[Chronic postsurgical pain]. / Douleurs chroniques postchirurgicales.

OBJECTIVES: Update reviewing of chronic postsurgical pain. DATA SOURCES: The following review is based on the English and French literature published in PubMed database between January 1998 and 2013. The research articles were made with following keywords alone or in combination: "chronic pain", "surgery", "postsurgical pain". These keywords were combined with "epidemiology", "incidence", "predictive factors" and "prevention". Study selection Publications were deemed relevant if they contained information about CPSP after 8 weeks post surgery. Animal publications were not included. Only randomized controlled studies were taken into consideration for the pharmacological prevention. DATA EXTRACTION: Data extracted were related to epidemiology, impact, predictive factors and prevention of CPSP. DATA SYNTHESIS: Epidemiology of CPSP is more recognized as it is experienced by 10-50% of individuals after classical operations. CPSP can be severe in about 5 to 10% of these patients. CPSP is a major public health problem still rarely diagnosed and treated. Twenty percent of patients consulting in a pain clinic have a CPSP. The frequency of neuropathic pain is important but the difference in the proportion to CPSP falls between 6-68% and depend on the type of surgery. Clinical risk factors and physiopathology of CPSP are subject of wide development. Human studies allowed better understanding of the neurophysiological as well psychological aspect of the development of CPSP. Finally, the possibility of pharmacological prevention of CPSP seems to have increased in the past years. Nevertheless, there are still many questions that need to be answers about the problem. We should clearly define the optimal characteristics of clinical and experimental studies as this will allow the better understanding of the prevention of CPSP. Anesthesiologists play a crucial role in this development. They are involved in all of the stages of the operative care of patients and play a decisive role in the evaluation of the risk, the development of a preventive strategy, and in the early detection and treatment of CPSP.

Beyond neuropathy in hereditary sensory and autonomic neuropathy type V: cognitive evaluation.

BACKGROUND AND PURPOSE: Hereditary sensory and autonomic neuropathy (HSAN) type V is a very rare disorder. It is characterized by the absence of thermal and mechanical pain perception caused by decreased number of small diameter neurons in peripheral nerves. Recent genetic studies have pointed out the aetiological role of nerve growth factor beta, which is also involved in the development of the autonomic nervous system and cholinergic pathways in the brain. HSAN type V is usually reported not to cause mental retardation or cognitive decline. However, a structured assessment of the cognitive profile of these patients has never been made. METHODS AND RESULTS: We performed a throughout evaluation of four HSAN type V patients and compared their performance with 37 normal individuals. Our patients showed no cognitive deficits, not even mild ones. DISCUSSION AND CONCLUSIONS: Although newer mutations on this and related disorders are continuously described, their clinical characterization has been restricted to the peripheral aspects of these conditions. A broader characterization of this rare disorder may contribute to better understand the mechanisms of the nociceptive and cognitive aspects of pain.

[Place and role of neuropsychological exam in elderly depression]. / Place et intérêt de l'examen neuropsychologique dans la dépression du sujet âgé.

PURPOSE: Neuropsychology provides essential information to all participants (physicians, psychologists, occupational therapists) involved in the treatment of the elderly. When treating depressed elderly patients, a comprehensive neuropsychological examination is required for diagnosis, prognosis and to control the effectiveness of antidepressant treatment. KEY MESSAGE AND RECENT FACTS: Depression in elderly people is frequent and difficult to diagnose. Some forms of depression usher in or are associated with a neurodegenerative disease. In the case of diagnosis, the neuropsychological examination should furnish useful information to guide the clinician. The qualitative analysis of results (strategies used and type of errors) and the weakening of cognitive processes efficiency provides supplementary information and increases the reliability of the diagnosis. It also gives information about the long term evolution of cognitive deficits. It should reveal the presence of characteristics which help to distinguish patients who are developing dementia (predictive power of certain tests). Finally, it enables the clinician to evaluate the outcome of antidepressant treatment, to adjust the prescription according to the performance and to adapt an holistic treatment. PERSPECTIVE AND PROJECTS: A neuropsychological examination may provide new perspectives, such as the possibility of predicting the outcome of dementia which are accompanied by affective disorders, such as Alzheimer's disease, vascular dementia and frontotemporal dementia. Neuropsychology may thus improve the treatment of these patients by providing information to a better understanding of their deficits and their impact on daily living abilities.

Neuroprotective gene therapy for Huntington's disease, using polymer-encapsulated cells engineered to secrete human ciliary neurotrophic factor: results of a phase I study.

Huntington's disease (HD) is a monogenic neurodegenerative disease that affects the efferent neurons of the striatum. The protracted evolution of the pathology over 15 to 20 years, after clinical onset in adulthood, underscores the potential of therapeutic tools that would aim at protecting striatal neurons. Proteins with neuroprotective effects in the adult brain have been identified, among them ciliary neurotrophic factor (CNTF), which protected striatal neurons in animal models of HD. Accordingly, we have carried out a phase I study evaluating the safety of intracerebral administration of this protein in subjects with HD, using a device formed by a semipermeable membrane encapsulating a BHK cell line engineered to synthesize CNTF. Six subjects with stage 1 or 2 HD had one capsule implanted into the right lateral ventricle; the capsule was retrieved and exchanged for a new one every 6 months, over a total period of 2 years. No sign of CNTF-induced toxicity was observed; however, depression occurred in three subjects after removal of the last capsule, which may have correlated with the lack of any future therapeutic option. All retrieved capsules were intact but contained variable numbers of surviving cells, and CNTF release was low in 13 of 24 cases. Improvements in electrophysiological results were observed, and were correlated with capsules releasing the largest amount of CNTF. This phase I study shows the safety, feasibility, and tolerability of this gene therapy procedure. Heterogeneous cell survival, however, stresses the need for improving the technique.

Retest effects and cognitive decline in longitudinal follow-up of patients with early HD.

OBJECTIVE: To assess the natural progression of cognitive impairment in Huntington's disease (HD) and to reveal factors that may mask this progression. BACKGROUND: Although numerous cross-sectional studies reported cognitive deterioration at different stages of the disease, progressive cognitive deterioration has been, up to now, difficult to demonstrate in neuropsychological longitudinal studies. METHODS: The authors assessed 22 patients in early stages of HD at yearly intervals for 2 to 4 years (average, 31.2 +/- 10 months), using a comprehensive neuropsychological battery based on the Core Assessment Program for Intracerebral Transplantation in Huntington's Disease (CAPIT-HD). RESULTS: The authors observed a significant decline in different cognitive functions over time: these involved primarily attention and executive functions but also involved language comprehension, and visuospatial immediate memory. Episodic memory impairment that was already present at the time of enrollment did not show significant decline. The authors found a significant retest effect at the second assessment in many tasks. CONCLUSION: Many attention and executive tasks adequately assess the progression of the disease at an early stage. For other functions, the overlapping of retest effects and disease progression may confuse the results. High interindividual and intraindividual variability seem to be hallmarks of the disease.

Motor and cognitive improvements in patients with Huntington's disease after neural transplantation.

BACKGROUND: Huntington's disease is a neurodegenerative disease of genetic origin that mainly affects the striatum. It has severe motor and cognitive consequences and, up to now, no treatment. Motor and cognitive functions can be restored in experimental animal models by means of intrastriatal transplantation of fetal striatal neuroblasts. We explored whether grafts of human fetal striatal tissue could survive and have detectable effects in five patients with mild to moderate Huntington's disease. METHODS: After 2 years of preoperative assessment, patients were grafted with human fetal neuroblasts into the right striatum then, after a year, the left striatum. Final results were assessed 1 year later on the basis of neurological, neuropsychological, neurophysiological, and psychiatric tests. The results obtained were compared with those of a cohort of 22 untreated patients at similar stages of the disease who were followed up in parallel. Repeated magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning with fluorine-18-labelled fluorodeoxyglucose was also done to assess metabolic activity. FINDINGS: The final PET-scan assessment showed increased metabolic activity in various subnuclei of the striatum in three of five patients, contrasting with the progressive decline recorded in the two other patients in the series, as seen in patients with untreated Huntington's disease. Small areas of even higher metabolic activity, coregistering with spherical hyposignals on MRI were also present in the same three patients, suggesting that grafts were functional. Accordingly, motor and cognitive functions were improved or maintained within the normal range, and functional benefits were seen in daily-life activities in these three patients, but not in the other two. INTERPRETATION: Fetal neural allografts could be associated with functional, motor, and cognitive improvements in patients with Huntington's disease.

Neuroprotective gene therapy for Huntington's disease using a polymer encapsulated BHK cell line engineered to secrete human CNTF.

Huntington's disease (HD) is an autosomal dominant genetic disease with devastating clinical effects on cognitive, psychological, and motor functions. These clinical symptoms primarily relate to the progressive loss of medium-spiny GABA-ergic neurons of the striatum. There is no known treatment to date. Several neurotrophic factors have, however, demonstrated the capacity to protect striatal neurons in various experimental models of HD. This includes the ciliary neurotrophic factor (CNTF), the substance examined in this protocol. An ex vivo gene therapy approach based on encapsulated genetically modified BHK cells will be used for the continuous and long-term intracerebral delivery of CNTF. A device, containing up to 106 human CNTF-producing BHK cells surrounded by a semipermeable membrane, will be implanted into the right lateral ventricle of 6 patients. Capsules releasing 0.15-0.5 microg CNTF/day will be used. In this phase I study, the principal goal will be the evaluation of the safety and tolerability of the procedure. As a secondary goal, HD symptoms will be analyzed using a large battery of neuropsychological, motor, neurological, and neurophysiological tests and the striatal pathology monitored using MRI and PET-scan imaging. It is expected that the gene therapy approach described in this protocol will mitigate the side effects associated with the peripheral administration of recombinant hCNTF and allow a well-tolerated, continuous intracerebroventricular delivery of the neuroprotective factor.