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The projection neurons of the striatum, the principal nucleus of the basal ganglia, belong to one of the following two major pathways: the striatopallidal (indirect) pathway or the striatonigral (direct) pathway. Striatonigral axons project long distances and encounter ascending tracts (thalamocortical) while coursing alongside descending tracts (corticofugal) as they extend through the internal capsule and cerebral peduncle. These observations suggest that striatal circuitry may help to guide their trajectories. To investigate the developmental contributions of striatonigral axons to internal capsule formation, we have made use ofSox8-EGFP(striatal direct pathway) andFezf2-TdTomato(corticofugal pathway) BAC transgenic reporter mice in combination with immunohistochemical markers to trace these axonal pathways throughout development. We show that striatonigral axons pioneer the internal capsule and cerebral peduncle and are temporally and spatially well positioned to provide guidance for corticofugal and thalamocortical axons. UsingIsl1conditional knock-out (cKO) mice, which exhibit disrupted striatonigral axon outgrowth, we observe both corticofugal and thalamocortical axon defects with either ventral forebrain- or telencephalon-specificIsl1inactivation, despite Isl1 not being expressed in either cortical or thalamic projection neurons. Striatonigral axon defects can thus disrupt internal capsule formation. Our genome-wide transcriptomic analysis inIsl1cKOs reveals changes in gene expression relevant to cell adhesion, growth cone dynamics, and extracellular matrix composition, suggesting potential mechanisms by which the striatonigral pathway exerts this guidance role. Together, our data support a novel pioneering role for the striatal direct pathway in the correct assembly of the ascending and descending axon tracts within the internal capsule and cerebral peduncle.SIGNIFICANCE STATEMENTThe basal ganglia are a group of subcortical nuclei with established roles in the coordination of voluntary motor programs, aspects of cognition, and the selection of appropriate social behaviors. Hence, disruptions in basal ganglia connectivity have been implicated in the motor, cognitive, and social dysfunction characterizing common neurodevelopmental disorders such as attention-deficit/hyperactivity disorder, autism spectrum disorder, obsessive–compulsive disorder, and tic disorder. Here, we identified a novel role for the striatonigral (direct) pathway in pioneering the internal capsule and cerebral peduncle, and in guiding axons extending to and from the cortex. Our findings suggest that the abnormal development of basal ganglia circuits can drive secondary internal capsule defects and thereby may contribute to the pathology of these disorders.

Accurate prediction of topographical correlation between craniopharyngiomas (CPs) and hypothalamus is important for treatment. This study sought to develop a predicting tool based on preoperative-MRI through radiological–surgical–pathological–outcome analysis. Third ventricle floor (TVF), mammillary bodies and cerebral peduncle were evaluated through preoperative-MRI. An eagle-head-like sign named “eagle sign” was observed. Normal TVF on sagittal-MRI was defined as the baseline. Variants of the sign were analyzed by comparing with the baseline and corresponding correlations of CPs with hypothalamus were verified using intraoperative records, histopathology and outcome evaluation. A total of 146 CPs patients, who undergone endoscopic endonasal procedure were divided into four groups based on the variants of “eagle sign”. Group A: 24 patients with the upward sign; group B: 81 with the downward sign; group C: 21 with the anterior TVF upward sign and group D: 20 with the unidentifiable sign. Surgical–pathological analysis showed significant correlations between 95.8% CPs in group A and 95.2% in group C with tumor topography and tumor adherence to the hypothalamus. These CPs had their origins beneath the hypothalamus. In contrast, groups B and D, with hypothalamic origin, showed hypothalamic infiltration by tumor in 97.5% and 95% of cases in groups B and D, respectively. Outcomes of groups A and C were relatively better than groups B and D. Predictive sensitivity and specificity of “eagle sign” were more than 90%. “Eagle sign” is an accurate tool for predicting topographic correlations between CPs and hypothalamus with high sensitivity and specificity.

The anterior choroidal artery (AChA) is a small artery commonly arising from the supraclinoid segment of the internal carotid artery (ICA). The significance of the AChA is related to its strategic supply to various important structures of the brain, such as the optic tract, the posterior limb of the internal capsule, the cerebral peduncle, the lateral geniculate body, medial temporal lobe, medial area of pallidum, and the choroid plexus [J Neurol. 1988;235:387–91]. The AChA syndrome in its complete form consists of the triad of hemiplegia, hemisensory loss, and hemianopia. However, incomplete forms are more frequent in clinical practice [Stroke. 1994;25:837–42]. Isolated infarction in the AChA territory is relatively rare. The presumed pathogenic mechanisms of AChA infarction are cardiac emboli, large-vessel atherosclerosis, dissection of the ICA, small-vessel occlusion, or other determined or undetermined causes [Stroke. 1994;25:837–42 and J Neurol Sci. 2009;281:80–4].

Ipsilateral hemiparesis is a rare and challenging sign in clinical neurological practice. Although the etiology of this manifestation is poorly understood, recent studies have attempted to probe the pathomechanism of this sign with advanced radiological techniques. Additional knowledge about the lesion and unraveling the pathomechanisms causing neurological impairments are important to predict the prognosis and clinical course and to aid in rehabilitation. Therefore, we present a case of a patient with a traumatic subdural hematoma on the left hemisphere and left spastic hemiparesis. Using diffusion tensor imaging (DTI), we concluded that the right corticospinal tract injury caused by compression of the cerebral peduncle accounted for the ipsilateral hemiparesis, also known as Kernohan's notch phenomenon. Thus, this case report highlights the usefulness of the newer radiological techniques, such as DTI, to identify the pathomechanisms of neurological presentations.

G Protein-Coupled Receptor Kinase-Interacting Protein-1 (GIT1) regulates neuronal functions, including cell and axon migration and synapse formation and maintenance, and GIT1 knockout (KO) mice exhibit learning and memory deficits. We noted that male and female GIT1-KO mice exhibit neuroimaging phenotypes including microcephaly, and altered cortical layering, with a decrease in neuron density in cortical layer V. Micro-CT and magnetic resonance microscopy (MRM) were used to identify morphometric phenotypes for the skulls and throughout the GIT1-KO brains. High field MRM of actively-stained mouse brains from GIT1-KO and wild type (WT) controls (n = 6 per group) allowed segmenting 37 regions, based on co-registration to the Waxholm Space atlas. Overall brain size in GIT1-KO mice was ~32% smaller compared to WT controls. After correcting for brain size, several regions were significantly different in GIT1-KO mice relative to WT, including the gray matter of the ventral thalamic nuclei and the rest of the thalamus, the inferior colliculus, and pontine nuclei. GIT1-KO mice had reduced volume of white matter tracts, most notably in the anterior commissure (~26% smaller), but also in the cerebral peduncle, fornix, and spinal trigeminal tract. On the other hand, the basal ganglia appeared enlarged in GIT1-KO mice, including the globus pallidus, caudate putamen, and particularly the accumbens - supporting a possible vulnerability to addiction. Volume based morphometry based on high-resolution MRM (21.5 μm isotropic voxels) was effective in detecting overall, and local differences in brain volumes in GIT1-KO mice, including in white matter tracts. The reduced relative volume of specific brain regions suggests a critical, but not uniform, role for GIT1 in brain development, conducive to brain microcephaly, and aberrant connectivity.

Wrist drops are usually due to a peripheral neuropathy affecting the radial nerve. Cortical wrist drops may occur, usually due to a lesion in the contralateral hand area of the motor cortex. We report a unique case of “cortical” wrist drop due to an acute infarction of the contralateral cerebral peduncle. The patient is a 70-year-old gentleman with the vascular factors of hypertension, hyperlipidaemia, and prior cerebellar strokes, who developed sudden onset of right wrist weakness without numbness. Neurological examination showed a right wrist and finger drop. Nerve conduction study of the radial nerve was normal. MRI brain revealed an acute infarct in the medial part of the left cerebral peduncle, extending slightly to the medial thalamus; there were also old medial posterior cerebellar infarcts. Time of flight MR angiography was normal, with hypoplastic right vertebral artery. Echocardiography was normal but for a dilated right atrium. Electrocardiogram was normal, and 24-hour Holter monitoring detected infrequent atrial and ventricular ectopics. X-ray wrist showed an old ulnar styloid fracture. Nerve conduction study of the radial nerve was normal. He was switched from aspirin to clopidogrel and underwent rehabilitation. The cerebral peduncle should not be forgotten when attempting to anatomically localise the site of the lesion when evaluating a patient with a wrist drop.

Not a single human organ, as well as higher animals, presents such a difficulty in studying as the brain and spinal cord. Each section of the central nervous system, even relatively insignificant in size, is an independent anatomical unit and requires a detailed and accurate study.

Background The early diagnosis of basal ganglia and thalamus germinomas is often difficult due to the absence of elevated tumor markers, and atypical clinical symptoms and neuroimaging features. Case summary Four male children aged 8 to 15 years were diagnosed with germinomas in the basal ganglia and thalamus by stereotactic biopsy from 2017 to 2019. All patients developed hemiplegia except patient 4 who also had cognitive decline, speech disturbance, nocturnal enuresis, polydipsia, polyuria, precocious puberty and abnormalities of thermoregulation. All four cases were alpha-fetoprotein and beta-human chorionic gonadotrophin (β-HCG) negative except patient 3 who had slightly elevated β-HCG in cerebrospinal fluid (CSF). No malignant cells were detected in the patients' CSF. Brain magnetic resonance imaging findings were diverse in these patients with the exception of the unique and common characteristics of ipsilateral hemisphere atrophy, especially in the cerebral peduncle. All patients were diagnosed with germinomas of the basal ganglia and thalamus by stereotactic brain biopsy. Conclusion Stereotactic brain biopsy is necessary to confirm the diagnosis of ectopic germinomas. Serial neuroimaging studies can not only differentiate disease but also determine the biopsy site.

Objective To investigate the effect and medical imaging of modified hemispherectomy on patients with infantile hemiparesis and medically refractory epilepsy. Patients and methods Forty-three patients with infantile hemiparesis and refractory epilepsy who underwent hemispherectomy were enrolled. The treatment effect and medical imaging were analyzed. Results Anatomical hemispherectomy was successfully performed in all patients (100%). In all patients, the muscular tension decreased and the contracted limbs relaxed. In the pathological examination of the resected brain tissue, secondary cicatricial gyri with concomitant cortical dysplasia was present in 36 cases and polycerebellar gyrus malformation and porencephalia in the other 7 cases. Followed up for 7–15 years (mean 11.3), all patients were alive without a long-term sequela. Epilepsy was satisfactorily controlled, with complete seizure relief in 39 cases (91%) classified as Engel I and basic control in the other 4 (9%) defined as Engel II. The posthemispherectomy medical imaging demonstrated that the intracranial space on the operative side shrank, and the healthy cerebral hemisphere shifted markedly toward the hemispherectomy side, with expanded lateral ventricle on the healthy side and thickened skull and enlarged frontal sinus on the operative side. After 4–5 years, the intracranial space on the operative side disappeared in 75% of the patients, demonstrating enlarged cerebral peduncle on the healthy side. Conclusion Further modified hemispherectomy in patients with infantile hemiparesis and medically refractory epilepsy demonstrated markedly ameliorated effects on epilepsy control and the prevention of superficial cerebral hemosiderosis in the long-term follow-up.

Background Increased cerebral signal intensity (SI) has been reported in patients undergoing MRI with gadolinium-based contrast agents (GBCAs). Published data on gadobenate dimeglumine have been somewhat contradictory. Purpose To evaluate the relationship between dosage of gadobenate dimeglumine and SI change at MRI following multiple gadobenate dimeglumine administrations. Materials and Methods In this retrospective study, patients referred for clinically indicated brain MRI from January 2006 through May 2016 were evaluated for inclusion. Eligible patients were between 18 and 90 years old at their baseline brain MRI and had never received a GBCA, had undergone three or more MRI examinations with gadobenate dimeglumine, and had the baseline scan and another brain MRI scan available for comparison. The primary group consisted of patients with four or fewer supratentorial lesions smaller than 3 cm who underwent axial T1-weighted MRI at 1.5 T. One patient had also undergone prior radiation therapy. The secondary group consisted of patients with a history of brain radiation therapy or craniotomy who underwent 1.5-T and 3-T same-plane T1-weighted MRI (in any order). The SI for up to eight brain MRI examinations per patient was measured, and relative SI changes from baseline to interval scans were calculated. A subgroup analysis was performed to assess the gadobenate dimeglumine washout since the last gadolinium exposure. All patients had normal renal and liver functions. Linear mixed regression analyses were performed for variables with P < .05. Results In 43 patients (14 men, 29 women; median age, 49 years; age range, 25-73 years), the dentate nucleus (DN)-to-middle cerebral peduncle (MCP) SI ratio showed a mean increase of 6.7% ± 3.9 in the primary group and 4.0% ± 2.7 in the secondary group (both P < .001) following the administration of 134 mL ± 141 gadobenate dimeglumine over 55 months ± 35.2. The DN/MCP SI ratio increased linearly with the amount of gadobenate dimeglumine, with a mean increase of 0.015% ± 0.004 per 1 mL of gadobenate dimeglumine (R2 = 0.3, P < .001). Conclusion In patients receiving multiple doses of gadobenate dimeglumine, a linear relationship existed between gadobenate dimeglumine administrations and an increase in the dentate nucleus-to-middle cerebral peduncle signal intensity ratio at MRI. © RSNA, 2020 See also the editorial by McDonald and Kallmes in this issue.

Although many studies have focused on functional impairment after intracerebral hemorrhage, little is known about the relationship between secondary injuries to distal regions and neurological function. Our study aimed to evaluate the secondary injuries after intracerebral hemorrhage and explore their relationship to neurological functional outcome. Twenty-one patients with hemorrhages in supratentorial, deep locations and 10 healthy subjects were recruited. Longitudinal examinations of diffusion tensor imaging, hydrogen proton magnetic resonance spectroscopy imaging and neuropsychological assessment were performed after weeks 1 and 12 to elucidate the relationship between magnetic resonance imaging parameters and neurologic outcomes. By week 12, motor function had significantly improved, but cognitive function had deteriorated compared to week 1. Fractional anisotropy values for the ipsilateral cerebral peduncle correlated with motor function at week 1. No significant correlation between fractional anisotropy for the ipsilateral cerebral peduncle and the Fugl-Meyer Motor Scale was found at week 12. Fractional anisotropy values for the ipsilateral hippocampus were related to the Montreal Cognitive Assessment and Mini-Mental State Examination at weeks 1 and 12. Deep supratentorial hemorrhage may result in injury to distal regions, which correlate with impaired motor and cognitive function.

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.

Stereotactic biopsy of posterior fossa lesions is often regarded as hazardous due to the critical structures in that area. Therefore, the aim of the study was to evaluate the diagnostic accuracy and safety of infratentorial stereotactic biopsy of brainstem or cerebellar lesions and its associations with other clinical, laboratory, and radiological parameters. From January 2000 to May 2021, 190 infratentorial stereotactic biopsies of posterior fossa tumors, including 108 biopsies of brainstem lesions, were performed. Moreover, 63 supratentorial biopsies of cerebral peduncle lesions were analyzed to compare the safety and efficacy of both approaches. Additionally, the presence of antibodies against Toxoplasma gondii and Epstein–Barr Virus (EBV) were documented in 67 and 66 patients, respectively, and magnetic resonance imaging (MRI) scans were evaluated in 114 patients. Only 4% of patients had minor complications and 1.5% had major complications, including one patient who died from intracranial bleeding. Nine (4.7%) biopsies were non-diagnostic. Isocitrate dehydrogenase 1 (IDH1) mutation, 1p/19q codeletion, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status were assessed in 29 patients, and were non-diagnostic in only 3 (10.3%) cases. Patients with high-grade gliomas (HGG) were more frequently seropositive for T. gondii than individuals with low-grade gliomas (LGG, p &lt, 0.001). A total of 27% of HGG and 41% of LGG were non-enhancing on MRI. The infratentorial approach is generally safe and reliable for biopsy of brainstem and cerebellar lesions. In our study, the safety and efficacy of supratentorial biopsy of the cerebral peduncle and infratentorial biopsy of lesions below the cerebral peduncle were comparably high. Moreover, patients with HGG were more frequently seropositive for T. gondii than patients with LGG, and the relationship between toxoplasmosis and gliomagenesis requires further investigation.

Wallerian degeneration of the cerebral peduncle is a common MRI finding after cerebral injury. The degree of peduncular atrophy reflects the extent of damage in the corticospinal tract. The acute phase of Wallerian degeneration is visible with Diffusion-Weighted-Imaging. New investigation with Diffusion-Tensor-Imaging quantifies Wallerian degeneration in the subacute ischemic phase and is a good predictor for later functional recovery after stroke.

Quantitative post-mortem magnetic resonance imaging (PMMR) allows for measurement of T1 and T2 relaxation times and proton density (PD) of brain tissue. Quantitative PMMR values may be used for advanced post-mortem neuro-imaging diagnostics such as computer aided diagnosis. So far, the quantitative T1, T2 and PD post-mortem values of regular anatomical brain structures were unknown for a 3 Tesla PMMR application. The goal of this basic research study was to evaluate the quantitative values of post-mortem brain structures for a 3 T post-mortem magnetic resonance application with regard to various corpse temperatures. In 50 forensic cases, a quantitative PMMR brain sequence was applied prior to autopsy. Measurements of T1 (in ms), T2 (in ms), and PD (in %) values of cerebrum (Group 1: frontal grey matter, frontal white matter, thalamus, caudate nucleus, globus pallidus, putamen, internal capsule) brainstem and cerebellum (Group 2: cerebral peduncle, substantia nigra, red nucleus, pons, middle cerebellar peduncle, cerebellar hemisphere, medulla oblongata) were conducted in synthetically calculated axial PMMR brain images. Assessed quantitative values were corrected for corpse temperature. Temperature dependence was observed mainly for T1 values. ANOVA testing resulted in significant differences of quantitative values between the investigated anatomical brain structures in both groups. It can be concluded that temperature corrected 3 Tesla PMMR T1, T2 and PD values are feasible for characterization and discrimination of regular anatomical brain structures. This may provide a base for future advanced diagnostics of forensically relevant brain lesions and pathology.

Purpose Parkinson's disease is a neurodegenerative disease with movement disorders caused by degeneration of the substantia nigra (SN) in the midbrain. Magnetic resonance imaging (MRI) is used to exclude similar diseases. Recently, neuro-melanin imaging (NMI) has been proposed as an imaging method for evaluating the SN. However, the evaluation of the image using this is qualitative, and normal SN cannot be visualized at 1.5 T. This study aimed to investigate whether the SN can be quantitatively evaluated by using phase-sensitive inversion recovery (PSIR) at 1.5 T. Method The phantom was imaged by PSIR and the accuracy of T1 value was verified. Next, the healthy volunteers were imaged by PSIR, and the T1 value and area of the SN were measured. Result As a result of the phantom study, the difference of the T1value between PSIR and inversion recovery spin-echo in the range of the T1 value the SN and the cerebral peduncle (500 to 1000 ms) was lesser than ±10%. The difference between the average of T1 values of the SN measured by PSIR and the previously reported T1 values of the SN was about 1.1%. Furthermore, the average of the area of the SN measured by PSIR was measured independently of imaging parameters by using the T1 value as a reference. Conclusion These results indicate the possibility of a quantitative evaluation of the SN by measuring its area and T1 value by using PSIR at 1.5 T.

The lenticulostriate arteries (LSA) supply the lateral half of the head of the caudate nucleus, entire putamen, anterior limb, genu and the superior part of the internal capsule (IC) and a part of the corona radiata. The LSA consists with medial, intermediate and lateral branches. The medial branches perfuse the lateral segment of the globus pallidus, the head of the caudate nucleus and the anterior limb of the IC. The intermediate branches supply the anterior half of the LSA territory, while the lateral branches supply the posterior half. The anterior cerebral artery (ACA) perforators, predominantly Heubner's artery, perfuse the inferomedial part of the caudate head, the anteromedial part of putamen, the anterior part of the lateral segment of the globus pallidus and anterior limb of the internal capsule. Such territories can be represented by the anterior and ventral basal ganglions. The anterior choroidal artery (AChA) gives off three main groups of branches including the lateral branches that supply the medial temporal lobe, the medial branches that supply the cerebral peduncle and the superior branches that supply the internal capsule and the basal ganglia. The superior branches are further discriminated into proximal branches that supply the anterior one third of the posterior limb of internal capsule (PLIC) and the medial segment of the globus pallidus and distal branches that supply the posterior two-third of PLIC, retro-lenticular part of the internal capsule and the lateral thalamic nuclei. The superficial penetrating arteries, i.e. medullary arteries, arise from the cortical branches of the middle cerebral artery (MCA) and supply the deep white matter. Infarcts caused by the medullary artery occlusion are located in the centrum-semiovale and half of them were caused by embolic mechanism. The centrum-semiovale corresponds to cortical border-zone (BZ) while the corona radiate corresponds to internal BZ.

Diffusion tensor imaging is often used to assess white matter (WM) changes following traumatic brain injury (TBI), but is limited in voxels that contain multiple fibre tracts. Fixel‐based analysis (FBA) addresses this limitation by using a novel method of analysing high angular resolution diffusion‐weighted imaging (HARDI) data. FBA examines three aspects of each fibre tract within a voxel: tissue micro‐structure (fibre density [FD]), tissue macro‐structure (fibre‐bundle cross section [FC]) and a combined measure of both (FD and fibre‐bundle cross section [FDC]). This study used FBA to identify the location and extent of micro‐ and macro‐structural changes in WM following TBI. A large TBI sample (N mild = 133, N moderate–severe = 29) and control group (healthy and orthopaedic; N = 107) underwent magnetic resonance imaging with HARDI and completed reaction time tasks approximately 7 months after their injury (range: 98–338 days). The TBI group showed micro‐structural differences (lower FD) in the corpus callosum and forceps minor, compared to controls. Subgroup analyses revealed that the mild TBI group did not differ from controls on any fixel metric, but the moderate to severe TBI group had significantly lower FD, FC and FDC in multiple WM tracts, including the corpus callosum, cerebral peduncle, internal and external capsule. The moderate to severe TBI group also had significantly slower reaction times than controls, but the mild TBI group did not. Reaction time was not related to fixel findings. Thus, the WM damage caused by moderate to severe TBI manifested as fewer axons and a reduction in the cross‐sectional area of key WM tracts.

Background Progress in extending the survival of glioblastoma (GBM) patients has been slow. A better understanding of why patient survival remains poor is critical to developing new strategies. Postmortem studies on GBM can shed light on why patients are dying. Methods The brains of 33 GBM patients were autopsied and examined for gross and microscopic abnormalities. Clinical-pathologic correlations were accomplished through detailed chart reviews. Data were compared with older published autopsy GBM studies that predated newer treatment strategies, such as more extensive surgical resection and adjuvant temozolomide. Results In older GBM autopsy series, mass effect was observed in 72% of brains, with herniation in 50% of all cases. Infiltration of tumor into the brainstem was noted in only 21% of those older cases. In the current series, only 10 of 33 (30%) GBMs showed mass effect (P = 0.0003), and only 1 (3%) showed herniation (P < 0.0001). However, extensive GBM infiltration of the brainstem was present in 22 cases (67%, P < 0.0001), with accompanying destruction of the pons and white matter tracts. There was a direct correlation between longer median patient survival and the presence of brainstem infiltration (16.1 mo in brainstem-invaded cases vs 9.0 mo in cases lacking extensive brainstem involvement; P = 0.0003). Conclusions With improving care, severe mass effect appears to be less common in GBM patients today, whereas dissemination, including life-threatening brainstem invasion, is now more pronounced. This has major implications regarding preclinical GBM models, as well as the design of clinical trials aimed at further improving patient survival.

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.

Common neurodegenerative diseases feature progressive accumulation of disease-specific protein aggregates in selectively vulnerable brain regions. Increasing experimental evidence suggests that misfolded disease proteins exhibit prion-like properties, including the ability to seed corruptive templating and self-propagation along axons. Direct evidence for transneuronal spread in patients, however, remains limited. To test predictions made by the transneuronal spread hypothesis in human tissues, we asked whether tau deposition within axons of the corticospinal and corticopontine pathways can be predicted based on clinical syndromes and cortical atrophy patterns seen in frontotemporal lobar degeneration (FTLD). Sixteen patients with Pick’s disease, 21 with corticobasal degeneration, and 3 with FTLD-MAPT were included, spanning a range of clinical syndromes across the frontotemporal dementia (FTD) spectrum. Cortical involvement was measured using a neurodegeneration score, a tau score, and a composite score based on semiquantitative ratings and complemented by an MRI-based cortical atrophy W-map based on antemortem imaging. Midbrain cerebral peduncle and pontine base descending fibers were divided into three subregions, representing prefrontopontine, corticospinal, and parieto-temporo-occipital fiber pathways. Tau area fraction was calculated in each subregion and related to clinical syndrome and cortical measures. Within each clinical syndrome, there were predicted relationships between cortical atrophy patterns and axonal tau deposition in midbrain cerebral peduncle and pontine base. Between syndromes, contrasting and predictable patterns of brainstem axonal tau deposition emerged, with, for example, greater tau in prefrontopontine fibers in behavioral variant FTD and in corticospinal fibers in corticobasal syndrome. Finally, semiquantitative and quantitative cortical degeneration scores predicted brainstem axonal tau deposition based on anatomical principles. Taken together, these findings provide important human evidence in support of axonal tau spreading in patients with specific forms of tau-related neurodegeneration.

Purpose. The aim of the paper is to evaluate if advanced dMRI techniques, including diffusion kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI), could provide novel insights into the subtle microarchitectural modifications occurring in the corticospinal tract (CST) of stroke patients in subacute and chronic phases. Methods. Seventeen subjects (age 68 ± 11 years) in the subacute phase (14 ± 3 days post-stroke), 10 of whom rescanned in the chronic phase (231 ± 36 days post-stroke), were enrolled. Images were acquired using a 3-T MRI scanner with a two-shell EPI protocol (20 gradient directions, b = 700 s/mm2, 3 b = 0; 64 gradient directions, b = 2000 s/mm2, 9 b = 0). DTI-, DKI-, and NODDI-derived parameters were calculated in the posterior limb of the internal capsule (PLIC) and in the cerebral peduncle (CP). Results. In the subacute phase, a reduction of FA, AD, and KA values was correlated with an increase of ODI, RD, and AK parameters, in both the ipsilesional PLIC and CP, suggesting that increased fiber dispersion can be the main structural factor. In the chronic phase, a reduction of FA and an increase of ODI persisted in the ipsilesional areas. This was associated with reduced Fic and increased MD, with a concomitant reduction of MK and increase of RD, suggesting that fiber reduction, possibly due to nerve degeneration, could play an important role. Conclusions This study shows that advanced dMRI approaches can help elucidate the underpinning architectural modifications occurring in the CST after stroke. Further follow-up studies on bigger cohorts are needed to evaluate if DKI- and NODDI-derived parameters might be proposed as complementary biomarkers of brain microstructural alterations.

Deep brain stimulation (DBS) has shown to have antidepressant effects in both human trials and animal studies. However, the optimal target and the underlying therapeutic mechanisms remain to be determined. In this study, we investigated if high frequency (HF) DBS in the dorsal peduncular cortex (DPC) alleviates depressive-like behavior in an experimental model of depression. Surprisingly, HF DBS in the DPC caused acute induction of seizures in similar to 40% of animals stimulated with clinically relevant stimulation parameters. Reducing the stimulation's amplitude by 50% did not alter seizure occurrence. Electroencephalographic (EEG) recordings showed seizures up to Racine stage IV lasting up to 4 min after cessation of stimulation. We conclude that HF DBS in the DPC is not suitable for mood-related experiments in rats but could be a potential model for seizure induction. (C) 2019 Elsevier Inc. All rights reserved.

In Alzheimer's disease, the apolipoprotein E gene (APOE) ε2 allele is a protective genetic factor, whereas the APOE ε4 allele is a genetic risk factor. However, both the APOE ε2 and the APOE ε4 alleles are genetic risk factors for lobar intracerebral hemorrhage. The reasons for the high prevalence of lobar intracerebral hemorrhage and the low prevalence of Alzheimer's disease with the APOE ε2 allele remains unknown. Here, we describe the case of a 79-year-old Japanese female with Alzheimer's disease, homozygous for the APOE ε2 allele. This patient presented with recurrent lobar hemorrhages and multiple cortical superficial siderosis. The findings on the 11C-labeled Pittsburgh Compound B-positron emission tomography (PET) were characteristic of Alzheimer's disease. 18F-THK5351 PET revealed that the accumulation of 18F-THK 5351 in the right pyramidal tract at the pontine level, the cerebral peduncle of the midbrain, and the internal capsule, reflecting the lesions of the previous lobar intracerebral hemorrhage in the right frontal lobe. Moreover, 18F-THK5351 accumulated in the bilateral globus pallidum, amygdala, caudate nuclei, and the substantia nigra of the midbrain, which were probably off-target reaction, by binding to monoamine oxidase B (MAO-B). 18F-THK5351 were also detected in the periphery of prior lobar hemorrhages and a cortical subarachnoid hemorrhage, as well as in some, but not all, areas affected by cortical siderosis. Besides, 18F-THK5351 retentions were observed in the bilateral medial temporal cortices and several cortical areas without cerebral amyloid angiopathy or prior hemorrhages, possibly where tau might accumulate. This is the first report of a patient with Alzheimer's disease, carrying homozygous APOE ε2 allele and presenting with recurrent lobar hemorrhages, multiple cortical superficial siderosis, and immunohistochemically vascular amyloid β. The 18F-THK5351 PET findings suggested MAO-B concentrated regions, astroglial activation, Waller degeneration of the pyramidal tract, neuroinflammation due to CAA related hemorrhages, and possible tau accumulation.

Patients with the ciliopathy Joubert syndrome present with physical anomalies, intellectual disability, and a hindbrain malformation described as the “molar tooth sign” due to its appearance on an MRI. This radiological abnormality results from a combination of hypoplasia of the cerebellar vermis and inappropriate targeting of the white matter tracts of the superior cerebellar peduncles. ARL13B is a cilia-enriched regulatory GTPase established to regulate cell fate, cell proliferation and axon guidance through vertebrate Hedgehog signaling. In patients, mutations in ARL13B cause Joubert syndrome. In order to understand the etiology of the molar tooth sign, we used mouse models to investigate the role of ARL13B during cerebellar development. We found ARL13B regulates superior cerebellar peduncle targeting and these fiber tracts require Hedgehog signaling for proper guidance. However, in mouse the Joubert-causing R79Q mutation in ARL13B does not disrupt Hedgehog signaling nor does it impact tract targeting. We found a small cerebellar vermis in mice lacking ARL13B function but no cerebellar vermis hypoplasia in mice expressing the Joubert-causing R79Q mutation. Additionally, mice expressing a cilia-excluded variant of ARL13B that transduces Hedgehog normally, showed normal tract targeting and vermis width. Taken together, our data indicate that ARL13B is critical for control of cerebellar vermis width as well as superior cerebellar peduncle axon guidance, likely via Hedgehog signaling. Thus, our work highlights the complexity of ARL13B in molar tooth sign etiology.Summary statementJoubert syndrome is diagnosed by the hindbrain “molar tooth sign” malformation. Using mouse models, we show loss of the ciliary GTPase ARL13B, mutations in which lead to Joubert syndrome, result in two features of the molar tooth sign: hypoplasia of the cerebellar vermis and inappropriate targeting of the superior cerebellar peduncles. Furthermore, we demonstrate that loss of vertebrate Hedgehog signaling may be the underlying disrupted mechanism as we extend its role in axon guidance to the superior cerebellar peduncles.

Objectives: To set age-specific normal reference values for brainstem, cerebellar vermis, and peduncles measurements and characterize values’ variations according to gender, age, and age by gender interaction. Methods: 565 normal brain magnetic resonance examinations with normal anatomy and signal intensity of the supra- and infratentorial structures were categorized into six age groups (infant, child, adolescent, young adult, middle-age adult, and old aged adults). Patients with congenital malformations, gross pathology of the supra- or infratentorial brain, brain volume loss, developmental delay, metabolic disorders, and neuropsychological disorders (n = 2.839) were excluded. On midsagittal T1 weighted and axial T2 weighted images specific linear diameters and ratios of the brainstem, cerebellar vermis, and peduncles were attained. Two observers assessed a random sample of 100 subjects to evaluate the inter- and intraobserver reproducibility. Intraclass correlation coefficients, means ± standard deviation, one and two-way analysis of variance tests were used in the statistical analysis. Results: Good to excellent inter- and intraobserver measurements’ reproducibility were observed, except for the transverse diameter of the midbrain, the anteroposterior diameter of the medulla oblongata at the pontomedullary and cervicomedullary junctions, cerebellar vermis anteroposterior diameter, and thickness of the superior cerebellar peduncle. Age-specific mean values of the investigated measurements were established. A significant gender-related variation was recorded in the anteroposterior diameter of the basis pontis (p = 0.044), the anteroposterior diameter of the medulla oblongata at the cervicomedullary junction (p = 0.044), and cerebellar vermis height (p = 0.018). A significant age-related change was detected in all measurements except the tectal ratio. Age by gender interaction had a statistically significant effect on the tectal ratio, inferior, and middle cerebellar peduncles’ thickness (p = 0.001, 0.022, and 0.028, respectively). Conclusion: This study provides age-specific normal mean values for various linear dimensions and ratios of the posterior fossa structures with documentation of measurements’ variability according to gender, age, and their interaction. Advances in knowledge: It provides a valuable reference in the clinical practice for easier differentiation between physiological and pathological conditions of the posterior fossa structures especially various neurodegenerative diseases and congenital anomalies.

Objective. Schizencephaly is a rare congenital malformation that causes motor impairment. To determine the treatment strategy, each domain of the motor functions should be appropriately evaluated. We correlated a color map of diffusion tensor imaging (DTI) and transcranial magnetic stimulation (TMS) with the hand function test (HFT) to identify the type of hand function that each test (DTI and TMS) reflects. Further, we attempted to demonstrate the motor neuron organization in schizencephaly. Method. This retrospective study was conducted on 12 patients with schizencephaly. TMS was conducted in the first dorsal interosseous (FDI), biceps (BB), and deltoid muscles of the upper extremity, and contralateral MEP (cMEP) and ipsilateral MEP (iMEP) were recorded. The HFT included the grip strength, box and block (B&B), and 9-hole peg test. The schizencephalic cleft was confirmed using magnetic resonance imaging, and the corticospinal tract (CST) was identified using the color map of DTI. The symmetry indices for the peduncle and CST at pons level were calculated as the ratios of the cross-sectional area of the less-affected side and that of the more-affected side. Result. In the more-affected hemisphere TMS, no iMEP was obtained. In the less-affected hemisphere TMS, the iMEP response was detected in 9 patients and cMEP in all patients, which was similar to the pattern observed in unilateral lesion. Paretic hand grip strength was strongly correlated with the presence of iMEP ( p = 0.044 ). The symmetry index of the color map of DTI was significantly correlated with the B&B ( p = 0.008 , R 2 = 0.416 ), whereas the symmetry index of the peduncle was not correlated with all HFTs. Conclusion. In patients with schizencephaly, the iMEP response rate is correlated with the hand function related to strength, while the symmetricity of the CST by the color map of DTI is correlated with the hand function associated with dexterity. Additionally, we suggest the possible motor organization pattern of schizencephaly following interhemispheric competition.

Background: There is limited literature documenting hemichorea-hemiballism (HCHB) resulting from co-infection of toxoplasmosis and tuberculosis (TB) in acquired immunodeficiency syndrome (AIDS). Toxoplasmic abscess is the most common cause while TB is a rare etiology. Case Description: We describe a 24-year-old male with AIDS-related HCHB as the presentation of cerebritis on the right subthalamic nucleus and cerebral peduncle from intracranial toxoplasma and TB co-infection. Antimicrobials and symptomatic therapy were given. Marked improvement was seen on follow-up. Discussion: HCHB may be the initial presentation of intracranial involvement of this coinfection in the setting of AIDS and is potentially reversible with timely management. Highlights: Hemichorea-hemiballismus (HCHB) may be an initial presentation of intracranial involvement of concomitant toxoplasmosis and tuberculosis causing focal cerebritis in the contralateral subthalamic nucleus and cerebral peduncle, particularly in the setting of human immunodeficiency virus infection. Acquired immunodeficiency syndrome-related HCHB is potentially reversible with timely diagnosis and treatment.

Highlights • PSP patients can show marked ventricular enlargement (PSP-vd). • PSP-vd patients had increased FA and AxD in CST regions close to lateral ventricles. • CST alterations in PSP-vd are due to CST compression by the enlarged ventricles. • CST alterations in PSP-vd are similar to those found in NPH but of lesser degree. • Higher ventriculomegaly is associated with higher severity of the CST alterations., Background Microstructural alterations of corticospinal tract (CST) have been found in idiopathic normal pressure hydrocephalus (iNPH). No study, however, investigated the effect of ventricular dilatation on CST in Progressive Supranuclear Palsy (PSP). Objective The aim of this study was to investigate CST diffusion profile in a large cohort of PSP patients with and without ventricular dilatation. Methods Twenty-three iNPH patients, 87 PSP patients and 26 controls were enrolled. Evans index (EI) and ventricular volume (VV) were measured in all patients. CST tractography was performed to calculate FA, MD, AxD and RD in six different anatomical regions: medulla oblungata (MO), pons (P), cerebral peduncle (CP), posterior limb of internal capsule (PLIC), corona radiata (CR), subcortical white matter (SWM). ANCOVA was used for comparing CST diffusion profiles between the groups and association between CST microstructural metrics and measures of ventricular dilatation (EI and VV) was assessed. Results Thirty-three PSP patients had ventricular dilatation (EI > 0.30, PSP-vd) while 54 PSP patients had normal ventricular system (EI ≤ 0.30, PSP-wvd). iNPH patients had the most marked FA and AxD increase in PLIC and CR of CST followed by PSP-vd, PSP-wvd and controls; RD was altered only in iNPH. A strong correlation was found between CST diffusion metrics and EI or VV. Conclusions Our findings confirm the microstructural changes of CST in iNPH patients and demonstrate for the first time similar alterations in PSP-vd patients, suggesting a crucial role of ventricular dilatation in the mechanical compression of CST.