The use of stereotactic MRI-guided laser interstitial thermal therapy for the treatment of pediatric cavernous malformations: the SUNY Upstate Golisano Children's Hospital experience.

PURPOSE: Cavernous malformations (CM) are central nervous system lesions characterized by interlaced vascular sinusoids coated with endothelial cells without intervening parenchyma. Magnetic resonance imaging-guided laser interstitial thermal therapy (MRIgLITT) is a minimally invasive treatment modality that can precisely treat pathologic cerebral tissue, making it an effective alternative for the management of cavernomas. We describe the outcomes of a series of pediatric patients with cavernous brain malformations treated with MRIgLITT between 2014 and 2018 at our institution. METHODS: We retrospectively analyzed 11 cavernomas in 6 pediatric patients treated with MRIgLITT. Both the Visualase System® and/or Neuroblate® systems were used. A variation of the surgical technique on the application of the laser was developed. Post-ablation MRIs were obtained to assess ablated areas. RESULTS: A total of 11 cavernomas in 6 patients were treated with MRIgLITT. Median age was 15 years (12 to 17 years); 75% were males. Presenting symptoms were headache (75%) and seizures (25%). Two patients presented with multiple CMs. All lesions in this study were supratentorial (cerebral hemispheres 81.8%, corpus callosum 9.1%, basal ganglia 9.1%). Our surgical technique was well-tolerated, with no significant adverse events observed. Hospital stay for all patients was less than 48 hours. CONCLUSION: MRIgLITT is an effective minimally invasive technique for the treatment of pediatric CMs. It represents a useful and safe tool, when other therapeutic alternatives may represent a greater risk of surgical morbidity.

Repurposing Mebendazole as a Replacement for Vincristine for the Treatment of Brain Tumors.

The microtubule inhibitor vincristine is currently used to treat a variety of brain tumors, including low-grade glioma and anaplastic oligodendroglioma. Vincristine, however, does not penetrate well into brain tumor tissue, and moreover, it displays dose-limiting toxicities, including peripheral neuropathy. Mebendazole, a Food and Drug Administration-approved anthelmintic drug with a favorable safety profile, has recently been shown to display strong therapeutic efficacy in animal models of both glioma and medulloblastoma. Importantly, appropriate formulations of mebendazole yield therapeutically effective concentrations in the brain. Mebendazole has been shown to inhibit microtubule formation, but it is not known whether its potency against tumor cells is mediated by this inhibitory effect. To investigate this, we examined the effects of mebendazole on GL261 glioblastoma cell viability, microtubule polymerization and metaphase arrest, and found that the effective concentrations to inhibit these functions are very similar. In addition, using mebendazole as a seed for the National Cancer Institute (NCI) COMPARE program revealed that the top-scoring drugs were highly enriched in microtubule-targeting drugs. Taken together, these results indicate that the cell toxicity of mebendazole is indeed caused by inhibiting microtubule formation. We also compared the therapeutic efficacy of mebendazole and vincristine against GL261 orthotopic tumors. We found that mebendazole showed a significant increase in animal survival time, whereas vincristine, even at a dose close to its maximum tolerated dose, failed to show any efficacy. In conclusion, our results strongly support the clinical use of mebendazole as a replacement for vincristine for the treatment of brain tumors.

Follow-up Brain Imaging Within 30 Days of Gamma-Knife Surgery for New Symptoms: Retrospective Analysis.

OBJECTIVE: Gamma Knife surgery is a complementary procedure to open microsurgery for several indications. However, posttreatment symptomatic complaints are common and often result in short-term follow-up imaging. Here we evaluate the efficacy of repeat brain imaging within 30 days of a Gamma Knife procedure by analyzing the frequency with which that imaging reveals addressable pathology. METHODS: All patients who underwent Gamma Knife treatments at our institution between January 2013 and August 2019 were retrospectively analyzed, and any patient who received imaging of the brain within 30 days for a symptomatic complaint was evaluated. RESULTS: Of the 956 Gamma Knife cases performed, 78 (8.2%) scans were performed within a 30-day time frame for symptomatic complaints. Of these, the most common complaint was headache (25%). Most images demonstrated no changes when compared with the treatment scan (68%) and there were no hemorrhages and only 1 stroke (<1%). Univariate analysis revealed that sex (P = 0.046), treatment volume (P < 0.001), and treatments for metastasis (P < 0.001) or glioma (P < 0.001) were associated with symptomatic complaints leading to imaging, but no factors were associated with higher rates of abnormal imaging. CONCLUSIONS: Gamma Knife therapy remains a safe treatment for multiple indications, but it is not risk free and acute symptomatic complaints are common. However, our data suggest that the need for reimaging within 30 days for symptomatic complaints is likely overestimated as obtained imaging does not usually show any change and the rate of significant complication is exceedingly low.

Laminopedicular Osteotomy for En-bloc Resection of Posterolateral Thoracic Osteoblastoma: Technical Note.

BACKGROUND: Osteoblastomas are a type of primary osseous neoplasm that exhibit a proclivity for the spine, primarily the posterior elements. While generally considered benign, some variants of osteoblastoma exhibit aggressive growth with lytic osseous destruction and soft tissue invasion, with some recurring after initial treatment. Given their proximity to vital structures and potential for rapid growth, these tumors are often managed with aggressive surgery, with en-bloc resection preferred. METHODS: Here we describe our osteotomy technique for resecting en bloc a posterolateral thoracic osteoblastoma causing rapidly progressive myelopathy in a 17-year-old male. RESULTS: Successful treatment of osteoblastoma in a 17-year-old male demonstrates the efficacy of our laminopedicular osteotomy technique in treating 1 instance of a rapidly presenting spinal tumor. CONCLUSIONS: This case bolsters the growing body of literature that favors the outcomes of a more conservative approach to en-bloc resection of spinal tumors.

Treatment strategies for genu recurvatum in adult patients with hemiparesis: a case series.

OBJECTIVE: To report our clinical experience and propose a biomechanical factor-based treatment strategy for improvement of genu recurvatum (GR) to reduce the need for knee-ankle-foot orthosis (KAFO) or surgical treatment. DESIGN: Case series. SETTING: Outpatient clinic of a Department of Physical Medicine and Rehabilitation in an academic medical center. SUBJECTS AND INTERVENTIONS: Adult subjects (n = 22) with hemiparesis and GR who received botulinum injections alone or in combination with multiple types of orthotic interventions that included solid ankle-foot orthosis (AFO) ± heel lift, hinged AFO with an adjustable posterior stop ± heel lift, AFO with dual-channel ankle joint ± heel lift, or KAFO with offset knee joint. Biomechanical factors reviewed included muscle strength, modified Ashworth score for spasticity, presence of clonus, posterior capsule laxity, sensory deficits, and proprioception. OUTCOME MEASUREMENTS: Outcome factors were improvement or elimination of GR based on subjective assessment before and after the interventions by the same experienced clinician. RESULTS: More than one biomechanical factor contributed to GR in all patients. Botulinum toxin A injection was used in patients who had significant plantar flexor spasticity and/or clonus. Four types of orthotic interventions were used based on the biomechanical factor: solid AFO in patients with severe ankle dorsiflexion and plantar flexion weakness or clonus; hinged ankle joint with adjustable posterior stop in patients with less severe ankle dorsiflexion weakness in the absence of clonus; AFO with a dual-channel ankle joint for quadriceps weakness or severe proprioceptive deficits; and KAFO with offset knee joints in patients with Achilles tendon contracture or severe proprioceptive deficits. Adjunctive options included the addition of heel lifts and toeplate modifications. Combinatorial interventions of botulinum injection, modified AFOs, and heel lifts improved or eliminated GR and avoided the need for cumbersome orthotics or surgical interventions. CONCLUSIONS: GR in hemiparesis is multifactorial and can be successfully controlled by using a conservative biomechanical factor-based approach and combined medical and orthotic interventions. An algorithmic approach and a prospective study design is proposed to determine a combination of effective interventions to correct GR.

Isolated cortical vein thrombosis: case series.

OBJECT: Isolated cortical vein thrombosis (ICVT) accounts for less than 1% of all cerebral infarctions. ICVT may cause irreversible parenchymal damage, rendering early and accurate diagnosis critical. This case series and literature review presents the clinical and radiological findings in 7 patients with ICVT, and highlights risk factors and imaging modalities that may be most beneficial in rendering an accurate and timely diagnosis. METHODS: Patients with CT and MRI findings consistent with ICVT examined between January 2011 and June 2014 were included in this retrospective review. RESULTS: Seven patients (5 females, 2 males), ranging in age from 11 months to 34 years, met the inclusion criteria. The most common clinical presentations were headaches (n = 4) and seizures (n = 3). The most common comorbidities noted in these patients were hypercoagulable states (n = 4) and intracranial hypotension (n = 3). Five patients had intraparenchymal involvement. CT suggested the correct diagnosis in 4 patients, and MRI confirmed the diagnosis in all 7 patients. All patients who received anticoagulation therapy (n = 5) experienced complete resolution of their symptoms. CONCLUSIONS: The majority of these patients were adult females, consistent with published data. Seizures and headaches were the most common presenting symptoms. Hypercoagulable state and intracranial hypotension, both known risk factors for thrombosis, were the most commonly noted ICVT risk factors. Intraparenchymal involvement was prevalent in nearly all ICVT cases and presented as vasogenic edema, early intraparenchymal hemorrhage, or hemorrhagic venous infarction. Susceptibility-weighted imaging was the most sensitive imaging technique in diagnosing ICVT.