Robot-assisted stereotactic biopsy of pediatric brainstem and thalamic lesions.

OBJECTIVE: Biopsies of tumors located in deep midline structures require highly accurate stereotaxy to safely obtain lesional tissue suitable for molecular and histological analysis. Versatile platforms are needed to meet a broad range of technical requirements and surgeon preferences. The authors present their institutional experience with the robotic stereotactic assistance (ROSA) system in a series of robot-assisted biopsies of pediatric brainstem and thalamic tumors. METHODS: A retrospective analysis was performed of 22 consecutive patients who underwent 23 stereotactic biopsies of brainstem or thalamic lesions using the ROSA platform at Rady Children's Hospital in San Diego between December 2015 and January 2020. RESULTS: The ROSA platform enabled rapid acquisition of lesional tissue across various combinations of approaches, registration techniques, and positioning. No permanent deficits, major adverse outcomes, or deaths were encountered. One patient experienced temporary cranial neuropathy, and 3 developed small asymptomatic hematomas. The diagnostic success rate of the ROSA system was 91.3%. CONCLUSIONS: Robot-assisted stereotactic biopsy of these lesions may be safely performed using the ROSA platform. This experience comprises the largest clinical series to date dedicated to robot-assisted biopsies of brainstem and diencephalic tumors.

Pediatric Thalamic Gliomas: An Updated Review.

CONTEXT: - Neoplasms originating in the thalamus are rare overall (1% of all brain tumors); however, they comprise approximately 5% of pediatric intracranial tumors and approach 15% of all malignant pediatric intracranial tumors in some series. OBJECTIVE: - To update readers about the current understanding of the diverse histology, biology, and behavior of pediatric thalamic tumors. Histologic verification is now thought to be critical for planning treatment, and, as a result, biopsy and total/subtotal resections are much more common today than in the past. DATA SOURCES: - A PubMed search using the keywords "pediatric + thalamic + glioma" yielded 45 publications with a total of 445 cases of thalamic gliomas in patients less than 18 years of age. We found only 9 substantial institutional series tabulating all encountered thalamic histologic types in children. This survey confirmed a high proportion of astrocytomas, 81% (214 of 265), of which approximately two-thirds were diffuse astrocytomas (146 of 214) and one-third were pilocytic astrocytomas (68 of 214). Of the diffuse astrocytomas, 34% (49 of 146) were low grade (World Health Organization grade II) and 55% (81 of 146) were high grade (World Health Organization grade III or IV), making the latter subgroup the largest single category of all pediatric thalamic tumors. Oligodendrogliomas and ependymomas (mostly anaplastic in both cases) comprised 10% and 3% of all pediatric thalamic tumors, respectively. CONCLUSIONS: - Tissue diagnosis is now thought crucial for prognostication and treatment, particularly as more potentially therapeutic molecular targets are discovered. Secure diagnosis allows identification of tumors for which resection is more feasible and beneficial.

Third Ventricular Cerebrospinal Fluid Cysts of Thalamic Origin: Review of Embryologic Origin, Presentation, and Management Strategies with a Case Series.

OBJECTIVE: Third ventricular cerebrospinal fluid (CSF) cysts of thalamic origin are rare. The objective of this study is to review their possible pathogenesis, clinical presentation, and management strategies with a case series describing management via an endoscopic approach with fenestration using a single burr-hole technique. METHODS: A systematic literature review of reported cases of thalamic cysts was conducted with further meta-analysis of CSF cysts that involve the third ventricle. The mode of presentation, pathologic analysis, surgical management, and outcomes were analyzed. RESULTS: Twenty-two studies reported between 1990 and 2013 described 42 cases of thalamic cyst. Of those cases, 13 were consistent with CSF cyst that originated in the thalamus and involved the third ventricle. Eight cases (61.5%) were treated via endoscopic fenestration, 2 cases (15.4%) were surgically drained, 2 cases (15.4%) were stereotactically aspirated, and 1 case (7.69%) was observed. The most common presenting symptoms were gait disturbance (26.3%) and headaches (26.3%) followed by tremors (15.8%) and weakness (15.8%). In our series, a single burr-hole technique was a successful definitive treatment, with an average period of 23 months. CONCLUSIONS: Third ventricular CSF cysts of thalamic origin most commonly present with hydrocephalus. They can be safely definitively treated via endoscopic fenestration to the CSF circulation using a single burr-hole technique. Long-term follow-up shows lasting improvement in symptoms without reaccumulation of the cyst.

Distant recurrences limit the survival of patients with thalamic high-grade gliomas after successful resection.

The indications of surgery for thalamic high-grade gliomas are not well established. The present study investigated the outcome of 21 patients treated by surgery and reports the high incidence of distant recurrences including disseminations after successful removal. Twenty-one patients with thalamic high-grade gliomas not invading the pyramidal tract or midbrain underwent cytoreductive surgery at our institute from June 1997 to August 2015. Surgery was performed with the aid of a neuronavigation system, electrophysiological monitoring, and fluorescence navigation. Tumor histology included 12 cases of the World Health Organization grade III and nine cases of grade IV. Gross total resection was achieved in six cases, subtotal in 13, and partial in two. Motor weakness accompanied by sensory disturbance deteriorated immediately after surgery in 13 patients. However, five patients were determined to show deterioration at 2 months after surgery. Postoperative radiation and chemotherapy were given to every patient, and median progression-free survival of patients with grade III and IV tumors was 12.1 and 7.0 months, respectively. Median overall survival of patients with grade III and IV tumors was 25.6 and 12.6 months, respectively. High incidence of distant recurrences was found, with distant lesions at recurrence in 13 of 19 patients with recurrence, suggesting the life-restricting factor in these patients. Thalamic high-grade glioma without invasion into the pyramidal tract and brainstem can be considered as a candidate for surgical resection. Distant lesion limits the survival of patients after successful resection.

High-Definition Fiber Tractography in Evaluation and Surgical Planning of Thalamopeduncular Pilocytic Astrocytomas in Pediatric Population: Case Series and Review of Literature.

OBJECTIVE: Thalamopeduncular tumors (TPTs) of childhood present a challenge for neurosurgeons due to their eloquent location. Preoperative fiber tracking provides total or near-total resection, without additional neurologic deficit. High-definition fiber tractography (HDFT) is an advanced white matter imaging technique derived from magnetic resonance imaging diffusion data, shown to overcome the limitations of diffusion tensor imaging. We aimed to investigate alterations of corticospinal tract (CST) and medial lemniscus (ML) caused by TPTs and to demonstrate the application of HDFT in preoperative planning. METHODS: Three pediatric patients with TPTs were enrolled. CSTs and MLs were evaluated for displacement, infiltration, and disruption. The relationship of these tracts to tumors was identified and guided surgical planning. Literature was reviewed for publications on pediatric thalamic and TPTs that used diffusion imaging. RESULTS: Two patients had histologic diagnosis of pilocytic astrocytoma. One patient whose imaging suggested a low-grade glioma was managed conservatively. All tracts were displaced (1 CST anteriorly, 2 CSTs, 1 ML anteromedially, 1 ML medially, and 1 ML posteromedially). Literature review revealed 2 publications with 15 pilocytic astrocytoma cases, which investigated CST only. The condition of sensory pathway or anteromedial displacement of the CST in these tumors was not reported previously. CONCLUSIONS: Displacement patterns of the perilesional fiber bundles by TPTs are not predictable. Fiber tracking, preferably HDFT, should be part of preoperative planning to achieve maximal extent of resection for longer survival rates in this young group of patients, while preserving white matter tracts and thus quality of life.

Bilateral Thalamic Glioma: Case Report and Review of the Literature.

Bilateral thalamic glioma is extremely rare and the incidence cannot be adequately expressed. We present the case of a 72 years old male suffering from the rapid deterioration of cognitive function to moderately severe dementia in a short period of time. Magnetic resonance studies demonstrated a bilateral thalamic glioma with a minimal focal gadolinium uptake in the left thalamus. Biopsy was performed and pathology report was of anaplastic astrocytoma, WHO grade III. Radiotherapy was proposed but was rejected by the patient's relatives. The patient deceased 57 days later. We performed an extensive review of the literature and by updating the previous described series we can state that to the best of our knowledge this is the 60th case described in the literature and the second eldest patient presented. Patients suffering from this disease present a poor prognosis, the longest survival described being of 3 years in patients diagnosed with grade II bilateral thalamic glioma. Adjuvant therapy in form of radiotherapy to the thalami is most commonly used but the benefits are unclear. The natural progression of WHO grade III bilateral thalamic glioma left untreated, as can be seen from our case, has an even poorer outcome.

A case report on 1-year follow-up of bilateral thalamic glioma.

Bilateral thalamic glioma is one of the rarest tumor occurrences, representing a small fraction of thalamic gliomas, which only accounts for 1-1.5% of all brain tumors. It is usually a diffuse, low-grade astrocytoma (WHO grade II), seen mainly in adults, with approximately 25% of them involving children under the age of 15. Radiotherapy is the main mode of treatment since surgical intervention is limited to a role of biopsy and management of secondary effects, due to the deep brain location of the lesion and the complexity of the involved structures. We report a 1-year follow-up of a 55-year-old female patient with bilateral WHO grade II thalamic astrocytoma. Following histological and neuroradiological consensus regarding the diagnosis, the patient was referred for radiotherapy. The effectiveness of available therapy and long-term neuroradiological follow-up is not reliably established due to rapid fatal evolution following diagnosis. Contrary to the norm, our patient showed stable disease with radiotherapy for a 1-year period.

Low grade glioma in an adult patient with Sotos syndrome.

Sotos syndrome is a rare overgrowth syndrome with an increased risk of tumorigenesis. To our knowledge we report the first case of astrocytoma in an adult patient with Sotos syndrome and describe the clinical course.

Thalamic lesions: a radiological review.

BACKGROUND: Thalamic lesions are seen in a multitude of disorders including vascular diseases, metabolic disorders, inflammatory diseases, trauma, tumours, and infections. In some diseases, thalamic involvement is typical and sometimes isolated, while in other diseases thalamic lesions are observed only occasionally (often in the presence of other typical extrathalamic lesions). SUMMARY: In this review, we will mainly discuss the MRI characteristics of thalamic lesions. Identification of the origin of the thalamic lesion depends on the exact localisation inside the thalamus, the presence of extrathalamic lesions, the signal changes on different MRI sequences, the evolution of the radiological abnormalities over time, the history and clinical state of the patient, and other radiological and nonradiological examinations.

H3F3A K27M mutations in thalamic gliomas from young adult patients.

INTRODUCTION: Mutations in H3F3A, which encodes histone H3.3, commonly occur in pediatric glioblastoma. Additionally, H3F3A K27M substitutions occur in gliomas that arise at midline locations (eg, pons, thalamus, spine); moreover, this substitution occurs mainly in tumors in children and adolescents. Here, we sought to determine the association between H3F3A mutations and adult thalamic glioma. METHODS: Genomic H3F3A was sequenced from 20 separate thalamic gliomas. Additionally, for 14 of the 20 gliomas, 639 genes--including cancer-related genes and chromatin-modifier genes--were sequenced, and the Infinium HumanMethylation450K BeadChip was used to examine DNA methylation across the genome. RESULTS: Of the 20 tumors, 18 were high-grade thalamic gliomas, and of these 18, 11 were from patients under 50 years of age (median age, 38 y; range, 17-46), and 7 were from patients over 50 years of age. The H3F3A K27M mutation was present in 10 of the 11 (91%) younger patients and absent from all 7 older patients. Additionally, H3F3A K27M was not detected in the 2 diffuse astrocytomas. Further sequencing revealed recurrent mutations in TP53, ATRX, NF1, and EGFR. Gliomas with H3F3A K27M from pediatric or young adult patients had similar, characteristic DNA methylation profiles. In contrast, thalamic gliomas with wild-type H3F3A had DNA methylation profiles similar to those of hemispheric glioblastomas. CONCLUSION: We found that high-grade thalamic gliomas from young adults, like those from children and adolescents, frequently had H3F3A K27M.

Further delineation of the clinical spectrum in RNU4ATAC related microcephalic osteodysplastic primordial dwarfism type I.

We describe five patients from three different families with microcephalic osteodysplastic primordial dwarfism type I (MOPD I), which was molecularly confirmed by homozygosity for the g.51G >A and g.55G >A mutations in RNU4ATAC, respectively. The patients showed the classical phenotype and demonstrated in addition variable degrees of gyration abnormalities and malformations of the callosal body with an interhemispheric cyst. One patient also showed underdevelopment of the cerebellar vermis. This confirms that cortical malformations should be considered cardinal manifestations of MOPD I. Oculocutaneous albinism, brain hemorrhage and chilblains have been found to be associated with MOPD I. The present study showed lack of retinal pigmentation in three patients of whom two had an unusually fair complexion of hair and skin. One patient was found to have a hematoma in the left thalamus. This may indicate that both pigmentary abnormalities and vascular anomalies may be part of the phenotype of MOPD I as well.

Bilateral central pain sensitization in rats following a unilateral thalamic lesion may be treated with high doses of ketamine.

BACKGROUND: Central post-stroke pain is a neuropathic pain condition caused by a vascular lesion, of either ischemic or hemorrhagic origin, in the central nervous system and more precisely involving the spinothalamocortical pathway responsible for the transmission of painful sensations. Few animal models have been developed to study this problem. The objectives of this study were to evaluate different modalities of pain in a central neuropathic pain rat model and to assess the effects of ketamine administered at different doses. Animals were evaluated on the rotarod, Hargreaves, Von Frey and acetone tests. A very small hemorrhage was created by injecting a collagenase solution in the right ventral posterolateral thalamic nucleus. Following the establishment of the neuropathy, ketamine was evaluated as a therapeutic drug for this condition. RESULTS: Histopathological observations showed a well localized lesion with neuronal necrosis and astrocytosis following the collagenase injection that was localized within the VPL. No significant change in motor coordination was observed following surgery in either the saline or collagensae groups. In the collagenase group, a significant decrease in mechanical allodynia threshold was observed. A sporadic and transient cold allodynia was also noted. No thermal hyperalgesia was seen following the collagenase injection. Ketamine was then tested as a potential therapeutic drug. A significant decrease in motor coordination was seen only following the administration of 25 mg/kg of ketamine in both groups. An alleviation of mechanical allodynia was achieved only with the high ketamine dose. The minimal effective ketamine serum concentration (150 ng/mL) was only achieved in animals that received 25 mg/kg. CONCLUSIONS: An intrathalamic hemorrhage induced a bilateral mechanical allodynia in rats. Cold hyperalgesia was observed in 60% of these animals. Mechanical allodynia was alleviated with high doses of ketamine which corresponded with therapeutic plasmatic concentrations.

Surgical management of thalamic gliomas: case selection, technical considerations, and review of literature.

This study aimed to identify (1) the thalamic gliomas suitable for surgical resection and (2) the appropriate surgical approach based on their location and the displacement of the posterior limb of the internal capsule (PLIC). A retrospective study over a 5-year period (from 2006 to 2010) was performed in 41 patients with thalamic gliomas. The mean age of these patients was 20.4 years (range, 2-65 years). Twenty (49 %) tumors were thalamic, 19 (46 %) were thalamopeduncular, and 2 (5 %) were bilateral. The PLIC, based on T2-weighted magnetic resonance axial sections, was displaced anterolaterally in 23 (56 %) cases and laterally in 6 (14 %) cases. It was involved by lesion in eight (20 %) cases and could not be identified in four (10 %) cases. Resection, favored in patients with well-defined, contrast-enhancing lesions, was performed in 34 (83 %) cases, while a biopsy was resorted to in 7 (17 %) cases. A gross total resection or near total resection (>90 %) could be achieved in 26 (63 %) cases. The middle temporal gyrus approach, used when the PLIC was displaced anterolaterally, was the commonly used approach (63.5 %). Common pathologies were pilocytic astrocytoma (58 %) in children and grade III/IV astrocytomas (86 %) in adults. Preoperative motor deficits improved in 64 % of the patients with pilocytic lesions as compared to 0 % in patients with grade III/IV lesions (P value, 0.001). Postoperatively, two patients (5 %) had marginal worsening of motor power, two patients developed visual field defects, and one patient developed a third nerve paresis. Radical resection of thalamic gliomas is a useful treatment modality in a select subset of patients and is the treatment of choice for pilocytic astrocytomas. Tailoring the surgical approach, depending on the relative position of the PLIC, has an important bearing on outcome.

Minimally invasive procedures reduced the damages to motor function in patients with thalamic hematoma: observed by motor evoked potential and diffusion tensor imaging.

BACKGROUND: The purpose of this study was to observe changes in motor function using diffusion tensor imaging (DTI) and motor-evoked potential (MEP) in patients with thalamic hematoma treated by minimally invasive procedures. METHODS: Forty-three patients with thalamic hematoma were randomized to either a minimally invasive group (MI group) or a medical treatment group (MT group). The patients in the MI group underwent whole-brain DTI and MEP measurements both before and 2 weeks after the thalamic hematoma was evacuated by minimally invasive procedures. The fractional anisotropy (FA) values of the corticospinal tract (CST) in the internal capsule and MEP ipsilateral to the hematoma side and the contralateral side were determined and then compared with the MT group. RESULTS: DTI showed that fibers in the internal capsule ipsilateral to the hematoma decreased either in number or were interrupted because of hematoma-induced damages, and in both groups, the CST FA values on admission were significantly lower (0.428 ± 0.032 and 0.415 ± 0.048 for the MI and MT groups, respectively) than the control values. Two weeks after the hematoma was evacuated, the number of fibers and the FA values of the CST in the internal capsule had both increased significantly relative to the values on admission. MEP was recorded simultaneously in all patients who were treated with minimally invasive procedures, and the latency of MEP decreased compared with the MT group. As FA values of the CST in internal capsule increased and MEP appeared with its latency decreased, the modified National Institutes of Health Stroke Scale score decreased after the surgery. CONCLUSIONS: Minimally invasive procedures for thalamic hematoma evacuation could effectively reduce the degree of injury to the function as observed by a combination of DTI and MEP measurements.

Pial arteriovenous fistula as a cause of bilateral thalamic hyperintensities--an unusual case report and review of the literature.

INTRODUCTION: Isolated bilateral thalamic congestion due to an arteriovenous malformation (AVM) is a rare entity. Few case reports of dural arteriovenous fistula associated with it have been reported in the literature. The association of pial arteriovenous fistula (pial AVF) with thalamic hyperintensities has never been described before. The pial AVF is a recently recognized lesion in which the multiple pial arterial feeders drain into a single venous channel without a nidus like in conventional AVM. In spite of being congenital in origin, these lesions may have expression in adulthood due to abrupt change in the venous drainage system. Successful management of pial AVF associated with bilateral thalamic hyperintensities is described here with review of the literature. CASE PRESENTATION: A 60-year-old man presented with rapidly progressive gait disturbance and cognitive decline. Magnetic resonance imaging (MRI) showed hyperintensities in the thalami on T2-weighted and fluid attenuated inversion recovery image. Digital subtraction angiography revealed a pial AVF near the splenium of corpus callosum. It had feeders from posterior choroidal arteries and drained into the vein of Galen through an abnormal mesencephalic vein. The stagnation and increase of pressure in the deep venous system led to congestion in the thalami. He was treated by partial transarterial embolization of the feeders followed by gamma knife therapy (GKT). The clinical symptoms and MRI improved rapidly after embolization and further reduction in shunt flow was observed after GKT. CONCLUSION: Strong suspicion of vascular malformation as a cause of bilateral thalamic hyperintensities helps in early detection. Such lesions like pial AVF presented here require active intervention by surgery or endovascular therapy. GKT is an important adjuvant in lesions refractory to either of them.

Thalamic astrocytic hamartoma and associated meningoangiomatosis in a German shepherd dog.

The present paper describes an astrocytic thalamic hamartoma associated with tectal meningoangiomatosis in a 3-month-old female German shepherd dog showing strabismus, opistotonus, circling, and fore limb hypermetria. MR images of the brain showed a well-defined intra-axial mass in the tectal region. The mass was hypointense to gray matter on T2-weighted images and hyperintense to gray matter on precontrast T1-weighted images. Histologically, glial cells arranged in a multinodular pattern characterized the mass. More caudally the lesion merged with subpial abnormal newly formed plaque-like shaped tissue characterized by thick branching bundles of spindle-shaped cells surrounding a central vessel. In the nodules, GFAP and vimentin were diffusely expressed. In the vascular proliferation Factor VIII-positive reaction was limited to endothelial cells while the remaining spindle-shaped cells were diffusely SMA-positive. The glial nodules did not express lysozyme and MAC387, nor neurofilaments and nestin.

Interhemispheric endoscopic resection of large intraventricular and thalamic tumors.

A transfrontal route is the traditional endoscopic approach to intraventricular tumors. Small lesions can be biopsied using the parallel port channel of the endoscope. For larger tumors a ventriculoport can be used for resection. This technique nevertheless requires traversing the brain tissue, is difficult in the setting of small ventricles, and allows only limited mobility. The authors describe the endoscopic resection of large intraventricular tumors via an interhemispheric route using rigid suction with a mounted endoscope, and thus circumventing some of the problems with the traditional approach.

Use of 5-ALA fluorescence guided endoscopic biopsy of a deep-seated primary malignant brain tumor.

The introduction of fluorescence-guided resection of primary malignant brain tumors was a milestone in neurosurgery. Deep-seated malignant brain tumors are often not approachable for microsurgical resection. For diagnosis and therapy, new strategies are recommended. The combination of endoscopy and 5-aminolevulinic acid-induced protoporphyrin IX (5-ALA-induced Pp IX) fluorescence-guided procedures supported by neuronavigation seems an interesting option. Here the authors report on a combined approach for 5-ALA fluorescence-guided biopsy in which they use an endoscopy system based on an Xe lamp (excitation approximately λ = 407 nm; dichroic filter system λ = 380-430 nm) to treat a malignant tumor of the thalamus and perform a ventriculostomy and septostomy. The excitation filter and emission filter are adapted to ensure that the remaining visible blue remission is sufficient to superimpose on or suppress the excited red fluorescence of the endogenous fluorochromes. The authors report that the lesion was easily detectable in the fluorescence mode and that biopsy led to histological diagnosis.