DBS-implanted Parkinson\u27s Disease Patients Show Better Olfaction Than Those Treated Medically

Dysosmia in PD (Parkinson’s Disease) may result from changes in the olfactory apparatus or in structures involved in olfactory perception. Previous work1,2 has suggested that deep brain stimulation (DBS) pa-tients have improved odor discrimination in stimulation-on/medication-off state in comparison to their own scores in a stimulation-off/medication-off state. What remains unclear is whether it is the ON state itself or an effect of stimulation that leads to improved olfaction. In this study we evaluate dysosmia in two PD cohorts in the ON state, those treated with medication alone and those treated with medication and DBS. A prospective study geared at improving predictive value of olfactory testing with a battery of psychological tests enrolled 45 PD patients and 44 controls. Of the PD patients, 9 had bilateral STN (subthalamic nucleus) DBS and 36 were medically treated. Subset analysis of PD patients with and without DBS placement revealed no difference in apathy or depression. DBS patients had better olfaction on UPSIT (Univ of Pennsylvania Smell Identification Test) (p This study provides further data that DBS patients have improved ol-faction. It also provides preliminary evidence that DBS with medica-tion improves dysosmia to a greater extent than medication alone. This may result from indirect stimulation of olfactory processing cen-ters or changes in olfactory circuitry metabolism

Assessment of Olfactory Processing in Parkinson’s Disease Patients

Background: Hyposmia is an early symptom of Parkinson’s Disease (PD) that often predates motor symptoms by years. Hyposmia has been shown to have a more consistent link to idiopathic PD than to other movement disorders. Olfaction has the potential to be used as a biomarker for PD, either through clinical evaluation or imaging. Objectives: This study uses functional magnetic resonance imaging (fMRI) to assess differences in olfaction pathways between anosmic early PD patients and age and gender-matched controls. Methods: 12 PD patients and 12 age- and gender-matched control subjects were recruited from the subject panel of a previous UMMS study on olfaction and PD. All PD patients were determined to be anosmic, and all controls were determined to have normal olfaction for their age and gender. All subjects underwent fMRI including periods with and without odorant exposure. Statistical analysis was performed using SPM8, using a general linear model to calculate BOLD signal changes for each scent relative to room air. A random effect model was used to infer general population effects. Results: Control subjects showed significant activation in the piriform cortex, anterior olfactory nucleus, insula, hippocampus and temporal lobe, all regions associated with olfactory processing. Relative to control subjects, PD patients showed no significant BOLD activation in the olfactory pathways of the brain. In response to a citrus scent, PD patients showed activation in the superior and middle frontal lobe, as well as the cingulate gyrus. In response to a cinnamon scent, PD patients showed significant activation in the precuneus and paracentral lobule as well as lower levels of activation in the frontal lobe. PD patients showed no significant areas of activation in response to a mint scent. Conclusion: Our results suggest that anosmic PD patients do not show activation of the olfactory pathways in the brain on exposure to these odorants. Taken together with previous studies, this suggests that BOLD activation in these regions of the brain can reflect clinical olfactory capability. In addition, PD patients show areas of increased activation, particularly in the frontal lobe. These distinct patterns of BOLD activation allow us to consider the feasibility of fMRI as a biomarker for diagnosis and evaluation of PD

Isolation of bacterial extrachromosomal DNA from human dental plaque associated with periodontal disease,using transposonaided capture (TRACA)

The human oral cavity is host to a complex microbial community estimated to comprise > 700 bacterial species, of which at least half are thought to be not yet cultivable in vitro. To investigate the plasmids present in this community, we used a transposon-aided capture system, which allowed the isolation of plasmids from human oral supra- and subgingival plaque samples. Thirty-two novel plasmids and a circular molecule that could be an integrase-generated circular intermediate were isolated

Gabapentin treatment in a child with delayed-onset hemichorea/hemiballismus

A 13-year, 6-month-old female was evaluated for subacute onset of left-sided hemichorea/hemiballismus, with an old, right parietal, cortical, and subcortical stroke as the presumed cause. Treatment with gabapentin was initiated, with good results at 6-month follow-up. Discussion of the differential diagnosis and evaluation of delayed-onset movement disorders in children and the mechanism of action of gabapentin is included

Treatment of multiple system atrophy using intravenous immunoglobulin

<p>Abstract</p> <p>Background</p> <p>Multiple system atrophy (MSA) is a progressive neurodegenerative disorder of unknown etiology, manifesting as combination of parkinsonism, cerebellar syndrome and dysautonomia. Disease-modifying therapies are unavailable. Activation of microglia and production of toxic cytokines suggest a role of neuroinflammation in MSA pathogenesis. This pilot clinical trial evaluated safety and tolerability of intravenous immunoglobulin (IVIG) in MSA.</p> <p>Methods</p> <p>This was a single-arm interventional, single-center, open-label pilot study. Interventions included monthly infusions of the IVIG preparation Privigen®, dose 0.4 gram/kg, for 6 months. Primary outcome measures evaluated safety and secondary outcome measures evaluated preliminary efficacy of IVIG. Unified MSA Rating Scale (UMSARS) was measured monthly. Quantitative brain imaging using 3T MRI was performed before and after treatment.</p> <p>Results</p> <p>Nine subjects were enrolled, and seven (2 women and 5 men, age range 55–64 years) completed the protocol. There were no serious adverse events. Systolic blood pressure increased during IVIG infusions (p<0.05). Two participants dropped out from the study because of a non-threatening skin rash. The UMSARS-I (activities of daily living) and USMARS-II (motor functions) improved significantly post-treatment. UMSARS-I improved in all subjects (pre-treatment 23.9 ± 6.0 vs. post-treatment 19.0±5.9 (p=0.01). UMSARS-II improved in 5 subjects, was unchanged in 1 and worsened in 1 (pre-treatment 26.1±7.5 vs. post-treatment 23.3±7.3 (p=0.025). The MR imaging results were not different comparing pre- to post-treatment.</p> <p>Conclusions</p> <p>Treatment with IVIG appears to be safe, feasible and well tolerated and may improve functionality in MSA. A larger, placebo-controlled study is needed.</p

Limbic and motor function comparison of deep brain stimulation of the zona incerta and subthalamic nucleus

BACKGROUND: Psychiatric and neuropsychological side effects of subthalamic nucleus (STN) stimulation have been increasingly recognized. Most programming regimens focus on contacts 0 and 1, whereas contact 3, which often is located near or in the zona incerta (ZI), is usually not used. The question of whether ZI stimulation may limit limbic effects has not been answered. OBJECTIVE: To examine the effects of short-term stimulation near or in the ZI (contact 3) compared with stimulation of the STN using standard trajectories and targeting as measured by limbic and motor functions. METHODS: Motor and limbic functions of 11 patients with STN DBS were assessed with the Unified Parkinson Disease Rating Scale-3, structured gait video analysis, Visual Analog Scale mood scales, task testing of impulsivity, and facial recognition under routine STN programming and under stimulation in or near the ZI. Postoperative magnetic resonance imaging confirmed the location of contact 3 near or in the ZI. RESULTS: Data analysis with repeated-measures analysis of variance revealed that motor scores remained stable with both stimulation settings, with specific improvements in finger taps (P = .02) and rapid alternating movements (P = .03) in ZI stimulation. Stimulation near or in the ZI led to a decrease in self- reported anxiety and depression (P = .03 for both) and an improvement in fear recognition (P = .02). CONCLUSION: We provide preliminary evidence that stimulation in or near the ZI results in maintained motor function while improving self-reported depression and anxiety in patients with bilateral STN DBS. Stimulation in or near the ZI may provide a useful programming setting for patients prone to psychiatric side effects

Randomized Phase II Study of Cilengitide, an Integrin-Targeting Arginine-Glycine-Aspartic Acid Peptide, in Recurrent Glioblastoma Multiforme

Purpose Cilengitide, an inhibitor of αvβ3 and αvβ5 integrin receptors, demonstrated minimal toxicity and durable activity across a wide range of doses administered to adults with recurrent glioblastoma multiforme (GBM) in a prior phase I study. The current multicenter phase II study was conducted to evaluate the activity and safety of cilengitide in GBM patients at first recurrence. Patients and Methods Eligible patients were randomly assigned to receive either 500 or 2,000 mg of cilengitide twice weekly on a continuous basis. Patients were assessed every 4 weeks. The primary end point was 6-month progression-free survival (PFS) rate. Secondary end points included PFS, overall survival (OS), and radiographic response, as well as quality-of-life and pharmacokinetic assessments. Results Eighty-one patients were enrolled, including 41 on the 500-mg arm and 40 on the 2,000-mg arm. The safety profile of cilengitide was excellent, with no significant reproducible toxicities observed on either arm. Antitumor activity was observed in both treatment cohorts but trended more favorably among patients treated with 2,000 mg, including a 6-month PFS of 15% and a median OS of 9.9 months. Conclusion Cilengitide monotherapy is well tolerated and exhibits modest antitumor activity among recurrent GBM patients. Additional studies integrating cilengitide into combinatorial regimens for GBM are warranted