Several recent reports have suggested that foetal ventral mesencephalic transplants could alleviate motor symptoms in patients with Parkinson's disease. Expectations of future success must be clarified by precise analysis of the extent and limitation of recovery associated with an assessment of function of the graft using [18F]fluorodopa (18F-dopa) PET. Two patients with idiopathic Parkinson's disease, severely impaired despite optimal medication, have been followed 10 and 17 months after stereotaxic unilateral intrastriatal transplantation of neural cells dissociated from human foetal ventral mesencephalon. Analysis of the clinical evolution complied with the protocol established in the 'Core Assessment Program for Intracerebral Transplantation'. Both patients have benefited from the transplantation in their daily activities and in motor timed tests, although they still exhibit parkinsonian symptoms and require L-dopa therapy. This is associated with a gradual increase in 18F-dopa uptake at the site of grafting. There are two major clinical changes: (i) a bilateral motor improvement for the speed of movements (the quality of movements improved almost exclusively on the side contralateral to the graft); (ii) a change in the outcome of the L-dopa treatment as exemplified by a postoperative transient period of heavy dyskinesias and subsequent additive actions of the two treatments. These results confirm that neural transplantation may be useful for patients with Parkinson's disease. The improvement recorded on the side ipsilateral to the graft does not match that observed on the contralateral side and it is proposed that bilateral transplantation may be necessary. The existence of a transient postoperative period of heavy dyskinesias suggests that the patients may benefit from a controlled decrease of L-dopa intake after grafting.

Five patients with Parkinson's disease, unilaterally transplanted with foetal mesencephalic cells into putamen (n=1) or putamen and caudate (n=4), were followed throughout a period of 15-36 months after surgery, according to the recommendations of the core assessment programme for intracerebral transplantations (CAPIT). All these patients exhibited an increase in the fluorodopa uptake in the grafted putamen, which was most significant in the first and last patient of the series. Long-term bilateral improvement of skilled hand movements was observed, starting between the third and sixth month after grafting, and confirmed by the statistical analysis of CAPIT timed tests. A mild to moderate effect on the amount of 'off' time and 'on-off' fluctuations was observed, whereas, apart from one case, no other clear effect on gait, walking and speech was found. One patient included in the study, already suffering slight cognitive impairment, clearly exhibited progression of a dementia process after surgery. Daily living activities were clearly improved in only one of the other four patients. At the end of the study period, all patients needed L-dopa therapy at a similar or higher dose than before grafting, but, in most of them, other dopaminergic drugs were reduced or stopped. All patients exhibited bilateral dyskinesias before grafting that were greatly decreased in intensity a few months after surgery. Delayed asymmetrical dyskinesias, occurring on the side displaying the better motor improvement, i.e. contralateral to the graft, were observed in three patients. These results suggest that neural transplants may influence two central mechanisms involved in motor function and the onset of dyskinesias. These effects are likely to occur through complex interactions with the post-synaptic dopaminergic receptors. The occurrence of dyskinesias might simply reflect increased presynaptic storage and release of dopamine. Alternatively, it might, in part, represent some other long-term deleterious effect of the graft. Since PET-scan data indicate that the reinnervation obtained is sub-optimal, it will be of interest to obtain a larger and denser reinnervation of the host striatum and to try, thereafter, to reduce the dose of L-dopa.

Glutamate decarboxylase (GAD) activity was estimated in various areas of the brain in 21 control and 26 parkinsonian subjects matched for age, postmortem delay and premortem state. Retrospective analysis of clinical data was used to define a premortem severity index (PMSI), scaled from 0 to 6, based upon a semiquantitative estimation of the duration of anoxia (0-3) and hypovolaemia (0-3). A significant correlation was found between GAD activity and PMSI in most regions of the brain. In the prefrontal cortex and caudate nucleus, GAD activity was not correlated with age, postmortem delay, sepsis, being bedridden, or with cachexia. Dosage and duration of drug treatment did not influence striatal or cortical GAD levels. In Parkinson's disease, GAD activity did not differ from controls in many brain areas except in the caudate nucleus, hippocampus and the frontal and occipital cortex. No difference in striatal and cortical GAD activity was observed when 10 control and 9 parkinsonian brains were selected for an optimal premortem state which approximated to sudden death (PMSI less than or equal to 2). GAD activity in the caudate nucleus and prefrontal cortex was not significantly influenced by the duration of L-DOPA treatment or withdrawal, disease duration, or severity of intellectual deterioration. Although the number of samples in certain brain areas was too small to allow a definitive conclusion, these results make it doubtful that GABAergic neurons are damaged in this disease.

The aim of this article is to suggest that hostile behavior in elderly patients is often caused by a reversible mood disorder rather than by a personality disorder or dementia, even if these two last diagnoses are already well established. Sedatives, often prescibed for hostile behavior, can induce confusion, falls, and bedridden states, and can actually increase the rate of mortality. The mood disorder can be a hostile agitated depression or a mixed affective state. The hypothesis of a mood disorder calls for an antidepressant trial, possibly combined with a mood stabilizer.

Objectives: To validate the Psychogeriatric Inventory of Disconcerting Symptoms and Syndromes (PGI-DSS), a single scale in A4 format comprising four disconcerting syndromes (violence, refusal, words, and acts). The scale enables an immediate conversion of a qualitative assessment to a quantitative assessment. The PGI-DSS was compared with the Neuro Psychiatric Inventory for Nursing Homes (NPI-NH). Design: Cross-sectional descriptive and correlational studies. Setting: Thirty geriatric care units and nursing homes. Participants: Raters interviewed nurses and nursing assistants in charge of older adults hospitalized in geriatric care units or living in nursing homes (N = 226). Measurements: The French version of the PGI-DSS and the French version of the NPI-NH. Results: The correlation coefficient between the PGI-DSS and the NPI-NH was 0.70 (p < 0.0001). The PGI-DSS threshold score corresponding to the NPI threshold score was 17 (specificity: 87%, sensitivity: 63%). Four statistical factors, corresponding to the four clinical syndromes, explained 53.4% of the total variance. The internal consistency of the PGI-DSS (Cronbach’s alpha = 0.695) was higher than that of the NPI-NH (Cronbach’s alpha = 0.474). Test–retest reliability was better for the PGI-DSS than for the NPI-NH. The intraclass correlations were 0.80 [0.73; 0.86] and 0.75 [0.67; 0.83], respectively. Interrater reliability was better for the PGI-DSS than for the NPI-NH. The intraclass correlations were 0.65 [0.55–0.76] and 0.55 [0.43–0.68], respectively. Conclusion: The PGI-DSS was developed to overcome the limitations of the NPI-NH. New, brief, easy to administer in less than 4 minutes, foldable in four parts, pocket-sized, easy-to-read in the palm of the hand, PGI-DSS could have similar or better statistical properties than the NPI-NH. Whereas the 10 domains in the NPI-NH have clinical utility for clinicians, the four easily understandable syndromes in the PGI-DSS can help avoid inappropriate attitudes and can guide psychosocial interventions. It could likewise improve dialogue between caregivers and clinicians.