David Garcia-Garcia

Posterior parietooccipital hypometabolism may differentiate mild cognitive impairment from dementia in Parkinson’s disease

PurposePatients with Parkinson’s disease (PD) may have normal cognition, mild cognitive impairment (MCI) or dementia. We investigated differences in cerebral metabolism associated with these three cognitive states and the relationship between metabolism and cognitive dysfunction.MethodsFDG PET and a battery of neuropsychological tests were used to study PD patients with dementia (n = 19), MCI (n = 28) and normal cognition (n = 21), and control subjects (n = 20). Regional glucose metabolism in patients and controls was analysed using statistical parametric mapping (SPM8) corrected for age, motor severity and depression. Correlations between the mini-mental state examination score and Z-score values of the different cognitive domains with respect to cerebral FDG uptake were assessed using SPM8.ResultsPD patients with MCI (PD-MCI patients) exhibited decreased FDG uptake in the frontal lobe, and to a lesser extent in parietal areas compared with cognitively normal patients. Patients with dementia showed reduced metabolism in the parietal, occipital and temporal areas and a less extensive reduction in the frontal lobe compared with PD-MCI patients, while widespread hypometabolism was seen in comparison with patients with normal cognition. PD-MCI patients exhibited reduced FDG uptake in the parietal and occipital lobes and in localized areas of the frontal and temporal lobes compared with controls, whereas patients with dementia showed a widespread reduction of cortical metabolism. Mini-mental state examination score correlated positively with metabolism in several lobes, executive function with metabolism in the parietooccipitotemporal junction and frontal lobe, memory with temporoparietal metabolism, visuospatial function with occipitoparietal and temporal metabolism, and language with frontal metabolism.ConclusionPD patients with MCI exhibited hypometabolism in several cortical regions compared with controls, and in the frontal and parietal regions compared with cognitively normal patients. Hypometabolism was higher in patients with dementia than in those with MCI, mainly in the posterior cortical areas where it was correlated with visuospatial, memory and executive functions.

High beta activity in the subthalamic nucleus and freezing of gait in Parkinson's disease.

OBJECTIVE Oscillatory activity in the beta band is increased in the subthalamic nucleus (STN) of Parkinsons disease (PD) patients. Rigidity and bradykinesia are associated with the low-beta component (13-20Hz) but the neurophysiological correlate of freezing of gait in PD has not been ascertained. METHODS We evaluated the power and coherence of the low- and high-beta bands in the STN and cortex (EEG) of PD patients with (p-FOG) (n=14) or without freezing of gait (n-FOG) (n=8) in whom electrodes for chronic stimulation in the STN had been implanted for treatment with deep brain stimulation. RESULTS p-FOG patients showed higher power in the high-beta band (F=11.6, p=0.002) that was significantly reduced after l-dopa administration along with suppression of FOG (F=4.6, p=0.042). High-beta cortico-STN coherence was maximal for midline cortical EEG electrodes, whereas the low-beta band was maximal for lateral electrodes (χ(2)=20.60, p<0.0001). CONCLUSIONS The association between freezing of gait, high-beta STN oscillations and cortico-STN coherence suggests that this oscillatory activity might interfere in the frontal cortex-basal ganglia networks, thereby participating in the pathophysiology of FOG in PD.

Neuronal activity of the red nucleus in Parkinson's disease

Precise placement of the electrodes for stimulation of the subthalamic nucleus (STN) in Parkinsons disease (PD) is crucial for the therapeutic benefit. As a result of the mistargeting and misplacement of the electrodes during surgery in 2 patients with PD, we have characterized the neuronal firing in the red nucleus (RN) and observed the effects of stimulation of this nucleus. Although the neuronal firing (mean ± SD) of the RN (34 ± 4.4 Hz) resembles that described for the STN (33.1 ± 16.6 Hz), a higher proportion of cells responded to the movement of the contralateral limbs (70–80%). Stimulation in the area of the RN‐induced intolerable side effects without motor improvement. We conclude that the STN and RN have some similar neurophysiological features but can be distinguished intraoperatively. This initial description of the physiological characteristics of the RN in humans will draw attention to the possibility of confusing the RN and STN during intraoperative recording.

Stimulation sites in the subthalamic nucleus and clinical improvement in Parkinson's disease: a new approach for active contact localization.

OBJECTIVE Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is widely used in patients with Parkinsons disease (PD). However, which target area of this region results in the highest antiparkinsonian efficacy is still a matter of debate. The aim of this study was to develop a more accurate methodology to locate the electrodes and the contacts used for chronic stimulation (active contacts) in the subthalamic region, and to determine the position at which stimulation conveys the greatest clinical benefit. METHODS The study group comprised 40 patients with PD in whom bilateral DBS electrodes had been implanted in the STN. Based on the Morel atlas, the authors created an adaptable 3D atlas that takes into account individual anatomical variability and divides the STN into functional territories. The locations of the electrodes and active contacts were obtained from an accurate volumetric assessment of the artifact using preoperative and postoperative MR images. Active contacts were positioned in the 3D atlas using stereotactic coordinates and a new volumetric method based on an ellipsoid representation created from all voxels that belong to a set of contacts. The antiparkinsonian benefit of the stimulation was evaluated by the reduction in the Unified Parkinsons Disease Rating Scale Part III (UPDRS-III) score and in the levodopa equivalent daily dose (LEDD) at 6 months. A homogeneous group classification for contact position and the respective clinical improvement was applied using a hierarchical clustering method. RESULTS Subthalamic stimulation induced a significant reduction of 58.0% ± 16.5% in the UPDRS-III score (p < 0.001) and 64.9% ± 21.0% in the LEDD (p < 0.001). The greatest reductions in the total and contralateral UPDRS-III scores (64% and 76%, respectively) and in the LEDD (73%) were obtained when the active contacts were placed approximately 12 mm lateral to the midline, with no influence of the position being observed in the anteroposterior and dorsoventral axes. In contrast, contacts located about 10 mm from the midline only reduced the global and contralateral UPDRS-III scores by 47% and 41%, respectively, and the LEDD by 33%. Using the ellipsoid method of location, active contacts with the highest benefit were positioned in the rostral and most lateral portion of the STN and at the interface between this subthalamic region, the zona incerta, and the thalamic fasciculus. Contacts placed in the most medial regions of the motor STN area provided the lowest clinical efficacy. CONCLUSIONS The authors report an accurate new methodology to assess the position of electrodes and contacts used for chronic subthalamic stimulation. Using this approach, the highest antiparkinsonian benefit is achieved when active contacts are located within the rostral and the most lateral parts of the motor region of the STN and at the interface of this region and adjacent areas (zona incerta and thalamic fasciculus).

Significance of visual hallucinations and cerebral hypometabolism in the risk of dementia in Parkinson's disease patients with mild cognitive impairment.

Mild cognitive impairment (MCI) and visual hallucinations (VH) are common co‐morbidities and risk factors for dementia in Parkinsons disease (PD). The relative value of each of them in the progression to dementia is unknown. We investigated cognitive impairment and cerebral hypometabolism in PD‐MCI patients with VH (VH‐positive) and without (VH‐negative).