Blood-brain barrier damage associates with glia-related cytokines in the cerebrospinal fluid of patients with Multiple Sclerosis.

BACKGROUND: The presence of Blood-Brain Barrier (BBB) dysfunction is defined by albumin quotient (QALB) and characterize a group of Multiple Sclerosis (MS) patients at clinical onset. We evaluated the concentration in cerebrospinal fluid (CSF) of 87 cytokines, to better characterize the CSF inflammatory pattern in presence of BBB damage. MATERIALS AND METHOD: In an exploratory cohort, CSF cytokines were evaluated by means of Multiplex technology (Bio-Plex Pro-Human Cytokine, GF and Diabetes 27-Plex Panel, Bio-Plex Pro-Human Chemokines 40-Plex Panel, Bio-Plex Pro-Human Inflammation Assays 37-Plex Panel) in a cohort of Other Not Inflammatory Neurological Disorders (ONIND) and in cohort of patients with MS, stratified according to BBB damage into QALB+ and QALB- MS patients. In the validation cohort, we evaluated the relevant molecules in a cohort of MS patients, stratified again into QALB+ and QALB-, including also Neurofilament Light (NfL) and Chitinase 3-like 1 (CHI3L1) CSF concentration. RESULTS: While MIP-1α, CXCL-13, and CCL-22 CSF concentrations were higher in both MS groups compared to ONIND, in QALB+ MS CSF concentrations of CXCL-9 (17.85 ± 4.69 pg/mL), CXCL-10 (476.5 ± 324.3 pg/mL), and IL-16 (96.08 ± 86.17 pg/mL) were higher than in QALB- MS (8.98 ± 5368 pg/mL, p < 0.005, 281.0 ± 180.9 pg/mL, p < 0.05, and 47.35 ± 36.87 pg/mL, p < 0.005, respectively) and ONIND (8.98 ± 5368 pg/mlL, p < 0.005, 281.0 ± 180.9 pg/mL, p < 0.005, and 47.35 ± 36.87 pg/mL, p < 0.001, respectively). A strong correlation was observed between CXCL-9 and CXCL-10 in all MS groups (all r>0.75, all p < 0.001). In the validation cohort again CXCL-10 CSF concentration were higher in QALB+ MS than in QALB- MS (94.25 ± 64.75 vs 153.8 ± 99.52, p < 0.05), while no difference was observed in serum. CSF NfL (1642 ± 1963 vs 3231 ± 3492 pg/mL, p < 0.05) and CHI3L1 (183.9 ± 86.62 vs 262 ± 137.5 ng/mL, p < 0.05) were increased in QALB+ MS. CONCLUSIONS: BBB damage in MS is linked to a specific CSF cytokines pattern (CXCL-9, CXCL-10, IL-16), that are also involved in astrocyte-microglia interaction. To what extent their continuous production in the CNS may mark a more severe disease course merits to be investigated.

Practical tips for prescribing exercise for fall prevention.

CLINICAL RELEVANCE: There is strong evidence from meta-analyses that exercise as a single intervention can reduce the number and risk of falls in community-dwelling older adults, yet not all types of exercise are equal. OBSERVATIONS: Programs that include 3 h a week of exercise and provide a high challenge to balance can reduce falls by almost 40%. Reactive and volitional stepping interventions have also been shown to reduce falls by about 50%. Evidence is less clear regarding the efficacy of exercise in individuals who have experienced a stroke, who live in long-term care, who have been recently discharged from the hospital, or who have visual impairments, but there is some evidence that multifactorial programs may be useful. CONCLUSION: Depending on the population, exercise as a single or as part of a multifactorial intervention may be beneficial in reducing falls.

Catecholaminergic drugs in chronic schizophrenia.

The effect of dopaminergic-related and stimulatory drugs have been studied in chronic hebephrenic schizophrenics untreated with neuroleptic drugs. 6 patients received therapy of 2 g L-dopa + 200 mg carbodopa per day orally for 30 days, then placebo for 30 days. Following that 3 of the same patients received therapy of 2 g L-dopa + 200 mg carbodopa + 300 mg imipramine orally for 30 days, then placebo for 30 days. Following that the same 3 patients received 1 mg apomorphine s.c. for 15 days, then placebo for 15 days, then 1 mg apomorphine s.c. + 2 g L-dopa + 200 mg carbodopa per os daily for 15 days, then placebo for 15 days. The patients were examined psychologically by the Wittenborn Rating Scale, the Weigl Object-Sorting Test, and tests for verbal learning and verbal association, before and after each therapeutic trial. Levels of FSH, LH, testosterone and GH were assayed radioimmunologically before, in the middle of and after each course of therapy. 2 patients showed improvement in the affective-behavioural symptomatology during therapy, while the other 4, who had a more severe degree of mental deterioration and destruction, were unchanged. FSH and LH levels, very low under basal conditions, did not change under therapy. Testosterone was very low before therapy and increased in only 1 subject. Normal basal GH levels increased during therapy in some of the patients, but not constantly. The results obtained are discussed in relation to the catecholamine hypotheses of schizophrenia.

Sleep, psychophysiological functioning and learning processes in schizophrenia.

Sleep research has underlined how sleep is a specific functional moment inserted in the more complex system of circadian psychobiological rhythms. Many experimental data have evidenced that in particular REM sleep is involved in information processing and cognitive processes. The authors examine correlations between daytime cognitive performances and sleep patterns in a group of 11 schizophrenic patients, and in a control group made of 11 non-schizophrenic (borderline, depressed, character disorders) patients. Results show that there exists a relationship between REM sleep and cognitive activities, beyond nosographic partitions. They on the other side suggest caution in using sleep as a means of discrimination between schizophrenic and non-schizophrenic patients.

Neurophysiological aspects and learning processes in schizophrenic patients.

Two groups of schizophrenic patients (acute and chronic subjects) were observed in order to study possible differences in neuropsychological performances and their relationship with symptomatology. 16 acute and 16 chronic patients, aged 18 to 35 years were tested with a battery of neuropsychological tests (Word Association Test, Serial Verbal Learning, Weigl's test, Simple Reaction Times, Choice Continuous Reaction Time). Clinical profiles were evaluated by means of MMPI and WAIS (Wechsler Adult Intelligence Scale). Findings concerning cognitive processes show no significant differences between the two groups. Results suggest a correlation between clinical profiles and performances in acute patients, whereas in chronic subjects this correlation seems markedly reduced. Finally, chronicity (i.e. the length of illness) does not seem so be an important factor in determining consistent defects in neuropsychological performances.