Apathy in Parkinson's disease: differences between caregiver's report and self-evaluation.

Apathy is a state of diminished goal-directed speech, motor activity and emotions. The prevalence of apathy in Parkinson's disease (PD) ranges from 16 to 62%. Several studies have investigated the relationships between apathy and other dimensions of PD, but little is known about possible discrepancies between self-evaluation (SE) and caregiver reporting (CR) of this symptom. The aim of this study is twofold: 1) to investigate the differences in apathy evaluations according to the point of view from which apathy is reported (SE vs CR); 2) to identify the possible relationships between each of the two evaluations (SE and CR) and cognitive and affective dimensions of PD. Forty-eight patients with PD were assessed using the Apathy Evaluation Scale (AES) in its SE and CR versions (AES-SE and AES-CR); cognitive, affective and behavioral symptoms were also assessed. AES-SE scores were significantly higher than AESCR ones. Neither AES version correlated with depression, whereas both correlated with motor impairment, disease stage and behavioral symptoms. Mini-Mental State Examination and Frontal Assessment Battery scores showed significant negative correlations only with AES-SE scores. Our findings suggest that the point of view from which apathy is seen can lead to significant discrepancies, even when using the same tool. This should be taken into account in order to obtain correct assessment of this disabling and distressing symptom.

Behavioural sensitization in 6-hydroxydopamine lesioned rats involves the dopamine signal transduction: changes in DARPP-32 phosphorylation.

"Priming" is a phenomenon of behavioural sensitization observed in unilaterally 6-hydroxydopamine lesioned rats following exposure to a dopamine agonist. After priming, a single dose of the D1 agonist SKF 38393 (3 mg/kg) produces contralateral turning, while the same dose is inactive in drug-naive, lesioned animals. The molecular mechanisms of "priming" were investigated here by studying the phosphorylation of dopamine and adenosine 3'-5' monophosphate regulated phosphoprotein (DARPP-32), a dopamine- and cyclic AMP-regulated phosphoprotein functionally linked to D1 receptors in striatum. Dephospho-form of DARPP-32 were measured by a back-phosphorylation assay. All assays were performed in striata from both lesioned and unlesioned sides. A significant decrease of dephospho-DARPP-32 (27%) was observed in the denervated striatum of primed rats, indicating an increased phosphorylation in vivo of DARPP-32 in response to the D1 agonist. The levels of DARPP-32 protein, as measured by quantitative immunoblotting, remained unchanged in all experimental groups. This study shows that priming is expressed as an increased transduction of the D1 receptor message.

Dopaminergic regulation of epileptic activity.

We evaluated the role of dopamine systems in the propagation of epileptic Focal, limbic seizures were produced by systemically administered pilocarpine (200 mg/kg, i.p.); as previously described this dose produces limbic stereotypes but neither convulsions nor seizure-related brain damage. The systemic pretreatment with D-1, but not D-2, agonists induced convulsions identical to those produced by a higher, convulsant dose of pilocarpine (400 mg/kg). Conversely, the pretreatment with D-1 receptor antagonists prevented the convulsions whereas the D-2 antagonists facilitated the pilocarpine-induced seizures. Furthermore, we studied the effects of intracerebral injections of dopamine agents on seizures induced by pilocarpine. Nigral microinjection of D-1 agonists strongly induced motor seizures in rats treated with the low dose of pilocarpine. On the other hand, microinjection of D-1 antagonists prevented the motor seizures induced by the high dose of pilocarpine. This study indicates that the two dopamine receptor subtypes, D-1 and D-2, exert opposing roles in the control of epilepsy propagation. Substantia nigra pars reticulata appears to be primarily involved in the dopamine-mediated modulation of seizures.

Dopamine mediated responses in 6-hydroxydopamine lesioned rats involve changes of the signal transduction.

A single dose of the D1 agonist SKF 38393 (3 mg/kg) produces contralateral turning in unilaterally 6-hydroxydopamine lesioned rats only after a previous exposure of the animals to a dopamine agonist. This priming phenomenon is here investigated by studying the phosphorylation of DARPP-32, a dopamine- and cyclic AMP-regulated phosphoprotein functionally linked to D1 receptors in striatum. Dephospho-form of DARPP-32 in striatal tissue was measured by a back-phosphorylation assay. While the levels of DARPP-32 protein, as measured by quantitative immunoblotting, remained unchanged, a significant decrease of dephospho-DARPP-32 was observed in the denervated striatum of primed rats, indicating an increased phosphorylation in vivo of DARPP-32 in response to the D1 agonist. This study shows that an alteration of the dopamine-dependent signal transduction is related to the behavioral response to dopamine agents, suggesting a possible mechanism involved in the effects of these drugs in parkinsonian patients.

Expression of c-fos protein in the experimental epilepsy induced by pilocarpine.

The expression of the c-fos proto-oncogene, as estimated by immunohistochemistry of the FOS nuclear protein, was studied in both focal and generalized seizures induced in rats by systemic administration of pilocarpine. Focal seizures, as indicated by the occurrence of stereotyped oral movements, chewing and sniffing, were evoked by either a subconvulsant dose of pilocarpine (200 mg/kg) or the association of a convulsant dose of pilocarpine (400 mg/kg) with SCH 23390, a selective D-1 dopamine receptor antagonist. This seizure pattern resulted in FOS accumulation in certain limbic areas, namely, the piriform cortex, amygdala, and olfactory tubercle. On the other hand, in rats developing generalized seizures, accumulation of FOS was also found in hippocampus, cingulate cortex, frontal cortex, striatum, accumbens, as well as in certain thalamic nuclei. Generalized seizures, including motor limbic seizures and status epilepticus, were induced by either a convulsant dose of pilocarpine (400 mg/kg) or a low dose of pilocarpine (15-200 mg/kg) combined with either lithium or the D-1 selective agonist SKF 38393. These findings indicate a close correlation between the sequence of behavioural alterations induced by pilocarpine and the proto-oncogene activation. The results provide the basis for mapping the areas of origin and the pathways of generalization of seizure activity. As shown by the effects of dopamine receptor agonists and antagonists, the process of generalization appears to be controlled by the dopamine system.

Post-apopletic trigeminal trophic syndrome.

Trigeminal trophic syndrome is an uncommon clinical entity in which cutaneous trophic ulceration develops with continuous manipulation of trigeminal dermatomes. Patients spontaneously refer picking, rubbing and/or scratching at the affected areas because of hypo-anaesthesia, paraesthesia and/or pain following damage of the sensory trigeminal fibres or nuclei. We herein describe a patient who developed the syndrome as a sequela of brain stem infarction. Diagnosis by scrape cytology in ruling-out basal cell carcinoma and other ulcerative skin diseases is discussed and the importance of neurological examination in disclosing hemi-anaesthesia of trigeminal dermatome(s) is emphasized.

Clinical and neurological abnormalities in adult celiac disease.

We assessed the occurrence of neurological signs and symptoms in adult patients with celiac disease and evaluated the correlation between neurological features and diet. A total of 176 patients and 52 age-matched controls underwent a semistructural interview and a neurologic examination. The effect of gluten-free diet was evaluated by comparing the prevalence of signs and symptoms among patients adhering to a gluten-free diet and patients on an unrestricted diet. The occurrence of headache, dysthymia and signs of peripheral neuropathy was significantly higher in patients with celiac disease than in control subjects. Adherence to a strict gluten-free diet was associated with a significant reduction of headache, dysthymia, cramps and weakness, but did not modify the occurrence of paresthesia or hyporeflexia. Neurological signs and symptoms are associated with celiac disease and can be ameliorated by a gluten-free diet.