Thalamic Lesions Research Articles

SURGICAL APPROACH TO THALAMIC CAVERNOUS MALFORMATIONS

Introduction Thalamus is a high eloquent brain region, because it contains important relay nucleus and is surrounded by vital neural and vascular structures. Cavernous malformations involving deep structures such as the basal ganglia and thalamus account for 5–10% of all cerebral cavernomas and can cause devastating neurological deficits. Surgical approach to thalamic cavernomas is associated with risks of new or worsening neurologic deficits. The benefit of surgery must be carefully weighed on an individualized basis. There are several surgical routes that can be used to approach thalamic lesions, mainly transcortical and interhemispheric approaches. A particular approach should be selected based on the location of the cavernoma in the thalamus to minimize lesion of the unaffected brain. Methods We present the case of a 43-year-old right-handed lady with right bleeding posterolateral thalamic cavernoma, admitted to the neurosurgery department of Sibiu MedLife Polisano Hospital in February 2024. The patient underwent surgery, through a transcortical trans-sulcal para-fascicular, navigation guided approach. Preoperative tractography imaging, tubular cerebral corridor retractor system and intraoperative monitoring of the cortico-spinal tract, through motor evoked potentials (transcortical, cortical and subcortical mapping) and of the spinotahamic tract through somatosensory evoked potentials were used. The postoperative course was uneventful and the patient was discharged on the 7th postoperative day. Conclusions Thalamus is a complex structure located in a deep brain area and surgery for these region carries high risks, so the surgeon must carefully tailor these patients. The transcortical transsulcal para-fascicular approach is feasible and safe using the cerebral tubular corridor, neuronavigation and neuromonitoring. Advanced surgical technology offers the advantages of minimizing the risks of new neurological deficits.

Advanced Quantitative MRI Unveils Microstructural Thalamic Changes Reflecting Disease Progression in Multiple Sclerosis.

In patients with multiple sclerosis (PwMS), thalamic atrophy occurs during the disease course. However, there is little understanding of the mechanisms leading to volume loss and of the relationship between microstructural thalamic pathology and disease progression. This cross-sectional and longitudinal study aimed to comprehensively characterize in vivo pathologic changes within thalamic microstructure in PwMS using advanced multiparametric quantitative MRI (qMRI). Thalamic microstructural integrity was evaluated using quantitative T1, magnetization transfer saturation, multishell diffusion, and quantitative susceptibility mapping (QSM) in 183 PwMS and 105 healthy controls (HCs). The same qMRI protocol was available for 127 PwMS and 73 HCs after a 2-year follow-up period. Inclusion criteria for PwMS encompassed either an active relapsing-remitting MS (RRMS) or inactive progressive MS (PMS) disease course. Thalamic alterations were compared between PwMS and HCs and among disease phenotypes. In addition, the study investigated the relationship between thalamic damage and clinical and conventional MRI measures of disease severity. Compared with HCs, PwMS exhibited substantial thalamic alterations, indicative of microstructural and macrostructural damage, demyelination, and disruption in iron homeostasis. These alterations extended beyond focal thalamic lesions, affecting normal-appearing thalamic tissue diffusely. Over the follow-up period, PwMS displayed an accelerated decrease in myelin volume fraction [mean difference in annualized percentage change (MD-ApC) = -1.50; p = 0.041] and increase in quantitative T1 (MD-ApC = 0.92; p < 0.0001) values, indicating heightened demyelinating and neurodegenerative processes. The observed differences between PwMS and HCs were substantially driven by the subgroup with PMS, wherein thalamic degeneration was significantly accelerated, even in comparison with patients with RRMS. Thalamic qMRI alterations showed extensive correlations with conventional MRI, clinical, and cognitive disease burden measures. Disability progression over follow-up was associated with accelerated thalamic degeneration, as reflected by enhanced diffusion (β = -0.067; p = 0.039) and QSM (β = -0.077; p = 0.027) changes. Thalamic qMRI metrics emerged as significant predictors of neurologic and cognitive disability even when accounting for other established markers including white matter lesion load and brain and thalamic atrophy. These findings offer deeper insights into thalamic pathology in PwMS, emphasizing the clinical relevance of thalamic damage and its link to disease progression. Advanced qMRI biomarkers show promising potential in guiding interventions aimed at mitigating thalamic neurodegenerative processes.

Boiling Histotripsy in Ex Vivo Human Brain: Proof-of-concept

ObjectiveNon-invasive surgical approaches, including boiling histotripsy (BH), are currently being developed for treatment of brain disorders aiming to avoid craniotomy and exposure of intervening tissues, and, thus, minimize associated complications. This work aimed to demonstrate the feasibility of BH for mechanical fractionation of human brain tissues ex vivo under B-mode guidance, with preliminary measurements of tissue stiffness via shear wave elastography (SWE). MethodsYoung's moduli of N=25 human autopsy brain samples obtained from de-identified patients of 51–91 y.o. (median 77 y.o.) were measured via SWE prior to BH sonication. N = 17 volumetric BH lesions (1–4 layers of 5×5 points with 1-mm step) were produced near brain surface (n = 10), in white matter (n = 3), in thalamus (n = 2) and globus pallidus (n = 2) using 12-element 1.5-MHz sector transducer under B-mode guidance with 10-ms or 2-ms pulses delivered 10 or 15 times per sonication point with 1% duty cycle. Post-treatment, the lesions were evaluated grossly through bisection, histologically with H&E staining, and ultrastructurally via scanning and transmission electron microscopy. ResultsYoung's moduli of autopsy brain samples were lower in older patients (from 32.9±6.6 kPa in 51 y.o. to 10±2 kPa in 91 y.o.) and at higher temperature (6–50% lower at 37°С vs 23°С), and were within the range observed clinically. All tested BH treatments performed near the brain surface (i.e., mostly in grey matter) resulted in formation of well demarcated rectangular lesions with homogenized content and sharp boundaries, with majority of residual fragments below 100 microns. The use of shorter pulses (2 ms vs 10 ms) accelerated the treatment at least threefold, and the highest liquefaction rate was 568 mm3/min. White matter was more resistant to BH vs grey matter: at least 15 pulses of 2-ms duration were required per each sonication point, and liquefaction rate was three times lower. The ability of BH to produce lesions in thalamus and globus pallidus was also confirmed. ConclusionThis work presents the first demonstration of boiling histotripsy proof-of-concept in human brain tissues ex vivo under B-mode guidance with clinically relevant treatment rates.

A hiatus in the rivalry between Pierre Marie and Jules Dejerine: a collaborative study on sensory disorders by Andre Pierre Marie and Gustave Roussy.

Personal and professional rivalries involving prominent neurologists mark the history of nineteenth-century French neurology. One of the great examples is the feud between Pierre Marie and Jules Dejerine. The dispute between the two, nevertheless, did not prevent Pierre Marie's son, André Marie, and Gustave Roussy - one of Dejerine's favorite pupils, from collaborating on significant research that led to the doctoral dissertation by Andre Marie regarding sensory disturbances associated with painful hemiagnosia found in thalamic lesions.

Coexistence of epilepsy or seizure and multiple sclerosis; review of the literature with a single center experience

ObjectivesThere is evidence that the inflammatory demyelinating disorder in Multiple Sclerosis (MS) is associated with acute seizures and epilepsy. Additionally, the likelihood of developing epilepsy increases with neurodegeneration. This study aims to reveal the clinical and radiological features of MS-epilepsy/seizure coexistence. MethodsAmong all patients diagnosed with MS that we followed in our center between April 2002 and July 2023, patients with a single seizure history or diagnosed with epilepsy (MS-seizure/epilepsy) were randomized 1:1 in terms of age and gender with MS patients without a diagnosis of epilepsy or seizures. Clinical (comorbidities, annualized relapse rate, disability, seizures during attacks, initial diagnosis, disease duration, disease-modifying therapies (DMTs), refractory epilepsy, anti-seizure drugs), electroencephalography (EEG) and MRI (lesion localization and new lesion(s)) data were retrospectively evaluated. ResultsThe mean EDSS was 4.07±2.81. 29.4 % of patients had progressive MS (n = 10). Refractory epilepsy was 52.9 % (n = 18), and SE history was 14.7 % (n = 5). Pathology was detected in 69.7 % (n = 23) of patients in the EEG. The most common slow wave activation was detected in 51.5 % (n = 17). Refractory epilepsy was more common in cases under 45 and patients with lesions in thalamic localization. Lesions in the temporal and thalamic regions and cerebral atrophy were more common in the MS-seizure/epilepsy group. ConclusionPatients with demyelinating lesions in the temporal and thalamic regions should be questioned more carefully for epilepsy, and an EEG should be performed in case of clinical suspicion. Since thalamus lesions are more common in patients with refractory epilepsy, anti-seizure treatment strategies should be applied more carefully. The presence of atrophy on MRI confirms the link between neurodegeneration processes and the development of epilepsy.

West Nile Virus Neuroinvasive Disease: Lessons From Two Cases.

West Nile neuroinvasive disease (WNND) displays a wide range of clinical manifestations due to its involvement of various structures within the central nervous system and peripheral nervous system, often including prolonged unresponsiveness as the presenting symptom. We describe 2 patients presenting with coma and bilateral thalamic lesions on brain magnetic resonance imaging, found to have WNND after extensive workup. These cases illustrate some of the challenges associated with evaluating coma in general and specifically in diagnosing WNND. The clinical diagnosis of WNND requires a high index of suspicion, particularly in immunocompromised and elderly patients. Brain and spine magnetic resonance imaging findings can help narrow down the differential diagnosis, although other diseases may manifest similarly. Serological studies on the cerebrospinal fluid are essential to confirm the diagnosis but have inherent limitations. Given these challenges, WNND should be considered in all patients living in endemic areas who present with unexplained altered mental status during the late summer and early fall seasons.

Dengue-Associated Acute Necrotizing Encephalopathy Is an Acute Necrotizing Encephalopathy Variant Rather than a Mimic: Evidence From a Systematic Review

BackgroundBilateral hemorrhagic thalamic lesions in dengue encephalitis resemble lesions seen in acute necrotizing encephalopathy (ANE). We investigate whether dengue-associated ANE (DANE) should be considered an ANE variant or a mimic. MethodsSystematic review of dengue encephalitis literature from PubMed and SCOPUS (inception to December 31, 2022). Diagnostic criteria for ANE, acute encephalitis (AE), acute disseminated encephalomyelitis (ADEM), and infection-triggered encephalopathy syndromes were applied. ResultsData on 162 patients (median age 20 [0.4 to 79] years; 69 [42.3%] female; 72 [44.4%] aged ≤18 years) from 103 articles were analyzed. DANE (62, 38.3%) was the commonest, followed by AE (56, 34.6%) and ADEM (27, 16.7%). The main clinical features were fever (100%), thrombocytopenia (79.0%), headache (57.8%), and seizures (43.7%). Patients with DANE had earlier neurological deterioration (3.5 [1 to 8] vs 5 [1 to 14] days in other encephalitis syndromes, P = 0.0127), seizures (54.2% vs 37.4%, P = 0.0471), higher cerebrospinal fluid (CSF) protein (0.92 [0.18 to 4.8] vs 0.73 [1 to 16] g/L, P = 0.0469), thalamic (100% vs 8.0%) and hemorrhagic brain lesions (73.3% vs 7.5%, P < 0.0001). CSF pleocytosis and positive CSF dengue IgM/viral polymerase chain reaction were reported in 66.7% and 78.6% with DANE. Mortality was 16.1% in DANE, and 40.6% of survivors had disability. High-risk ANE severity scores predicted poor outcomes (positive predictive value 64.3% [95% confidence interval 38.8% to 83.7%]). ConclusionDANE differs from other dengue encephalitis syndromes and is clinicoradiologically indistinguishable from sporadic ANE with sufficient evidence to be considered an ANE variant.

Methylfenidaat als behandeling voor hypersomnolentie als gevolg van een thalamusinfarct

Methylphenidate as a treatment for hypersomnolence due to a thalamic infarction Fatigue after a stroke can persist for a long time and has consequences for the patient’s rehabilitation. Fatigue is also associated with a higher mortality and a reduced quality of life. Hypersomnia (or hypersomnolence) is much less common after a stroke, but can seriously hinder a person’s recovery and treatment. In this article, 2 cases of severely disabling hypersomnolence after an ischemic stroke in the thalamus are presented and the typical features and treatment options are discussed. The clinical course of thalamic lesions, as well as the contribution of the electroencephalogram and medical imaging are reported. The stimulating effect of methylphenidate on the central nervous system explains the beneficial influence on the hypersomnolence in the 2 cases described here. Treatment of hypersomnia improves a patient’s recovery and quality of life after a stroke.

Speech-language performance and comorbid disorders in children with perisylvian syndrome induced by viral encephalitis.

Viral encephalitis is one of the main causes of the perisylvian syndrome, which can cause damage to children's language-speech, feeding, and swallowing functions. Comprehensive assessment of language-speech and swallowing function and comorbidity research on these children will help children's rehabilitation workers to better understand the disease and strengthen the systematic management of comorbid disorders. To describe speech and language pathology and the occurrence of comorbid disorders in children with perisylvian syndrome induced by viral encephalitis. Twenty-two children with acquired perisylvian syndrome were recruited in this study. Language and speech functions, including oral motor function, swallowing function, language ability, and dysarthria were assessed in these patients. Craniocerebral magnetic resonance imaging (MRI), electroencephalogram examination, and intelligence evaluation were performed to determine brain lesions and comorbid disorders. All children exhibited different degrees of oral movement, dysphagia, and speech and language disorders. There was a significant difference between expressive and receptive language ability (P<0.05). There were 10, 8, and 12 children who had an intellectual disability, limb disability, and epilepsy, respectively. In addition to the damage of the peri-tegmental cortex found in MRI, thalamus lesions occurred in 19 cases and white matter involvement in six cases. Children with acquired perisylvian syndrome caused by viral encephalitis are characterized by persistent pseudobulbar dysfunction, speech and language impairment, and orofacial diplegia. They have a high probability of secondary epilepsy and are prone to motor and cognitive impairment, which need systematic management.

Exploring the impact of the interthalamic adhesion on human cognition: insights from healthy subjects and thalamic stroke patients

The interthalamic adhesion (IA) is a structure that connects the median borders of both thalami. Its anatomical variants and functions remain poorly studied. The main objective of this study was to explore the role of the IA on cognition. 42 healthy subjects and 40 patients with chronic isolated thalamic strokes underwent a neuroimaging and a neuropsychological assessment. The presence, absence, or lesion of the IA and its anatomical variants were evaluated. 76% of participants had an IA, with a higher prevalence among women (92%) than men (61%). The presence or absence of an IA did not affect the neuropsychological performance of healthy subjects nor did the type of IA variant. Across all the tests and when compared to healthy subjects using a Bayesian rmANOVA, patients exhibiting more cognitive impairments were those without an IA (n = 10, BF10 = 10,648), while those with an IA were more preserved (n = 18, BF10 = 157). More specifically, patients without an IA performed more poorly in verbal memory or the Stroop task versus healthy subjects. This was not explained by age, laterality of the infarct, volume or localization of the lesion. Patients with a lesioned IA (n = 12) presented a similar trend to patients without an IA, which could however be explained by a greater volume of lesions. The IA does not appear to play a major role in cognition in healthy subjects, but could play a compensatory role in patients with thalamic lesions.

Digital outcome measures are associated with brain atrophy in patients with multiple sclerosis

BackgroundDigital monitoring of people with multiple sclerosis (PwMS) using smartphone-based monitoring tools is a promising method to assess disease activity and progression.ObjectiveTo study cross-sectional and longitudinal associations between active and passive digital monitoring parameters and MRI volume measures in PwMS.MethodsIn this prospective study, 92 PwMS were included. Clinical tests [Expanded Disability Status Scale (EDSS), Timed 25 Foot Walk test (T25FW), 9-Hole Peg Test (NHPT), and Symbol Digit Modalities Test (SDMT)] and structural MRI scans were performed at baseline (M0) and 12-month follow-up (M12). Active monitoring included the smartphone-based Symbol Digit Modalities Test (sSDMT) and 2 Minute Walk Test (s2MWT), while passive monitoring was based on smartphone keystroke dynamics (KD). Linear regression analyses were used to determine cross-sectional and longitudinal relations between digital and clinical outcomes and brain volumes, with age, disease duration and sex as covariates.ResultsIn PwMS, both sSDMT and SDMT were associated with thalamic volumes and lesion volumes. KD were related to brain, ventricular, thalamic and lesion volumes. No relations were found between s2MWT and MRI volumes. NHPT scores were associated with lesion volumes only, while EDSS and T25FW were not related to MRI. No longitudinal associations were found for any of the outcome measures between M0 and M12.ConclusionOur results show clear cross-sectional correlations between digital biomarkers and brain volumes in PwMS, which were not all present for conventional clinical outcomes, supporting the potential added value of digital monitoring tools.

Trans-temporal trans-choroidal resection of thalamic and thalamopeduncular tumors: how I do it.

Surgical resection is the cornerstone of treatment for low-grade tumors, albeittotal excision is beneficial. As the thalamus is surrounded by vital neurovascular system,lesions here present a surgical challenge. This article aims to demonstrate the trans-temporal, trans-choroidal fissureapproach's effective surgical therapy on patients with thalamic lesions. With this approach,we were able to remove the tumor completely in three patients and almost completely in sixmore. Here we discuss a few technical details and potential hazards of the procedure with anoperative video. This approach provides excellent access to the deep areas of brain.

An atypical stroke manifestation: Sleep disturbance in unilateral thalamic lesion

Thalamic strokes may present with a wide variety of symptoms depending on their location, volume and lateralization. Hypersomnia is a less frequent manifestation, that has been associated with unilateral paramedian thalamic ischemic lesions. We report a case of a patient who presented to the emergency department (ED) with sudden onset of hypersomnolence. Initial head computed tomography (CT) showed no signs of acute ischemia. Follow-up head CT 24 h after thrombolysis exposed a hypodense lesion on the left ventromedial thalamic and mesencephalic regions, with corresponding T2/FLAIR hyperintensity and diffusion restriction on brain magnetic resonance imaging, confirming a recent ischemic stroke. Clinicians should be aware of the association between acute hypersomnia and strategic unilateral thalamic infarcts, particularly when the initial CT scan has no signs of acute ischemia.

Microsurgical anatomy and approaches to thalamic gliomas. Part 1: A cartography guide for navigating to the thalamus. Integrating 3D model rendering with anatomical dissections.

The selection of appropriate microsurgical approaches to treat thalamic pathologies is currently largely subjective. The objective of this study was to provide a structured cartography map for surgical navigation to treat gliomas involving different surfaces of the thalamus. Fifteen formalin-fixed, silicone-injected cadavers (30 sides) were dissected, and 10 adult brain specimens (20 sides) were used to illustrate thalamic microsurgical anatomy using the Klingler fiber dissection technique. Exposures and trajectories for the six most common microsurgical approaches were depicted using MR data from healthy subjects converted into surface-rendered 3D virtual brain models. Additionally, thalamic surfaces exposed with all six approaches were color mapped on the virtual 3D model and compared side-by-side in 360° views with previously reported microsurgical approaches. These 3D models were then used in conjunction with topographic data to guide cadaveric dissection steps. There are two general surgical routes to thalamic lesions: the subarachnoid transcisternal and transcortical routes. The transcisternal route consists of the following three approaches: 1) anterior interhemispheric transcallosal approach, which exposes the anterior and superior thalamus; 2) posterior interhemispheric transcallosal approach, which exposes the posterosuperior thalamus; and 3) supracerebellar infratentorial approach, which exposes the posteromedial cisternal thalamus and can be extended laterally to approach the posterolateral thalamus by cutting the tentorium. The three transcortical approaches are the 1) superior parietal lobule approach, which exposes the posterosuperior thalamus and is particularly advantageous in the setting of hydrocephalus; 2) transtemporal gyrus approach, which exposes the inferolateral thalamus; and 3) transsylvian transinsular approach, which exposes the lateral thalamus (slightly more superiorly and posteriorly) and is advantageous for pathologies extending laterally into the peduncle, lenticular nucleus, or insula. Microsurgical approaches to thalamic gliomas continue to be challenging. Nonetheless, safe and effective cisternal, ventricular, and cortical corridors can be developed with thoughtful planning, anatomical understanding, and knowledge of the advantages, risks, and limitations of each approach. In some cases, it is wise to combine these approaches with staged procedures, as the authors demonstrate in Part 2. In Part 1 of this two-part series, they discuss thalamic microsurgical anatomy and illustrate the trajectory and exposures of all six approaches to guide decision-making. Part 2 discusses their thalamic glioma microsurgical case series, which utilizes these microsurgical approaches.

Cerebrospinal Fluid-In Gradient of Cortical and Deep Gray Matter Damage in Multiple Sclerosis.

A CSF-in gradient in cortical and thalamic gray matter (GM) damage has been found in multiple sclerosis (MS). We concomitantly explored the patterns of cortical, thalamic, and caudate microstructural abnormalities at progressive distances from CSF using a multiparametric MRI approach. For this cross-sectional study, from 3T 3D T1-weighted scans, we sampled cortical layers at 25%-50%-75% depths from pial surface and thalamic and caudate bands at 2-3-4 voxels from the ventricular-GM interface. Using linear mixed models, we tested between-group comparisons of magnetization transfer ratio (MTR) and R2* layer-specific z-scores, CSF-in across-layer z-score changes, and their correlations with clinical (disease duration and disability) and structural (focal lesions, brain, and choroid plexus volume) MRI measures. We enrolled 52 patients with MS (33 relapsing-remitting [RRMS], 19 progressive [PMS], mean age: 46.4 years, median disease duration: 15.1 years, median: EDSS 2.0) and 70 controls (mean age 41.5 ± 12.8). Compared with controls, RRMS showed lower MTR values in the outer and middle cortical layers (false-discovery rate [FDR]-p ≤ 0.025) and lower R2* values in all 3 cortical layers (FDR-p ≤ 0.016). PMS had lower MTR values in the outer and middle cortical (FDR-p ≤ 0.016) and thalamic (FDR-p ≤ 0.048) layers, and in the outer caudate layer (FDR-p = 0.024). They showed lower R2* values in the outer cortical layer (FDR-p = 0.003) and in the outer thalamic layer (FDR-p = 0.046) and higher R2* values in all 3 caudate layers (FDR-p ≤ 0.031). Both RRMS and PMS had a gradient of damage, with lower values closer to the CSF, for cortical (FDR-p ≤ 0.002) and thalamic (FDR-p ≤ 0.042) MTR. PMS showed a gradient of damage for cortical R2* (FDR-p = 0.005), thalamic R2* (FDR-p = 0.004), and caudate MTR (FDR-p ≤ 0.013). Lower MTR and R2* of outer cortical, thalamic, and caudate layers and steeper gradient of damage toward the CSF were significantly associated with older age, higher T2-hyperintense white matter lesion volume, higher thalamic lesion volume, and lower brain volume (β ≥ 0.08, all FDR-p ≤ 0.040). Lower MTR of outer caudate layer was associated with more severe disability (β = -0.26, FDR-p = 0.040). No correlations with choroid plexus volume were found. CSF-in damage gradients are heterogeneous among different GM regions and through MS course, possibly reflecting different dynamics of demyelination and iron loss/accumulation.

Subacute Degeneration of Fibers After Vertical Parasagittal Hemispherotomy.

After vertical parasagittal hemispherotomy arestricted diffusion is often seen ipsilaterally and even distant from the adjacent resection margin. This retrospective cohort study analyses the anatomic site and the time course of the diffusion restriction after vertical parasagittal hemispherotomy. Fifty-nine patients were included into this study, all of them having had one pre-operative and at least one post-operative MRI, including diffusion imaging at b‑values of 0and 1000 s/mm2 with acalculated ADC. Diffusion restriction occurred exclusively on the operated site in all patients. In the basal ganglia, diffusion restriction was present in 37of 38patients at the first postoperative day with aduration of 38days. In the midbrain, the posterior limb of the internal capsule and the thalamus, arestricted diffusion became postoperatively prominent at day9 in all three localizations, with aduration of 36, 34and 36days, respectively. The incidence of thalamic lesions was lower if apreoperative damage had occurred. The restricted diffusion in the basal ganglia resembles direct effects of the operation at its edges, whereas the later appearing diffusion restriction in the midbrain and the posterior limb of the internal capsule rather belong to adegeneration of the descending fibers being transected by the hemispherotomy in the sense of aWallerian degeneration. The presence of preoperative hemispheric lesions influences the development of diffusion restriction at subacute fiber degeneration.

DIPG-78. OSSEOUS METASTASIS IN DIFFUSE MIDLINE GLIOMA: A CASE REPORT AND REVIEW OF LITERATURE

Abstract BACKGROUND Diffuse midline glioma (DMG), H3K 27M-altered are uniformly fatal CNS tumors with 2-year overall survival of less than 10%. Neuroaxis dissemination with disease progression is well known. However, osseous metastasis is a rare occurrence. METHODS We report a patient with localized DMG at diagnosis with subsequent craniospinal and osseous metastasis. We also performed an updated literature review on DMG with extra-neural metastasis (ENM). RESULTS At 11 years of age, the patient presented with progressively worsening headache and vomiting and was found to have a tumor within the right thalamus with mild mass effect on the right lateral ventricle without hydrocephalus. The patient underwent stereotactic tumor biopsy with pathology consistent with DMG, H3K 27-altered. Whole exome sequencing revealed alterations in H3-3A, TP53 and PTPN11. Treatment consisted of upfront focal radiation therapy with subsequent stabilization of the thalamic lesion. However, within 1.5 months of completing radiotherapy, the patient developed drop metastasis, intracranial leptomeningeal dissemination, and diffuse osseous metastasis within the spine, bilateral iliac wings, and ribs. The patient died from disease progression within 2 months of metastatic progression, 6 months from initial diagnosis. Review of literature yielded 11 cases of ENM in pediatric patients with DMG, H3K 27M-altered. Four patients had ENM at diagnosis. The remaining seven patients developed extra CNS metastasis within 1-6 months of diagnosis. Eight patients received upfront radiotherapy with variation in adjuvant chemotherapy. All patients died with median overall survival of 9 months (range, 0.5-24) from diagnosis and 6 months (range, 0.5-22) from ENM occurrence. CONCLUSION ENM in DMG, H3K 27-altered is uncommon. Mechanisms for development of ENM in DMG is unclear. Biopsy and molecular testing for both primary site and ENM should be considered to help elucidate biologic mechanisms of ENM and potentially guide management.

Developmental anatomy of the thalamus, perinatal lesions, and neurological development.

The thalamic nuclei develop before a viable preterm age. GABAergic neuronal migration is especially active in the third trimester. Thalamic axons meet cortical axons during subplate activation and create the definitive cortical plate in the second and third trimesters. Default higher-order cortical driver connections to the thalamus are then replaced by the maturing sensory networks, in a process that is driven by first-order thalamic neurons. Surface electroencephalographic activity, generated first in the subplate and later in the cortical plate, gradually show oscillations based on the interaction of the cortex with thalamus, which is controlled by the thalamic reticular nucleus. In viable newborn infants, in addition to sensorimotor networks, the thalamus already contributes to visual, auditory, and pain processing, and to arousal and sleep. Isolated thalamic lesions may present as clinical seizures. In addition to asphyxia and stroke, infection and network injury are also common. Cranial ultrasound can be used to classify neonatal thalamic injuries based on functional parcelling of the mature thalamus. We provide ample illustration and a detailed description of the impact of neonatal focal thalamic injury on neurological development, and discuss the potential for neuroprotection based on thalamocortical plasticity.

Fronto-thalamic networks and the left ventral thalamic nuclei play a key role in aphasia after thalamic stroke

Thalamic aphasia results from focal thalamic lesions that cause dysfunction of remote but functionally connected cortical areas due to language network perturbation. However, specific local and network-level neural substrates of thalamic aphasia remain incompletely understood. Using lesion symptom mapping, we demonstrate that lesions in the left ventrolateral and ventral anterior thalamic nucleus are most strongly associated with aphasia in general and with impaired semantic and phonemic fluency and complex comprehension in particular. Lesion network mapping (using a normative connectome based on fMRI data from 1000 healthy individuals) reveals a Thalamic aphasia network encompassing widespread left-hemispheric cerebral connections, with Broca’s area showing the strongest associations, followed by the superior and middle frontal gyri, precentral and paracingulate gyri, and globus pallidus. Our results imply the critical involvement of the left ventrolateral and left ventral anterior thalamic nuclei in engaging left frontal cortical areas, especially Broca’s area, during language processing.

Contralateral interhemispheric transcallosal transchoroidal approach to a thalamic glioma: illustrative case.

Thalamic lesions located in the floor of the lateral ventricle pose significant surgical challenges, given their proximity to critical neurovascular structures. Transcortical approaches are often limited by risks of injuring the eloquent cortex and nearby vessels. Furthermore, lesions extending into the third ventricle further impede accessibility. The corticospinal tract (CST), situated close to the thalamus, presents a major obstacle. Diffusion tensor imaging plays a crucial role in overcoming these challenges by accurately delineating the CST's location relative to the lesion, enabling surgeons to plan minimally invasive and safe access. A 32-year-old female presented with progressive right-sided hemiparesis over several days. Magnetic resonance imaging revealed a cystic ring-enhancing thalamic lesion extending into the third ventricle. While supine, the patient underwent surgery via a right pericoronal parasagittal craniotomy followed by a contralateral interhemispheric transcallosal transchoroidal approach. This case exemplifies the utility of the contralateral interhemispheric transcallosal approach for treating thalamic lesions, particularly those extending into the third ventricle. This minimally invasive approach minimizes retraction of the eloquent cortex and reduces the risk of neurovascular injury, potentially leading to improved surgical outcomes and faster recovery.