Jean Lhermitte (1877–1959) was one of the pioneers of behavioral neurology, including the field of hallucinations. This article focuses on his work concerning the relationship between hallucinations, ...sleep, and dreams. From 1910, Lhermitte became interested in sleep and its disorders, particularly narcolepsy and its accompanying symptoms. He also reported on sleep disorders and hallucinations occurring in people with lesions of the diencephalic region (“infundibular syndrome”), and later encephalitis lethargica. In 1922, he described a syndrome of complex, predominantly visual hallucinations in patients with vascular damage to the midbrain, known as peduncular hallucinosis. Twelve historical cases of peduncular hallucinosis, including 10 from Lhermitte, are reviewed. He gave a precise phenomenological description of peduncular hallucinosis, and put forward the hypothesis that the lesion disrupted the anatomy and connections of a center regulating wakefulness and sleep, thus enabling a dissociation of the mechanisms of dream and waking states. Although the pathophysiology of peduncular hallucinosis remains to this day partly obscure, the model of a limited subcortical lesion acting through complex mechanisms and ultimately involving the cortex remains valid. Lhermitte was also a pioneer in characterizing what contemporary sleep specialists call dissociation of states.
Abstract Psychotic symptoms are frequent and disabling in patients with Parkinson's disease (PD). Methodological issues in the epidemiology of PD associated psychosis (PDP) include differences in the ...symptoms assessed, the methods of assessment, and the selection of patients. Most studies are prospective clinic-based cross-sectional studies providing point prevalence rates in samples on dopaminergic treatment. Visual hallucinations are present in about one quarter to one third of the patients, auditory in up to 20%. Tactile/somatic, and olfactory hallucinations are usually not systematically sought. Minor phenomena such as sense of presence and visual illusions affect 17 to 72% of the patients, and delusions about 5%. Lifetime prevalence of visual hallucinations reaches approximately 50%. Prospective longitudinal cohort studies suggest that hallucinations persist and worsen in individual patients, and that their prevalence increases with time. A facilitating role of treatment on PDP is demonstrated at least for dopaminergic agonists, but there is no simple dose–effect relationship between dopaminergic treatment and the presence or severity of hallucinations. The main endogenous non-modifiable risk factor is cognitive impairment. Other associated factors include older age/longer duration of PD, disease severity, altered dream phenomena, daytime somnolence, and possibly depression and dysautonomia. PDP reduces quality of life in patients and increases caregiver distress, and is an independent risk factor for nursing home placement and development of dementia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Psychosis in Parkinson's disease refers to a combination of hallucinations and delusions occurring with a clear sensorium and a chronic course. Hallucinations may involve several sensory modalities. ...Complex visual hallucinations are the most common type. "Minor" hallucinatory phenomena are frequently present and include visual illusions, passage hallucinations, and sense of presence. Insight may be lost in patients with cognitive impairment. Delusions of a paranoid type are more rare than hallucinations. Both hallucinations and delusions are more frequent in Parkinson's disease patients with dementia. Pathogenesis involves complex and probably multifactorial mechanisms, including pharmacologic (dopaminergic treatment and others) and disease-related factors.
Patients with Parkinson disease (PD) can experience hallucinations (spontaneous aberrant perceptions) and illusions (misinterpretations of real perceptual stimuli). Of such phenomena, visual ...hallucinations (VHs) and illusions are the most frequently encountered, although auditory, olfactory and tactile hallucinations can also occur. In cross-sectional studies, VHs occur in approximately one-third of patients, but up to three-quarters of patients might develop VHs during a 20-year period. Hallucinations can have substantial psychosocial effects and, historically, were the main reason for placing patients in nursing homes. Concomitant or overlapping mechanisms are probably active during VHs, and these include the following: central dopaminergic overactivity and an imbalance with cholinergic neurotransmission; dysfunction of the visual pathways, including specific PD-associated retinopathy and functional alterations of the extrastriate visual pathways; alterations of brainstem sleep-wake and dream regulation; and impaired attentional focus. Possible treatments include patient-initiated coping strategies, a reduction of antiparkinson medications, atypical neuroleptics and, potentially, cholinesterase inhibitors. Evidence-based studies, however, only support the use of one atypical neuroleptic, clozapine, and only in patients without dementia. Better phenomenological discrimination, combined with neuroimaging tools, should refine therapeutic options and improve prognosis. The aim of this Review is to present epidemiological, phenomenological, pathophysiological and therapeutic aspects of hallucinations in PD.
Whether chronic hallucinations belong to the natural history of untreated Parkinson disease (PD) remains undetermined. For early authors such as Gowers or Charcot and his followers, hallucinations ...that occurred in the course of PD either accompanied the final phase of the disease or reflected comorbidities. However, a few authors observed that hallucinations could occur in PD patients with severe depression, confusion, or dementia. Interest in hallucinations with parkinsonism increased with the outbreak of von Economo encephalitis, as they were more frequent than in PD, provoking new pathophysiologic questions. Later studies on mental symptoms in parkinsonism were often based on series that pooled patients with PD and postencephalitic syndromes, confounding a clear analysis. It remains difficult to estimate the prevalence of hallucinations in the natural course of PD before the introduction of levodopa therapy. The lack of prospective studies, the wide early use of anticholinergics and ergots compounds, and the absence of dementia with Lewy bodies in the nosology of the time are further limitations. Even with these limitations, historical descriptions of PD from the prelevodopa era suggest that hallucinations may be part of PD itself, especially in the context of late dementia, depression, or nonspecific encephalopathy.
Abstract
Platelet-derived growth factor receptor beta (PDGFRB) is one of the genes associated with primary familial brain calcification (PFBC), an inherited neurological disease (OMIM:173410). ...Genetic analysis of patients and families revealed at least 13 PDGFRB heterozygous missense variants, including two novel ones described in the present report. Limited experimental data published on five of these variants had suggested that they decrease the receptor activity. No functional information was available on the impact of variants located within the receptor extracellular domains. Here, we performed a comprehensive molecular analysis of PDGFRB variants linked to PFBC. Mutated receptors were transfected in various cell lines to monitor receptor expression, signaling, mitogenic activity and ligand binding. Four mutants caused a complete loss of tyrosine kinase activity in multiple assays. One of the novel variants, p.Pro154Ser, decreased the receptor expression and abolished binding of platelet-derived growth factor (PDGF-BB). Others showed a partial loss of function related to reduced expression or signaling. Combining clinical, genetic and molecular data, we consider nine variants as pathogenic or likely pathogenic, three as benign or likely benign and one as a variant of unknown significance. We discuss the possible relationship between the variant residual activity, incomplete penetrance, brain calcification and neurological symptoms. In conclusion, we identified distinct molecular mechanisms whereby PDGFRB variants may result in a receptor loss of function. This work will facilitate genetic counseling in PFBC.
Hallucinations, mainly of a visual nature, are considered to affect about one-quarter of patients with Parkinson's disease. They are commonly viewed as a side-effect of antiparkinsonian treatment, ...but other factors may be involved. The aim of this study was to determine the phenomenology, prevalence and risk factors of hallucinations in Parkinson's disease. Two-hundred and sixteen consecutive patients fulfilling clinical criteria for Parkinson's disease were studied. Demographic and clinical variables were recorded, including motor and cognitive status, depressive symptoms and sleep-wake disturbances. Patients with and without hallucinations were compared using non-parametric tests, and logistic regression was applied to significant data. Hallucinations had been present during the previous 3 months in 39.8% of the patients, and fell into three categories: minor forms, consisting of a sensation of a presence (person), a sideways passage (commonly of an animal) or illusions were present in 25.5% of the patients (an isolated occurrence in 14.3%), formed visual hallucinations were present in 22.2% (isolated in 9.3%) and auditory hallucinations were present in 9.7% (isolated in 2.3%). Patients with minor hallucinations had a higher depression score than non-hallucinators but did not differ in other respects. Logistic regression analysis identified three factors independently predictive of formed visual hallucinations: severe cognitive disorders, daytime somnolence and a long duration of Parkinson's disease. These findings indicate that, when minor hallucinations are included, the total prevalence is much higher than previously reported. A simple side-effect of dopaminergic treatment is not sufficient to explain the occurrence of all visual hallucinations. The main risk factor in treated patients is cognitive impairment, although sleep-wake cycle disturbances, and possibly other factors related to the duration of the disease, act as cofactors.
Feeling of presence in Parkinson's disease Fénelon, Gilles; Soulas, Thierry; Cleret de Langavant, Laurent ...
Journal of neurology, neurosurgery and psychiatry,
11/2011, Volume:
82, Issue:
11
Journal Article
Peer reviewed
Open access
A feeling of presence (FP), that is, the vivid sensation that somebody (distinct from oneself) is present nearby, is commonly reported by patients with Parkinson's disease (PD), but its phenomenology ...has not been described precisely. The objective of this study was to provide a detailed description of FP in PD and to discuss its possible mechanisms.
The authors studied 52 non-demented PD patients reporting FP in the preceding month (38 consecutive outpatients and 14 inpatients). FP characteristics were recorded with a structured questionnaire. The outpatients with FP were compared with 78 consecutive outpatients without FP.
About half the patients said they recognised the 'identity' of the presence. More than 75% of patients said the FP were not distressing, were short-lasting, were felt beside and/or behind the patient, and occurred while indoors; most patients checked for a real presence, but their insight was generally preserved. In 31% of cases, the patients had an unformed visual hallucination simultaneously with the FP. A higher daily levodopa-equivalent dose and the presence of visual illusions or hallucinations were independently associated with FP.
Although FP is not a sensory perception, projection of the sensation into the extrapersonal space, along with the frequent co-occurrence of elementary visual hallucinations and the strong association with visual hallucinations or illusions, supports its hallucinatory nature. FP may be viewed as a 'social' hallucination, involving an area or network specifically activated when a living being is present, independently of any perceptual clue.
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