Roy E. Strowd

Dynamic Glucose-Enhanced (DGE) MRI: Translation to Human Scanning and First Results in Glioma Patients

Recent animal studies have shown that d-glucose is a potential biodegradable magnetic resonance imaging (MRI) contrast agent for imaging glucose uptake in tumors. We show herein the first translation of that use of d-glucose to human studies. Chemical exchange saturation transfer (CEST) MRI at a single frequency offset optimized for detecting hydroxyl protons in d-glucose was used to image dynamic signal changes in the human brain at 7 T during and after d-glucose infusion. Dynamic glucose enhanced (DGE) image data from 4 normal volunteers and 3 glioma patients showed a strong signal enhancement in blood vessels, while a spatially varying enhancement was found in tumors. Areas of enhancement differed spatially between DGE and conventional gadolinium-enhanced imaging, suggesting complementary image information content for these 2 types of agents. In addition, different tumor areas enhanced with d-glucose at different times after infusion, suggesting a sensitivity to perfusion-related properties such as substrate delivery and blood-brain barrier (BBB) permeability. These preliminary results suggest that DGE MRI is feasible for studying glucose uptake in humans, providing a time-dependent set of data that contains information regarding arterial input function, tissue perfusion, glucose transport across the BBB and cell membrane, and glucose metabolism.

Predictors of 30-Day Hospital Readmission Following Ischemic and Hemorrhagic Stroke

Stroke patients have a high rate of 30-day readmission. Understanding the characteristics of patients at high risk of readmission is critical. A retrospective case-control study was designed to determine factors associated with 30-day readmission after stroke. A total of 79 cases with acute ischemic or hemorrhagic strokes readmitted to the same hospital within 30 days were compared with 86 frequency-matched controls. Readmitted patients were more likely to have had ≥2 hospitalizations in the year prior to stroke (21.5% vs 2.3% in controls, P < .001), and in the multivariate model, admission National Institutes of Health Stroke Score (NIHSS; odds ratio [OR] = 1.072; 95% confidence interval [CI] = 1.021-1.126 per 1 point increase; P = .005), prior hospitalizations (OR = 2.205; 95% CI = 1.426-3.412 per admission; P < .001), and absence of hyperlipidemia (OR = 0.444; 95% CI = 0.221-0.894; P = .023) were independently associated with readmission. The research team concludes that admission NIHSS and frequent prior hospitalizations are associated with 30-day readmission after stroke. If validated, these characteristics identify high-risk patients and focus efforts to reduce readmission.

Association between subthalamic nucleus deep brain stimulation and weight gain: Results of a case–control study

OBJECTIVE To evaluate whether weight change in patients with Parkinsons disease (PD) is different in those undergoing deep brain stimulation (DBS) of the subthalamic nucleus (STN) compared to those not undergoing DBS. PATIENTS AND METHODS A retrospective case-control study was performed in PD patients who had undergone STN DBS (cases) compared to matched PD patients without DBS (controls). Demographic and clinical data including Unified Parkinsons Disease Rating Scale (UPDRS) motor scores were collected. Repeated measures mixed model regression was used to identify variables associated with weight gain. RESULTS Thirty-five cases and 34 controls were identified. Baseline age, gender, diagnosis and weight were similar. Duration of diagnosis was longer in cases (6.3 vs 4.9 years, p=0.0015). At 21.3 months, cases gained 2.9 kg (+4.65%) while controls lost 1.8 kg (-3.05%, p<0.02). Postoperative UPDRS motor scores improved by 49% indicating surgical efficacy. Only younger age (p=0.0002) and DBS (p=0.008) were significantly associated with weight gain. CONCLUSION In this case-control study, PD patients undergoing STN DBS experienced post-operative weight gain that was significantly different from the weight loss observed in non-DBS PD controls. Patients, especially overweight individuals, should be informed that STN DBS can result in weight gain.

Impacting student anxiety for the USMLE Step 1 through process-oriented preparation

Background: Standardized examinations are the key components of medical education. The USMLE Step 1 is the first of these important milestones. Success on this examination requires both content competency and efficient strategies for study and review. Students employ a wide variety of techniques in studying for this examination, with heavy reliance on personal study habits and advice from other students. Nevertheless, few medical curricula formally address these strategies. Methods: In response to student-generated critique at our institution, a five-part seminar series on process-oriented preparation was developed and implemented to address such concerns. The series focused on early guidance and preparation strategies for Step 1 and the many other important challenges in medical school. Emphasis was placed on facilitating conversation and mentorship opportunities between students. Results & Conclusions: A profoundly positive experience was reported by our medical students that included a decreased anxiety level for the Step 1 examination.

Impact of timing of radiotherapy in patients with newly diagnosed glioblastoma

OBJECTIVE To further evaluate if a delay in the start of radiation therapy (RT) affects patient outcomes for glioblastoma (GBM). PATIENTS AND METHODS From May 1999 to May 2010, a total of 161 patients underwent surgery followed by RT for GBM. We assessed overall survival (OS) and progression free survival (PFS), stratified by extent of surgical resection. Included in the analysis were genomic predictors of progression. RESULTS Median time from surgery to start of RT was 20days for biopsy alone, 28days for subtotal resection (STR) and 28days for gross total resection (GTR). For all patients, a delay >28days did not result in a difference in PFS when compared to no delay (6.7 vs. 6.9 months, p=0.07). PFS was improved in biopsy or STR patients with a >28day delay to start of RT (4.2 vs. 6.7 months, p=0.006). OS was also improved in patients receiving biopsy or STR with a >28day delay to start of RT (12.3 vs. 7.8 months, p=0.005). Multivariable analysis (MVA) demonstrated an improvement in OS and PFS with time to RT >28days for biopsy or STR patients (HR 0.52 p=0.008 and HR 0.48 p=0.02, respectively). CONCLUSION In this retrospective review of GBM patients treated at a single institution, OS and PFS were not different between time to RT >28days compared to <28 days. There was a modest improvement in both PFS and OS in patients who received biopsy or STR with time to RT >28 days.

Angiofollicular lymph node hyperplasia resembling a spinal nerve sheath tumor: a rare case of Castleman's disease

BACKGROUND CONTEXT Angiofollicular lymph node hyperplasia (Castlemans disease) is a lymphoproliferative disorder of unknown etiology. Although uncommon, the localized form of this disease can manifest in the central nervous system, typically as a meningeal-based intracranial lesion. Castlemans disease involving the spine is exceedingly rare. This represents only the second reported case of a patient with Castlemans disease whose presentation mimicked that of a spinal nerve sheath tumor. PURPOSE We report a rare case of angiofollicular lymph node hyperplasia that mimicked a spinal nerve sheath tumor and was treated with gross total resection. STUDY DESIGN Case report. PATIENT SAMPLE A 31-year-old female with angiofollicular lymph node hyperplasia presenting with a paraspinal mass. OUTCOME MEASURES The patients outcome was based on clinical history, physical and radiographic examinations. METHODS A 31-year-old woman with a mediastinal mass previously diagnosed as sarcoid via biopsy presented with the new onset of radicular pain and radiographic enlargement of her mass. Magnetic resonance imaging demonstrated a 4.3x5.7x6.0 cm homogenously enhancing soft-tissue lesion that emanated from and widened the T3/T4 neural foramen on the left. The differential diagnosis based on the location of the lesion and imaging characteristics included schwannoma, neurofibroma, paraganglioma, sarcoid, and lymphoma. Gross total resection was performed via thoracotomy. Histological examination identified angiofollicular lymph node hyperplasia (Castlemans disease) of the hyaline-vascular subtype. The patient did not receive adjuvant chemotherapy or radiation therapy. RESULTS The patient had resolution of her symptoms without any clinical or radiographic evidence of recurrence at 1-year follow-up using magnetic resonance imaging with and without contrast. CONCLUSIONS Castlemans disease is a rare pathologic entity that should be considered in the differential diagnosis of a patient with a paraspinal mass. Spine surgeons should be aware of this diagnosis as it has treatment and follow-up implications that differ from the neoplasms it can mimic. Complete surgical excision is an effective treatment for solitary lesions. Screening for concurrent and future malignancies in these patients is prudent.

Head drop after botox: Electrodiagnostic evaluation of iatrogenic botulinum toxicity

BACKGROUND Botulinum is a potent neurotoxin with increasing indications for neurologic disorders. While clinical benefit manifests primarily due to local actions at the neuromuscular junction, regional and systemic effects do occur. Rarely, systemic symptoms including weakness, dysarthria, dysphagia and other side effects occur as a result of iatrogenic botulinum neurotoxicity. CASE A 72 year-old female with right leg dystonia developed head drop, bulbar and systemic weakness following right lower extremity botulinum toxin injection. Routine nerve conduction studies were normal. Repetitive stimulation of the spinal accessory nerve showed decrement; electromyography (EMG) demonstrated slightly small units with subtle signs of denervation, and single fiber EMG revealed increased jitter with blocking, all of which are consistent with systemic botulism. CONCLUSION This case highlights and reviews the important electrodiagnostic features of iatrogenic systemic botulinum neurotoxicity.

Leptomeningeal failure in patients with breast cancer receiving stereotactic radiosurgery for brain metastases

PURPOSE Prior studies suggest a high incidence of leptomeningeal failure (LMF) in breast cancer metastatic to brain. This study examines breast cancer-specific variables affecting development of LMF and survival after Gamma-Knife Radiosurgery (GKS). METHODS Between 2000-2010, 149 (breast) and 658 other-histology patients were treated with GKS. Hormone/HER2, age, local/distant brain failure, prior craniotomy, and prior whole-brain radiotherapy (WBRT) were assessed. Median follow-up was 54months (range, 0-106). Serial MRI determined local and distant-brain failure and LMF. Statistical analysis with categorical/continuous data comparisons were done with Fishers-exact, Wilcoxon rank-sum, log-rank tests, and Cox-Proportional Hazard models. RESULTS Of 149 patients, 21 (14%) developed LMF (median time of 11.9months). None of the following predicted for LMF: Her2-status (HR=0.49, p=0.16), hormone-receptor status (HR=1.15, p=0.79), prior craniotomy (HR=1.58, p=0.42), prior WBRT (HR=1.36, p=0.55). Non-significant factors between patients that did (n=21) and did not (n=106) develop LMF included neurologic death (p=0.34) and median survival (8.6 vs 14.2months, respectively). Breast patients who had distant-failure after GKS (65/149; 43.6%) were more likely to later develop LMF (HR 4.2, p=0.005); including 15/65 (23%) patients who had distant-failure and developed LMF. Median time-to-death for patients experiencing LMF was 6.1months (IQR 3.4-7.8) from onset of LMF. Median survival from LMF to death was much longer in breast (6.1months) than in other (1.7months) histologies CONCLUSION: Breast cancer patients had a longer survival after diagnosis of LMF versus other histologies. Neither ER/PR/HER2 status, nor prior surgery or prior WBRT predicted for development of LMF in breast patients.

Hippocampal dose volume histogram predicts Hopkins Verbal Learning Test scores after brain irradiation

Purpose Radiation-induced cognitive decline is relatively common after treatment for primary and metastatic brain tumors; however, identifying dosimetric parameters that are predictive of radiation-induced cognitive decline is difficult due to the heterogeneity of patient characteristics. The memory function is especially susceptible to radiation effects after treatment. The objective of this study is to correlate volumetric radiation doses received by critical neuroanatomic structures to post–radiation therapy (RT) memory impairment. Methods and materials Between 2008 and 2011, 53 patients with primary brain malignancies were treated with conventionally fractionated RT in prospectively accrued clinical trials performed at our institution. Dose-volume histogram analysis was performed for the hippocampus, parahippocampus, amygdala, and fusiform gyrus. Hopkins Verbal Learning Test-Revised scores were obtained at least 6 months after RT. Impairment was defined as an immediate recall score ≤15. For each anatomic region, serial regression was performed to correlate volume receiving a given dose (VD(Gy)) with memory impairment. Results Hippocampal V53.4Gy to V60.9Gy significantly predicted post-RT memory impairment (P < .05). Within this range, the hippocampal V55Gy was the most significant predictor (P = .004). Hippocampal V55Gy of 0%, 25%, and 50% was associated with tumor-induced impairment rates of 14.9% (95% confidence interval [CI], 7.2%-28.7%), 45.9% (95% CI, 24.7%-68.6%), and 80.6% (95% CI, 39.2%-96.4%), respectively. Conclusions The hippocampal V55Gy is a significant predictor for impairment, and a limiting dose below 55 Gy may minimize radiation-induced cognitive impairment.

Right Brain: Breaking bad news Communication education for neurology trainees

The stories are frighteningly similar—a normal pregnancy taken to term, a perinatal crisis, followed by an emergent cesarean section and infant transport to a tertiary hospital, where therapeutic hypothermia is initiated. I usually meet the family shortly after arrival, at which point I am charged with helping them understand the next steps. Like so many others, I frequently find myself in complex discussions with families about prognostic uncertainty, advanced care planning, and lifelong disability. Navigating these conversations poorly can have devastating consequences. In many conditions I treat, whether or not a child dies does not rest on my ability to learn, understand, or recommend treatment, but instead on the outcome of conversations in which a family considers whether to withdraw or withhold life-sustaining treatment. As a neonatal neurointensivist, these high-stakes conversations are the most critical interventions I perform.