Depression and cognitive sequelae after a traumatic brain lesion.

INTRODUCTION: To improve rehabilitation in young people with an acquired brain injury, the Danish Ministry of Health initiated the "National study on young brain injury survivors" in 2012. Using data from this initiative, we examined the changes in depression, cognition, global functional outcome and return to work/school among young traumatic brain injury (TBI) survivors. METHOD: This was an observational one-year follow-up study based on data from "Danish registry for young adults with acquired brain injury". The main measures were Major Depression Inventory, neuropsychological examination, and Glasgow Outcome Scale - extended (GOS-E). RESULTS: A total of 76 young TBI survivors attended two interdisciplinary examinations and had complete data. Sixty-six (86.8%) had rehabilitation between the two visits, and the global functional outcome was vastly higher at the second visit (z = -3.373, p = 0.0007). At the first versus the second visit, the prevalence proportion of depression was 14.5% (95% confidence interval (CI): 7.5-24.4) versus 10.5% (95% CI: 4.7-19.7), and for cognitive sequelae it was 31.6% (95% CI: 21.4-43.3) versus 19.7% (95% CI: 11.5-30.5). Patients with depression and/or cognitive sequelae had a lower GOS-E score (p = 0.0016) than patients without depression/cognitive sequelae and a negative association was found between depression, cognitive sequelae and return to work/school (p = 0.045). CONCLUSION: Emotional and cognitive rehabilitation for young TBI survivors seems essential as depression and cognitive sequelae are associated with a lower global functional outcome and return to work/school. FUNDING: none. TRIAL REGISTRATION: not relevant.

Depression and cognitive sequelae registered within the first year among young Danish TBI survivors.

The aim of the study was to determine the proportion of depression and cognitive sequelae among young (15-30 years) Danish TBI survivors referred to interdisciplinary evaluation through a nationwide government-initiated health initiative. The cross-sectional study is based on data from the "Danish register for young adults with acquired brain injury" on TBI survivors included from October 2013 to December 2016. The main measures were Major depression inventory, Trail making test A and B, Fluency, Word learning with selective reminding, Matrix reasoning, Coding and Glasgow outcome scale - extended (GOS-E). During the study period, 131 young TBI survivors were referred to one of five national outpatient clinics. Ninety-six had complete data and of these 14.6% fulfilled the ICD-10 diagnostic criteria for depression and 34.4% had cognitive sequelae. An association was found between depression and cognitive sequelae (p = 0.004). Patients with both depression and cognitive sequelae (n = 10) had a significantly lower mean score on GOS-E (p = 0.0001). Depression and cognitive sequelae were frequent and associated with a poorer global functional outcome among young TBI survivors referred within a year after trauma. This finding and the notion that only 20% of the expected TBI population was referred to this nationwide health initiative indicate an unacknowledged need for interdisciplinary follow-up.

A case report revealing acute onset psychosis and cognitive impairment as primary manifestation in relapsing-remitting multiple sclerosis.

Acute psychosis and cognitive impairment is a significant problem in RRMS. As it concerns in relatively young age group, our case report underscores the importance of early recognition which could impose diagnostic challenge in multiple sclerosis.

Prevalence of depression after moderate to severe traumatic brain injury among adolescents and young adults: A systematic review.

To review the prevalence of depression among adolescents and young adults after moderate to severe TBI. A systematic literature search was conducted on literature published up to December 2018 in PubMed, EMBASE, Cochrane and PsychInfo. A systematic review of the identified literature was based on PRISMA guidelines. Risk of Bias was evaluated based on the aspects of Risk of Bias assessment described by the Agency of Health Research and Quality. Seven studies were deemed eligible and information on the prevalence of depression among adolescents and young adults (age 13-35) after moderate to severe TBI was extracted. Depression was assessed at 12 months (n = 2), >12 months (n = 2) or at varying times (n = 3) after TBI. The identified studies reported a prevalence proportion of depression from 1.6% to 60%. The Risk of Bias assessment showed a range of study quality with the selection of subjects and analysis of attrition being problematic. Although literature is sparse and of varying quality, depression was found to be common among adolescents and young adults with moderate to severe TBI which implies a need to focus on depression in the rehabilitation process and calls for further research.

Continuous MPTP intoxication in the Göttingen minipig results in chronic parkinsonian deficits.

Parkinson's disease (PD) is a common neurodegenerative disorder, resulting from progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Neuroprotective therapies in PD are still not available, perhaps because animal models do not imitate the chronic and progressive nature of the clinical state of PD. To address this, we performed a feasibility study aimed at establishing a chronic non-primate large animal PD model in Göttingen minipigs based on continuous infusion of the neurotoxin 1-methyl-4-phenyl­1,2,3,6-tetrahydropyridine (MPTP). Twelve female Göttingen minipigs were divided into groups of 2-4 animals and implanted with infusion pumps for continuous intramuscular MPTP delivery of 4-24 mg MPTP/day for 11 weeks. The animals showed parkinsonian symptoms with bradykinesia, rigidity, coordination and chewing difficulties. Symptoms were stable in the 12 and 18 mg MPTP/day groups, whereas the remaining groups showed partial or full behavioral recovery. Digital gait analysis, high performance liquid chromatography (HPLC) measurements and stereological counts of tyrosine hydroxylase-positive (TH+) neurons in the SNc revealed a dose-related decrease in gait velocity, striatal metabolite levels and neuron numbers with increasing doses of MPTP. No neuronal inclusions were observed, but alpha-synuclein staining intensified with increased cumulative MPTP dosages. We conclude that this large-animal model of chronic MPTP administration in Göttingen minipigs shows trends of stable parkinsonian deficits at 18 mg MPTP/day in all modalities examined. This PD model shares many of the characteristics seen in patients and, although preliminary, holds considerable promise for future pre-clinical trials of neuroprotective therapies.

Gait analysis after total hip replacement with hip resurfacing implant or Mallory-head Exeter prosthesis: a randomised controlled trial.

A key to the analysis of function after total hip replacement (THR) is the ability to identify gait adaptations specific to design features and surgical procedures. In a randomised controlled design, we evaluated the mechanics of gait after THR with a hip resurfacing system or conventional prosthesis. We also investigated whether gait adaptations returned to normal postoperatively. Similar improvements in mechanics of gait were found, except for peak abductor moments, which improved more in the conventional group. Gait speed increased significantly, but with no differences between groups. The increase in walking speed was reflected as significant improvement within groups in most kinematic and kinetic variables. Significant differences between the operated and non-operated hip were seen in all patients, but with no difference between groups. Mean curves of joint angle profiles and moments in all anatomical planes during a gait cycle revealed that gait impairment persisted with no differences between the conventional prosthesis and the resurfacing system.

Direct MRI-guided stereotaxic viral mediated gene transfer of alpha-synuclein in the Göttingen minipig CNS.

The aim was to establish a non-primate large animal PD model by lentiviral vector mediated mutant alpha-synuclein overexpression in the substantia nigra. Lentivirus encoding A53T alpha-synuclein (6 x 2.5 µl) was stereotaxically injected into the substantia nigra of six adult female Göttingen minipigs. Contralateral control injections encoding enhanced green fluorescent protein (EGFP) were performed. Gait-analysis was performed pre- and postoperatively. PCR of the transgenes and immunohistochemical staining against alpha-synuclein, EGFP, GFAP and TH was performed after 20 weeks. Gait analysis revealed a significant increase in step length and height, and a decrease in the double stand phase. PCR verified the mesencephalic presence of transgenes. IHC analysis showed alpha-synuclein expression in nigral neurons, around the injection tract and in related nigrostriatal projections. The alpha-synuclein positive neurons appeared swollen and vacuolated, in contrast to the EGFP-injected control side. To transduct all nigrostriatal cells with few microinjections, wider dissemination of the transgene must be achieved.

Improved asymmetry of gait in Parkinson's disease with DBS: gait and postural instability in Parkinson's disease treated with bilateral deep brain stimulation in the subthalamic nucleus.

Postural instability is a sign of progression of Parkinson's disease (PD) and often resistant to levodopa treatment. To explore the effect of bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) on postural stability and gait, full body gait analyses were performed without medication, OFF and ON DBS in eight PD patients and 12 healthy age-matched controls. DBS setting was changed at least 3 hours before gait analysis. To describe asymmetry most and least affected sides (MAS and LAS) were rated with the Unified Parkinson's Disease Rating Scale, motor part and quantitative gait analysis with the Vicon 612 gait analysis system. Stride length and gait velocity but not cadence improved ON DBS. The distances between the heel markers and center of mass (COM) were asymmetric and reduced OFF DBS. STN DBS increased the distances significantly and reduced asymmetry. The improvement in heel to COM distance was larger on the MAS compared with the LAS. OFF DBS knee momentum asymmetry was inversed so that LAS was more impaired than MAS. ON DBS asymmetry improved. PD patients OFF DBS place the heel too close to COM. The most affected body side has the most impaired swing and the result is a smaller knee moment on the opposite and least affected body side and an asymmetric gait pattern with disturbed balance OFF STN DBS. The asymmetry OFF DBS improved ON DBS. We suggest that DBS facilitates symmetric gait and thereby improves balance during gait.