ABSTRACT
AIM: This study concerns the aetiologies, comorbidities and places and causes of death of a population of persons with severe polyhandicap (PLH). METHODS: Based on the medical files of all deceased PLH patients, who were cared for between 2006-2012. Data collected were aetiological diagnosis of the polyhandicap, duration and type of hospitalization, age, place and cause of death, comorbidities: chronic respiratory insufficiency, recurrent attacks of pulmonary infections, urinary infections, active epilepsy, scoliosis, chronic digestive disorders and behavioural problems. RESULTS: One hundred and thirty-three patients died, 70 children and 63 adults. The sex ratio was 84 men to 49 women. The average stay in these institutions was 10 years 4 months. The average age at the time of death was 21 years, in 60% of cases the place of death was in the specialist rehabilitation centres. The causes of death in decreasing order were: pulmonary infections (63.2%), sudden death (18%) and status epilepticus (6.8%); 79.7% of patients suffered from chronic respiratory insufficiency, 60.2% suffered serious scoliosis, 66.9% drug-resistant epilepsy and 78.9% had digestive disorders. The main aetiologies of the polyhandicap were: pre- and perinatal encephalopathies (31.6%), metabolic encephalopathies (18%) and convulsive encephalopathies (11.3%). CONCLUSION: The main comorbidity and main cause of death in patients with severe PLH is respiratory failure.
Subject(s)
Chronic Disease/mortality , Disabled Persons , Rehabilitation Centers , Adolescent , Adult , Cause of Death , Child , Child, Preschool , Comorbidity , Disabled Persons/rehabilitation , Epilepsy/mortality , Female , Follow-Up Studies , France/epidemiology , Hospitalization/statistics & numerical data , Humans , Intellectual Disability/mortality , Length of Stay , Lung Diseases/mortality , Male , Mental Disorders/mortality , Mental Health Services , Middle Aged , Patient Admission , Rehabilitation Centers/statistics & numerical data , Scoliosis/mortality , Severity of Illness Index , Surveys and Questionnaires , Urinary Tract Infections/mortalityABSTRACT
We previously reported that some N-methyl-D-aspartate (NMDA)-receptor antagonists enhanced histamine neuron activity in rodents. Here, we have investigated the effects of memantine, an NMDA-receptor antagonist used for the treatment of Alzheimer's disease, on histaminergic neurotransmission. In vitro, memantine antagonized native NMDA receptors with a micromolar potency but had no effect at recombinant human histamine receptors. In vivo, a single administration of memantine increased histamine neuron activity, as shown by the 60% increase of tele-methylhistamine (t-MeHA) levels observed in the brain of mice. This increase occurred with an ED(50) of 0.3 ± 0.1 mg/kg, similar to that found on inhibition of ex vivo [(3)H]dizocilpine maleate (MK-801) binding (1.8 ± 1.3 mg/kg). Two days after pretreatment of mice with memantine at 5 mg/kg twice daily for 5 days, t-MeHA levels were enhanced by 50 ± 7% (p < 0.001), indicating a long-lasting activation of histamine neurons. Quantitative polymerase chain reaction analysis was used to explore genes involved in this persistent effect. H(3) receptor mRNAs were strongly increased, but the density of H(3) receptor binding sites was increased solely in hypothalamus (by 141 ± 24%). Up-regulations of brain-derived neurotrophic factor and NMDA-receptor 1 subunit mRNAs were also found but were restricted to hippocampus. mRNA expression of α7-nicotinic receptors remained unchanged in any region. Considering the well established cognitive effects of histamine neurons, the increase in brain t-MeHA levels after single or repeated administration of therapeutic doses of memantine suggests that the drug exerts its beneficial effects on cognitive deficits of Alzheimer's disease, at least partly, by activating histamine neurons.
