Jacky T. Yeung

LOH in the HLA Class I region at 6p21 is Associated with Shorter Survival in Newly Diagnosed Adult Glioblastoma

Purpose: Glioblastoma (GBM) shows downregulated expression of human leukocyte antigen (HLA) class I, thereby escaping from cytotoxic T cells and limiting the efficacy of immunotherapy. Loss of heterozygosity (LOH) of HLA class I (6p21) and/or β-2 microglobulin (B2m) (15q21) regions represents irreversible downregulation. In this study, we examined the prevalence of these LOH events and their relations with overall survival in GBM. Experimental Design: In a cross-sectional analysis on 60 adult patients with GBM, DNA from formalin-fixed, paraffin-embedded specimens were evaluated for 10 microsatellite regions of HLA class I, B2m, HLA class II, HLA class III, and 6q by PCR as well as immunohistochemical evaluation of HLA class I expression and CD8+ T-cell infiltration. Results: LOH in HLA class I, B2m, HLA class II, HLA class III, and 6q regions was present in 41.4%, 18.2%, 9.4%, 77.8%, and 36.0% of informative cases, respectively. LOH of HLA class I was associated with shorter overall survival (HR = 4.89, P = 0.0078). HLA class I was downregulated in 22% to 43% of cases based on immunohistochemistry. Cases that displayed negative staining were significantly younger. HLA class I expression correlated with intratumoral CD8+ T-cell infiltration. Conclusion: LOH in the HLA class I region is frequent in adult GBMs. The association of shorter survival with LOH in this region suggests a crucial role for these genes in immunosurveillance. Clin Cancer Res; 19(7); 1816–26. ©2013 AACR.

Hemifacial Spasm and Neurovascular Compression

Hemifacial spasm (HFS) is characterized by involuntary unilateral contractions of the muscles innervated by the ipsilateral facial nerve, usually starting around the eyes before progressing inferiorly to the cheek, mouth, and neck. Its prevalence is 9.8 per 100,000 persons with an average age of onset of 44 years. The accepted pathophysiology of HFS suggests that it is a disease process of the nerve root entry zone of the facial nerve. HFS can be divided into two types: primary and secondary. Primary HFS is triggered by vascular compression whereas secondary HFS comprises all other causes of facial nerve damage. Clinical examination and imaging modalities such as electromyography (EMG) and magnetic resonance imaging (MRI) are useful to differentiate HFS from other facial movement disorders and for intraoperative planning. The standard medical management for HFS is botulinum neurotoxin (BoNT) injections, which provides low-risk but limited symptomatic relief. The only curative treatment for HFS is microvascular decompression (MVD), a surgical intervention that provides lasting symptomatic relief by reducing compression of the facial nerve root. With a low rate of complications such as hearing loss, MVD remains the treatment of choice for HFS patients as intraoperative technique and monitoring continue to improve.

Pegylated interferon-α-2b for children with recurrent craniopharyngioma

OBJECT Previous studies of systemic and intralesional administration of nonpegylated interferon have shown efficacy against craniopharyngioma. Pegylaion of interferon-α-2b (PI) prolongs the half-life, allowing sustained exposure of the drug over time, and enhances efficacy. The authors report the results of the use of PI in 5 children with recurrent craniopharyngiomas. METHODS Five children, ranging in age from 9 to 15 years, with recurrent craniopharyngiomas were treated for up to 2 years with subcutaneous injections of PI at a dose of 1-3 μg/kg/week. Tumor response was assessed using MRI. RESULTS All patients had stable disease or better in response to PI. One patient experienced a recurrence after gross-total resection (GTR). She initially showed an increase in the predominantly cystic tumor after 3 months of treatment, followed by a complete response. She required no further intervention and remains without evidence of disease 10 years after starting treatment. Another patient experienced recurrence 3.3 years after subtotal resection (STR) and radiation therapy. He had complete disappearance of the predominantly cystic component after 4 months of treatment, and a small residual calcified mass remains 5 years later. The third patient experienced recurrence after 3 GTRs. He had a complete response after 7 months of treatment and remains without evidence of disease 19 months after starting treatment. The fourth patient experienced recurrence after 2 STRs. He had a 30% decrease in tumor size after 4 months of treatment, which was maintained for 12 months at which point the cyst began to increase in size. The final patient experienced recurrence after GTR and has stable disease 6 months after starting treatment with PI. CONCLUSIONS The use of PI in children with recurrent craniopharyngiomas can result in significant and durable responses and potentially delay or avoid the need for radiation therapy.

Optic pathway glioma as part of a constitutional mismatch-repair deficiency syndrome in a patient meeting the criteria for neurofibromatosis type 1.

Patients with constitutional mismatch repair‐deficiency (CMMR‐D) caused by the biallelic deletions of mismatch repair (MMR) genes have a high likelihood of developing malignancies of the bone marrow, bowel, and brain. Affected individuals often have phenotypic features of neurofibromatosis type 1 (NF‐1), including café‐au‐lait spots. Optic pathway gliomas (OPGs), a common manifestation of NF‐1, have not been reported. We report the case of a 3‐year‐old male with an extensive OPG who met the diagnostic criteria for NF‐1. He was subsequently found to have multiple colonic polyps and bi‐allelic loss of PMS2. Testing for NF‐1 was negative. Pediatr Blood Cancer 2013; 60: 137–139.

Endovascular Revascularization for Basilar Artery Occlusion

Basilar artery occlusion is one of the most devastating neurological conditions known to man. Though rare, patients with clinical syndromes localized to this anatomical region are often referred to acute stroke and endovascular units. Recent studies evaluating the efficacy of endovascular approaches to stroke have focused on anterior circulation syndromes. In this review, we examine the approaches to stroke syndromes due to basilar artery thrombosis. We share the relevant data for intravenous and intra-arterial tissue plasminogen activator as well as mechanical approaches to restoring perfusion in this critical area of the brain. i 2014 S. Karger AG, Basel

High-resolution Vessel Wall Magnetic Resonance Imaging in Intracranial Aneurysms and Brain Arteriovenous Malformations.

Abstract Over the last several years, the advent of intracranial high-resolution vessel wall magnetic resonance imaging (VW-MRI) has provided a new lens with which to view cerebrovascular disease that has not previously been available with conventional imaging. It has already fundamentally changed the way that steno-occlusive diseases are evaluated at many academic centers. This review focuses on current and emerging applications of intracranial high-resolution VW-MRI in the clinical evaluation of intracranial aneurysms and brain arteriovenous malformations. Examples are provided from our clinical practice.

Effect of cocaine use on outcomes in traumatic brain injury

Context: Animal and molecular studies have shown that cocaine exerts a neuroprotective effect against cerebral ischemia. Aims: To determine if the presence of cocaine metabolites on admission following traumatic brain injury (TBI) is associated with better outcomes. Settings and Design: Level-1 trauma center, retrospective cohort. Materials and Methods: After obtaining Institutional Review Board (IRB) approval, the trauma registry was searched from 2006 to 2009 for all patients aged 15-55 years with blunt head trauma and non-head AIS <3. Exclusion criteria were pre-existing brain pathology and death within 30 min of admission. The primary outcome was in-hospital mortality; secondary outcomes were hospital length of stay (LOS), and Glasgow Outcome Score (GOS). Statistical Analysis: Logistic regression was used to determine the independent effect of cocaine on mortality. Hospital LOS was compared with multiple linear regression. Results: A total of 741 patients met criteria and had drug screens. The screened versus unscreened groups were similar. Cocaine positive patients were predominantly African-American (46% vs. 21%, P < 0.0001), older (40 years vs. 30 years, P < 0.0001), and had ethanol present more often (50.7% vs. 37.8%, P = 0.01). There were no differences in mortality (cocaine-positive 1.4% vs. cocaine-negative 2.7%, P = 0.6) on both univariate and multivariate analysis. Conclusions: Positive cocaine screening was not associated with mortality in TBI. An effect may not have been detected because of the low mortality rate. LOS is affected by many factors unrelated to the injury and may not be a good surrogate for recovery. Similarly, GOS may be too coarse a measure to identify a benefit.

Tectal plate glioblastoma multiforme.

Background: Tectal plate tumors have traditionally been considered low-grade, indolent lesions. We report a patient who presented with a tectal region glioblastoma multiforme (GBM), a rare pathology in this anatomic location. Case Description: This is a case report of a 45-year-old female that presented with worsening confusion, memory loss, and loss of bladder control for 3 days. There was no family history of brain malignancy. The patient presented with Parinauds phenomenon. Pronator drift was not present. The patient had dysarthric speech. An elevated white blood cell count was also noted. Non-contrast CT scan of the head showed the presence of a tectal region mass and hydrocephalus. A follow-up MRI with and without contrast confirmed the presence of a 4.2 × 3.3 × 4.6 cm3 mass. Magnetic Resonance Spectroscopy (MRS) demonstrated an elevated choline/N-acetylaspartate ratio and an increase in lactate suggesting an aggressive neoplasm. A ventriculoperitoneal shunt was initially placed to relieve the hydrocephalus. The patient subsequently underwent a suboccipital craniotomy for debulking of tumor and for tissue diagnosis. Pathology of the lesion was consistent with GBM. The patient declined postoperative treatment with chemotherapy and radiation. Conclusion: Although tectal region masses are predominantly low-grade lesions, high-grade lesions can present in this anatomical location. Furthermore, MRS can help to differentiate benign lesions from more aggressive lesions in the tectal plate. Biopsy of tectal plate lesions should be considered in select cases to establish diagnosis and prognosis in order to optimize treatment.

Familial glioblastoma: A case report of glioblastoma in two brothers and review of literature.

Background: Gliomas that aggregate in families with history of malignancy may have an inheritable genetic basis. Gliomas can occur in several well known tumor syndromes. However, their occurrence in the absence of these syndromes is quite rare. High-grade gliomas, such as glioblastoma multiforme (GBM), are the most common and most lethal primary cancers of the central nervous system (CNS). Case Description: We present a case of two brothers both diagnosed with GBM. Both siblings underwent biopsy with debulking of the tumors by different surgeons. Only one sibling elected to undergo chemotherapy and radiation. Cytogenetic studies were possible only on one sibling and the tumor specimen revealed multiple chromosomal abnormalities, including triploidies 4, 8, 12, 22 and loss of heterozygosity of 1p, 9p, and 10. Histological samples for both tumors were similar, both revealing increased cellularity consisting of gemistocytic astrocytes, central necrosis, and microvascularization. Conclusion: We present two brothers who display a rare familial relationship in the development of their GBMs. Supplementary and improved genetic studies may allow for specific treatment modalities as certain genetic abnormalities have better response to tailored treatments and carry better prognoses.

Macrovascular Lesions Underlying Spontaneous Intracerebral Hemorrhage

Spontaneous intracerebral hemorrhage (ICH) is a morbid disease with a high case fatality rate. Prognosis, rehemorrhage rates, and acute, clinical decision making are greatly affected by the underlying etiology of hemorrhage. This review focuses on the evaluation, diagnosis, and management of structural, macrovascular lesions presenting with ICH, including ruptured aneurysms, brain arteriovenous malformations, cranial dural arteriovenous fistulas, and cerebral cavernous malformations.