Andrew Feigin

Effect of treatment with L-dopa/carbidopa or L-selegiline on striatal dopamine transporter SPECT imaging with [123I]β-CIT

The effect of subchronic treatment with l‐dopa/carbidopa or l‐selegiline on striatal dopamine transporters (DAT) was examined in patients with idiopathic Parkinsons disease with SPECT (single photon emission computed tomography) using [123I]β‐CIT (2β‐carbomethoxy‐3β‐[4‐iodophenyl]tropane) as the radiotracer. Patients who were not currently being treated with these medications were given either 750 mg l‐dopa/carbidopa per day (n = 8) or 10 mg l‐selegiline per day (n = 8). [123I]β‐CIT imaging was performed three times in each patient: at baseline before treatment, while on medication and after 4–6 weeks of drug treatment, and following withdrawal from medication (approximately 1 week for l‐dopa/carbidopa and 9 weeks for l‐selegiline). Comparison of scans 2 and 3 provided a measure of drug occupancy of the [123I]β‐CIT binding site; comparison of scans 1 and 2 provided a measure of both up‐ or downregulation of DAT levels and drug occupancy following subchronic drug treatment. DAT levels were assessed from an image acquired approximately 22 hours after radiotracer injection as a ratio of regional brain activities: (striatum − occipital)/occipital. Striatal DAT levels were not significantly different when any two of the three scans were compared for both drug treatments. These results suggest that typical clinical doses of l‐dopa/carbidopa and l‐selegiline do not induce significant occupancy of the [123I]β‐CIT binding site and that 4–6 weeks of treatment causes no significant modulation of DAT levels. These results support the validity of measuring DAT levels with [123I]β‐CIT without the need to withdraw patients from medication treatment.

Parkinson's disease spatial covariance pattern: noninvasive quantification with perfusion MRI.

Parkinsons disease (PD) is associated with elevated expression of a specific disease-related spatial covariance pattern (PDRP) in radiotracer scans of cerebral blood flow and metabolism. In this study, we scanned nine early-stage patients with PD and nine healthy controls using continuous arterial spin labeling (CASL) perfusion magnetic resonance imaging (pMRI). Parkinsons disease-related metabolic pattern expression in CASL pMRI scans was compared with the corresponding 18F-fluorodeoxyglucose positron emission tomography values. The PDRP expression was abnormally elevated (P<0.01) in patients scanned with either modality, and the two values were highly intercorrelated (P<0.0001). Perfusion MRI methods can be used for accurate quantification of disease-related covariance patterns.

Basal Ganglia and Kinematics Modulation: Insights from Parkinson's and Huntington's diseases

Movement kinematic variables related to force production can be modulated to respond appropriately to different contexts. We previously showed that in a choice-reaction time and a predictable timed-response task, normal subjects perform reaching movements to the same targets with two different kinematic patterns, a marker of flexibility. Here, we used the two tasks to determine whether basal ganglia are involved in the selection and modulation of movement kinematics and therefore in flexible force production. We tested seventeen patients in the early stages of Parkinsons disease, eleven pre-symptomatic Huntingtons disease carriers and sixteen age-matched normal controls with the above-mentioned motor tasks. In both patient groups, the difference in kinematics (movement duration, peak velocity and acceleration) between the two tasks was significantly reduced compared to controls, indicating a limited range of choices or flexibility. However, this reduction was skewed in opposite directions in the two disorders, with force production being generally higher in Huntingtons carriers and lower in Parkinsons patients compared to controls. We conclude that basal ganglia are involved in adapting movement to different contexts and selecting the appropriate movement force. The opposite trends in Parkinsons and Huntingtons disease suggest that such regulation might depend on the balance between the outputs of direct and indirect pathways.

TOURETTE SYNDROME: UPDATE AND REVIEW OF THE LITERATURE

BACKGROUND- Tourette syndrome has become increasingly recognized as a relatively common disorder with onset in childhood that not only causes abnormal movements (tics), but also may cause significant behavioral disturbances.REVIEW SUMMARY- This article reviews the current knowledge of the clinical phenomenology, epidemiology, patho-genesis, and treatment of Tourette syndrome.CONCLUSION- Much has been learned about the manifestations and pathogenesis of Tourette syndrome, leading to effective therapies and suggesting new therapeutic possibilities. Nonetheless, there is still much to be learned about the genetics and neurobiology of this multifaceted and perplexing disorder.

Disease Modifying Agents for Huntington’s Disease

Huntington’s disease is an autosomal dominant neurodegenerative disorder characterised by abnormalities of motor function, cognition and behaviour. The striatum is particularly vulnerable to the disease process with selective loss of medium-sized spiny projection neurons and relative sparing of interneurons.Although the underlying mechanism initiating and propagating neuronal destruction is currently unknown, experimental evidence over the past decade has implicated mitochondrial dysfunction and excitotoxicity in the pathogenesis of Huntington’s disease. The current treatment of Huntington’s disease is limited to palliative care with secondary symptomatic management. Recent advances in the understanding of the pathophysiology of this disease may lead to the development of pharmacotherapeutic and neurosurgical interventions to effectively treat this devastating disease.