Bradykinesia and rigidity modulated by functional connectivity between the primary motor cortex and globus pallidus in Parkinson's disease.

The mechanisms underlying motor fluctuations in patients with Parkinson's disease (PD) are currently unclear. Regional brain stimulation reported the changing of motor symptoms, but the correlation with functional connectivity (FC) in the brain network is not fully understood. Hence, our study aimed to explore the relationship between motor symptom severity and FC using resting-state functional magnetic resonance imaging (rsfMRI) in the "on" and "off" states of PD. In 26 patients with sporadic PD, FC was assessed using rsfMRI, and clinical severity was analyzed using the motor part of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS Part III) in the on and off states. Correlations between FC values and MDS-UPDRS Part III scores were assessed using Pearson's correlation coefficient. The correlation between FC and motor symptoms differed in the on and off states. FC between the ipsilateral precentral gyrus (PreCG) and globus pallidus (GP) correlated with the total MDS-UPDRS Part III scores and those for bradykinesia/rigidity in the off state. Lateralization analysis indicated that FC between the PreCG and GP correlated with the contralateral total MDS-UPDRS Part III scores and those for bradykinesia/rigidity in the off state. Aberrant FC in cortico-striatal circuits correlated with the severity of motor symptoms in PD. Cortico-striatal hyperconnectivity, particularly in motor pathways involving PreCG and GP, is related to motor impairments in PD. These findings may facilitate our understanding of the mechanisms underlying motor symptoms in PD and aid in developing treatment strategies such as brain stimulation for motor impairment.

Left ventricular inflow obstruction due to a coronary arteriovenous fistula: a paediatric case report.

BACKGROUND: We report a rare case of left ventricular inflow obstruction from a branch of the left circumflex coronary artery to the right atrium caused by a coronary arteriovenous fistula (CAVF) in a young Japanese male child. CASE PRESENTATION: The patient was diagnosed with CAVF following a heart murmur shortly after birth. The left-to-right shunt caused right ventricular volume overload and pulmonary congestion. An emergency surgical intervention was performed for the CAVF on day 6 after birth. However, by 5 years of age, his left ventricular inflow obstruction worsened. We found an abnormal blood vessel originating from the proximal part of a branch of the left circumflex coronary artery, circling the outside of the mitral valve annulus along the medial side of the coronary sinus. As the child gets older, the blood inflow into the left ventricle might get restricted further, resulting in left-sided heart failure. CONCLUSION: Our findings suggest that even after CAVF closure surgery, it is essential to monitor for complications caused by progressive dilatation of a persistent CAVF.

Deep brain stimulation: Connectivity profile for bradykinesia alleviation.

OBJECTIVE: Subthalamic deep brain stimulation may alleviate bradykinesia in Parkinson patients. Research suggests that this stimulation effect may be mediated by brain networks like the corticocerebellar loop. This study investigated the connectivity between stimulation sites and cortical and subcortical structures to identify connections for effective stimulation. METHODS: We retrospectively investigated 21 patients with Parkinson disease with bilateral subthalamic deep brain stimulation. Stimulation effectiveness in reducing bradykinesia, tremor, and rigidity was evaluated for each electrode contact in brain hemispheres contralateral to the affected hemibody. Dysarthric side effects were also examined. Probabilistic tractography based on diffusion-weighted imaging was performed in individual patient-specific brains using electrode contacts as seeds. Connectivity profiles of contacts with effective and noneffective stimulation were compared. RESULTS: Connectivity profiles of effective and noneffective contacts differed. Moreover, the connectivity profile for bradykinesia differed from that for rigidity, tremor, or dysarthria. Regarding bradykinesia, effective contacts were significantly more often connected with the ipsilateral superior cerebellar peduncle and the ipsilateral dentate nucleus, which correspond to the ipsilateral portion of the cerebellothalamocortical pathway. Rigidity was mitigated by stimulation of ascending brainstem and intralaminar thalamic connections. Tremor alleviation was related to connections with the internal capsule (anterior limb) and the pallidum. Dysarthric side effects were associated with connections to the supplementary motor area and the decussating cerebellothalamocortical pathway. INTERPRETATION: Whereas bradykinesia seems to be mitigated by stimulation of the ascending, ipsilateral cerebellothalamocortical pathway, stimulation of the descending corticopontocerebellar pathway may be ineffective. Rigidity, tremor, and dysarthric side effects seem to be influenced by different neural networks. ANN NEUROL 2019;85:852-864.

Life-threatening acute water intoxication in a woman undergoing hysteroscopic myomectomy: a case report and review of the literature.

BACKGROUND: Acute water intoxication after hysteroscopy is a rare, life-threatening condition, often accompanied with delayed diagnosis owing to masked symptoms because of general anesthesia. CASE PRESENTATION: Herein we presented a 39-year-old female who presented with cardiac arrest after hysteroscopic myomectomy because of acute water intoxication and survived after extracorporeal membrane oxygenation, continuous venous-venous hemofiltration, and aggressive high sodium fluid resuscitation. CONCLUSION: Failure to recognize and treat this condition appropriately may lead to potentially lethal cardiopulmonary complications.

The role of dopamine in the brain - lessons learned from Parkinson's disease.

Parkinson's disease causes a characteristic combination of motor symptoms due to progressive neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta. The core impairment of dopaminergic neurotransmission has motivated the use of functional magnetic resonance imaging (fMRI) in patients with Parkinson's disease to elucidate the role of dopamine in motor control and cognition in humans. Here we review the main insights from functional brain imaging in Parkinson's disease. Task-related fMRI revealed many disease-related alterations in brain activation patterns. However, the interpretation of these findings is complicated by the fact that task-dependent activity is influenced by complex interactions between the amount of dopaminergic neurodegeneration in the task-relevant nuclei, the state of medication, genetic factors and performance. Despite these ambiguities, fMRI studies in Parkinson's disease demonstrated a central role of dopamine in the generation of movement vigour (bradykinesia) and the control of excessive movements (dyskinesia), involving changes of both activity and connectivity of the putamen, premotor and motor regions, and right inferior frontal gyrus (rIFG). The fMRI studies addressing cognitive flexibility provided convergent evidence for a non-linear, U-shaped, relationship between dopamine levels and performance. The amount of neurodegeneration in the task-relevant dopaminergic nuclei and pharmacological dopamine replacement can therefore move performance either away or towards the task-specific optimum. Dopamine levels also strongly affect processing of reward and punishment for optimal learning. However, further studies are needed for a detailed understanding of the mechanisms underlying these effects.

Echogenicity of basal ganglia structures in different Huntington's disease phenotypes.

In Huntington's disease (HD), a neurodegenerative-inherited disease, chorea as the typical kind of movement disorder is described. Beside chorea, however, all other kinds of movement disturbances, such as bradykinesia, dystonia, tremor or myoclonus can occur. Aim of the current study was to investigate alterations in the echogenicity of basal ganglia structures in different Huntington's disease phenotypes. 47 patients with manifest and genetically confirmed HD were recruited. All participants underwent a thorough neurological examination. According to a previously described method, classification into predominantly choreatic, mixed or bradykinetic-rigid motor phenotypes was performed depending on subscores of the Unified Huntington's Disease Rating Scale. In addition, findings in juvenile HD were compared to adult HD. Transcranial sonography was performed by investigators blinded to clinical classification. There were no significant differences in basal ganglia echogenicities between the three phenotypes. Size of echogenic area of substantia nigra (SN) correlated positively with CAG repeat and bradykinesia subscore, and negatively with age of onset and chorea subscore. Comparing juvenile and adult HD subtypes, SN hyperechogenicity was significantly more often detectable in the juvenile form (100 vs. 29.3 %, p = 0.002). Regarding echogenicity of caudate or lentiform nuclei, no significant differences were detected. HD patients with the juvenile variant exhibit marked hyperechogenicity of substantia nigra. No significant differences in basal ganglia echogenicities between predominantly choreatic, mixed or bradykinetic-rigid motor phenotypes were detected.

Metabolic Changes Induced by Electrical Stimulation of Prelemniscal Radiations for the Treatment of Parkinson Disease.

OBJECTIVE: The aim of this work was to study mechanisms of action of electrical stimulation of prelemniscal radiations (Raprl) in the treatment of Parkinson disease, using 2-deoxy-2-fluoro-D-glucose (18F-FDG) Positron Emission Tomography (PET/CT). Materialand Methods: Five patients with PD and predominant unilateral tremor, rigidity and bradykinesia underwent deep brain stimulation (DBS) in contralateral Raprl that improved symptoms from 82.4 to 94.5%. 18F-FDG PET studies were performed before electrode implantation and after DBS therapy. Changes in metabolic activity in PET were evaluated by the maximal standardized uptake value (MSUV) and statistical parametric mapping (SPM) for regions of interest (ROIs) ipsilateral and contralateral to the stimulation site. ROIs were derived from a preoperative probabilistic tractography and included primary motor, supplementary motor and orbitofrontal cortices: Raprl, ventrolateral thalamus, putamen and cerebellum. RESULTS: No significant MSUV changes occurred in ROIs contralateral to Raprl-DBS. In contrast, MSUV decreased ipsilateral to DBS in Raprl, the thalamus, and the primary and supplementary motor cortices. SPM analysis showed metabolic changes which were significantly different after DBS therapy in all ROIs ipsilateral to DBS compared to those in the contralateral side. CONCLUSION: Raprl-DBS decreases the metabolic activity of areas anatomically related to its fiber composition. Improvement of symptoms may result from a decrease in pathological overactivity of circuits related to the ROIs.

[Pulmonary hypertension associated with connective tissue diseases]. / Hipertensión arterial pulmonar por ecocardiografía en pacientes con enfermedades de tejido conectivo.

BACKGROUND: Pulmonary arterial hypertension is an important cause of complications among patients with connective tissue diseases. AIM: To describe the clinical and echocardiographic characteristics of patients with pulmonary hypertension associated with connective tissue diseases. MATERIAL AND METHODS: Retrospective, observational and descriptive study. We analyzed 35 patients with pulmonary hypertension associated with connective tissue diseases. All patients were evaluated and diagnosed by at least one medical specialist in rheumatology. Pulmonary arterial hypertension was defined as a pulmonary artery systolic pressure ≥ 40 mmHg by echocardiography. The group was divided as not severe when pressures ranged from 40 to 64 mmHg and severe, when pressures were ≥ 65 mmHg. RESULTS: The most common connective tissue disease associated with pulmonary arterial hypertension was diffuse scleroderma in 46% of cases. Eighty nine percent of patients were female. Time of evolution of the pulmonary hypertension was 18.8 ± 21.8 months. The distance walked in the six minute walk test was < 400 m both in patients with and without severe pulmonary hypertension. Fifty one percent of patients had pulmonary restriction. No differences in gas exchange parameters were observed between groups. Comparing echo cardio-graphic findings in patients with and without severe hypertension, the former had a higher frequency of right ventricular dilatation (85.7 and 52.3% respectively, p = 0.04), right ventricular hypertrophy (42.8 and 0% respectively, p = 0.02) and right ventricular hypokinesia (71.4 and 9.5% respectively p = < 0.01). CONCLUSIONS: Patients with severe pulmonary arterial hypertension associated to connective tissue diseases have more commonly dilated, hypertrophic and hypokinetic right ventricles.

Diagnostic accuracy of 123 I-FP-CIT SPECT in diagnosing drug-induced parkinsonism: a prospective study.

INTRODUCTION: Drug-induced parkinsonism is a major type of parkinsonism in our setting. Symptoms usually disappear after discontinuation of the drug. However, they may persist in patients with a variant known as subclinical drug-exacerbated parkinsonism; early identification of this entity has important prognostic and therapeutic implications. The most widely used complementary test in this diagnosis is single-photon emission computed tomography with ioflupane ((123)I), also known as (123)I-FP-CIT SPECT. The aim of our study is to verify its diagnostic accuracy. METHODS: We designed a prospective study of patients with drug-induced parkinsonism in which, after discontinuing the drug and undergoing a (123)I-FP-CIT SPECT scan, patients would be monitored for at least 6 months. Patients were categorised as having iatrogenic parkinsonism if symptoms disappeared, or as having subclinical drug-exacerbated parkinsonism if they persisted. Lastly, we verified concordance between the clinical diagnosis and results from the (123)I- FP-CIT SPECT scan. RESULTS: The sample included 19 patients. The most commonly prescribed drug class was neuroleptic agents. For the diagnosis of both subgroups, (123)I-FP-CIT SPECT showed a sensitivity of 66.7%, specificity and positive predictive value of 100%, a negative predictive value of 86.7%, and a negative likelihood ratio of 0.33. CONCLUSIONS: Although the study needs to be repeated in a larger sample of patients, (123)I-FP-CIT SPECT is useful in the diagnosis of drug-induced parkinsonism since it is a very precise tool for identifying patients with that illness.

Subtle changes in central dopaminergic tone underlie bradykinesia in essential tremor.

INTRODUCTION: In this research, our primary objective was to explore the correlation between basal ganglia dopaminergic neurotransmission, assessed using 123I-FP-CIT (DAT-SPECT), and finger movements abnormalities in patients with essential tremor (ET) and Parkinson's disease (PD). METHODS: We enrolled 16 patients with ET, 17 with PD, and 18 healthy controls (HC). Each participant underwent comprehensive clinical evaluations, kinematic assessments of finger tapping. ET and PD patients underwent DAT-SPECT imaging. The DAT-SPECT scans were subjected to both visual and semi-quantitative analysis using DaTQUANT®. We then investigated the correlations between the clinical, kinematic, and DAT-SPECT data, in patients. RESULTS: Our findings confirm that individuals with ET exhibited slower finger tapping than HC. Visual evaluation of radiotracer uptake in both striata demonstrated normal levels within the ET patient cohort, while PD patients displayed reduced uptake. However, there was notable heterogeneity in the quantification of uptake within the striata among ET patients. Additionally, we found a correlation between the amount of radiotracer uptake in the striatum and movement velocity during finger tapping in patients. Specifically, lower radioligand uptake corresponded to decreased movement velocity (ET: coef. = 0.53, p-adj = 0.03; PD: coef. = 0.59, p-adj = 0.01). CONCLUSION: The study's findings suggest a potential link between subtle changes in central dopaminergic tone and altered voluntary movement execution, in ET. These results provide further insights into the pathophysiology of ET. However, longitudinal studies are essential to determine whether the slight reduction in dopaminergic tone observed in ET patients represents a distinct subtype of the disease or could serve as a predictor for the clinical progression into PD.

A novel MRI-based volumetric index for monitoring the motor symptoms in Parkinson's disease.

BACKGROUND: Conventional MRI scans have limited usefulness in monitoring Parkinson's disease as they typically do not show any disease-specific brain abnormalities. This study aimed to identify an imaging biomarker for tracking motor symptom progression by using a multivariate statistical approach that can combine gray matter volume information from multiple brain regions into a single score specific to each PD patient. METHODS: A cohort of 150 patients underwent MRI at baseline and had their motor symptoms tracked for up to 10 years using MDS-UPDRS-III, with motor symptoms focused on total and subscores, including rigidity, bradykinesia, postural instability, and gait disturbances, resting tremor, and postural-kinetic tremor. Gray matter volume extracted from MRI data was summarized into a patient-specific summary score using Mahalanobis distance, MGMV. MDS-UPDRS-III's progression and its association with MGMV were modeled via linear mixed-effects models over 5- and 10-year follow-up periods. RESULTS: Over the 5-year follow-up, there was a significant increase (P < 0.05) in MDS-UPDRS-III total and subscores, except for postural-kinetic tremor. Over the 10-year follow-up, all MDS-UPDRS-III scores increased significantly (P < 0.05). A higher baseline MGMV was associated with a significant increase in MDS-UPDRS-III total, bradykinesia, postural instability and gait disturbances, and resting tremor (P < 0.05) over the 5-year follow-up, but only with total, bradykinesia, and postural instability and gait disturbances during the 10-year follow-up (P < 0.05). CONCLUSIONS: Higher MGMV scores were linked to faster motor symptom progression, suggesting it could be a valuable marker for clinicians monitoring Parkinson's disease over time.

Identifying dominant-negative actions of a dopamine transporter variant in patients with parkinsonism and neuropsychiatric disease.

Dysfunctional dopaminergic neurotransmission is central to movement disorders and mental diseases. The dopamine transporter (DAT) regulates extracellular dopamine levels, but the genetic and mechanistic link between DAT function and dopamine-related pathologies is not clear. Particularly, the pathophysiological significance of monoallelic missense mutations in DAT is unknown. Here, we use clinical information, neuroimaging, and large-scale exome-sequencing data to uncover the occurrence and phenotypic spectrum of a DAT coding variant, DAT-K619N, which localizes to the critical C-terminal PSD-95/Discs-large/ZO-1 homology-binding motif of human DAT (hDAT). We identified the rare but recurrent hDAT-K619N variant in exome-sequenced samples of patients with neuropsychiatric diseases and a patient with early-onset neurodegenerative parkinsonism and comorbid neuropsychiatric disease. In cell cultures, hDAT-K619N displayed reduced uptake capacity, decreased surface expression, and accelerated turnover. Unilateral expression in mouse nigrostriatal neurons revealed differential effects of hDAT-K619N and hDAT-WT on dopamine-directed behaviors, and hDAT-K619N expression in Drosophila led to impairments in dopamine transmission with accompanying hyperlocomotion and age-dependent disturbances of the negative geotactic response. Moreover, cellular studies and viral expression of hDAT-K619N in mice demonstrated a dominant-negative effect of the hDAT-K619N mutant. Summarized, our results suggest that hDAT-K619N can effectuate dopamine dysfunction of pathological relevance in a dominant-negative manner.

Accuracy of clinical diagnosis in tremulous parkinsonian patients: a blinded video study.

BACKGROUND: This study examines the clinical accuracy of movement disorder specialists in distinguishing tremor dominant Parkinson's disease (TDPD) from other tremulous movement disorders by the use of standardised patient videos. PATIENTS AND METHODS: Two movement disorder specialists were asked to distinguish TDPD from patients with atypical tremor and dystonic tremor, who had no evidence of presynaptic dopaminergic deficit (subjects without evidence of dopaminergic deficit (SWEDDs)) according to (123)I-N-ω-fluoro-propyl- 2ß-carbomethoxy-3ß-(4-iodophenyl) nortropane ([(123)I] FP-CIT) single photon emission computed tomography (SPECT), by 'blinded' video analysis in 38 patients. A diagnosis of parkinsonism was made if the step 1 criteria of the Queen Square Brain Bank criteria for Parkinson's disease were fulfilled. The reviewer diagnosis was compared with the working clinical diagnosis drawn from the medical history, SPECT scan result, long term follow-up and in some cases the known response to dopaminergic medications. This comparison allowed a calculation for false positive and false negative rate of diagnosis of PD. RESULTS: High false positive (17.4-26.1%) and negative (6.7-20%) rates were found for the diagnosis of PD. The diagnostic distinction of TDPD from dystonic tremor was reduced by the presence of dystonic features in treated and untreated PD patients. CONCLUSION: Clinical distinction of TDPD from atypical tremor, monosymptomatic rest tremor and dystonic tremor can be difficult due to the presence of parkinsonian features in tremulous SWEDD patients. The diagnosis of bradykinesia was particularly challenging. This study highlights the difficulty of differentiation of some cases of SWEDD from PD.

Brain morphological changes in hypokinetic dysarthria of Parkinson's disease and use of machine learning to predict severity.

BACKGROUND: Up to 90% of patients with Parkinson's disease (PD) eventually develop the speech and voice disorder referred to as hypokinetic dysarthria (HD). However, the brain morphological changes associated with HD have not been investigated. Moreover, no reliable model for predicting the severity of HD based on neuroimaging has yet been developed. METHODS: A total of 134 PD patients were included in this study and divided into a training set and a test set. All participants underwent a structural magnetic resonance imaging (MRI) scan and neuropsychological evaluation. Individual cortical thickness, subcortical structure, and white matter volume were extracted, and their association with HD severity was analyzed. After feature selection, a machine-learning model was established using a support vector machine in the training set. The severity of HD was then predicted in the test set. RESULTS: Atrophy of the right precentral cortex and the right fusiform gyrus was significantly associated with HD. No association was found between HD and volume of white matter or subcortical structures. Favorable and optimal performance of machine learning on HD severity prediction was achieved using feature selection, giving a correlation coefficient (r) of .7516 and a coefficient of determination (R2 ) of .5649 (P < .001). CONCLUSION: The brain morphological changes were associated with HD. Excellent prediction of the severity of HD was achieved using machine learning based on neuroimaging.

Dopamine-responsive and dopamine-resistant resting tremor in Parkinson disease.

OBJECTIVE: We tested the hypothesis that there are 2 distinct phenotypes of Parkinson tremor, based on interindividual differences in the response of resting tremor to dopaminergic medication. We also investigated whether this pattern is specific to tremor by comparing interindividual differences in the dopamine response of tremor to that of bradykinesia. METHODS: In this exploratory study, we performed a levodopa challenge in 76 tremulous patients with Parkinson tremor. Clinical scores (Movement Disorders Society-sponsored version of the Unified Parkinson's Disease Rating Scale part III) were collected "off" and "on" a standardized dopaminergic challenge (200/50 mg dispersible levodopa-benserazide). In both sessions, resting tremor intensity was quantified using accelerometry, both during rest and during cognitive coactivation. Bradykinesia was quantified using a speeded keyboard test. We calculated the distribution of dopamine-responsiveness for resting tremor and bradykinesia. In 41 patients, a double-blinded, placebo-controlled dopaminergic challenge was repeated after approximately 6 months. RESULTS: The dopamine response of resting tremor, but not bradykinesia, significantly departed from a normal distribution. A cluster analysis on 3 clinical and electrophysiologic markers of tremor dopamine-responsiveness revealed 3 clusters: dopamine-responsive, intermediate, and dopamine-resistant tremor. A repeated levodopa challenge after 6 months confirmed this classification. Patients with dopamine-responsive tremor had greater disease severity and tended to have a higher prevalence of dyskinesia. CONCLUSION: Parkinson resting tremor can be divided into 3 partially overlapping phenotypes, based on the dopamine response. These tremor phenotypes may be associated with different underlying pathophysiologic mechanisms, requiring a different therapeutic approach.

Prediction of age at onset in Parkinson's disease using objective specific neuroimaging genetics based on a sparse canonical correlation analysis.

The age at onset (AAO) is an important determinant in Parkinson's disease (PD). Neuroimaging genetics is suitable for studying AAO in PD as it jointly analyzes imaging and genetics. We aimed to identify features associated with AAO in PD by applying the objective-specific neuroimaging genetics approach and constructing an AAO prediction model. Our objective-specific neuroimaging genetics extended the sparse canonical correlation analysis by an additional data type related to the target task to investigate possible associations of the imaging-genetic, genetic-target, and imaging-target pairs simultaneously. The identified imaging, genetic, and combined features were used to construct analytical models to predict the AAO in a nested five-fold cross-validation. We compared our approach with those from two feature selection approaches where only associations of imaging-target and genetic-target were explored. Using only imaging features, AAO prediction was accurate in all methods. Using only genetic features, the results from other methods were worse or unstable compared to our model. Using both imaging and genetic features, our proposed model predicted the AAO well (r = 0.5486). Our findings could have significant impacts on the characterization of prodromal PD and contribute to diagnosing PD early because genetic features could be measured accurately from birth.

Acute hypokinetic-rigid syndrome following SARS-CoV-2 infection.

OBJECTIVE: To report a case of a patient infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who acutely developed a hypokinetic-rigid syndrome. METHODS: Patient data were obtained from medical records from the Hospital Universitario 12 de Octubre in Madrid, Spain. [123I]-ioflupane dopamine transporter (DaT) SPECT images were acquired 4 hours after a single dose of 185 MBq of 123I-FP-CIT. Quantitative analysis was performed with DaTQUANT software providing the specific binding ratio and z score values of the striatum. RESULTS: We report a previously healthy 58-year-old man who developed hyposmia, generalized myoclonus, fluctuating and transient changes in level of consciousness, opsoclonus, and an asymmetric hypokinetic-rigid syndrome with ocular abnormalities after a severe SARS-CoV-2 infection. DaT-SPECT confirmed a bilateral decrease in presynaptic dopamine uptake asymmetrically involving both putamina. Significant improvement in the parkinsonian symptoms was observed without any specific treatment. CONCLUSION: This case study provides clinical and functional neuroimaging evidence to support that SARS-CoV-2 can gain access to the CNS, affecting midbrain structures and leading to neurologic signs and symptoms.

Functional brain imaging in pure akinesia with gait freezing: [18F] FDG PET and [18F] FP-CIT PET analyses.

Pure akinesia with gait freezing (PAGF) has characteristic features, including freezing of gait and prominent speech disturbance without rigidity or tremor. The purpose of this study was to investigate changes in brain glucose metabolism and presynaptic dopaminergic function in PAGF. By using [(18)F] fluorodeoxyglucose (FDG) PET, 11 patients with PAGF were compared with 14 patients with probable progressive supranuclear palsy (PSP), 13 patients with Parkinson's disease (PD), and 11 normal controls. [(18)F] N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane (FP-CIT) PET was performed in 11 patients with PAGF and with 10 normal controls. The PAGF patients showed decreased glucose metabolism in the midbrain when compared with normal controls. PSP patients showed a similar topographic distribution of glucose hypometabolism with additional areas, including the frontal cortex, when compared with normal controls. The FP-CIT PET findings in patients with PAGF revealed severely decreased uptake bilaterally in the basal ganglia. These findings suggest that both PAGF and PSP may be part of the same pathophysiologic spectrum of disease. However, the reason why PAGF manifests clinically in a different manner needs to be further elucidated.

Connectivity-based selection of optimal deep brain stimulation contacts: A feasibility study.

BACKGROUND: The selection of optimal deep brain stimulation (DBS) parameters is time-consuming, experience-dependent, and best suited when acute effects of stimulation can be observed (e.g., tremor reduction). OBJECTIVES: To test the hypothesis that optimal stimulation location can be estimated based on the cortical connections of DBS contacts. METHODS: We analyzed a cohort of 38 patients with Parkinson's disease (24 training, and 14 test cohort). Using whole-brain probabilistic tractography, we first mapped the cortical regions associated with stimulation-induced efficacy (rigidity, bradykinesia, and tremor improvement) and side effects (paresthesia, motor contractions, and visual disturbances). We then trained a support vector machine classifier to categorize DBS contacts into efficacious, defined by a therapeutic window ≥2 V (threshold for side effect minus threshold for efficacy), based on their connections with cortical regions associated with efficacy versus side effects. The connectivity-based classifications were then compared with actual stimulation contacts using receiver-operating characteristics (ROC) curves. RESULTS: Unique cortical clusters were associated with stimulation-induced efficacy and side effects. In the training dataset, 42 of the 47 stimulation contacts were accurately classified as efficacious, with a therapeutic window of ≥3 V in 31 (66%) and between 2 and 2.9 V in 11 (24%) electrodes. This connectivity-based estimation was successfully replicated in the test cohort with similar accuracy (area under ROC = 0.83). CONCLUSIONS: Cortical connections can predict the efficacy of DBS contacts and potentially facilitate DBS programming. The clinical utility of this paradigm in optimizing DBS outcomes should be prospectively tested, especially for directional electrodes.