Deep brain stimulation of the subthalamic nucleus in severe Parkinson's disease: relationships between dual-contact topographic setting and 1-year worsening of speech and gait.

BACKGROUND: Subthalamic nucleus (STN) deep brain stimulation (DBS) alleviates severe motor fluctuations and dyskinesia in Parkinson's disease, but may result in speech and gait disorders. Among the suspected or demonstrated causes of these adverse effects, we focused on the topography of contact balance (CB; individual, right and left relative dual positions), a scantly studied topic, analyzing the relationships between symmetric or non-symmetric settings, and the worsening of these signs. METHOD: An observational monocentric study was conducted on a series of 92 patients after ethical approval. CB was specified by longitudinal and transversal positions and relation to the STN (CB sub-aspects) and totalized at the patient level (patient CB). CB was deemed symmetric when the two contacts were at the same locations relative to the STN. CB was deemed asymmetric when at least one sub-aspect differed in the patient CB. Baseline and 1-year characteristics were routinely collected: (i) general, namely, Unified Parkinson's Disease Rating Scores (UPDRS), II, III motor and IV, daily levodopa equivalent doses, and Parkinson's Disease Questionnaire of Quality of Life (PDQ39) scores; (ii) specific, namely scores for speech (II-5 and III-18) and axial signs (II-14, III-28, III-29, and III-30). Only significant correlations were considered (p < 0.05). RESULTS: Baseline characteristics were comparable (symmetric versus asymmetric). CB settings were related to deteriorations of speech and axial signs: communication PDQ39 and UPDRS speech and gait scores worsened exclusively with symmetric settings; the most influential CB sub-aspect was symmetric longitudinal position. CONCLUSION: Our findings suggest that avoiding symmetric CB settings, whether by electrode positioning or shaping of electric fields, could reduce worsening of speech and gait.

DTI Abnormalities Related to Glioblastoma: A Prospective Comparative Study with Metastasis and Healthy Subjects.

(1) Background: Glioblastoma multiforme (GBM) shows complex mechanisms of spreading of the tumor cells, up to remote areas, and little is still known of these mechanisms, thus we focused on MRI abnormalities observable in the tumor and the brain adjacent to the lesion, up to the contralateral hemisphere, with a special interest on tensor diffusion imaging informing on white matter architecture; (2) Material and Methods: volumes, macroscopic volume (MV), brain-adjacent-tumor (BAT) volume and abnormal color-coded DTI volume (aCCV), and region-of-interest samples (probe volumes, ipsi, and contra lateral to the lesion), with their MRI characteristics, apparent diffusion coefficient (ADC), fractional anisotropy (FA) values, and number of fibers (DTI fiber tracking) were analyzed in patients suffering GBM (n = 15) and metastasis (n = 9), and healthy subjects (n = 15), using ad hoc statistical methods (type I error = 5%) (3) Results: GBM volumes were larger than metastasis volumes, aCCV being larger in GBM and BAT ADC was higher in metastasis, ADC decreased centripetally in metastasis, FA increased centripetally either in GBM or metastasis, MV and BAT FA values were higher in GBM, ipsi FA values of GBM ROIs were higher than those of metastasis, and the GBM ipsi number of fibers was higher than the GBM contra number of fibers; (4) Conclusions: The MV, BAT and especially the aCCV, as well as their related water diffusion characteristics, could be useful biomarkers in oncology and functional oncology.

Early Deformation of Deep Brain Stimulation Electrodes Following Surgical Implantation: Intracranial, Brain, and Electrode Mechanics.

INTRODUCTION: Although deep brain stimulation is nowadays performed worldwide, the biomechanical aspects of electrode implantation received little attention, mainly as physicians focused on the medical aspects, such as the optimal indication of the surgical procedure, the positive and adverse effects, and the long-term follow-up. We aimed to describe electrode deformations and brain shift immediately after implantation, as it may highlight our comprehension of intracranial and intracerebral mechanics. MATERIALS AND METHODS: Sixty electrodes of 30 patients suffering from severe symptoms of Parkinson's disease and essential tremor were studied. They consisted of 30 non-directional electrodes and 30 directional electrodes, implanted 42 times in the subthalamus and 18 times in the ventrolateral thalamus. We computed the x (transversal), y (anteroposterior), z (depth), torsion, and curvature deformations, along the electrodes from the entrance point in the braincase. The electrodes were modelized from the immediate postoperative CT scan using automatic voxel thresholding segmentation, manual subtraction of artifacts, and automatic skeletonization. The deformation parameters were computed from the curve of electrodes using a third-order polynomial regression. We studied these deformations according to the type of electrodes, the clinical parameters, the surgical-related accuracy, the brain shift, the hemisphere and three tissue layers, the gyration layer, the white matter stem layer, and the deep brain layer (type I error set at 5%). RESULTS: We found that the implanted first hemisphere coupled to the brain shift and the stiffness of the type of electrode impacted on the electrode deformations. The deformations were also different according to the tissue layers, to the electrode type, and to the first-hemisphere-brain-shift effect. CONCLUSION: Our findings provide information on the intracranial and brain biomechanics and should help further developments on intracerebral electrode design and surgical issues.

Disrupted Pallido-Thalamo-Cortical Functional Connectivity in Chronic Disorders of Consciousness.

Chronic disorders of consciousness (DOC) encompass unresponsive wakefulness syndrome and minimally conscious state. Their anatomo-functional correlates are not clearly defined yet, although impairments of functional cortical networks have been reported, as well as the implication of the thalamus and deep brain structures. However, the pallidal functional connectivity with the thalamus and the cortical networks has not been studied so far. Using resting-state functional MRI, we conducted a functional connectivity study between the pallidum, the thalamus and the cortical networks in 13 patients with chronic DOC and 19 healthy subjects. We observed in chronic DOC patients that the thalami were no longer connected to the cortical networks, nor to the pallidums. Concerning the functional connectivity of pallidums, we reported an abolition of the negative correlation with the default mode network, and of the positive correlation with the salience network. The disrupted functional connectivity observed in chronic DOC patients between subcortical structures and cortical networks could be related to the mesocircuit model. A better understanding of the DOC underlying physiopathology could provide food for thought for future therapeutic proposals.

Progressive multifocal leukoencephalopathy: MRI findings in HIV-infected patients are closer to rituximab- than natalizumab-associated PML.

OBJECTIVES: To compare brain MRI findings in progressive multifocal leukoencephalopathy (PML) associated to rituximab and natalizumab treatments and HIV infection. MATERIALS AND METHODS: In this retrospective, multicentric study, we analyzed brain MRI exams from 72 patients diagnosed with definite PML: 32 after natalizumab treatment, 20 after rituximab treatment, and 20 HIV patients. We compared T2- or FLAIR-weighted images, diffusion-weighted images, T2*-weighted images, and contrast enhancement features, as well as lesion distribution, especially gray matter involvement. RESULTS: The three PML entities affect U-fibers associated with low signal intensities on T2*-weighted sequences. Natalizumab-associated PML showed a punctuate microcystic appearance in or in the vicinity of the main PML lesions, a potential involvement of the cortex, and contrast enhancement. HIV and rituximab-associated PML showed only mild contrast enhancement, punctuate appearance, and cortical involvement. The CD4/CD8 ratio showed a trend to be higher in the natalizumab group, possibly mirroring a more efficient immune response. CONCLUSION: Imaging features of rituximab-associated PML are different from those of natalizumab-associated PML and are closer to those observed in HIV-associated PML. KEY POINTS: • Nowadays, PML is emerging as a complication of new effective therapies based on monoclonal antibodies. • Natalizumab-associated PML shows more inflammatory signs, a perivascular distribution "the milky way," and more cortex involvement than rituximab- and HIV-associated PML. • MRI differences are probably related to higher levels of immunosuppression in HIV patients and those under rituximab therapy.

Differences in BOLD responses in brain reward network reflect the tendency to assimilate a surprising flavor stimulus to an expected stimulus.

External information can modify the subjective value of a tasted stimulus, but little is known about neural mechanisms underlying these behavioral modifications. This study used flavored drinks to produce variable degrees of discrepancy between expected and received flavor. During a learning session, 43 healthy young men learned 4 symbol-flavor associations. In a separate session, associations were presented again during an fMRI scan, but half of the trials introduced discrepancy with previously learned associations. Liking ratings of drinks were collected and were analyzed using a linear model to define the degree to which discrepant symbols affected liking ratings of the subjects during the fMRI session. Based on these results, a GLM analysis of fMRI data was conducted to determine neural correlates of observed behavior. Groups of subjects were composed based on their behavior in response to discrepant symbols, and comparison of brain activity between groups showed that activation in the PCC and the caudate nucleus was more potent in those subjects in which liking was not affected by discrepant symbols. These activations were not found in subjects who assimilated unexpected flavors to flavors preceeded by discrepant symbols. Instead, these subjects showed differences in the activity in the parietal operculum. The activity of reward network appears to be related to assimilation of received flavor to expected flavor in response to symbol-flavor discrepancy.

Using High Spatial Resolution to Improve BOLD fMRI Detection at 3T.

For different functional magnetic resonance imaging experiments using blood oxygenation level-dependent (BOLD) contrast, the acquisition of T2*-weighted scans at a high spatial resolution may be advantageous in terms of time-course signal-to-noise ratio and of BOLD sensitivity when the regions are prone to susceptibility artifacts. In this study, we explore this solution by examining how spatial resolution influences activations elicited when appetizing food pictures are viewed. Twenty subjects were imaged at 3 T with two different voxel volumes, 3.4 µl and 27 µl. Despite the diminution of brain coverage, we found that high-resolution acquisition led to a better detection of activations. Though known to suffer to different degrees from susceptibility artifacts, the activations detected by high spatial resolution were notably consistent with those reported in published activation likelihood estimation meta-analyses, corresponding to taste-responsive regions. Furthermore, these regions were found activated bilaterally, in contrast with previous findings. Both the reduction of partial volume effect, which improves BOLD contrast, and the mitigation of susceptibility artifact, which boosts the signal to noise ratio in certain regions, explained the better detection noted with high resolution. The present study provides further evidences that high spatial resolution is a valuable solution for human BOLD fMRI, especially for studying food-related stimuli.

Interest of local intra-arterial fibrinolysis in acute central retinal artery occlusion: Clinical experience in 16 patients.

OBJECTIVE: Central retinal artery occlusion (CRAO) is a rare disease with poor visual prognosis. We evaluated clinical effectiveness of in situ fibrinolysis with original angiographic scores describing the aspect of carotid siphon, proximal ophthalmic artery, and choroid blush. METHODS: Retrospective study of 16 consecutive cases of CRAO between 2007 and 2013. Fourteen underwent in situ fibrinolysis, two were excluded due to pre-occlusive internal carotid stenosis on pre-procedural diagnostic angio-CT. Fibrinolysis was performed with rt-PA (average injected dose: 35 mg), with an average onset delay of 8hours (4-17h). We reported angiographic scores pre- and post-fibrinolysis, visual acuity (VA) before and after treatment, and VA improvement evaluated by ophthalmologist 6 to 12 months after thrombolysis. RESULTS: Six patients (43%) recovered post-fibrinolysis VA significally improved, superior or equal to 1/10 (1/10 to 8/10). An irregular carotid siphon (2 cases) appeared as a predictive factor of failure. Fibrinolysis procedure led to a significant improvement of angiographic permeability of proximal ophthalmic artery (P=0.0498), but this result was not accompanied by any VA improvement. The aspect of choroid blush showed no correlation with the management of thrombolysis. CONCLUSION: In situ fibrinolysis was more effective than medical treatments or natural evolution of CRAO (VA improvement was respectively 40% and 20%). However, the benefit/risk ratio must be discussed, and an angio-CT of supra-aortic trunks could be systematically performed before thrombolysis, to assess the potential VA recovery compared with complications such as ischemic stroke.

Is R2* a new MRI biomarker for the progression of Parkinson's disease? A longitudinal follow-up.

PURPOSE: To study changes of iron content in basal ganglia in Parkinson's disease (PD) through a three-year longitudinal follow-up of the effective transverse relaxation rate R2*, a validated MRI marker of brain iron content which can be rapidly measured under clinical conditions. METHODS: Twenty-seven PD patients and 26 controls were investigated by a first MRI (t0). Longitudinal analysis was conducted among the 18 controls and 14 PD patients who underwent a second MRI (t1) 3 years after. The imaging protocol consisted in 6 gradient echo images obtained at different echo-times for mapping R2*. Quantitative exploration of basal ganglia was performed by measuring the variation of R2* [R2*(t1) - R2*(t0)] in several regions of interest. RESULTS: During the three-year evolution of PD, R2* increased in Substantia nigra (SN) (by 10.2% in pars compacta, p = 0.001, and 8.1% in pars reticulata, p = 0.013) and in the caudal putamen (11.4%, p = 0.011), without significant change in controls. Furthermore, we showed a positive correlation between the variation of R2* and the worsening of motor symptoms of PD (p = 0.028). CONCLUSION: Significant variation of R2* was longitudinally observed in the SN and caudal putamen of patients with PD evolving over a three-year period, emphasizing its interest as a biomarker of disease progression. Our results suggest that R2* MRI follow-up could be an interesting tool for individual assessment of neurodegeneration due to PD, and also be useful for testing the efficiency of disease-modifying treatments.

Silent cerebral infarcts after cardiac catheterization: a randomized comparison of radial and femoral approaches.

BACKGROUND: Single center studies using serial cerebral diffusion-weighted magnetic resonance imaging in patients having cardiac catheterization have suggested that cerebral microembolism might be responsible for silent cerebral infarct (SCI) as high as 15% to 22%. We evaluated in a multicenter trial the incidence of SCIs after cardiac catheterization and whether or not the choice of the arterial access site might impact this phenomenon. METHODS AND RESULTS: Patients were randomized to have cardiac catheterization either by Radial (n = 83) or Femoral (n = 77) arterial approaches by experimented operators. The main outcome measure was the occurrence of new cerebral infarct on serial diffusion-weighted magnetic resonance imaging. Patient and catheterization characteristics, including duration of catheterization, were similar in both groups. The risk of SCI did not differ significantly between the Femoral and Radial groups (incidence of 11.7% versus 17.5%; OR, 0.85; 95% CI, 0.62-1.16; P = .31). At multivariable analysis, the independent predictors of SCI were the patient's higher height and lower transvalvular gradient. CONCLUSIONS: The high rate of SCI after cardiac catheterization of patients with aortic stenosis was confirmed, but its occurrence was not affected by the selection of Radial and Femoral access.

Toxoplasmic pachymeningitis with visual field impairment in a single-eyed patient and a literature review.

To describe the clinical features of a patient with toxoplasmic pachymeningitis and provide a review of the recent cases of pachymeningitis in the literature.Retrospective, observational case report. A one-eyed patient who presented to our institution with blurred vision, floaters, and visual field shrinkage. Review of clinical, laboratory, perimetric, and radiologic records of the patient and description of the efficacy of antibiotic therapy. The signs of ocular impairment, including visual acuity, visual field, and magnetic resonance imaging (MRI) changes. A one-eyed patient who complained of blurred vision and unexplained visual field shrinkage was evaluated. The diagnosis of toxoplasmic pachymeningitis was confirmed by existence of a toxoplasmic seroconversion, cerebrospinal fluid abnormalities, radiological features, absence of other diagnoses, improvement of symptoms, and resolution of pachymeningitis in MRI with oral trimethoprim-sulfamethoxazole combination.Pachymeningitis is a rare disease and toxoplasmic pachymeningitis has never been described. Among the various infectious causes, screening for toxoplasmosis must be performed because it can lead to pachymeningitis and sequelae. Variable features may lead to misdiagnosis and delay in the treatment of this sight-threatening and potentially fatal disease.