BACKGROUND: 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. METHODS: This was a single-arm interventional, single-center, open-label pilot study. Interventions included monthly infusions of the IVIG preparation Privigen(R), 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. RESULTS: 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. CONCLUSIONS: Treatment with IVIG appears to be safe, feasible and well tolerated and may improve functionality in MSA. A larger, placebo-controlled study is needed.

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.

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.

BACKGROUND: Physical distress resulting from medical problems has been found to cause increased behaviour problems in patients with intellectual disabilities (ID). Despite this fact, little has been documented on the medical problems of individuals with ID admitted for inpatient psychiatric care. We conducted an exploratory investigation based on a retrospective chart review of the medical problems and medications for 198 people with ID who had been admitted to a specialised inpatient psychiatric unit. Most patients were referred for admission because of aggressive, disruptive and self-injurious behaviours. The average length of stay was 17.6 days. METHODS: We tallied the total number of medical problems and medications listed in the patients' discharge summaries. Because longer stays are disruptive, costly and associated with greater overall impairment, we examined the relationship between length of stay and frequency of discharge medical diagnoses. We also assessed whether or not the number of psychoactive medications correlated with the number of medical diagnoses. The effects of other demographic and diagnostic variables on rates of medical diagnoses and medications were also evaluated, including gender, age group (16-25, 26-45, 46-60, >60), level of ID (mild, moderate or severe ID) and diagnosis of an autism spectrum disorder or Down syndrome (DS). RESULTS: Inpatients with a higher number of medical diagnoses had longer lengths of stay (Spearman r = +0.32, P < 0.0001). There was a significant correlation between number of psychoactive medications and number of medical problems (Spearman r = +0.32, P < 0.0001). The most frequent medical comorbidity was constipation, reported in 60% of the inpatients (n = 118), while gastro-esophageal reflux disease was identified in 38% (n = 75). Older inpatients had an increased number of medical problems, as might be expected, but a diagnosis of an autism spectrum disorder, gender and level of ID had no detectible effect on rates of either medical diagnoses or medications. There were only 13 inpatients with DS; in this modest sample, it was found that they had higher rates of osteoarthritis, cardiac problems, hearing loss, hypothyroidism and sleep apnoea than peers without DS, as is consistent with previous findings on overrepresented conditions in this trisomy. CONCLUSIONS: In the present study, individuals with ID admitted for inpatient psychiatric care exhibited high rates of medical problems, and these were associated with duration of inpatient stay. Based on these findings, further investigation of the effects of medical problems on behaviour among individuals with ID admitted for inpatient psychiatric care is warranted.

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.