Volume Articles

A Commentary on Attitudes Towards Deep Brain Stimulation for Addiction

Karen E. Lee, Mahendra T. Bhati, Casey H. Halpern*

Deep brain stimulation (DBS) has proven to be an effective treatment for neurologic disorders such as Parkinson’s disease, and is currently being investigated as a therapy for psychiatric diseases such as addiction, major depressive disorder, and obsessive compulsive disorder. In this commentary, we review and discuss the findings presented in the Letter to the Editor entitled “Attitudes towards treating addiction with deep brain stimulation,” written by Ali et al1. The survey presented in this Letter reported general approval for examining the effects of DBS on addictive disorders in a clinical trial, but highlighted critical areas of concern including informed consent, patient autonomy, appropriate medical practice, passing of clinical trial milestones, and implications on law enforcement.

Commentary: Ginkgo Biloba for Mild Cognitive Impairment and Alzheimer 's disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Guoyan Yang^1,2, Dennis Chang¹, and Jianping Liu^2*

Background: Ginkgo biloba is a natural medicine used for cognitive impairment and Alzheimer’s disease.

Methods: This is a commentary on a systematic review that we conducted to evaluate the effectives and safety of Ginkgo biloba in treating mild cognitive impairment or Alzheimer’s disease.

Results: 21 articles with 2608 patients met the inclusion criteria. The general methodological quality of included studies was moderate to poor. Compared with conventional medicine alone, Ginkgo biboba in combination with conventional medicine was superior in improving Mini-Mental State Examination (MMSE) scores at 24 weeks for patients with Alzheimer’s disease (MD 2.39, 95% CI 1.28 to 3.50, P<0.0001) and mild cognitive impairment (MD 1.90, 95% CI 1.41 to 2.39, P<0.00001), and Activity of Daily Living (ADL) scores at 24 weeks for Alzheimer’s disease (MD -3.72, 95% CI -5.68 to -1.76, P=0.0002). When compared with placebo or conventional medicine in individual trials, Ginkgo biboba demonstrated similar but inconsistent findings. Adverse events were mild.

Conclusion: Ginkgo biloba is potentially beneficial for the improvement of cognitive function, activities of daily living, and global clinical assessment in patients with mild cognitive impairment or Alzheimer’s disease. However, due to limited sample size, inconsistent findings and methodological quality of included trials, more research are warranted to confirm the effectiveness and safety of Ginkgo biloba in treating mild cognitive impairment and Alzheimer’s disease.

COMMENTARY: Dementia after Three Months and One Year from Stroke: New Onset or Previous Cognitive Impairment?

Salvatore Caratozzolo*, Andrea Scalvini, Francesco Lanfranchi, Silvia Pelizzari, Marina Zanetti, Luca Rozzini, Alessandro Padovani

Feasibility study for remote assessment of cognitive function in multiple sclerosis

Michaela F. George, PhD^1*, Calliope B. Holingue, MPH^1*, Farren B.S. Briggs, PhD, ScM², Xiaorong Shao, MA¹, Kalliope H. Bellesis³, Rachel A. Whitmer, PhD³, Catherine Schaefer, PhD³, Ralph HB Benedict, PhD⁴, Lisa F. Barcellos, PhD, MPH^1,3,5

¹Division of Epidemiology, Genetic Epidemiology and Genomics Laboratory, School of Public Health, University of California, Berkeley, CA, USA
²Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, OH, USA
³Kaiser Permanente Division of Research, Oakland, CA, USA
⁴Jacobs MS Center, SUNY Buffalo School of Medicine, Buffalo, NY, USA

Background

Cognitive impairment is common in multiple sclerosis (MS), and affects employment and quality of life. Large studies are needed to identify risk factors for cognitive decline. Currently, a MS-validated remote assessment for cognitive function does not exist. Studies to determine feasibility of large remote cognitive function investigations in MS have not been published.

Objective

To determine whether MS patients would participate in remote cognitive studies. We utilized the Modified Telephone Interview for Cognitive Status (TICS-M), a previously validated phone assessment for cognitive function in healthy elderly populations to detect mild cognitive impairment. We identified factors that influenced participation rates. We investigated the relationship between MS risk factors and TICS-M score in cases, and score differences between cases and control individuals.

Methods

The TICS-M was administered to MS cases and controls. Linear and logistic regression models were utilized.

Results

11.5% of eligible study participants did not participate in cognitive testing. MS cases, females and individuals with lower educational status were more likely to refuse (p<0.001). Cases who did complete testing did not differ in terms of perceived cognitive deficit compared to cases that did participate. More severe disease, smoking, and being male were associated with a lower TICS-M score among cases (p<0.001). The TICS-M score was significantly lower in cases compared to controls (p=0.007).

Conclusions

Our results demonstrate convincingly that a remotely administered cognitive assessment is quite feasible for conducting large epidemiologic studies in MS, and lay the much needed foundation for future work that will utilize MS-validated cognitive measures.

Commentary: Critical role of JSAP1 and JLP in axonal transport in the cerebellar Purkinje cells of mice

Katsuji Yoshioka*

 Axonal transport is essential for the development, function, and survival of neurons, and impaired axonal transport has been implicated in many neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. To date, however, how axonal transport is regulated, and how defective transport leads to neurodegeneration, remain largely unknown. This study by Sato et al. shows that the loss of both JSAP1 and JLP in the cerebellar Purkinje cells (PCs) of mice causes axonal dystrophy followed by gradual, progressive PC degeneration. This study also suggests that JSAP1 and JLP regulate kinesin-1-dependent axonal transport in the brain with functional redundancy, which prevents axonal degeneration and subsequent neuronal death. There is increasing evidence that in neurodegenerative diseases, axonal degeneration precedes neuronal cell death. Thus, elucidating the mechanisms of axonal degeneration may provide promising targets for therapeutic intervention. The JSAP1-null, JLP-null mouse generated in this study may provide a useful animal model for studying the molecular basis of axonal degeneration in neurodegenerative diseases, and for developing therapeutic drugs for these diseases.

The Pathophysiology of Ischemic Stroke Studied by Radionuclide Imaging

Wolf-Dieter Heiss

Ischemic stroke is caused by interruption or significant impairment of blood supply to the brain, which leads to a cascade of metabolic and molecular alterations resulting in functional disturbance and morphological damage. The changes in regional cerebral blood flow and in regional metabolism can be assessed by radionuclide imaging, especially single photon emission tomography (SPECT) and positron emission tomography (PET). SPECT and PET have broadened our understanding of flow and metabolic thresholds critical for maintenance of brain function and morphology: PET was essential in the transfer of the concept of the penumbra to clinical stroke and thereby had a great impact on developing treatment strategies. Receptor-ligands can be applied as early markers of irreversible neuronal damage and can predict the size of the final infarcts, which is important for decisions of invasive therapy in large (“malignant”) infarction. With SPECT and PET the reserve capacity of blood supply can be tested in obstructive arteriosclerosis, which is essential for planning interventions. The effect of a stroke on surrounding and contralateral primarily not-affected tissue can be investigated helping to understand symptoms caused by disturbance in functional networks. Activation studies are useful to demonstrate alternative pathways to compensate for lesions and to test the effect of rehabilitative therapy. Radioisotope studies help to detect neuroinflammation and its effect on extension of tissue damage. Despite the limitations of broad clinical application of radionuclide imaging, this technology has a great impact on research in cerebrovascular diseases and still has various applications in the management of stroke. In this short review the contributions of PET- and SPECT-studies to the understanding of the pathophysiology of ischemic stroke are described.

Behavioral Dyscontrol Following Acquired Brain Injury: Effectiveness of Post-hospital Neurobehavioral Intensive Programs

Gordon J. Horn^1* & Frank D. Lewis²

¹Florida State University, College of Medicine, USA
²Medical College of Georgia at Augusta University, USA

The purpose of this research was to evaluate the effectiveness of post-hospital neurobehavioral intensive (NBI) programs for treating acquired brain injury survivors with significant symptoms of behavioral dyscontrol and to identify variables that predict functional outcome. Subjects were 219 adults with acquired brain injury (predominately traumatic brain injury, 81%) exhibiting moderate to severe irritability, agitation, and/or aggression (includes verbal or physical) that were discharged from six NBI programs across five states. Prior to treatment, all participants demonstrated neurobehavioral impairment preventing the individuals from living in the community. All participants were assessed using the Mayo-Portland Adaptability Inventory – 4 at admission and discharge from program. A Repeated Measures MANOVA revealed significant improvement on the three MPAI-4 subscales at time of discharge. With control for participant age, a hierarchical multiple regression analysis revealed three significant MPAI-4 predictors of outcome: initiation, impaired awareness, and fund of information. Findings demonstrated that significant functional improvement can be realized with extremely chronic behaviorally intensive brain injured adults. Treatment effects may be enhanced by early intervention focused on appropriate response initiation/ inhibition, self-awareness of behavior on others, and information integration to facilitate appropriate response formation.

Blood pressure variability and hemorrhagic transformation after intravenous thrombolysis in acute ischemic stroke

Hanna Choi, MD; Seo Young Choi, MD; Jae Guk Kim, MD; Sung-Yeon Sohn, MD; Do-Hyung Kim, MD; Soo Joo Lee, MD, PhD*

^{Department of Neurology, Eulji University Hospital, Eulji University School of Medicine, Daejeon, Republic of Korea}

The effectiveness of intravenous tissue plasminogen activator (t-PA) is well established in hyperacute ischemic stroke. Despite its efficacy, spontaneous intracranial hemorrhage after t-PA is a severe complication associated with poor prognosis. We evaluated the role of blood pressure (BP) and BP variability, measured before and after injection of t-PA within 24 hours. Herein, 116 patients were enrolled in this study. BP (systolic blood pressure, diastolic blood pressure, and pulse pressure) were recorded before t-PA and every hour after t-PA for 24 hours. The BP profiles were characterized by initial, mean, maximum (max), minimum (min), max-min, and standard deviation (sd). The intracranial hemorrhage was assessed via computed tomography, 24-36 hours after injection of t-PA. The hemorrhagic transformation was classified using clinical and radiological criteria as follows: hemorrhagic transformation (HT), parenchymal hemorrhage (PH), and symptomatic hemorrhage (SH). The intracranial hemorrhage occurred as follows: HT 25.52% (n=25), PH 10.81% (n=12), SH 3.60% (n=4). The PPsd during the 24-hour period post-injection (24h PPsd) was significantly higher in patients with HT (14.57±0.76 vs. 11.84±0.39, 95% confidence interval [CI] 1.07-4.40, p<0.001) and PH (16.74±4.17 vs. 11.93±3.48, 95% CI 2.65-6.97, p<0.001). The odds ratio per 5 mmHg of 24h-PPsd was 2.41 (95% CI 1.23-4.72) in HT and 4.76 (95% CI 1.60-12.17) in PH. The variability in pulse pressure during the first 24 hours may be associated with hemorrhagic transformation after thrombolytic therapy with t-PA in hyperacute infarction.

Cardiac injury in severe head trauma: a review of literature

Ahmed Hasanin^1*, Dina Zakaria¹, Ahmed Allam²

Neurogenic stress cardiomyopathy (NSC) is a stress induced cardiomyopathy reported in various neurological disorders. The most widely accepted theory for the mechanism of NSC is the “catecholamine hypothesis”. The available evidence suggests the presence of NSC in patients with severe TBI. The presence of cardiac injury could be a poor prognostic finding in patients with TBI. The possible cardiac injury in TBI patients would make the critical care physicians more cautious with hemodynamic management of these patients. Larger studies with more sophisticated asessment would help to confirm the presence of cardiac injury in these patients.

An evolutionary perspective on habenular asymmetry in humans

Miguel L. Concha^1,2,3*, Patricio Ahumada-Galleguillos^1,2

The habenula (Hb) of vertebrates is a dorsal and bilateral diencephalic nuclear complex that works as an anatomical hub integrating cognitive, emotional and sensory networks to regulate mood, motivation and value-based decision-making, among other functions. Across vertebrates, the Hb organises into two conserved separate components (medial and lateral in mammals equivalent to dorsal and ventral in more basal vertebrate species), which are thought to subserve different functions based on a partial independence of their connectivity systems. As a complex, the Hb shows morphological, molecular and connectivity differences between the left and right sides in a wide range of vertebrate species, which in some cases extend to the functional and behavioural levels. Habenular asymmetries are particularly prominent in basal vertebrate species but become less evident in amniotes and particular mammals. In humans, recent evidence reveals that, under an overall symmetry morphology, the Hb shows lateral differences in volume, activation, metabolism and susceptibility to damage that suggest an asymmetric condition of this nuclear complex. Here, we review the evidence supporting this view and discuss the possible origin of this asymmetric trait in humans from an evolutionary developmental perspective.