Functional Organization Of The Paramedian Reticular Nucleus Of The Cat

The functional organization of the PRN of the cat medulla was studied in light of its potential role as an integrator of postural and cardiovascular afferent information. Neurons in a large number of afferent sites including the cerebellar deep nuclei, vestibular, accessory oculomotor and solitary nuclei, superior colliculus, bulbar reticular formation, cerebral cortex and spinal cord were retrogradely labeled with HRP following injection of the dorsal and ventral PRN. Collateral axonal projections of PRN neurons were studied with fluorescence histochemistry focusing on their cerebello- and spinopetal connections. About 50% of PRN axons projecting to the ipsilateral anterior cerebellar lobe had collateral branches to the corresponding contralateral cortex. Similarly, 40% of PRN neurons projecting to the region of the intermediolateral nucleus (IML) at and caudal to the T2 level distributed collateral branches to the same region at and caudal to the T4 and T7 levels. The PRN was systematically explored for single units antidromically activated by electrical stimulation of the IML in chloralosed, paralyzed and artificially ventilated cats. Of 62 such PRN units, 40% were found to respond orthodromically to electrical stimulation of the carotid sinus nerve (CSN) and/or fastigial nucleus. Under similar anesthetic conditions, the region of the PRN was reexplored for single units orthodromically activated by electrical stimulation of the vestibular nuclear complex following chronic surgical ablation of the fastigioreticular input to the PRN. Of 47 such PRN units, 62% could be antidromically activated by electrical stimulation of the IML, however, none responded orthodromically to CSN stimulation. All units found responsive to IML stimulation in both preparations were located mainly in the ventral PRN. These experiments provide anatomical and electrophysiological evidence of direct pathways from the PRN to the IML region which mediate cardiovascular and vestibular afferent information. In addition to their obvious role in motor regulation, projections of the motor cortex, accessory oculomotor nuclei, superior colliculus and bulbar reticular formation to the PRN may influence sympathetic activity through its connections with the IML region. These extensive connections and functional autonomic relations of the PRN suggest a central role in mediating orthostatic reflex activity

Knowledge-Based Deformable Surface Model with Application to Segmentation of Brain Structures in MRI

We have developed a knowledge-based deformable surface for segmentation of medical images. This work has been done in the context of segmentation of hippocampus from brain MRI, due to its challenge and clinical importance. The model has a polyhedral discrete structure and is initialized automatically by analyzing brain MRI sliced by slice, and finding few landmark features at each slice using an expert system. The expert system decides on the presence of the hippocampus and its general location in each slice. The landmarks found are connected together by a triangulation method, to generate a closed initial surface. The surface deforms under defined internal and external force terms thereafter, to generate an accurate and reproducible boundary for the hippocampus. The anterior and posterior (AP) limits of the hippocampus is estimated by automatic analysis of the location of brain stem, and some of the features extracted in the initialization process. These data are combined together with a priori knowledge using Bayes method to estimate a probability density function (pdf) for the length of the structure in sagittal direction. The hippocampus AP limits are found by optimizing this pdf. The model is tested on real clinical data and the results show very good model performance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85930/1/Fessler166.pd

Prospective Quantitative Neuroimaging Analysis of Putative Temporal Lobe Epilepsy

Purpose: A prospective study of individual and combined quantitative imaging applications for lateralizing epileptogenicity was performed in a cohort of consecutive patients with a putative diagnosis of mesial temporal lobe epilepsy (mTLE). Methods: Quantitative metrics were applied to MRI and nuclear medicine imaging studies as part of a comprehensive presurgical investigation. The neuroimaging analytics were conducted remotely to remove bias. All quantitative lateralizing tools were trained using a separate dataset. Outcomes were determined after 2 years. Of those treated, some underwent resection, and others were implanted with a responsive neurostimulation (RNS) device. Results: Forty-eight consecutive cases underwent evaluation using nine attributes of individual or combinations of neuroimaging modalities: 1) hippocampal volume, 2) FLAIR signal, 3) PET profile, 4) multistructural analysis (MSA), 5) multimodal model analysis (MMM), 6) DTI uncertainty analysis, 7) DTI connectivity, and 9) fMRI connectivity. Of the 24 patients undergoing resection, MSA, MMM, and PET proved most effective in predicting an Engel class 1 outcome (\u3e80% accuracy). Both hippocampal volume and FLAIR signal analysis showed 76% and 69% concordance with an Engel class 1 outcome, respectively. Conclusion: Quantitative multimodal neuroimaging in the context of a putative mTLE aids in declaring laterality. The degree to which there is disagreement among the various quantitative neuroimaging metrics will judge whether epileptogenicity can be confined sufficiently to a particular temporal lobe to warrant further study and choice of therapy. Prediction models will improve with continued exploration of combined optimal neuroimaging metrics

Data mining MR image features of select structures for lateralization of mesial temporal lobe epilepsy

PURPOSE: This study systematically investigates the predictive power of volumetric imaging feature sets extracted from select neuroanatomical sites in lateralizing the epileptogenic focus in mesial temporal lobe epilepsy (mTLE) patients. METHODS: A cohort of 68 unilateral mTLE patients who had achieved an Engel class I outcome postsurgically was studied retrospectively. The volumes of multiple brain structures were extracted from preoperative magnetic resonance (MR) images in each. The MR image data set consisted of 54 patients with imaging evidence for hippocampal sclerosis (HS-P) and 14 patients without (HS-N). Data mining techniques (i.e., feature extraction, feature selection, machine learning classifiers) were applied to provide measures of the relative contributions of structures and their correlations with one another. After removing redundant correlated structures, a minimum set of structures was determined as a marker for mTLE lateralization. RESULTS: Using a logistic regression classifier, the volumes of both hippocampus and amygdala showed correct lateralization rates of 94.1%. This reflected about 11.7% improvement in accuracy relative to using hippocampal volume alone. The addition of thalamic volume increased the lateralization rate to 98.5%. This ternary-structural marker provided a 100% and 92.9% mTLE lateralization accuracy, respectively, for the HS-P and HS-N groups. CONCLUSIONS: The proposed tristructural MR imaging biomarker provides greater lateralization accuracy relative to single- and double-structural biomarkers and thus, may play a more effective role in the surgical decision-making process. Also, lateralization of the patients with insignificant atrophy of hippocampus by the proposed method supports the notion of associated structural changes involving the amygdala and thalamus

Deep brain and cortical stimulation for epilepsy

Background : Despite optimal medical treatment, including epilepsy surgery, many epilepsy patients have uncontrolled seizures. In the last decades, interest has grown in invasive intracranial neurostimulation as a treatment for these patients. Intracranial stimulation includes both deep brain stimulation (DBS) (stimulation through depth electrodes) and cortical stimulation (subdural electrodes). Objectives : To assess the efficacy, safety and tolerability of deep brain and cortical stimulation for refractory epilepsy based on randomized controlled trials. Search methods : We searched PubMed (6 August 2013), the Cochrane Epilepsy Group Specialized Register (31 August 2013), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 7 of 12) and reference lists of retrieved articles. We also contacted device manufacturers and other researchers in the field. No language restrictions were imposed. Selection criteria : Randomized controlled trials (RCTs) comparing deep brain or cortical stimulation to sham stimulation, resective surgery or further treatment with antiepileptic drugs. Data collection and analysis : Four review authors independently selected trials for inclusion. Two review authors independently extracted the relevant data and assessed trial quality and overall quality of evidence. The outcomes investigated were seizure freedom, responder rate, percentage seizure frequency reduction, adverse events, neuropsychological outcome and quality of life. If additional data were needed, the study investigators were contacted. Results were analysed and reported separately for different intracranial targets for reasons of clinical heterogeneity. Main results : Ten RCTs comparing one to three months of intracranial neurostimulation to sham stimulation were identified. One trial was on anterior thalamic DBS (n = 109; 109 treatment periods); two trials on centromedian thalamic DBS (n = 20; 40 treatment periods), but only one of the trials (n = 7; 14 treatment periods) reported sufficient information for inclusion in the quantitative meta-analysis; three trials on cerebellar stimulation (n = 22; 39 treatment periods); three trials on hippocampal DBS (n = 15; 21 treatment periods); and one trial on responsive ictal onset zone stimulation (n = 191; 191 treatment periods). Evidence of selective reporting was present in four trials and the possibility of a carryover effect complicating interpretation of the results could not be excluded in 4 cross-over trials without any washout period. Moderate-quality evidence could not demonstrate statistically or clinically significant changes in the proportion of patients who were seizure-free or experienced a 50% or greater reduction in seizure frequency (primary outcome measures) after 1 to 3 months of anterior thalamic DBS in (multi) focal epilepsy, responsive ictal onset zone stimulation in (multi) focal epilepsy patients and hippocampal DBS in (medial) temporal lobe epilepsy. However, a statistically significant reduction in seizure frequency was found for anterior thalamic DBS (-17.4% compared to sham stimulation; 95% confidence interval (CI) -32.1 to -1.0; high-quality evidence), responsive ictal onset zone stimulation (-24.9%; 95% CI -40.1 to 6.0; high-quality evidence)) and hippocampal DBS (-28.1%; 95% CI -34.1 to -22.2; moderate-quality evidence). Both anterior thalamic DBS and responsive ictal onset zone stimulation do not have a clinically meaningful impact on quality life after three months of stimulation (high-quality evidence). Electrode implantation resulted in asymptomatic intracranial haemorrhage in 3% to 4% of the patients included in the two largest trials and 5% to 13% had soft tissue infections; no patient reported permanent symptomatic sequelae. Anterior thalamic DBS was associated with fewer epilepsy-associated injuries (7.4 versus 25.5%; P = 0.01) but higher rates of self-reported depression (14.8 versus 1.8%; P = 0.02) and subjective memory impairment (13.8 versus 1.8%; P = 0.03); there were no significant differences in formal neuropsychological testing results between the groups. Responsive ictal-onset zone stimulation was well tolerated with few side effects but SUDEP rate should be closely monitored in the future (4 per 340 [= 11.8 per 1000] patient-years; literature: 2.2-10 per 1000 patient-years). The limited number of patients preclude firm statements on safety and tolerability of hippocampal DBS. With regards to centromedian thalamic DBS and cerebellar stimulation, no statistically significant effects could be demonstrated but evidence is of only low to very low quality. Authors' conclusions : Only short term RCTs on intracranial neurostimulation for epilepsy are available. Compared to sham stimulation, one to three months of anterior thalamic DBS ((multi) focal epilepsy), responsive ictal onset zone stimulation ((multi) focal epilepsy) and hippocampal DBS (temporal lobe epilepsy) moderately reduce seizure frequency in refractory epilepsy patients. Anterior thalamic DBS is associated with higher rates of self-reported depression and subjective memory impairment. SUDEP rates require careful monitoring in patients undergoing responsive ictal onset zone stimulation. There is insufficient evidence to make firm conclusive statements on the efficacy and safety of hippocampal DBS, centromedian thalamic DBS and cerebellar stimulation. There is a need for more, large and well-designed RCTs to validate and optimize the efficacy and safety of invasive intracranial neurostimulation treatments

Mechanical Thrombectomy for Acute Stroke: Early versus Late Time Window Outcomes

BACKGROUND AND PURPOSERecent trials have shown benefit of thrombectomy in patients selected by penumbral imaging in the late (>6 hours) window. However, the role penumbral imaging is not clear in the early (0‐6 hours) window. We sought to evaluate if time to treatment modifies the effect of endovascular reperfusion in stroke patients with evidence of salvageable tissue on CT perfusion (CTP).METHODSWe retrospectively analyzed consecutive patients who underwent thrombectomy in a single center. Demographics, comorbidities, National Institute of Health Stroke Scale (NIHSS), rtPA administration, ASPECTS, core infarct volume, onset to skin puncture time, recanalization (mTICI IIb/III), final infarct volume were compared between patients with good and poor 90‐day outcomes (mRS 0‐2 vs. 3‐6). Multivariable logistic regression analyses were used to identify independent predictors of a good (mRS 0‐2) 90‐day outcome.RESULTSA total of 235 patients were studied, out of which 52.3% were female. Univariate analysis showed that the groups (early vs. late) were balanced for age (P = .23), NIHSS (P = .63), vessel occlusion location (P = .78), initial core infarct volume (P = .15), and recanalization (mTICI IIb/III) rates (P = .22). Favorable outcome (mRS 0‐2) at 90 days (P = .30) were similar. There was a significant difference in final infarct volume (P = .04). Shift analysis did not reveal any significant difference in 90‐day outcome (P = .14). After adjustment; age (P < .001), NIHSS (P = .01), recanalization (P = .008), and final infarct volume (P < .001) were predictive of favorable outcome.CONCLUSIONSPenumbral imaging‐based selection of patients for thrombectomy is effective regardless of onset time and yields similar functional outcomes in early and late window patients.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155458/1/jon12698_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155458/2/jon12698.pd

Mechanisms of cerebellar tonsil herniation in patients with Chiari malformations as guide to clinical management

Background The pathogenesis of Chiari malformations is incompletely understood. We tested the hypothesis that different etiologies have different mechanisms of cerebellar tonsil herniation (CTH), as revealed by posterior cranial fossa (PCF) morphology. Methods In 741 patients with Chiari malformation type I (CM-I) and 11 patients with Chiari malformation type II (CM-II), the size of the occipital enchondrium and volume of the PCF (PCFV) were measured on reconstructed 2D-CT and MR images of the skull. Measurements were compared with those in 80 age- and sex-matched healthy control individuals, and the results were correlated with clinical findings. Results Significant reductions of PCF size and volume were present in 388 patients with classical CM-I, 11 patients with CM-II, and five patients with CM-I and craniosynostosis. Occipital bone size and PCFV were normal in 225 patients with CM-I and occipitoatlantoaxial joint instability, 55 patients with CM-I and tethered cord syndrome (TCS), 30 patients with CM-I and intracranial mass lesions, and 28 patients with CM-I and lumboperitoneal shunts. Ten patients had miscellaneous etiologies. The size and area of the foramen magnum were significantly smaller in patients with classical CM-I and CM-I occurring with craniosynostosis and significantly larger in patients with CM-II and CM-I occurring with TCS. Conclusions Important clues concerning the pathogenesis of CTH were provided by morphometric measurements of the PCF. When these assessments were correlated with etiological factors, the following causal mechanisms were suggested: (1) cranial constriction; (2) cranial settling; (3) spinal cord tethering; (4) intracranial hypertension; and (5) intraspinal hypotension