Gilles Fénelon

Epidemiology of psychosis in Parkinson's disease

Psychotic symptoms are frequent and disabling in patients with Parkinsons 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.

The changing face of Parkinson's disease-associated psychosis: a cross-sectional study based on the new NINDS-NIMH criteria.

New criteria for Parkinsons disease‐associated psychosis (PDAP) were recently proposed by a NINDS‐NIMH working group. We assessed 116 consecutive unselected outpatients with PD for the existence of psychotic symptoms during the previous month, using a structured questionnaire covering the whole spectrum of PDAP symptoms. Hallucinations occurred in 42% of the patients (visual: 16%; nonvisual: 35%), delusions in 4%, and minor symptoms in 45% (sense of presence, visual illusions, or passage hallucinations). The prevalence of PDAP was 43% when the usual definition was used (hallucinations and/or delusions) and 60% when the NINDS‐NIHM criteria were used. Correlations between PDAP and patient characteristics varied with the definition of PDAP. These findings suggest that the epidemiology of PDAP should be re‐evaluated with the new criteria. Minor symptoms and nonvisual hallucinations are an important part of the PDAP spectrum, which has commonly been restricted to visual hallucinations and delusions.

Topographic distribution of the axonal endings from the sensorimotor and associative striatum in the macaque pallidum and substantia nigra

The striatopallidonigral connection was studied by injecting anterograde tracers into either the associative or the sensorimotor striatum in ten macaques. The results were analyzed using a precise cartographic method. Injections into various parts of the associative striatum (caudate nucleus and ventromedial putamen) produced a labeling of axons in the dorsomedial and ventral pallidal regions. These associative regions occupied two-thirds of the lateral pallidum and one-third of the medial pallidum. Bands of labeled axons from the sensorimotor striatum (dorsolateral putamen) were found in the remaining, central part of the two pallidal nuclei. In the substantia nigra, the rostral associative striatum projected medially to the pars reticulata, while the caudal parts projected laterally. The whole pars reticulata and lateralis thus appeared to receive associative striatal inputs. The sensorimotor striatal territory projected to the central part of the pars reticulata/lateralis. It was concluded that the two functional territories remain separate in the two pallidal nuclei but overlap in the middle third of the substantia nigra. However, due to their great size, the pallidal neurons located at the border of the two territories may receive striatal inputs from both the associative and the sensorimotor components in the same way that nigral neurons do.

Topographic distribution of pallidal neurons projecting to the thalamus in macaques

The respective topographic distribution of the pallidal neurons projecting to the central complex (centre médian-parafascicular complex) and to the oral part of the lateral mass of the thalamus was studied by using a topographic technique based on ventricular landmarks. WGA-HRP was stereotactically injected into the central complex of 4 macaques and into the oral part of the lateral mass of the thalamus of 3 others. Neurons projecting to the central complex were located in the caudal, lateral and ventral region of the ipsilateral medial nucleus of the pallidum. Pallidal neurons projecting to the lateral mass of the thalamus were more numerous and occupied the entire volume of the medial pallidum apart from a small rostral and dorsomedial region. The location of the pallido-central complex neurons appeared to be included in that of the neurons projecting to the lateral mass. As very few neurons of this shared region were unlabeled, it is very likely that the same pallidal neurons project to both targets. The pallido-central complex neurons were located in the region crossed by axons coming from the putaminal sensorimotor territory of the striatum. These results provide further evidence that Nauta and Mehlers loop is a real closed loop probably involved in sensorimotor processing.

The Basal Ganglia Related System of Primates: Definition, Description and Informational Analysis

In the first IBAGS book we tried to define the basal ganglia and to determine their components using rational criteria. Eight years later, an answer, acceptable by most specialists, may be given. It now appears advisable to place the set of the basal ganglia in a more general system also including their inputs and outputs. Despite numerous attempts at finding direct descending connections to motoneurons, the motor action of the basal ganglia, as classically stressed, is exerted through the pyramidal system. The “basal ganglia related system” might then be seen as a cortico-baso-thalamo-cortical circuit comprising:(1) the cortico-striatal connection, (2) the striato-pallidonigral connection of the “basal ganglia core” made up of the striatum and its targets, the two pallidal nuclei and the substantia nigra (pars reticulata and lateralis), (3) the regulation of the core by the pars compacta of the substantia nigra, the subthalamic nucleus, the central complex (centre median-parafasciculaire) and the pedunculo-pontine complex, (4) the output of the core:the pallido-thalamic and nigro-thalamic connections, (5) the pallidal thalamocortical and the nigral thalamo-cortical connections, (6) cortico-cortical connections, and (7) the source of the cortico-spinal connection (see Fig. 1 and Table I). Our analysis, almost exclusively based on data obtained in primates, will follow these steps successively.

The Primate Motor Thalamus Analysed with Reference to Subcortical Afferent Territories

This paper analyses the internal organisation of the primate motor thalamus. A topographic study of the three main subcortical afferent territories (the cerebellar, pallidal and nigral territories) gives a much simpler and more functionally relevant partitioning of the thalamus than consideration of conflictual cytoarchitectonic nuclei.

Feeling of presence in Parkinson's disease

Background A feeling of presence (FP), that is, the vivid sensation that somebody (distinct from oneself) is present nearby, is commonly reported by patients with Parkinsons 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. Patients and methods 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. Results 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. Discussion 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.

Can nicotine be used medicinally in Parkinson’s disease?

The risk of Parkinson’s disease is reduced by cigarette smoking, which raises some unanswered questions. Nicotine, a major component of tobacco smoke, could exert either nonreceptor-mediated biological effects or, more importantly, act on the different subtypes of nicotinic brain receptors, in particular those associated with the nigrostriatal dopaminergic pathway. There is now robust experimental evidence for a neuroprotective effect of nicotine upon dopaminergic neurons. By contrast, in animal models of Parkinson’s disease, nicotine alone has slight or no motor effects. However, nicotine may modulate dopamine transmission and has clear motor effects when associated with L-DOPA, reducing L-DOPA-induced dyskinesias. Clinical trials have yielded inconclusive results thus far and are hampered by different designs and small cohorts. Ongoing studies address either symptomatic motor or nonmotor symptoms, or neuroprotection. There is still no agreement on the daily dosage of nicotine or the method of administration. Together, these data suggest that nicotine or nicotinic receptor drugs have therapeutic potential for Parkinson’s disease, although the specific treatment regimens remain to be determined.

The Primate Central Complex as One of the Basal Ganglia

It was in human brain, that Jules Bernard Luys (1865) first discovered what he called his “centre median”. Figure lA shows that his “centre” was located lateral to Meynert’s bundle and ventral to the medial nucleus. For a long time it was considered as the ventral element of a so-called medial part of the thalamus of which the nucleus medialis (hence called medialis dorsalis) was the dorsal element. The description of the nucleus medial to the bundle, the nucleus parafascicularis, was not done until forty years later, in monkey brains, by Mrs Vogt (1909) and Friede-man (1911). This was later included into the “hyperchromic circular formation” (Foix and Nicolesco, 1925) encircling the medial nucleus and also comprising the intralaminar and periventricular elements. The centre median and the nucleus parafascicularis together are nowadays considered to constitute a “complex” often called the centre median-parafascicular complex.

13 – The Pallidal and Nigral Thalamic Territories and the Problem of the Anterior Part of the Lateral Region in Primates

Publisher Summary This chapter explains that the anterior part of the lateral region of the thalamus of primates is the place of discrepant interpretations. The main inconsistency concerns the distinction of a polar, most anterior subdivision. Therefore, the chapter focuses on the topography of the subcortical afferent territories—the thalamic spaces filled by sets of axonal arborizations from the same source—and addresses the question of the existence of a polar subdivision by precisely comparing the three-dimensional positions and shapes of the pallidal and nigral thalamic territories to those of the anterior part of the lateral region of the thalamus. The precise three-dimensional cartography of the pallidal and nigral territories in the anterior part of the thalamus shows that there is no thalamic subdivision in front of the two territories. There is also no polar part degenerating after hemidecortication. Thalamo-striate neurons are located in the whole extent of the pallidal and nigral territories.