signalling possible diagnosis, although further ocular and extra-ocular neurological signs should accompany it, like ‘‘combined activation of frontalis/superior orbicularis and platysma muscles, giving a frightened expression’’ [6], vertical supranuclear gaze palsy, blepharospasm and blepharocolysis (apraxia of eyelid opening/closing). Despite this emphasis on ELR in PSP, ELR may be present in Parkinson’s disease (PD), as it was observed in patients with autoptically detected Lewy bodies [7]. Yet it is not clear whether ELR occurs early or late during the disease course, whether it is concealed or reduced by dopaminergic treatments, or whether it is present in different forms of atypical parkinsonism other than PSP. With the present report we evidence that ELR unaccompanied by other ocular motor signs is consistently observed in early phase of dementia with Lewy bodies (DLB), is more frequent than in PD and is responsive to dopaminergic treatment. Electronic supplementary material The online version of this article (doi:10.1007/s00415-011-5942-z) contains supplementary material, which is available to authorized users.

Delayed blink reflex in dementia with Lewy bodies is sensitive to cholinergic modulation.

Objectives: To assess the possible responsiveness of blink reflex alterations present in dementia with Lewy bodies (DLB) to treatment with cholinesterase inhibitors. Methods: Twenty-six patients with DLB and 20 patients with Alzheimer disease underwent clinical, neuropsychological (including assessment of cognitive fluctuations, with the Cognitive Assessment of Fluctuations and the One-Day Fluctuation Assessment questionnaires), and the blink reflex evaluation at baseline, 1 week after vitamin E administration (to assess test-retest reliability), and 1 and 2 weeks after donepezil administration at the dose of 10 mg/d. Results were compared with data obtained from 30 healthy controls treated with vitamin E capsules for 2 weeks. Results: Treatment with donepezil did not cause modifications of cognitive or motor performances in both groups of patients. In DLB patients, One-Day Fluctuation Assessment scores were modified by donepezil treatment with a mean reduction of 2.8 ± 1.8 compared with baseline (P < 0.05). After 2 weeks of treatment with donepezil, R2 latency was significantly decreased in DLB patients. The mean R2 latency reduction was by 3.0 ± 3.2 milliseconds (P < 0.0001 compared with baseline). R2 mean latency reduction was significantly correlated with R2 mean latency delay at baseline (Spearman rho = 0.8). Conclusions: Short-term donepezil administration can correct the alterations of the blink response together with the daily occurrence of cognitive fluctuations present in DLB patients.