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We herein report a case of corticobasal syndrome (CBS) due to asymmetric degeneration of the motor cortex and substantia nigra with transactivation response DNA-binding protein of 43 kDa (TDP-43) proteinopathy, associated with Alzheimer's disease (AD) pathology. An 85-year-old man initially noticed that he had difficulty in walking and had trouble in moving his right hand and lower limb one year later. His gait disturbance was aggravated, and at the age of 87 years, his neurological examination revealed parkinsonism and positive frontal lobe signs. Brain magnetic resonance imaging (MRI) revealed atrophy of the left frontotemporal lobe and cerebral peduncle, and cerebral blood flow scintigraphy revealed hypoperfusion of the left frontotemporal lobe, leading to a possible diagnosis of CBS. At the age of 89 years, he was bedridden, and rarely spoke. He died of aspiration pneumonia five years after the onset of initial symptoms. At the autopsy, the brain weighed 1280 g and showed left-sided hemiatrophy of the cerebrum and cerebral peduncle. Neuropathological examination revealed AD pathology (Braak AT8 stage V, Braak stage C, CERAD B, Thal classification 5). Phosphorylated TDP-43 (p-TDP-43) immunohistochemistry revealed widespread deposits of dystrophic neurites (DNs), glial cytoplasmic inclusions (GCIs), and neuronal cytoplasmic inclusions (NCIs), which were most remarkable in layers II/III of the motor cortex and predominant on the left hemisphere of the frontal cortex, these neuropathology being consistent with frontotemporal lobar degeneration with TDP-43 (FTLD-TDP) type A. Interestingly, neuronal loss in the substantia nigra was more severe on the left than the right side, with a few phosphorylated tau (p-tau) and p-TDP-43 deposits. It is highly likely that asymmetric TDP-43 pathology rather than symmetric tau pathology contributed to the laterality of degeneration of the cerebral cortex, substantia nigra, and pyramidal tract, which led us to suggest that TDP-43 proteinopathy might be a primary cause.

Diffusion tensor imaging (DTI) can be used to index white matter integrity of the corticospinal tract (CST) after stroke; however, the psychometric properties of DTI‐based measures of white matter integrity are unknown. The purpose of this study was to examine test–retest reliability as determined by intraclass correlation coefficients (ICC) and calculate minimal detectable change (MDC) of DTI‐based measures of CST integrity using three different approaches: a Cerebral Peduncle approach, a Probabilistic Tract approach, and a Tract Template approach. Eighteen participants with chronic stroke underwent DTI on the same magnetic resonance imaging scanner 4 days apart. For the Cerebral Peduncle approach, a researcher hand drew masks at the cerebral peduncle. For the Probabilistic Tract approach, tractography was seeded in motor areas of the cortex to the cerebral peduncle. For the Tract Template approach, a standard CST template was transformed into native space. For all approaches, the researcher performing analyses was blind to participant number and day of data collection. All three approaches had good to excellent test–retest reliability for fractional anisotropy (FA; ICCs >0.786). Mean diffusivity, axial diffusivity, and radial diffusivity were less reliable than FA. The ICC values were highest and MDC values were the smallest for the most automated approach (Tract Template), followed by the combined manual/automated approach (Probabilistic Tract) then the manual approach (Cerebral Peduncle). The results of this study may have implications for how DTI‐based measures of CST integrity are used to define impairment, predict outcomes, and interpret change after stroke.

BACKGROUND The degeneration of the corticospinal tract (CST) in chronic stroke has been widely described using diffusion tensor imaging and correlates with the extent of motor deficits. However, only a few studies have reported the early degeneration in the distal CST during the acute stage of stroke and pathological changes in the distal CST have not been described. PURPOSE To study the microstructural changes along the CST beyond the ischemic lesion in acute stroke using diffusion kurtosis imaging (DKI). STUDY TYPE Prospective. POPULATION In all, 48 patients (26 males, 22 females; mean age 58.27 ± 12.89 years) with acute ischemic stroke. SEQUENCE A DKI sequence with three b-values (0, 1000, and 2000 s/mm2 ) at 3.0T MRI. ASSESSMENT The kurtosis and tensor parameters were derived from DKI and were compared along the length of the CST beyond the ischemic lesion between the affected and unaffected hemispheres using both voxelwise and slicewise analysis. The degree of neurological deficits was evaluated using the National Institute of Health Stroke Score (NIHSS) and the Barthel index and the clinical outcome at 3 months was evaluated using a modified Rankin scale. STATISTICAL TESTS Paired t-tests, a linear mixed model, and multivariate linear regression. RESULTS Voxelwise analysis demonstrated increased mean kurtosis, increased axial kurtosis, and decreased axial diffusivity in the affected CST, which were seen only at the level of the cerebral peduncle (all corrected P

Hemispherectomy in Adults and Adolescents: Seizure and Functional Outcomes in 47 Patients McGovern RA, NV Moosa A, Jehi L, Busch R, Ferguson L, Gupta A, et al. Epilepsia. 2019;60(12):2416-2427. http://doi.org/10.1111/epi.16378.Objective:To examine longitudinal seizure and functional outcomes after hemispherectomy in adults and adolescents.Methods:We reviewed 47 consecutive patients older than 16 years who underwent hemispherectomy between 1996 and 2016 at our center. Clinical, electroencephalographic (EEG), imaging, neuropsychological, surgical, and functional status data were analyzed.Results:Thirty-six patients were 18 years or older at surgery; 11 were aged between 16 and 18 years. Brain injury leading to hemispheric epilepsy occurred before 10 years of age in 41 (87%) patients. At a mean follow-up of 5.3 postoperative years (median = 2.9 years), 36 (77%) had Engel class I outcome. Longitudinal outcome analysis showed 84% seizure freedom (Engel IA) at 6 months, 76% at 2 years, and 76% at 5 years and beyond, with stable longitudinal outcomes up to 12 years from surgery. Multivariate analysis demonstrated that acute postoperative seizures and contralateral interictal spikes at 6-month follow-up EEG were associated with seizure recurrence. Patients who could walk unaided preoperatively and had no cerebral peduncle atrophy on brain magnetic resonance imaging were more likely to experience worsening of motor function postoperatively. Otherwise, postoperative ambulatory status and hand function were unchanged. Of the 19 patients who completed neuropsychological testing, 17 demonstrated stable or improved postoperative outcomes.Significance:Hemispherectomy in adults is a safe and effective procedure, with seizure freedom rates and functional outcome similar to those observed in children.

We assessed the sex and the lateralization differences in the corticospinal tract (CST) during the early postnatal period. Twenty-five healthy term neonates (13 girls, aged 39.2 ± 1.2 weeks, and 12 boys aged 38.6 ± 3.0 weeks) underwent Diffusion Tensor Imaging (DTI). Fiber tracking was performed to extract bilaterally the CST pathways and to quantify the parallel (E1 ) and perpendicular (E23 ) diffusions, the apparent diffusion coefficient (ADC), and fractional anisotropy (FA). The measurements were performed on the entire CST fibers and on four segments: base of the pons (CST-Po), cerebral peduncles (CST-CP), posterior limb of the internal capsule (CST-PLIC), and corona-radiata (CST-CR). Significantly higher E1 , lower E23, and higher FA in the right compared to the left were noted in the CST-PLIC of the girls. Significantly lower E23 and lower ADC with higher FA in the right compared to left were observed in the CST-CP of the boys. Moreover, the CST-PLIC of the boys had significantly higher E1 in the right compared to the left. There was a significant increase in left CST E1 of boys when compared with girls. Girls had a significantly lower E1 , lower E23 and, lower ADC in the left CST-CP compared with boys. In addition, girls had a significantly lower E23 and higher FA in the right CST-PLIC compared with boys. Sex differences and lateralization in structure-based segments of the CST were found in healthy term infants during early postnatal period. These findings are vital to understanding motor development of healthy term born neonates to better interpret newborn infants with abnormal neurodevelopment.

Advances in neuroimaging have enabled the mapping of white matter connections across the entire brain, allowing for a more thorough examination of the extent of white matter disconnection after stroke. To assess how cortical disconnection contributes to motor impairments, we examined the relationship between structural brain connectivity and upper and lower extremity motor function in individuals with chronic stroke. Forty-three participants [mean age: 59.7 (±11.2) years; time poststroke: 64.4 (±58.8) months] underwent clinical motor assessments and MRI scanning. Nonparametric correlation analyses were performed to examine the relationship between structural connectivity amid a subsection of the motor network and upper/lower extremity motor function. Standard multiple linear regression analyses were performed to examine the relationship between cortical necrosis and disconnection of three main cortical areas of motor control [primary motor cortex (M1), premotor cortex (PMC), and supplementary motor area (SMA)] and motor function. Anatomical connectivity between ipsilesional M1/SMA and the (1) cerebral peduncle, (2) thalamus, and (3) red nucleus were significantly correlated with upper and lower extremity motor performance (P ≤ 0.003). M1-M1 interhemispheric connectivity was also significantly correlated with gross manual dexterity of the affected upper extremity (P = 0.001). Regression models with M1 lesion load and M1 disconnection (adjusted for time poststroke) explained a significant amount of variance in upper extremity motor performance (R2 = 0.36-0.46) and gait speed (R2 = 0.46), with M1 disconnection an independent predictor of motor performance. Cortical disconnection, especially of ipsilesional M1, could significantly contribute to variability seen in locomotor and upper extremity motor function and recovery in chronic stroke. Hum Brain Mapp 39:120-132, 2018. © 2017 Wiley Periodicals, Inc.

This work evaluates the potential in diagnostic application of a new advanced neuroimaging method, which delineates the profile of tissue properties along the corticospinal tract (CST) in amyotrophic lateral sclerosis (ALS), by means of diffusion tensor imaging (DTI). Twenty-four ALS patients and twenty-four demographically matched healthy subjects were enrolled in this study. The Automated Fiber Quantification (AFQ), a tool for the automatic reconstruction of white matter tract profiles, based on a deterministic tractography algorithm to automatically identify the CST and quantify its diffusion properties, was used. At a group level, the highest non-overlapping DTI-related differences were detected in the cerebral peduncle, posterior limb of the internal capsule, and primary motor cortex. Fractional anisotropy (FA) decrease and mean diffusivity (MD) and radial diffusivity (RD) increases were detected when comparing ALS patients to controls. The machine learning approach used to assess the clinical utility of this DTI tool revealed that, by combining all DTI metrics measured along tract between the cerebral peduncle and the corona radiata, a mean 5-fold cross validation accuracy of 80% was reached in discriminating ALS from controls. Our study provides a useful new neuroimaging tool to characterize ALS-related neurodegenerative processes by means of CST profile. We demonstrated that specific microstructural changes in the upper part of the brainstem might be considered as a valid biomarker. With further validations this method has the potential to be considered a promising step toward the diagnostic utility of DTI measures in ALS. Hum Brain Mapp 38:727-739, 2017. © 2016 Wiley Periodicals, Inc.

Fetal alcohol spectrum disorders (FASD) are characterized by a range of neurodevelopmental deficits that result from prenatal exposure to alcohol. These can include cognitive, behavioural, and neurological impairment, as well as structural and functional brain damage. Eyeblink conditioning (EBC) is among the most sensitive endpoints affected in FASD. The cerebellar peduncles, large bundles of myelinated nerve fibers that connect the cerebellum to the brainstem, constitute the principal white matter element of the EBC circuit. Diffusion tensor imaging (DTI) is used to assess white matter integrity in fibre pathways linking brain regions. DTI scans of 54 children with FASD and 23 healthy controls, mean age 10.1 ± 1.0 years, from the Cape Town Longitudinal Cohort were processed using voxelwise group comparisons. Prenatal alcohol exposure was related to lower fractional anisotropy (FA) bilaterally in the superior cerebellar peduncles and higher mean diffusivity (MD) in the left middle peduncle, effects that remained significant after controlling for potential confounding variables. Lower FA and higher MD in these regions were associated with poorer EBC performance. Moreover, effects of alcohol exposure on EBC decreased significantly after inclusion of these DTI measures in regression models, suggesting that these white matter deficits partially mediate the relation of prenatal alcohol exposure to EBC. The associations of greater alcohol consumption with these DTI measures are largely attributable to greater radial diffusivity, possibly indicating poorer myelination. Thus, these data suggest that fetal alcohol-related deficits in EBC are attributable, in part, to poorer myelination in key regions of the cerebellar peduncles.

BACKGROUND AND PURPOSE Diffusion tensor imaging (DTI) is shown to reveal changes caused by cerebral infarction. The aim of this study is to reveal those changes also in the conventional magnetic resonance (MR) images using a quantitative image analysis method, texture analysis (TA). METHODS Thirty patients who had suffered their first ever infarction located on the right hemisphere underwent DTI and conventional MRI studies in the chronic phase. DTI parameters fractional anisotropy and mean diffusivity, as well as four second-order texture parameters were calculated. Interhemispheric differences and correlations between DTI and TA parameters were evaluated. RESULTS Our DTI findings supported earlier studies as fractional anisotropy values were lowered and mean diffusivity values elevated in the lesion site, and ipsilateral cerebral peduncle, thalamus, and centrum semiovale compared to the unaffected side. Textural homogeneity parameters showed lower and complexity parameters higher values in the lesion site and ipsilateral centrum semiovale compared to the contralateral hemisphere. Correlation between the two methods was found in ipsilateral mesencephalon. CONCLUSIONS In addition to DTI method, TA could assist in revealing the changes caused by infarction, also outside the lesion site. Damaged areas were found more heterogeneous and random in texture compared to unaffected sites.

Bilateral cerebral peduncles are rarely simultaneously infarcted unless the basilar artery is involved. A 60-year-old man developed locked-in syndrome because of bilateral cerebral peduncle infarctions with right intracranial vertebral artery occlusion. Dysarthria occurred a day before admission. His neurological condition rapidly deteriorated, and he subsequently became quadriplegic. His left vertebral artery showed a posterior inferior cerebellar artery end pattern, and anastomosis between the anterior and posterior circulations through the hypoplastic right P1 and fine left posterior communicating artery was insufficient; therefore, severe hypoperfusion and multiple infarctions in the distribution of the posterior circulation were induced by right intracranial vertebral artery occlusion. These findings highlight the fact that large-artery atherosclerosis represents an important cause of mesencephalic infarctions. Several neurological manifestations are caused by intracranial vertebral artery occlusion, and when collateral flow to the posterior circulation is insufficient, intracranial vertebral artery occlusion results in bilateral cerebral peduncle infarctions and locked-in syndrome without basilar artery occlusion.

To investigate the fetal cerebral lobes development between 20 and 28 weeks gestational age, 36 fetus specimen without CNS abnormality, with 4 fetuses in each gestation week, were scanned with 3.0T MR. Lobular parameters were measured, including the parenchyma thickness of the frontoparietal and the temporal lobes, the margin length of frontoparietal, the insula and the temporal lobes, the Sylvian fissure and the perimeter of hippocampus, on the plane perpendicular to the longitudinal axis of hippocampus body across the base of cerebral peduncle. The relative value of parenchyma thickness and the lobes' length ratios to the same side hemisphere were calculated and their correlation with gestational weeks was analyzed. All measured parameters were positively correlated with gestational age. No significant tendency was found for relative value of the parenchyma thickness (P0.05). The temporal lobe length ratio increased while the frontoparietal ratio decreased before 24 weeks GA and then the two reversed. The Sylvian fissure length ratio increased (P0.001) and the hippocampus decreased (P0.001) throughout this period. In conclusion, the early fetal cerebrum lobes developed asynchronously during this period, the 24 weeks GA could be a turning point for cerebrum development pattern changing from primitive to mature.

BACKGROUND AND PURPOSE We attempted to measure DTI parameters of the brainstem pyramidal tract using two approaches, ie, simple ROI and tract-specific analyses. Results obtained for healthy subjects and ALS patients were compared. METHODS DTI was performed using a single shot SE-EPI with 25 noncollinear diffusion gradient directions (b= 1000 second/mm2) and with no diffusion gradient on a 3.0-T MR system in 10 ALS patients and in 8 age- and sex-matched normal controls. To delineate the brainstem pyramidal tract, tractography was performed using two ROIs, ie, a seed ROI at the cerebral peduncle (ROI-1) and a target ROI at the lower pons (ROI-2). ROI-1 was subsequently restricted to voxels that contained streamlines in the tract reconstruction, thus creating a sub-ROI. RESULTS Mean fractional anisotropy (FA) and mean diffusivity values were highly reproducible by tract specific analysis, whereas simple ROI analysis yielded larger variabilities between operators. FA values were significantly lower in ALS patients than in normal controls in the tractography-derived sub-ROI (P= .01), but not in the seed or target ROIs. CONCLUSIONS These results suggest, compared with simple ROI analysis, that tract-specific analysis using DTI fiber-tracking is more reliable and sensitive for detecting upper motor neuron pathology in ALS.

WOS: 000243637000014, PubMed ID: 17250509, Background: The purpose of this study was to emphasize the clinical and imaging findings of 19 child cases of cerebral hemiatrophy. Methods:A total of 11 male and eight female patients underwent assessment with computed tomography and magnetic resonance imaging. The patients ranged from 1 to 17 years in age. The evaluated parameters were: location of the lesions, midline structural shift effect, ipsilateral calvarial and parenchymal changes. Results:Left cerebral hemiatrophy was seen in 14 of the cases while right cerebral hemiatrophy was observed in five cases. Unilateral calvarial thickening was seen in 11 cases, hyperpneumatization of paranasal sinuses in five, and hypoplasia of the middle frontal cranial fossa in three patients. Cerebral peduncle atrophy was noted in seven cases. In total, 11 patients had thalamic atrophy and lentiform nucleus hypoplasia. In one case, cerebral hemiatrophy was associated with ipsilateral large schizencephalic cleft and absence of the septum pellucidum, whereas in another case, there was diffuse cerebellar atrophy associated with cerebral hemiatrophy. Conclusions: Computed tomography and, in particular, magnetic resonance imaging are the procedures of choice with respect to assessment of the etiology and extent of cerebral parenchymal involvement in cerebral hemiatrophy.

Purpose To evaluate the feasibility of performing diffusion tensor tractography (DTT) to map and quantify the pyramidal white matter tracts of premature newborns. Materials and Methods Fourteen diffusion tensor MRI (DTI) examinations of nine premature newborns were evaluated. DTT was performed to segment bilateral pyramidal tracts, using a fiber-tracking algorithm originating in the cerebral peduncle (CP) and filtering through the posterior limb of the internal capsule (PLIC) and precentral gyrus (PCG). Voxels containing the resulting tracts were then used for quantitation of DTI parameters along the tract. The DTT-based tract measurements were compared with standard manually placed region-of-interest (ROI) measurements at four locations along the pyramidal tract, and the reproducibility of each technique was evaluated. Results DTT demonstrated improved reproducibility over manual ROI measurement for pyramidal tract quantitation and was less subject to intra-operator variability (P < 0.0001, Fisher test for equal variance). In general, the anatomic locations and measurements obtained with the two techniques were in good agreement, although some systematic differences were identified in the PLIC and CP. Conclusion Fiber DTT is feasible in premature newborns, provides more reproducible tract measurements than manual ROI methods, and allows quantitation along the entire tract for more detailed DTI assessment of white matter maturation. J. Magn. Reson. Imaging 2005. © 2005 Wiley-Liss, Inc.

In this study we investigated the potential of in vivo MRI detection of axonal Mn2+ transport for tracing neuronal projections originating in the sensorimotor cortex in healthy and lesioned rat brains. Special attention was given to the potential of visualizing neuronal sprouting of central nervous system across the midline. After injecting unchelated MnCl2 into the forelimb area of sensorimotor cortex of 18 healthy and 10 lesioned rats corticofugal projections could be traced through the internal capsule to the cerebral peduncle and the pyramidal decussation. Although the neuronal tract was visible as early as 6 h after MnCl2 injection, best contrast was achieved after 24–48 h. Beside the cortico-spinal tract, the cortico-thalamic fibres were also visualized by anterograde Mn2+ transport. Cortico-striatal fibres were partially masked by the very high signal near the MnCl2 injection site but could be discerned as well. Slight, diffuse signal enhancement of cortical tissue contralateral to the MnCl2 injection site in healthy rat brains suggests interhemispheric connections or passive diffusion of Mn2+. However, enhanced fibre tract contrast connecting both hemispheres was visible 16 weeks after onset of focal photothrombotic cortical injury. In conclusion our study has shown that we were able to visualize reproducibly the main descending corticofugal projections and interhemispheric connections by non-invasive MRI after localized injection of MnCl2. The appearence of interhemispheric Mn2+-enhanced fibres after photothrombotic focal injury indicates that the method may bear potential to follow non-invasively gross plastic changes of connectivity in the brain after injury. Copyright © 2001 John Wiley & Sons, Ltd.

We report a case of a fetal haemangioblastoma located in the cerebellopontine angle. On prenatal ultrasonographic examination a hyperechogenic and heterogeneous mass with a major vascularization on colour Doppler imaging was observed. It increased progressively and laminated the cerebellum. A neoplastic tumour was suspected but its extent into the cerebral peduncle was unclear. Diagnosis was made at autopsy using histological, immunohistochemical and flow cytometric evaluation. Haemangioblastoma is an exceptional congenital tumour, which is either sporadic or integrated in von Hippel-Lindau disease (VHLD). We discuss the obstetrical management of prenatal brain tumours and the genetic counselling of haemangioblastoma.

The Eph family of receptor tyrosine kinases and their ligands, the ephrins, are important regulators of axon guidance and cell migration in the developing nervous system. Inactivation of the EphA4 gene results in axon guidance defects of the corticospinal tract, a major descending motor pathway that originates in the cortex and terminates at all levels of the spinal cord. In this investigation, we report that although the initial development of the corticospinal projection is normal through the cortex, internal capsule, cerebral peduncle, and medulla in the brain of EphA4 deficient animals, corticospinal axons exhibit gross abnormalities when they enter the gray matter of the spinal cord. Notably, many corticospinal axons fail to remain confined to one side of the spinal cord during development and instead, aberrantly project across the midline, terminating ipsilateral to their cells of origin. Given the possible repulsive interactions between EphA4 and one of its ligands, ephrinB3, this defect could be consistent with a loss of responsiveness by corticospinal axons to ephrinB3 that is expressed at the spinal cord midline. Furthermore, we show that EphA4 deficient animals exhibit ventral displacement of the mature corticospinal termination pattern, suggesting that developing corticospinal axons, which may also express ephrinB3, fail to be repelled from areas of high EphA4 expression in the intermediate zone of the normal spinal cord. Taken together, these results suggest that the dual expression of EphA4 on corticospinal axons and also within the surrounding gray matter is very important for the correct development and termination of the corticospinal projection within the spinal cord.

We report on two patients with unilateral hyperkinetic movement disorders associated with contralateral hemiparesis and ipsilateral basal ganglia lesions. The first patient, a 47-year-old woman, had a low-grade astrocytoma located in the right basal ganglia extending into the subthalamic area and the cerebral peduncle. She presented with left hemiparesis, right hemichorea, and intermittent right-sided tremor at rest. The second patient, a 85-year-old woman, had hypertensive hemorrhage to the right posterior basal ganglia, the posterior limb of the internal capsule, the lateral thalamus, and the subthalamic region with accompanying intraventricular bleeding. She developed right-sided transient hemichorea-hemiballism. A videotape illustration of one of the patients is provided. The literature on the rare occurrence of ipsilateral hemichorea-hemiballism is discussed and possible pathomechanisms are reviewed. We postulate that hemiparesis contralateral to basal ganglia lesions might have a conditioning effect on the appearance of ipsilateral dyskinetic movement disorders.

Painful tonic spasms (PTS) are now regarded as a typical symptom of multiple sclerosis but pathologic or radiologic findings rarely have been described. We report clinical and magnetic resonance imaging records of five original cases. In all of them, lesions likely responsible for unilateral PTS involved the motor pathway at the level of the posterior limb of the internal capsule or the cerebral peduncle on the opposite side. Closeness of motor fibers seems to be the most important underlying anatomic factor because it enables involvement of a higher proportion of axons by a single demyelinating lesion and radial spread of ephaptic activation. In turn, preservation of the underlying pyramidal-spinal tract could make it easier for the pathologic discharge to reach the peripheral effectors and generate PTS.

A 64-year-old man progressively developed ataxic gait, 3-Hz high-amplitude, intentional/postural tremor, and dysarthric speech. FMR1 gene analysis revealed a premutation (89 CGG repeats) and a brain MRI showed mesencephalon atrophy with normal pons morphometry (the so-called “hummingbird” or “penguin” sign) along with middle cerebral peduncle hyperintensity, the radiological hallmark of fragile X-associated tremor/ ataxia syndrome (FXTAS). The disease achieved mild severity in 2 years: Neither psychiatric symptoms nor dementia or impairment in daily living activities were reported.

The corticopontine projection develops exclusively by collateral branches that form along the length of corticospinal axons days after they have passed their hindbrain target, the basilar pons. In vitro evidence suggests that the basilar pons releases a diffusible activity that initiates and directs the growth of collateral branches. This study investigates whether contact-dependent mechanisms may also influence the formation of collateral branches. By using immunocytochemistry, electron microscopy, and neuronal tracing techniques, we examined the region of the axon tract, the cerebral peduncle, overlying the basilar pons for cellular structures that correlate spatially and temporally with collateral branch formation. We found that radial glia are excluded from the tract. Oligodendrocyte precursors are found only at low density. Although mature astrocytes are absent, immature astrocytes are present throughout the tract. However, our evidence does not suggest a direct role for glial cell types in collateral branch formation. In contrast, dendrites of basilar pontine neurons are transiently present in the tract during the time of collateral branch formation. Although collateral branches are observed in regions of the tract devoid of dendrites, the orientation and location of most collateral branches correlates at the light microscopic level with dendrites. Electron microscopy reveals sites of increased collateral branch formation near neuronal cell bodies or dendrites. However, cell processes, whether dendritic or otherwise, are rarely found in direct contact with collateral branch points. A common and unexpected feature is the bundles of corticopontine collateral branches, oriented transversely to their parent corticospinal axons and directed across the tract to the basilar pons. Dendrites were often apposed to or embedded within the transverse bundles. These findings suggest that dendrites are not essential for collateral branch formation but that they may enhance this process and define discrete preferred locations for collateral branch initiation and elongation within the cerebral peduncle.

The organisation of the long descending corticofugal pathways is poorly understood. We have examined these pathways to determine the fibre relationships along the extent of their course through the internal capsule, cerebral peduncle, longitudinal pontine fasciculus, pyramid, pyramidal decussation, and dorsal column of the spinal cord. Different cytoarchitectonic regions (e.g., lateral agranular and granular) of the rat's neocortex were injected with the axonal tracer biotinylated dextran. In other experiments, each animal had different-coloured fluorescent tracers (Fluoro Ruby and dextran-fluorescein) injected into separate cortical areas. Our results show that in the anterior and posterior limbs of the internal capsule, axons arising from spatially separate sites in rat neocortex occupy distinct regions of the cross-sectional area of the pathway. More caudally, within the cerebral peduncle and the longitudinal pontine fasciculus, axons from more distant cortical areas remain largely separate, but those from adjacent cortical areas begin to overlap. By the medullary pyramid, the pyramidal decussation, and the dorsal column of the spinal cord, the representations of all the cortical regions injected overlap completely; in these structures, the axons arising from each cortical area are widely intermingled. Thus, along the rostral-to-caudal course of the corticofugal pathways, there is a change in the organisation of axons. At rostral levels, the order corresponds roughly to the spatial distribution of the cells of origin, but more caudally, this changes to an arrangement of axons that has no readily apparent order. A similar change has been observed along the course of the retinofugal pathway, where a decrease of spatial order in the fibre distribution has been associated with a reordering of axons according to their temporal sequence of outgrowth.

Purpose: To assess early effects of proton therapy on the structural integrity of cerebral white matter in relation to the subsequent near-term development of such effects. Methods: Sixteen children (aged 2–19 years) with craniopharyngioma underwent proton therapy of 54 Cobalt Gray Equivalent (CGE) in a prospective therapeutic trial. Diffusion tensor imaging (DTI) was performed at baseline before proton therapy and every 3 months thereafter. Tract-based spatial statics analysis of DTI data was performed to derive the fractional anisotropy (FA) and radial diffusivity (RD) in 26 volumes of interest (VOIs). The dose distributions were spatially normalized to identify VOIs prone to high doses. The longitudinal percentage changes of the FA and RD in these VOIs at 3 and 12 months from the baseline were calculated, and their relationships were evaluated. Results: The average dose was highest to the cerebral peduncle (CP), corticospinal tract (CST) in the pons, pontine crossing tract (PCT), anterior/posterior limbs of the internal capsule (ALIC/PLIC), and genu of the corpus callosum (GCC). It ranged from 33.3 GCE (GCC) to 49.7 GCE (CP). A mild but statistically significant (P

In our Golgi collection of adult monkey brains the striatal efferents, i.e., the radial fibers in the globus pallidus and the “comb” bundle fibers in the internal capsule and in the cerebral peduncle, are well impregnated in the horizontally sectioned brain and in a sagittal sectioned brain. Since collaterals emerging from radial fibers are seen only in the horizontal series and not in the sagittal series, the interpretation is that they proceed anteriorly and posteriorly only, following the curvature of the pallidal segments, and do not run superiorly or inferiorly as they emerge. Although radial fibers emitting collaterals in the lateral segment and in the medial segment of the globus pallidus have been observed, it has not been possible to observe the same radial fiber emitting collaterals in both pallidal segments and the prospects of ever doing so are not good. The radial fibers converging in the globus pallidus pursue many radii and there is little coincidence between the plane of section and the planes in which they travel. At most only severed radial fiber segments 100–150 microns in length can be found in the horizontal sections needed to observe the collaterals. Moreover, sagittal sections show that radial fibers are deflected in their course, either dorsoventrally or ventrodorsally, as they pass through the internal medullary lamina to enter the medial segment of the globus pallidus. The radial fibers in the medial segment of the globus pallidus are continuous with the “comb” bundle fibers and appear to be thinner than the radial fibers in the lateral segment of the globus pallidus. It is not proved; nonetheless, the view expressed here is that the radial fibers are thinner in the medial segment of the globus pallidus because they may be the same fibers that gave off collaterals in the lateral segment of the globus pallidus. This is discussed in the light of the electrophysiological disclosure of Yoshida et al. ('71, '72) that caudatopallidal fibers are collaterals off caudatonigral fibers. The afferent plexuses of fine, “bouton en passage” fibers, which completely ensheath the long radiating dendrites in the globus pallidus (Fox et al., '66) are well impregnated in the horizontal series. Obviously, they are formed by a number of ultimate branches converging from the collateral branches of a number of different radial fibers. The divergence, too, in this system must be considerable; however, its true extent can only be surmised from the severed radial fibers and radial fiber collaterals seen in the incompletely impregnated Golgi section. One severed segment of a radial fiber displays three collaterals and one of these collaterals has five branches, one of which can be traced to a point where it gives off an ultimate branch in an afferent, dendrite-ensheathing plexus.

In a series of young adult albino rats the terminal projections of corticorubral fibers were studied by light and electron microscopic methods following unilateral sensorimotor cortex suction ablation. Degenerating axons could be traced from the ipsilateral cerebral peduncle to the periphery of the red nucleus. Within the red nucleus the degeneration was sparse. No degeneration was seen contralaterally. With the electron microscope degenerating axons showed electron dense axoplasm and seemed devoid of their normal complement of organelles. Electron-dense degenerating synaptic terminals, one to two per grid square, were found in the more rostral portions of the red nucleus. These terminals were of the asymmetrical type with increased density of the post-synaptic membrane and made contact with small to medium sized dendrites. No degenerating axosomatic or axoaxonal knobs were seen. No degenerating terminals were seen in the caudal regions of the red nucleus. This study finds that following ablation of the sensorimotor cortex in the rat there is a projection to the ipsilateral red nucleus and that the contacts are primarily of the axodendritic type as revealed by the electron microscope.

The accessory optic system (AOS) was studied in an anthropoid primate by using anterograde transport of tritiated amino acids and autoradiographic techniques. The course of the accessory optic tract (AOT) and the retinal projection to the terminal nuclei are described in the gibbon and compared to that of other mammals. The AOT consists of a superior fasciculus, which includes both an anterior and a posterior fiber branch. An inferior fasciculus of the AOT is absent. In contrast to previous reports in haplorhine primates, which describe the AOS as consisting of only the dorsal (DTN) and the lateral (LTN) terminal nuclei, we find that in the gibbon, three cellular groups receive a bilateral projection, predominantly from the contralateral retina. According to cytoarchitecture and topographic location, two of these nuclei correspond to the DTN and the LTN. The third cellular group, situated dorsomedial to the substantia nigra, receives a distinct retinal projection and extends rostrocaudally for 2.0 mm in the mesencephalon. This nucleus is homologous to the dorsal division of the medial terminal nucleus (MTN) in other mammals. There was no evidence for a ventral division of the MTN, which in nonprimates is typically situated at the ventromedial base of the cerebral peduncle. Examination of brain morphology in primates suggests that the ventral division of the MTN has been displaced from its phylogenetically stable location in the medial part of the ventral midbrain to a more dorsal position. This shift appears to be a consequence of the overall morphological influences resulting from the relative enlargement of the pons in this region. The demonstration of a direct retinal projection to the MTN in the gibbon, as well as recent reports in other primates, indicates that a complete AOS consisting of three terminal nuclei is a feature common to all mammals.

The accessory optic system of the ferret has been studied both by silver degeneration staining and by autoradiography after intraocular 3H leucine injections. There is no anterior accessory optic tract but a posterior tract containing only crossed fibres leaves the brachium of the superior colliculus and ends in the two nuclei, the medial and lateral terminal nuclei, lying either side of the cerebral peduncle. Both suprachiasmatic nuclei receive retinal fibres visible only on autoradiographs; most fibres end in the contralateral nucleus. No other area in the hypothalamus appears to receive retinal fibres demonstrated by these methods.

The three-dimensional fiber pathways of the accessory optic system in three species of rodents (rat, golden hamster, guinea pig) were examined on whole-mounted preparations of the diencephalon and the midbrain, without sectioning, by anterograde labeling of retinal axons with horseradish peroxidase (HRP). HRP histochemical studies on the serial coronal sections were also done. In this study, only the accessory optic system on the side contralateral to the eye injection of HRP was clearly detected. The rat accessory optic system consisted of the inferior fasciculus, the superior fasciculus, the medial terminal nucleus, the lateral terminal nucleus, and the dorsal terminal nucleus. After the inferior fasciculus arrived at the ventromedial border of the cerebral peduncle, some fibers from the inferior fasciculus ran caudally to the medial terminal nucleus. The remaining fibers from the inferior fasciculus further proceeded dorsocaudally on the surface of the cerebral peduncle and left the inferior fasciculus at various levels of the cerebral peduncle to be mixed up with the fibers from the superior faciculus. The golden hamster accessory optic system also consisted of the inferior fasciculus, the superior fasciculus, the medial terminal nucleus, the lateral terminal nucleus, and the dorsal terminal nucleus. However, all fibers of the inferior fasciculus ran caudally on the lateral surface of the hypothalamus or along the ventromedial border of the cerebral peduncle to terminate at the medial terminal nucleus. The guinea pig accessory optic system and rat accessory optic system were similar, but the posterior fibers of the superior fasciculus decreased in number, and the dorsal terminal nucleus and the posterior portion of the lateral terminal nucleus were not observed in the guinea pig accessory optic system.

Two of 27 patients treated with intraventricular chemotherapy via an Ommaya reservoir developed unusual life-threatening complications attributable to the reservoir. In one patient treated for meningeal Burkitt's lymphoma, the cause of death was a large mass of tumor cells growing around the cannula. Also the tip of the cannula was found in the contralateral cerebral peduncle. In the other patient, the tip of the cannula apparently perforated the ventricular wall postoperatively and migrated into the contralateral thalamus. In both cases evidence for methotrexate-associated leukoencephalopathy was present at autopsy. Based on the experience with these two patients, we offer specific recommendations for reservoir insertion and use.

The subthalamic nucleus (ST) of kittens was studied by means of the rapid Golgi silver impregnation method. The neurons of the ST were classified into three types. Type I neurons, the main constituents of the ST, had oval or polygonal cell bodies with a mean diameter of 26 micrometer by 36 micrometer and four to six primary dendrites. Type II neurons had multipolar or polygonal cell bodies, which measured an average 31 micrometer by 43 micrometer and emitted four to seven primary dendrites. The cell bodies of the type III neurons were polygonal in shape, measured 23 micrometer by 26 micrometer in average and emitted four to six primary dendrites. The dendrite bundle and the dendrite pallisade were observed. Frequently dendrites of the ST extended into the cerebral peduncle (CP), and even cell bodies of some ST neurons were located within the CP. All of the parent axons of the ST neurons coursed rostrally, although intra- and extra-nuclear axon-collaterals arising from the ST neurons travelled rostrally, caudally or caudomedially. The afferent fibers to the ST were divided into three groups; afferents via the Meynert's commissure (MC), decending and ascending afferents. The MC fibers, which ran across the CP, gave terminals to the ST. The descending afferents were axon-collaterals of fibers descending in the CP and those of fibers running through the ST. The ascending afferents were also axon-collaterals arising from ascending fibers in the CP. In addition to these afferents, many descending and ascending fibers of passage ran through the ST without emitting axon-collaterals.

The pyramidal tract was studied in 12 adult opossums. The method employed consisted of unilateral ablation of the motor cortex followed by selective staining of the resulting fiber degeneration with Nauta's silver technique. The results showed that in the upper part of its course the pyramidal tract followed a course similar to that found in other mammals. It descends in the internal capsule, cerebral peduncle, basal pons and the pyramids of the medulla oblongata where it decussates. It then continues to descend in the dorsal funiculus through the entire cervical cord. In the spinal cord fibers appeared to terminate among neurons at the base of the dorsal gray column. No degeneration could be traced directly into cranial and spinal nerve nuclei.

This report consists of two cases who died after a neurological disorder of the central nervous system consistent with Behcet's disease clinically and pathologically. Post-mortem examination of the central nervous system revealed mild diffuse meningo- encephalitis with multiple foci of softening, demyelination and glial cell accumulation in the pons, midbrain, cerebral peduncle and internal capsule. The significance of these morphological findings has been discussed from an etiological viewpoint of Neuro-Behcet's syndrome.

The method of Nauta was used to stain axons which degenerated after lesions of the thalamic projection nucleus and cortical zone subserving gustation in the rat. Lesions of the medial subnucleus of the thalamic ventral nuclear complex resulted principally in degeneration which passed rostrolaterally through the thalamus, internal capsule, globus pallidus, and striatum to terminate in insular and inferior parietal cortex around the region of the middle cerebral artery. Lesions of this cortical projection zone resulted in degeneration which passed caudomedially through the same striatal and pallidal areas traversed by the thalamocortical fibers. One component of these fibers continued into the thalamus to terminate just dorsal to the medial subnucleus. A second component turned caudally into the cerebral peduncle to terminate in the substantia nigra. There was evidence of terminal degeneration in the striatum but not in the pallidum after both thalamic and cortical lesions. There was no evidence of degeneration in any structures primarily associated with olfactory or alimentary functions.

The morphology and the structures supplied by the extraventricular segment of the anterior choroidal artery was studied in 22 human brains. The pertinent arterial sections were injected with a gelatin-india ink mixture and the brains serially sectioned and cleared after formalin fixation. The area of distribution of the anterior choroidal artery varied widely. There is good supply to the globus pallidus, the posterior and retrolenticular portions of the internal capsule, the cerebral peduncle, the optic tract and the lateral geniculate body. A lesser supply is furnished to the genu of the internal capsule, thalamus, hypothalamus, subthalamus, and amygdala.

Recently, seven young, healthy chimpanzees were subjected to an experimental surgical procedure known as mesial cerebral incision.! This procedure consists of incision and separation of corpus callosum, lamina terminalis, floor of third ventricle, pineal region, pons, cerebellum, and medulla oblongata. Actually, it is staged in two parts. The first, a parasagittal craniotomy, provides access to corpus callosum, the third ventricle and its floor, as well as the pineal regions. In this first stage, the diaphragma sellae can be visualized if care is taken during the incision of the third ventricular floor (FIGURE 1). Some time after recovery, a suboccipital craniectomy is performed (FIGURE 2). This is the second stage of mesial cerebral incision and provides exposure of vermis and medulla, both of which are incised under direct vision (FIGURE 1). The pons must be separated indirectly through the rostral apex of the suboccipital craniectomy on the caudal part of the exposure provided in stage 1. The basilar artery can be felt pulsating at the lowest extremity of this incision. In all stages and parts of mesial cerebral incision, gentle blunt separation of white fibers with the Sachs dissector permits almost bloodless access to the various anatomical levels and structural areas. For example, the dissector is introduced into the full depth of the callosum through a small incision in the pia. Then it is drawn slowly backward (or forward) with pressure sufficient to separate the white fibers but not to tear blood vessels. The resistance of the latter is greater, and, with some practice, vessels can be spared in a series of fenestrations while the surrounding fibers are clearly and cleanly cut. Five more chimpanzees have undergone this procedure since the original report, bringing the total to twelve. The techniques of mesial cerebral incision have been extended by microdissection in the macaque so as to expose the contents of the third ventricle and thus expose the anterior and mesial parts of the thalamus.2 Thereafter, the rostral thalamus was sucked out by micropipette. This local unilateral microexcision resulted in a chronic epileptic animal, which has been described in detail by Milhorat and Baldwin.2,3 The primates subjected to mesial cerebral incision recover promptly and can return to usual cage or run activity within ten days after either operative stage. These chimpanzees have exhibited normal bilateral synergistic motor activity except in two cases, in which a monoparesis of right or left upper extremity occurred. Five such animals that did not show any neurological deficit after mesial cerebral incision were also subjected to unilateral incisions of the brain stem on right or left sides. The incision was made just below the inferior colliculus and calculated so as to extend to, but not across, the midline, while sparing the cerebral peduncle. In order to accomplish this brain-stem section, the animal was carefully anesthetized with endotracheal halothane and, after shaving of the head, was postured for a left (or right) occipitoparietal craniotomy. Following aseptic preparation, the scalp was infiltrated with 111,500 nupercaine solution containing

We describe a patient with peduncular hallucinosis and a mesencephalic infarct; the infarct was diagnosed during life by magnetic resonance imaging.