overcoming the clinical mr imaging paradox of multiple sclerosis mr imaging data assessed with a random forest approach

BACKGROUND AND PURPOSE: In MS, the relation between clinical and MR imaging measures is still suboptimal. We assessed the correlation of disability and specific impairment of the clinical functional system with overall and regional CNS damage in a large cohort of patients with MS with different clinical phenotypes by using a random forest approach. MATERIALS AND METHODS: Brain conventional MR imaging and DTI were performed in 172 patients with MS and 46 controls. Cervical cord MR imaging was performed in a subgroup of subjects. To evaluate whether MR imaging measures were able to correctly classify impairment in specific clinical domains, we performed a random forest analysis. RESULTS: Between-group differences were found for most of the MR imaging variables, which correlated significantly with clinical measures ( r ranging from −0.57 to 0.55). The random forest analysis showed a high performance in identifying impaired versus unimpaired patients, with a global error between 7% (pyramidal functional system) and 31% (Ambulation Index) in the different outcomes considered. When considering the performance in the unimpaired and impaired groups, the random forest analysis showed a high performance in identifying patients with impaired sensory, cerebellar, and brain stem functions (error below 10%), while it performed poorly in defining impairment of visual and mental systems (error of 91% and 70%, respectively). In analyses with a good level of classification, for most functional systems, damage of the WM fiber bundles subserving their function, measured by using DTI tractography, had the highest classification power. CONCLUSIONS: Random forest analysis, especially if applied to DTI tractography data, is a valuable approach, which might contribute to overcoming the MS clinical−MR imaging paradox

Effect of acute physostigmine and verapamil treatment on aggressive and depressive behavior in rats with lesioned nucleus basalis magnocellularis

In order to investigate the effects of physostigmine and verapamil on aggressive (test of foot shock induced aggression) and depressive (learned helplessness test) behavior, ten days after bilateral lesions of the nucleus basalis magnocellularis (NBM), adult male Wistar rats were acute treated (30 min before the test) with physostigmine (0.045, 0.060 and 0.075 mg/kg, s.c.) or verapamil (1.0, 2.5, 5.0 and 10.0 mg/kg, s.c.) Physostigmine in dose of 0.075 mg/kg and verapamil in doses 2.5 and 5.0 mg/kg significantly prolongated the escape latency period in the learned helplessness test and thus produced a consolidation of depressiveness in NBM-lesioned rats. Tn contrast to that, there was no restitution of aggressive behavior in NBM-lesioned rats treated with both drugs. It could be concluded that both physostigmine and verapamil exerts a significant influence on depressive, but not on aggressive reaction in an animal model of Alzheimer's disease

Effect of neural transplantation on depressive behavior in rats with lesioned nucleus basalis magnocellularis

Recent data of our group have shown that bilateral electrolytic lesions of the nucleus basalis magnocellularis (NBM) in rats reduced the escape behavior deficit that occurs in the learned helplessness test. The present study was done to establish the effect of intracerebral neural transplantation on the change in escape behavior of NBM-lesioned adult male Wistar rats in the learned helplessness test. At 2 days (NBM-ET) or 10 days (NBM-DT) after bilateral electrolytic NBM-lesions, small fragments of fetal frontal cortex (18th day of gestation) were allotransplanted into the lesioned NBM. Ten days after neural transplantation, the learned helplessness test was performed. The number of shocks that animals received before making an escape response was significantly reduced in NBM-lesioned rats (p lt .001, compared to intact control and sham-operated rats). In comparison to NBM-lesioned and sham-ET rats, the NBM-ET rats showed a marked (p lt .001) increase in the number of shocks delivered before the animal made such an escape response. On the other hand, NBM-DT rats did not show this increase. These results indicate that neural transplantation performed at an early time after lesioning of NBM reversed the effect of this lesion in rats exposed to learned helplessness test

Applications of the European Parkinson’s Disease Association sponsored Parkinson’s Disease Composite Scale (PDCS)

This study was addressed to determine the presence of Parkinson disease (PD) manifestations, their distribution according to motor subtypes, and the relationships with health-related quality of life (QoL) using the recently validated European Parkinson’s Disease Association sponsored Parkinson’s Disease Composite Scale (PDCS). Frequency of symptoms was determined by the scores of items (present if >0). Using ROC analysis and Youden method, MDS-UPDRS motor subtypes were projected on the PDCS to achieve a comparable classification based on the PDCS scores. The same method was used to estimate severity levels from other measures in the study. The association between the PDCS and QoL (PDQ-39) was analyzed by correlation and multiple linear regression. The sample consisted of 776 PD patients. We found that the frequency of PD manifestations with PDCS and MDS-UPDRS were overlapping, the average difference between scales being 5.5% only. Using the MDS-UPDRS subtyping, 215 patients (27.7%) were assigned as Tremor Dominant (TD), 60 (7.7%) Indeterminate, and 501 (64.6%) Postural Instability and Gait Difficulty (PIGD) in this cohort. With this classification as criterion, the analogous PDCS-based ratio provided these cut-off values: TD subtype, ≥1.06; Indeterminate, <1.06 but >0.65; and PIGD, <0.65. The agreement between the two scales on this classification was substantial (87.6%; kappa = 0.69). PDCS total score cut-offs for PD severity were: 23/24 for mild/moderate and 41/42 for moderate/severe. Moderate to high correlations (r = 0.35–0.80) between PDCS and PDQ-39 were obtained, and the four PDCS domains showed a significant independent influence on QoL. The conclusions are: (1) the PDCS assessed the frequency of PD symptoms analogous to the MDS-UPDRS; (2) motor subtypes and severity levels can be determined with the PDCS; (3) a significant association between PDCS and QoL scores exists. © 2019, The Author(s)