Visuomotor priming effects in Parkinson's disease patients depend on the match between the observed and the executed action.

Evidence exists that action observation activates the same cortical motor areas that are involved in the performance of the observed actions. An untested idea is whether subcortical structures such as the basal ganglia play a role in the coding of other people's actions. This study used kinematics to examine how Parkinson's disease patients react to the observation of an action which they were subsequently requested to perform. In each trial a model and an observer, which could be either a Parkinsonian patient or a neurologically healthy participant, were seated facing each other. The model was requested to grasp a stimulus (action condition), to perform a kicking action towards the stimulus (control-action condition), and to not perform any action (control condition). The task for the observer was always to grasp the stimulus after having watched the model performing her task. Results show that Parkinson's disease patients did show facilitation effects only when the model was a Parkinsonian patient. Whereas, neurologically healthy participants' movements were facilitated following the observation of either the Parkinsonian and the healthy model grasping the object. No facilitation effects were found for both the control and the control-action conditions. The fact that normal visuomotor priming takes place in PD patients when the observed action matches with what they can perform suggests that basal ganglia might not be necessary for it. However, damage to the basal ganglia might become relevant when such a match does not occur. In such circumstances, a damage to these structures might prevent the deployment of additional activity which might be necessary to influence cortical functions related to the representations of observed actions.

The arginine growth hormone stimulation test in bradykinetic-rigid parkinsonisms.

The arginine growth hormone (GH) stimulation test differentiates the Parkinsonian variant of multiple system atrophy (MSA-P) from idiopathic Parkinson's disease (PD). Our aim was to evaluate the accuracy of the arginine GH stimulation test in distinguishing between PSP, MSA-P, and PD. We measured the GH response to arginine in serum samples of 26 MSA-P, 23 PSP, and 26 PD patients, and in 80 healthy controls. We used ANOVA followed by the Bonferroni test to compare GH values and peaks among groups. We used receiver operating characteristic curve analysis to establish the arginine cut-off level that best differentiated between MSA-P, PSP, and PD. The GH peak was significantly lower (P < 0.01) in MSA-P (1.46 +/- 0.29 microg/L) than in both PD (8.74 +/- 0.98 microg/L) and PSP (6.64 +/- 0.82 microg/L) patients, and controls (8.59 +/- 0.44 microg/L). Growth hormone peaked later in PSP patients than in PD patients and controls. At a cut-off level of 4 microg/L, arginine test distinguished MSA-P from PD with a sensitivity of 92% and a specificity of 96%, and MSA-P from PSP with a sensitivity of 78% and a specificity of 96%. The GH response to arginine differentiates MSA-P from PD and PSP with a good diagnostic accuracy. The neuroendocrine response to arginine of PSP patients differed from that of MSA-P patients, but was not identical to that of normal controls and PD patients. Our results suggest that the impairment of the central mechanisms modulating GH release differs between PSP and MSA-P.

Dopamine depletion affects communicative intentionality in Parkinson's disease patients: Evidence from action kinematics.

Appropriate communication is at the heart of successful, healthy social interactions in humans. Deficits in social communication are a hallmark of several neurological and psychiatric disorders. Yet, very little research has been devoted to understanding the mechanisms underlying these issues. It has been suggested that dopamine is a candidate neurotransmitter system involved in stimulating communication in individuals that are not highly motivated to communicate. A typical model to study dopaminergic dysfunctions in humans is represented by Parkinson's disease (PD) patients, who show motor, cognitive and motivational symptoms. Our study aimed to investigate the effects of social communication on actions in non-demented PD patients receiving dopamine replacement therapy (Levodopa = l-Dopa) and in neurologically healthy control participants. Patients' ability to modulate motor patterning depending on the communicative intention motivating the action to be performed was evaluated both in "on" (with l-Dopa) and "off" (without l-Dopa) states. In two main conditions, participants were requested to reach towards, grasp an object, and either simply lift it (individual condition) or lift it with the intent to communicate a meaning to a partner (communicative condition). Movements' kinematics was recorded using a three-dimensional motion analysis system. The results indicate that kinematics is sensitive to communicative intention and that l-Dopa treatment has positive effects on translating communicative intentions into specific motor patterns in PD patients. Although the to-be-grasped object remained the same both the controls and the PD patients in an 'on' state adopted different kinematic patterning for the 'individual' and the 'communication' conditions. The PD patients in the 'off' state, instead, were unable to kinematically differentiate between the two conditions. We contend that social and communicative impairments are associated with abnormalities in dopaminergic pathways.

It's all in the type of the task: Dopamine modulates kinematic patterns during competitive vs. cooperative interaction in Parkinson's disease.

Increasing evidence suggests that a dysfunctional dopaminergic system affects the ability to socially interact. Since Parkinson's disease (PD) provides a model for assessing dopaminergic dysfunctions in humans, our study was designed to investigate social interactions in PD patients receiving dopamine replacement therapy (Levodopa=l-Dopa) and in neurologically healthy controls. We focused on the kinematics of one action, reaching to grasp a wooden block, which was performed within the context of two basic modes of social cognition, namely cooperation and competition. During the cooperative tasks, two participants were instructed to reach and grasp their respective objects and to cooperate in forming a specific configuration on the working table. During the competitive tasks, two participants were instructed to compete to place their own object at the bottom of a tower to be built on the working table. PD patients' ability to modulate motor patterning depending on the intention motivating the action they were about to perform was evaluated in both "on" (with l-Dopa) and "off" (without l-Dopa) states. Study results revealed that both the healthy controls and the 'on' PD patients had distinct kinematic patterns for cooperative and competitive actions and that these differed from patterns mirroring similar actions performed by those same participants in non social conditions. The kinematic patterns of the healthy controls and the 'on' patients were highly correlated during the cooperative tasks. The 'off' PD patients were, instead, unable to differentiate between isolated and social conditions. These results support the hypothesis that dopaminergic neurotransmission is involved in shaping the mechanisms underlying social interactions.

Neurology residency training in Europe: an Italian perspective.

Education is the most important part of medical-science training. Assessment of training programmes and examination of trainees' skills are necessary to guarantee that trainees develop competence. Training programmes vary between and within countries. The impending integration of the medical-job market among European countries highlights the need for people training to be specialists to achieve a certain standard. Here, we review the neurological training programmes in Europe, principally those in Italy, and discuss the standardisation of the training of residents in Italy and the quality control of current residency training, or its absence, in Europe.

Social intentions in Parkinson's disease patients: A kinematic study.

Dysfunction of the dopaminergic system leads to motor, cognitive and motivational symptoms in brain disorders such as Parkinson's disease (PD). Moreover, the dopaminergic system plays an important role in social interactions. The dopaminergic input to the basal ganglia (BG) thought to integrate social cues during the planning and execution of voluntary movements remains, however, largely unexplored. Since PD provides a model to assess this function in humans, our study aimed to investigate the effects of social intentions on actions in non-demented PDpatients receiving dopamine replacement therapy (Levodopa = l-Dopa) and in neurologically healthy control participants. Patients' ability to modulate motor patterning depending on the intention motivating the action to be performed was evaluated both in "on" (with l-Dopa) and "off" (without l-Dopa) states. Participants were instructed to reach for and to grasp an object; they were then told to hand it to another person (social condition) or to place it on a concave frame (individual condition). A 'passive-observer' condition, which was similar to the 'individual' condition except for the presence of an onlooker who simply observed the scene, was also assessed to exclude the possibility that differences might be due to the presence of another person. Movement kinematics were recorded using a three-dimensional motion analysis system. Study results demonstrated that the controls and the PD patients in an 'on' state adopted different kinematic patterning for the 'social' and the 'individual' conditions; the PD patients in the 'off' state, instead, were unable to kinematically differentiate between the two conditions. These results suggest that l-Dopa treatment has positive effects on translating social intentions into specific motor patterns in PD patients.

The pathology of the spinal cord in progressive supranuclear palsy.

We describe the results of a study of the spinal cord of 5 patients with progressive supranuclear palsy (PSP). Examination of the 6th cervical, 7th thoracic, and 5th lumbar segments revealed variable degree of gliosis and density of neuropil threads (NTs), nerve cell loss, and tau-positive cytoplasmic staining of neurons, some of which was reminiscent of neurofibrillary tangles (NFT). Tau-positive neurons were seen at each spinal level and in the 3 zones in which each level was subdivided. Cells with the appearance of NFT predominated in the intermediate zone. Morphometric study revealed 47%, 52%, and 32% decrease in cell numbers in the motor area (lamina IX) at the 3 spinal levels, respectively, and 39% in the intermedio-lateral column. This is the first report describing severe neuronal loss throughout the whole spinal cord in patients with PSP and its results are in keeping with a previous study of the nucleus of Onufrowicz. The reasons why cell loss fails to produce clinical symptoms are analyzed and the clinico-pathological correlations between anatomical changes and dystonia are considered. On the basis of existing data, we conclude that previous suggestions implicating spinal interneurons in the pathogenesis of neck dystonia should not be supported.

Kinematics of the Reach-to-Grasp Movement in Vascular Parkinsonism: A Comparison with Idiopathic Parkinson's Disease Patients.

The performance of patients with vascular parkinsonism (VPD) on a reach-to-grasp task was compared with that of patients affected by idiopathic Parkinson's disease (IPD) and age-matched control subjects. The aim of the study was to determine how patients with VPD and IPD compare at the level of the kinematic organization of prehensile actions. We examined how subjects concurrently executed the transport and grasp components of reach-to-grasp movements when grasping differently sized objects. When comparing both VPD and IPD groups to control subjects, all patients showed longer movement duration and smaller hand opening, reflecting bradykinesia and hypometria, respectively. Furthermore, for all patients, the onset of the manipulation component was delayed with respect to the onset of the transport component. However, for patients with VPD this delay was significantly smaller than that found for the IPD group. It is proposed that this reflects a deficit - which is moderate for VPD as compared to IPD patients - in the simultaneous (or sequential) implementation of different segments of a complex movement. Altogether these findings suggest that kinematic analysis of reach-to-grasp movement has the ability to provide potential instruments to characterize different forms of parkinsonism.

Implicit olfactory processing attenuates motor disturbances in idiopathic Parkinson's disease.

Many reports in the literature indicate that idiopathic Parkinson's disease (IPD) patients have substantial olfactory dysfunctions even before motor symptoms become evident. It has not yet been clarified, however, if some form of implicit olfactory processing is preserved in this population. An olfactory visuomotor priming paradigm, which detects implicit olfactory processing in neurologically healthy participants, was utilized to investigate motor control in relation to olfactory signals in a group of IPD patients. Two control groups were also considered: 12 vascular Parkinson's disease (VPD) in whom normal olfactory abilities are typically reported and 12 neurologically healthy participants. All of the participants were asked to perform reach-to-grasp movements toward large or small targets following olfactory cues delivered by a computer-controlled olfactometer. The odor was either 'size' congruent with the target (e.g., strawberry or apple, respectively) or incongruent (e.g., apple or strawberry, respectively). A bend sensor glove (CyberGlove) was used to measure the hand kinematics. Facilitation effects were noted in all the groups with regard to movement time. If a congruent rather than an incongruent odor was delivered, the movement time of the reach-to-grasp was shortened and facilitation effects in maximum grip amplitude were noted in both the IPD and the VPD groups. The maximum grip amplitude was smaller when no odor, as compared to a congruent odor, was delivered. The present results suggest that implicit olfactory processing affects motor control in IPD patients favoring less severe bradykinesia and hand movement hypometria. Once confirmed, these findings could be useful when rehabilitation strategies are being hypothesized for these patients.

Multiple system atrophy is distinguished from idiopathic Parkinson's disease by the arginine growth hormone stimulation test.

OBJECTIVE: Multiple system atrophy (MSA) may be difficult to distinguish from idiopathic Parkinson's disease (PD). Our aim was to evaluate the accuracy of the arginine growth hormone (GH) stimulation test in distinguishing between MSA and PD in large populations of patients. METHODS: We measured the GH response to arginine in 69 MSA (43 MSAp [parkinsonism as the main motor feature] and 26 MSAc [cerebellar features predominated]) patients, 35 PD patients, and 90 healthy control subjects. We used receiver-operating curve analysis to establish the arginine cutoff value that best differentiated between MSA and PD. RESULTS: The GH response to arginine was significantly lower (p < 0.01) in MSA than in either PD patients or control subjects. At a cutoff level of 4 microg/L, arginine distinguished MSAp from PD with a sensitivity and specificity of 91% and MSAc from PD with a sensitivity of 96% and specificity of 91%. The arginine test had a positive predictive value for MSA of 95%. The GH response to arginine was not affected by disease duration or severity, MSA motor subtype, pyramidal signs, response to dopaminergic therapy, or magnetic resonance imaging findings. INTERPRETATION: The GH response to arginine differentiates MSA from PD with a high diagnostic accuracy. The results suggest an impairment of cholinergic central systems modulating GH release in MSA.

Progressive supranuclear palsy and corticobasal degeneration: lumping versus splitting.

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are both sporadic disorders with tau pathology. Criteria have been defined that in most instances allow for adequate diagnosis of the two disorders both clinically and neuropathologically; however, overlap is not uncommon. For example, patients with PSP may present with severe unilateral apraxia and supranuclear gaze palsy can occur in CBD. Pathological overlap also occurs and pathologically "mixed" cases are encountered. Common to both these two tauopathies is that isoforms of four-repeat tau due to splicing of exon 10 define the tau filamentous aggregates. This is in contrast to other tau disorders such as Pick's with three-repeat tau aggregates. Additional evidence for a causal link between PSP and CBD is the finding that both disorders are homozygous for the H1 tau haplotype. Furthermore, in some families with parkinsonism linked to defined mutations of the tau gene (FTDP-17), involved relatives have presented with PSP whereas others with the CBD phenotype. Although PSP and CBD frequently can be clearly separated clinically and pathologically, the degree of clinicopathological and genetic overlap is important and suggests that they represent different phenotypes of the same disorder, with differences occurring perhaps in relation to different genetic background. That PSP and CBD are distinct nosological entities occurring in patients with similar genetic predisposition cannot be ruled out.

Neuronal intranuclear inclusions in SCA2: a genetic, morphological and immunohistochemical study of two cases.

Spinocerebellar ataxia 2 (SCA2) belongs to the family of autosomal dominant cerebellar ataxias (ADCA), a genetically heterogeneous group of neurodegenerative diseases. The SCA2 gene maps to chromosome 12q24 and the causative mutation involves the expansion of a CAG repeat within the coding region of the gene. Pathologically, SCA2 presents as olivo-ponto-cerebellar atrophy (OPCA). We present the cases of a 41-year-old man and a 54-year-old woman who died after a long illness characterized by severe cerebellar ataxia. Diagnosis of SCA2 was confirmed by genetic analysis. The brains were moderately to severely atrophic and atrophy was particularly obvious in the cerebellum and brainstem. Histological examination revealed extreme loss of pontine and olivary nuclei and Purkinje cells, with preservation of the dentate nuclei, and of the pigmented cells in the substantia nigra. The whole spinal cord was also severely affected, with shrinkage of the dorsal columns and reduction in the number of neurones in the motor pool and Clarke's nuclei. Immunohistochemistry with 1C2 antibody showed granular neuronal cytoplasmic deposits in all the areas examined and widespread intranuclear inclusions, which were particularly numerous in the residual pontine nuclei. Intranuclear inclusions were not considered a feature in SCA2. Our results support the view that intranuclear inclusions are an integral part of the pathology of this mutation.