[Differential diagnostics of Parkinson's disease with nuclear medicine procedures]. / Differenzialdiagnostik des Parkinson-Syndroms mit nuklearmedizinischen Verfahren.

Early differential diagnosis of parkinsonism is of paramount therapeutic and prognostic importance. In the present review, the diagnostic value of routinely used nuclear medicine procedures is presented and critically discussed. The [(123)I]FP-CIT single-photon emission computed tomography (SPECT) is the method of choice for differentiation between neurodegenerative and non-neurodegenerative parkinsonism. The [(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) method provides a very high diagnostic accuracy for differentiating between Parkinson's disease (PD) and atypical Parkinsonian syndromes (APS), which is clearly superior to the accuracy of [(123)I]FP-CIT SPECT, [(123)I]IBZM SPECT and [(123)I]MIBG scintigraphy. Furthermore, [(18)F]FDG-PET is the only of the aforementioned techniques that also allows a reliable differentiation between APS subgroups (e.g., multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration). Current studies are investigating the probable value of [(18)F]FDG-PET for risk stratification of dementia in PD.

Transcranial sonography and [18F]fluorodeoxyglucose positron emission tomography for the differential diagnosis of parkinsonism: a head-to-head comparison.

BACKGROUND AND PURPOSE: Brain imaging with positron emission tomography using [(18) F]fluorodeoxyglucose (FDG-PET) and transcranial B-mode sonography (TCS) improves the differential diagnosis of parkinsonism. The diagnostic merits of these approaches in identifying and differentiating atypical parkinsonian syndromes (APS) are compared. METHODS: Data were included from 36 patients with clinically suspected APS who underwent PET and TCS. FDG-PET scans were analyzed by visual assessment (including voxel-based statistical maps) of a priori defined disease-specific metabolic patterns. Sonographers achieved diagnoses according to pre-defined criteria for echogenicities of the substantia nigra and lenticular nucleus, and third ventricle diameter. Patients with APS were identified and allocated to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD). RESULTS: After a median follow-up period of 9 months, the final clinical diagnoses (reference standard) were Parkinson's disease, n = 15; MSA, n = 9; PSP, n = 7; and CBD, n = 5 (n = 21 APS in total). Six patients (4 APS) showed an insufficient bone window for TCS. In the remaining 30 patients, sensitivity/specificity for diagnosing APS were 82%/100% and 82%/85% for FDG-PET and TCS, respectively. Diagnostic accuracies did not differ between FDG-PET (90%) and TCS (83%; P = 0.69). Likewise, overall accuracy of subgroup classification (non-APS, MSA, PSP and CBD) did not differ between modalities (FDG-PET 87% and TCS 83%; P = 1.00). CONCLUSIONS: FDG-PET and TCS show comparable accuracies for differential diagnosis of neurodegenerative parkinsonism. This preliminary study supports the use of TCS and warrants further prospective validation.

Neurostimulation for Parkinson's disease with early motor complications.

BACKGROUND: Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. METHODS: In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS: For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group. CONCLUSIONS: Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).

Balance training and ballistic strength training are associated with task-specific corticospinal adaptations.

The aim of this study was to investigate the role of presumably direct corticospinal pathways in long-term training of the lower limb in humans. It was hypothesized that corticospinal projections are affected in a training-specific manner. To assess specificity, balance training was compared to training of explosive strength of the shank muscles and to a nontraining group. Both trainings comprised 16 1-h sessions within 4 weeks. Before and after training, the maximum rate of force development was monitored to display changes in motor performance. Neurophysiological assessment was performed during rest and two active tasks, each of which was similar to one type of training. Hence, both training groups were tested in a trained and a nontrained task. H-reflexes in soleus (SOL) muscle were tested in order to detect changes at the spinal level. Corticospinal adaptations were assessed by colliding subthreshold transcranial magnetic stimulation to condition the SOL H-reflex. The short-latency facilitation of the conditioned H-reflex was diminished in the trained task and enhanced in the nontrained task. This was observable in the active state only. On a functional level, training increased the rate of force development suggesting that corticospinal projections play a role in adaptation of leg motor control. In conclusion, long-term training of shank muscles affected fast corticospinal projections. The significant interaction of task and training indicates context specificity of training effects. The findings suggest reduced motor cortical influence during the trained task but involvement of direct corticospinal control for new leg motor tasks in humans.

Task-specific changes in motor evoked potentials of lower limb muscles after different training interventions.

This study aimed to identify sites and mechanisms of long-term plasticity following lower limb muscle training. Two groups performing either a postural stability maintenance training (SMT) or a ballistic ankle strength training (BST) were compared to a non-training group. The hypothesis was that practicing of a self-initiated voluntary movement would facilitate cortico-spinal projections, while practicing fast automatic adjustments during stabilization of stance would reduce excitatory influence from the primary motor cortex. Training effects were expected to be confined to the practiced task. To test for training specificity, motor evoked potentials (MEP) induced by transcranial magnetic stimulation (TMS) were recorded at rest and during motor tasks that were similar to each training. Intracortical, cortico-spinal, as well as spinal parameters were assessed at rest and during these tasks. The results show high task and training specificity. Training effects were only observable during performance of the trained task. While MEP size was decreased in the SMT group for the trained tasks, MEP recruitment was increased in the BST group in the trained task only. The control group did not show any changes. Background electromyogram levels, M. soleus H-reflex amplitudes and intracortical parameters were unaltered. In summary, it is suggested that the changes of MEP parameters in both training groups, but not in the control group, reflect cortical motor plasticity. While cortico-spinal activation was enhanced in the BST group, SMT may be associated with improved motor control through increased inhibitory trans-cortical effects. Since spinal excitability remained unaltered, changes most likely occur on the supraspinal level.

Differential reflex adaptations following sensorimotor and strength training in young elite athletes.

In young elite athletes the influence of a sensorimotor training (SMT = balance training) on strength, jump height and spinal reflex excitability was compared with adaptations induced by strength training (ST). Seventeen athletes were randomly assigned to either a SMT or a ST group. Before and after 6 weeks of training, maximal isometric strength (MVC) and rate of force development (RFD (max)) were determined. Changes in jump height and EMG activity were assessed during squat- (SJ), countermovement- (CMJ) and drop-jump (DJ). To evaluate neural adaptations, H-reflex recruitment was recorded at rest and during dynamic activation of the plantarflexors following stance perturbation. MVC was enhanced after ST but not influenced by SMT. RFD (max) was not affected by any training. Both SMT and ST significantly improved jump performance in SJ, CMJ, and DJ. Maximum H-reflex to maximum M-wave ratios (H (max)/M (max)-ratios) at rest remained unchanged. During stance perturbation, H (max)/M (max)-ratios were significantly reduced following SMT whereas ST augmented H (max)/M (max)-ratios (p < 0.05). In contrast to other studies, no changes in RFD were found. This may be explained by methodological and/or training specific differences. However, both SMT and ST improved jump performance in well trained young athletes but induced opposing adaptations of the H (max)/M (max)-ratio when measured during dynamic contractions. These adaptations were task-specific as indicated by the unchanged reflexes at rest. Decreased spinal excitability following SMT was interpreted as the attempt to improve movement control, whereas augmented excitability following ST accounts for the effort to enhance motoneuron output. Functionally, our results emphasise that SMT is not only beneficial for prevention and rehabilitation but also improves athletic performance.

Training-specific adaptations of H- and stretch reflexes in human soleus muscle.

The authors investigated the effect of physical exercise on reflex excitability in a controlled intervention study. Healthy participants (N = 21) performed 4 weeks of either power training (ballistic strength training) or balance training (sensorimotor training [SMT]). Both training regimens enhanced balance control and rate of force development, whereas reductions in peak-to-peak amplitudes of stretch reflexes and in the ratio of the maximum Hoffman reflex to the maximum efferent motor response (Hmax:Mmax) measured at rest were limited to SMT. The differences in reflex excitability between the training regimens indicated different underlying neural mechanisms of adaptation. The reduced reflex excitability following SMT was most likely induced by supraspinal influence. The authors discuss an overall increase in presynaptic inhibition of Ia afferent fibers as a possible mechanism.

Neurotransmitter release and its presynaptic modulation in the rat hippocampus after selective damage to cholinergic or/and serotonergic afferents.

UNLABELLED: Male Long-Evans rats sustained injections of 5,7-dihydroxytryptamine (5,7-DHT) into the fimbria-fornix and the cingular bundle or/and intraseptal injections of 192 IgG-saporin to induce serotonergic or/and cholinergic hippocampal denervations; Sham-operated rats served as controls. Four to ten weeks after lesioning, we measured (i). the electrically evoked release of acetylcholine ([3H]ACh), noradrenaline ([3H]NA) and serotonin ([3H]5-HT) in hippocampal slices in the presence of drugs acting on auto- or heteroreceptors, (ii). the nicotine-evoked release of NA and (iii). the choline acetyltransferase (ChAT) activity and the concentration of monoamines in homogenates. Saporin lesions reduced the accumulation of [3H]choline, the release of [3H]ACh and the ChAT activity, but increased the concentration of NA and facilitated the release of [3H]NA evoked by nicotine. 5,7-DHT lesions reduced the accumulation and the release of [3H]5-HT, the concentration of 5-HT, and also facilitated the release of [3H]NA evoked by nicotine. Accumulation and electrically evoked release of [3H]NA were not altered by either lesion. The combination of both toxins resulted in an addition of their particular effects. The 5-HT(1B) receptor agonist, CP 93129, and the muscarinic agonist, oxotremorine, reduced the release of [3H]ACh in control and 5,7-DHT-lesioned rats; in rats injected with saporin, their effects could not be measured reliably. CP 93129 and the alpha(2)-adrenoceptor agonist, UK 14304, reduced the release of [3H]5-HT in all groups by about 65%. IN CONCLUSION: (i). selective neurotoxins can be combined to enable controlled and selective damage of hippocampal transmitter systems; (ii). 5-HT exerts an inhibitory influence on the nicotine-evoked release of NA, but partial serotonergic lesions do not influence the release of ACh at a presynaptic level and (iii). presynaptic modulatory mechanisms involving auto- and heteroreceptors may be conserved on fibres spared by the lesions.