Association of External Ventricular Drain Wean Strategy with Shunt Placement and Length of Stay in Subarachnoid Hemorrhage: A Prospective Multicenter Study.

BACKGROUND: Survivors of aneurysmal subarachnoid hemorrhage (SAH) face a protracted intensive care unit (ICU) course and are at risk for developing refractory hydrocephalus with the need for a permanent ventriculoperitoneal shunt (VPS). Management of the external ventricular drain (EVD) used to provide temporary cerebrospinal fluid diversion may influence the need for a VPS, ICU length of stay (LOS), and drain complications, but the optimal EVD management approach is unknown. Therefore, we sought to determine the effect of EVD discontinuation strategy on VPS rate. METHODS: This was a prospective multicenter observational study at six neurocritical care units in the United States. The target population included adults with suspected aneurysmal SAH who required an EVD. Patients were preassigned to rapid or gradual EVD weans based on their treating center. The primary outcome was the rate of VPS placement. Secondary outcomes were EVD duration, ICU LOS, hospital LOS, and drain complications. RESULTS: A rapid EVD wean protocol was associated with a lower rate of VPS placement, including a delayed posthospitalization shunt, in an adjusted Cox proportional analysis (hazard ratio 0.52 [p = 0.041]) and adjusted logistic regression model (odds ratio 0.43 [95% confidence interval 0.18-1.03], p = 0.057). A rapid wean was also associated with 2.1 fewer EVD days (p = 0.007) and saved an estimated 2.5 ICU days (p = 0.049), as compared with a gradual wean protocol. There were fewer nonfunctioning EVDs in the rapid group (odds ratio 0.32 [95% confidence interval 0.11-0.92]). Furthermore, we found that the time to first wean and the number of weaning attempts were important independent covariates that affected the likelihood of receiving a VPS and the duration of ICU admission. CONCLUSIONS: A rapid EVD wean was associated with decreased rates of VPS placement, decreased ICU LOS, and decreased drain complications in survivors of aneurysmal SAH. These findings suggest that a randomized multicentered controlled study comparing rapid vs. gradual EVD weaning protocols is justified.

Deconstructing Poststroke Delirium in a Prospective Cohort of Patients With Intracerebral Hemorrhage.

OBJECTIVES: Poststroke delirium may be underdiagnosed due to the challenges of disentangling delirium symptoms from underlying neurologic deficits. We aimed to determine the prevalence of individual delirium features and the frequency with which they could not be assessed in patients with intracerebral hemorrhage. DESIGN: Prospective observational cohort study. SETTING: Neurocritical Care and Stroke Units at a university hospital. PATIENTS: Consecutive patients with intracerebral hemorrhage from February 2018 to May 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An attending neurointensivist performed 257 total daily assessments for delirium on 60 patients (mean age 68.0 [SD 18.4], 62% male, median intracerebral hemorrhage score 1.5 [interquartile range 1-2], delirium prevalence 57% [n = 34]). Each assessment included the Confusion Assessment Method for the ICU, Intensive Care Delirium Screening Checklist, a focused bedside cognitive examination, chart review, and nurse interview. We characterized individual symptom prevalence and established delirium diagnoses using Diagnostic and Statistical Manual of Mental Disorders, fifth edition criteria, then compared performance of the Confusion Assessment Method for the ICU and Intensive Care Delirium Screening Checklist against reference-standard expert diagnosis. Symptom fluctuation (61% of all assessments), psychomotor changes (46%), sleep-wake disturbances (46%), and impaired arousal (37%) had the highest prevalence and were never rated "unable to assess," while inattention (36%), disorientation (27%), and disorganized thinking (18%) were also common but were often rated 'unable to assess' (32%, 43%, and 44% of assessments, respectively), most frequently due to aphasia (32% of patients). Including nonverbal assessments of attention decreased the frequency of 'unable to assess' ratings to 11%. Since the Intensive Care Delirium Screening Checklist may be positive without the presence of symptoms that require verbal assessment, it was more accurate (sensitivity = 77%, specificity = 97%, area under the receiver operating characteristic curve, 0.87) than the Confusion Assessment Method for the ICU (sensitivity = 41%, specificity = 88%, area under the receiver operating characteristic curve, 0.64). CONCLUSIONS: Delirium is common after intracerebral hemorrhage, but severe neurologic deficits may confound its assessment and lead to underdiagnosis. The Intensive Care Delirium Screening Checklist's inclusion of nonverbal features may make it more accurate than the Confusion Assessment Method for the ICU in patients with neurologic deficits, but novel tools designed for such patients may be warranted.

Technical note: Atlas-based Auto-segmentation of masticatory muscles for head and neck cancer radiotherapy.

PURPOSE: The study aimed to use quantitative geometric and dosimetric metrics to assess the accuracy of atlas-based auto-segmentation of masticatory muscles (MMs) compared to manual drawn contours for head and neck cancer (HNC) radiotherapy (RT). MATERIALS AND METHODS: Fifty-eight patients with HNC treated with RT were analyzed. Paired MMs (masseter, temporalis, and medial and lateral pterygoids) were manually delineated on planning computed tomography (CT) images for all patients. Twenty-nine patients were used to generate the MM atlas. Using this atlas, automatic segmentation of the MMs was performed for the remaining 29 patients without manual correction. Auto-segmentation accuracy for MMs was compared using dice similarity coefficients (DSCs), Hausdorff distance (HD), HD95, and variation in the center of mass (∆COM). The dosimetric impact on MMs was calculated (∆dose) using dosimetric parameters (D99%, D95%, D50%, and D1%), and compared with the geometric indices to test correlation. RESULTS: DSCmean ranges from 0.79 ± 0.04 to 0.85 ± 0.04, HDmean from 0.43 ± 0.08 to 0.82 ± 0.26 cm, HD95mean from 0.32 ± 0.08 to 0.42 ± 0.16 cm, and ∆COMmean from 0.18 ± 0.11 to 0.33 ± 0.23 cm. The mean MM volume difference was < 15%. The correlation coefficient (r) of geometric and dosimetric indices for the four MMs ranges between -0.456 and 0.300. CONCLUSIONS: Atlas-based auto-segmentation for masticatory muscles provides geometrically accurate contours compared to manual drawn contours. Dose obtained from those auto-segmented contours is comparable to that from manual drawn contours. Atlas-based auto-segmentation strategy for MM in HN radiotherapy is readily availalbe for clinical implementation.

Validation of NRG oncology/RTOG-0129 risk groups for HPV-positive and HPV-negative oropharyngeal squamous cell cancer: Implications for risk-based therapeutic intensity trials.

BACKGROUND: Radiation Therapy Oncology Group (RTOG)-0129 recursive partitioning analysis was the basis for risk-based therapeutic intensification trials for oropharyngeal cancer (OPC). To the authors' knowledge, the question of whether RTOG-0129 overall survival (OS) estimates for low-risk, intermediate-risk, and high-risk groups are similar in other data sets or applicable to progression-free survival (PFS) is unknown. Therefore, the authors evaluated whether survival differences between RTOG-0129 risk groups persist at 5 years, are reproducible in an independent clinical trial, and are applicable to PFS, and whether toxicities differ across risk groups. METHODS: Prospective randomized clinical trials were analyzed retrospectively. RTOG-0129 evaluated standard versus accelerated fractionation radiotherapy concurrent with cisplatin. RTOG-0522 compared the combination of cisplatin and accelerated fractionation with or without cetuximab. Patients with OPC with available p16 status and tobacco history were eligible. RESULTS: There was a total of 260 patients and 287 patients, respectively, from RTOG-0129 and RTOG-0522, with median follow-ups for surviving patients of 7.9 years (range, 1.7-9.9 years) and 4.7 years (range, 0.1-7.0 years), respectively. Previous OS differences in RTOG-0129 persisted at 5 years. In RTOG-0522, the 5-year OS rates for the low-risk, intermediate-risk, and high-risk groups were 88.1%, 69.9%, and 45.1%, respectively (P for trend, <.001). The 5-year PFS rates for the same 3 groups were 72.9%, 56.1%, and 42.2%, respectively. In RTOG-0522 among a subgroup of patients considered to be at very good risk (p16-positive disease, smoking history of ≤10 pack-years, and classified with T1-T2 disease with ipsilateral lymph nodes measuring ≤6 cm or T3 disease without contralateral or >6 cm lymph nodes), the 5-year OS and PFS rates were 93.8% and 82.2%, respectively. Overall rates of acute and late toxicities were similar by risk group. CONCLUSIONS: RTOG-0129 risk groups persisted at 5 years and were reproducible in RTOG-0522. However, there was variability in the estimates. These data underscore the importance of long-term follow-up and appropriate patient selection in therapeutic deintensification trials.

MET Genomic Alterations in Head and Neck Squamous Cell Carcinoma (HNSCC): Rapid Response to Crizotinib in a Patient with HNSCC with a Novel MET R1004G Mutation.

Identification of effective targeted therapies for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) remains an unmet medical need. A patient with platinum-refractory recurrent oral cavity HNSCC underwent comprehensive genomic profiling (CGP) that identified an activating MET mutation (R1004). The patient was treated with the oral MET tyrosine kinase inhibitor crizotinib with rapid response to treatment.Based on this index case, we determined the frequency of MET alterations in 1,637 HNSCC samples, which had been analyzed with hybrid capture-based CGP performed in the routine course of clinical care. The specimens were sequenced to a median depth of >500× for all coding exons from 182 (version 1, n = 24), 236 (version 2, n = 326), or 315 (version 3, n = 1,287) cancer-related genes, plus select introns from 14 (version 1), 19 (version 2), or 28 (version 3) genes frequently rearranged in cancer. We identified 13 HNSCC cases (0.79%) with MET alterations (4 point mutation events and 9 focal amplification events). MET-mutant or amplified tumors represent a small but potentially actionable molecular subset of HNSCC. KEY POINTS: This case report is believed to be the first reported pan-cancer case of a patient harboring a MET mutation at R1004 demonstrating a clinical response to crizotinib, in addition to the first documented case of head and neck squamous cell carcinoma (HNSCC) with any MET alteration responding to crizotinib.The positive response to MET inhibition in this patient highlights the significance of comprehensive genomic profiling in advanced metastatic HNSCC to identify actionable targetable molecular alterations as current treatment options are limited.

Retinal vascular abnormalities in schizophrenia and bipolar disorder: A window to the brain.

OBJECTIVES: The examination of retinal microvascular abnormalities through fundus photography is currently the best available non-invasive technique for assessment of cerebral vascular status. Several studies in the last decade have reported higher incidences of adverse cerebrovascular events in Schizophrenia (SCZ) and bipolar disorder (BD). However, retinal microvasculature abnormalities in SCZ and BD have remained under-explored, and no study has compared this aspect of SCZ and BD till date. METHODS: Retinal Images of 100 SCZ patients, BD patients, and healthy volunteers each were acquired by trained individuals using a non-mydriatic camera with a 40-degree field of view. The retinal images were quantified using a valid semi-automated method. The average of left and right eye diameters of the venules and arterioles passing through the extended zone between 0.5 and 2 disc diameters from the optic disc were calculated. RESULTS: The groups differed significantly with respect to average diameters of both retinal venules (P < 0.001) and retinal arterioles (P < 0.001), after controlling for age and sex. Both SCZ and BD patients had significantly narrower arterioles and wider venules compared to HV. There were also significant differences between SCZ and BD patients; patients with BD had narrower arterioles and wider venules. CONCLUSION: Considering the affordability and easy accessibility of the investigative procedure, retinal microvascular examination could serve as a potential screening tool to identify individuals at risk for adverse cerebrovascular events. The findings of the current study also provide a strong rationale for further systematic examination of retinal vascular abnormalities in SCZ and BD.

Health issues in a Bangalore slum: findings from a household survey using a mobile screening toolkit in Devarajeevanahalli.

BACKGROUND: Slums are home to nearly one billion people in the world and are expanding at an exponential rate. Devarjeevanahalli is a large notified slum in Bangalore, South India which is characterised by poverty, overcrowding, hazardous living environment and social complexities. The poor living conditions not only affect the health of the people living there but also poses distinctive challenges to conducting health surveys. The purpose of this paper is to report the findings of a household survey that was done to study the health condition of people living in a slum. METHODS: A community-based cross-sectional survey was designed to determine the prevalence of health conditions using a mobile screening toolkit-THULSI (Toolkit for Healthy Urban Life in Slums Initiative). Devarjeevanahalli slum was chosen purposively as it is fairly representative of any slum in a big city in India. Sample size was calculated as 1100 households and demographic parameters at the household level and parameters related to priority health conditions (hypertension, diabetes mellitus, anaemia and malnutrition) at the individual level were studied. Six zones within the slum were purposively selected and all the contiguous households were selected. The last of the six zones was partially surveyed as the desired sample size was achieved. RESULTS: A total of 1186 households were surveyed and 3693 people were screened. More than three fourth (70.4%) of the population were below poverty line. Only one third had a regular job and the average daily income was 5.3$ and 2.6$ in men and women respectively. The prevalence of hypertension (35.5%), diabetes (16.6%) and anaemia (70.9%) was high in the screened slum population. Most of the people (56.5% of hypertensives and 34.4% diabetics) were screened for the first time. Almost half of the children under the age of five years were stunted. CONCLUSIONS: Poor income security and huge burden of health issues were reported among adults and children in the household health screening in a large notified slum in South India. Most people were unaware of their disease condition prior to the screening. Relatively simple technological solutions enabled the local health team to screen the slum population despite many challenges.

Examination of retinal vascular trajectory in schizophrenia and bipolar disorder.

AIM: Evidence suggests microvascular dysfunction (wider retinal venules and narrower arterioles) in schizophrenia (SCZ) and bipolar disorder (BD). The vascular development is synchronous with neuronal development in the retina and brain. The retinal vessel trajectory is related to retinal nerve fiber layer thinning and cerebrovascular abnormalities in SCZ and BD and has not yet been examined. Hence, in this study we examined the retinal vascular trajectory in SCZ and BD in comparison with healthy volunteers (HV). METHODS: Retinal images were acquired from 100 HV, SCZ patients, and BD patients, respectively, with a non-mydriatic fundus camera. Images were quantified to obtain the retinal arterial and venous trajectories using a validated, semiautomated algorithm. Analysis of covariance and regression analyses were conducted to examine group differences. A supervised machine-learning ensemble of bagged-trees method was used for automated classification of trajectory values. RESULTS: There was a significant difference among groups in both the retinal venous trajectory (HV: 0.17 ± 0.08; SCZ: 0.25 ± 0.17; BD: 0.27 ± 0.20; P < 0.001) and the arterial trajectory (HV: 0.34 ± 0.15; SCZ: 0.29 ± 0.10; BD: 0.29 ± 0.11; P = 0.003) even after adjusting for age and sex (P < 0.001). On post-hoc analysis, the SCZ and BD groups differed from the HV on retinal venous and arterial trajectories, but there was no difference between SCZ and BD patients. The machine learning showed an accuracy of 86% and 73% for classifying HV versus SCZ and BD, respectively. CONCLUSION: Smaller trajectories of retinal arteries indicate wider and flatter curves in SCZ and BD. Considering the relation between retinal/cerebral vasculatures and retinal nerve fiber layer thinness, the retinal vascular trajectory is a potential marker for SCZ and BD. As a relatively affordable investigation, retinal fundus photography should be further explored in SCZ and BD as a potential screening measure.

Serum Troponin Level in Acute Ischemic Stroke Identifies Patients with Visceral Infarcts.

BACKGROUND AND PURPOSE: Patients with ischemic stroke of cardioembolic origin are at risk of visceral (renal or splenic) infarction. We hypothesized that serum troponin level at time of ischemic stroke would be associated with presence of visceral infarction. METHODS: Data were abstracted from a single center prospective stroke database over 18 months and included all patients with ischemic stroke who underwent contrast-enhanced computerized tomography (CT) of the abdomen and pelvis for clinical purposes within 1 year of stroke. The primary predictor was troponin concentration ≥.1ng/mL. The primary outcome was visceral infarct (renal and/or splenic) on CT abdomen and pelvis. Univariate and multivariable logistic regression models were used to estimate the odds ratio and 95% confidence intervals (OR, 95% CI) for the association of troponin with visceral infarction. RESULTS: Of 1233 patients with ischemic stroke, 259 patients had a qualifying visceral CT. Serum troponin level on admission was measured in 237 of 259 patients (93.3%) and 41 of 237 (17.3%) had positive troponin. There were 25 patients with visceral infarcts: 16 renal, 7 splenic, and 2 both. In univariate models, patients with a positive troponin level (versus negative) were more likely to have visceral infarcts (39.1% [9/23] versus 15.0% [32/214], P = .008) and this association persisted in multivariable models (adjusted OR 3.83; 95% CI 1.42-10.31, P = .006). CONCLUSIONS: In ischemic stroke patients, elevated serum troponin levels may help identify patients with visceral infarcts. This suggests that troponin in the acute stroke setting is a biomarker of embolic risk. Larger studies with systematic visceral imaging are needed to confirm our findings.

Patient-reported quality-of-life outcomes after de-escalated chemoradiation for human papillomavirus-positive oropharyngeal carcinoma: Findings from a phase 2 trial.

BACKGROUND: The current study represents a subset analysis of quality-of-life (QOL) outcomes among patients treated on a phase 2 trial of de-escalated chemoradiation for human papillomavirus (HPV)-associated oropharyngeal cancer. METHODS: Eligibility included newly diagnosed, (American Joint Committee on Cancer, 7th edition) stage III or IV oropharyngeal squamous cell carcinoma, p16 positivity, age ≥ 18 years, and a Zubrod performance status of 0 to 1. Treatment was induction paclitaxel at a dose of 175 mg/m2 and carboplatin at an area under the curve of 6 for 2 cycles followed by response-adapted, dose-reduced radiation of 54 Gy or 60 Gy with weekly concurrent paclitaxel at a dose of 30 mg/m2 . The University of Washington Quality of Life (UW-QOL) and the Functional Assessment of Cancer Therapy-Head and Neck questionnaires were used to assess patient-reported QOL as a secondary endpoint. RESULTS: A total of 45 patients were registered, 40 of whom completed QOL surveys and were evaluable. Nadirs for overall UW-QOL and Functional Assessment of Cancer Therapy-Head and Neck scores were reached at 4 weeks after treatment but returned to baseline at 3 months. Nearly all functional indices returned to baseline levels by 6 to 9 months. The mean overall UW-QOL score was 71.6 at baseline compared with 70.8, 73.0, 83.3, and 81.1, respectively, at 3 months, 6 months, 1 year, and 2 years after therapy. The percentage of patients rating their overall QOL as "very good" or "outstanding" at 6 months, 1 year, and 2 years using the UW-QOL was 50%, 77%, and 84%, respectively. CONCLUSIONS: This de-escalation regimen achieved QOL outcomes that were favorable compared with historical controls. These results serve as powerful evidence that ongoing de-escalation efforts lead to tangible gains in function and QOL. Cancer 2018;124:521-9. © 2017 American Cancer Society.

Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: a single-arm, phase 2 study.

BACKGROUND: Head and neck cancers positive for human papillomavirus (HPV) are exquisitely radiosensitive. We investigated whether chemoradiotherapy with reduced-dose radiation would maintain survival outcomes while improving tolerability for patients with HPV-positive oropharyngeal carcinoma. METHODS: We did a single-arm, phase 2 trial at two academic hospitals in the USA, enrolling patients with newly diagnosed, biopsy-proven stage III or IV squamous-cell carcinoma of the oropharynx, positive for HPV by p16 testing, and with Zubrod performance status scores of 0 or 1. Patients received two cycles of induction chemotherapy with 175 mg/m2 paclitaxel and carboplatin (target area under the curve of 6) given 21 days apart, followed by intensity-modulated radiotherapy with daily image guidance plus 30 mg/m2 paclitaxel per week concomitantly. Complete or partial responders to induction chemotherapy received 54 Gy in 27 fractions, and those with less than partial or no responses received 60 Gy in 30 fractions. The primary endpoint was progression-free survival at 2 years, assessed in all eligible patients who completed protocol treatment. This study is registered with ClinicalTrials.gov, numbers NCT02048020 and NCT01716195. FINDINGS: Between Oct 4, 2012, and March 3, 2015, 45 patients were enrolled with a median age of 60 years (IQR 54-67). One patient did not receive treatment and 44 were included in the analysis. 24 (55%) patients with complete or partial responses to induction chemotherapy received 54 Gy radiation, and 20 (45%) with less than partial responses received 60 Gy. Median follow-up was 30 months (IQR 26-37). Three (7%) patients had locoregional recurrence and one (2%) had distant metastasis; 2-year progression-free survival was 92% (95% CI 77-97). 26 (39%) of 44 patients had grade 3 adverse events, but no grade 4 events were reported. The most common grade 3 events during induction chemotherapy were leucopenia (17 [39%]) and neutropenia (five [11%]), and during chemoradiotherapy were dysphagia (four [9%]) and mucositis (four [9%]). One (2%) of 44 patients was dependent on a gastrostomy tube at 3 months and none was dependent 6 months after treatment. INTERPRETATION: Chemoradiotherapy with radiation doses reduced by 15-20% was associated with high progression-free survival and an improved toxicity profile compared with historical regimens using standard doses. Radiotherapy de-escalation has the potential to improve the therapeutic ratio and long-term function for these patients. FUNDING: University of California.

Dose-volume factors correlating with trismus following chemoradiation for head and neck cancer.

BACKGROUND: To investigate the dose-volume factors in mastication muscles that are implicated as possible causes of trismus in patients following treatment with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy for head and neck cancers. MATERIAL AND METHODS: All evaluable patients treated at our institution between January 2004 and April 2009 with chemotherapy and IMRT for squamous cell cancers of the oropharynx, nasopharynx, hypopharynx or larynx were included in this analysis (N = 421). Trismus was assessed using CTCAE 4.0. Bi-lateral masseter, temporalis, lateral pterygoid and medial pterygoid muscles were delineated on axial computed tomography (CT) treatment planning images, and dose-volume parameters were extracted to investigate univariate and multimetric correlations. RESULTS: Forty-six patients (10.9%) were observed to have chronic trismus of grade 1 or greater. From analysis of baseline patient characteristics, toxicity correlated with primary site and patient age. From dose-volume analysis, the steepest dose thresholds and highest correlations were seen for mean dose to ipsilateral masseter (Spearman's rank correlation coefficient Rs = 0.25) and medial pterygoid (Rs = 0.23) muscles. Lyman-Kutcher-Burman modeling showed highest correlations for the same muscles. The best correlation for multimetric logistic regression modeling was with V68Gy to the ipsilateral medial pterygoid (Rs = 0.29). CONCLUSION: Chemoradiation-induced trismus remains a problem particularly for patients with oropharyngeal carcinoma. Strong dose-volume correlations support the hypothesis that limiting dose to the ipsilateral masseter muscle and, in particular, the medial pterygoid muscle may reduce the likelihood of trismus.

External beam radiotherapy with or without concurrent chemotherapy in advanced or recurrent non-anaplastic non-medullary thyroid cancer.

BACKGROUND AND OBJECTIVES: To review clinical outcomes and toxicities in locally advanced differentiated thyroid cancer patients treated with external beam radiotherapy (EBRT) with or without concurrent chemotherapy (CCRT). METHODS: Between 1990 and 2012, 66 patients with gross residual/unresectable non-anaplastic non-medullary thyroid cancer were treated with EBRT. RESULTS: The median overall survival was 42.0 months. The overall locoregional progression-free survival (LPFS) at 3 years was 77.3%. CCRT resulted in a non-significant improvement in LPFS (90.0% vs. 73.0%, P = 0.347). Poorly differentiated histology had significantly improved LPFS (89.4% vs. 66.1%, P = 0.020), despite a significantly worse distant metastasis-free survival (43.9% vs. 82.5%, P = 0.023). Acute treatment-related toxicity included dermatitis, mucositis, and dysphagia with grade three rates of 12.1%, 19.7%, and 16.7%, respectively. The incidence of late toxicity was low. CCRT was only associated with a significant greater rate of acute grade 3 hoarseness (10.0% vs. 0.0%, P = 0.033), but with no difference in the rate of grade 2 late toxicity. CONCLUSIONS: EBRT is a safe and effective treatment modality with 90% LPFS at 3 years in patients with gross residual or unresectable non-anaplastic, non-medullary thyroid carcinoma treated with CCRT. Further incorporation of EBRT with concurrent chemotherapy may result in improved disease control.

Side-to-side axial movements. Adding a new sign to the asymmetry of the clonic phase and asymmetric seizure termination in differentiating primary and secondarily generalised tonic-clonic seizures.

AIM: To study new semiological signs which help distinguish between primary and secondarily generalised tonic-clonic seizures (GTCS). METHODS: We retrospectively studied 86 GTCS, 13 primary and 73 secondary, in 58 patients who underwent video-EEG (vEEG) evaluation in our epilepsy monitoring unit. Eleven patients had generalised epilepsy and 47 focal epilepsy. Two expert epileptologists, blinded to diagnosis, examined the vEEGs independently for the presence of five semiological signs. RESULTS: Asymmetry of limb movements in clonic phase, side-to-side axial movements, and asymmetric seizure termination occurred more frequently (p<0.05) in secondary GTCS compared to primary GTCS. Combining asymmetry of limb movements in clonic phase and side-to-side axial movements provided the greatest value in differentiating secondary GTCS from primary GTCS. CONCLUSION: Careful examination of GTCS seizure semiology can help differentiate primary from secondary GTCS. The semiological sign of side-to-side axial movements, which has not previously been studied in this context, may add to existing literature of semiological signs and be of value for the evaluation of surgical patients in the epilepsy monitoring unit. In the out-patient setting, a clear history of these signs may help guide drug treatment choices.

Results of photon radiotherapy for unresectable salivary gland tumors: is neutron radiotherapy's local control superior?

BACKGROUND: The results of RTOG-MRC randomized trial of photon (n=15) versus neutron (n=17) therapy in the 1980's reported an improved local control (LC) with neutron radiotherapy for unresectable salivary gland tumors. Due to increased severe toxicity with neutron radiotherapy and the paucity of neutron-therapy centers, we analyzed our institution's results of photon radiotherapy for unresectable salivary gland tumors. PATIENTS AND METHODS: From 1990 to 2009, 27 patients with unresectable salivary gland cancer underwent definitive photon radiotherapy at our institution. Nodal involvement on presentation was found in 9 patients. Median dose of radiotherapy was 70 Gy. Chemotherapy was given to 18 patients, most being platinum-based regimens. Local control (LC), locoregional control (LRC), distant metastasis-free survival (DMFS), overall survival (OS), and toxicity outcomes were assessed. RESULTS: With a median follow-up of 52.4 months, the 2/5-year actuarial LC was 69% (95%CI ± 21.0%)/55% (± 24.2%), LRC was 65% (± 21.4%)/47% (± 21.6%), and DMFS was 71% (± 21.8%)/51% (± 22.8%), respectively using competing risk analysis. The median OS was 25.7 months, and the 2/5-year OS rates were 50% (± 19.0%)/29% (± 16.6%), respectively. Higher histologic grade was significant for an increased rate of DM (intermediate grade vs. low grade, p=0.04, HR 7.93; high grade vs. low grade, p=0.01, HR 13.50). Thirteen (48%) patient's experienced acute grade 3 toxicity. Late grade 3 toxicity occurred in three (11%) patients. CONCLUSIONS: Our data compares favorably to neutron radiotherapy with fewer late complications. Photon radiotherapy is an acceptable alternative to neutron radiotherapy in patients who present with unresectable salivary gland tumors.

Long-term regional control in the observed neck following definitive chemoradiation for node-positive oropharyngeal squamous cell cancer.

Traditionally, patients treated with chemoradiotherapy for node-positive oropharyngeal squamous cell carcinoma (N+ OPSCC) have undergone a planned neck dissection (ND) after treatment. Recently, negative post-treatment positron-emission tomography (PET)/computed tomography (CT) imaging has been found to have a high negative predictive value for the presence of residual disease in the neck. Here, we present the first comprehensive analysis of a large, uniform cohort of N+ OPSCC patients achieving a PET/CT-based complete response (CR) after chemoradiotherapy, and undergoing observation, rather than ND. From 2002 to 2009, 302 patients with N+ OPSCC treated with 70 Gy intensity-modulated radiation therapy and concurrent chemotherapy underwent post-treatment clinical assessment including PET/CT. CR was defined as no evidence of disease on clinical examination and post-treatment PET/CT. ND was reserved for patients with

Age-specific periictal electroclinical features of generalized tonic-clonic seizures and potential risk of sudden unexpected death in epilepsy (SUDEP).

Generalized tonic-clonic seizure (GTCS) is the commonest seizure type associated with sudden unexpected death in epilepsy (SUDEP). This study examined the semiological and electroencephalographic differences (EEG) in the GTCSs of adults as compared with those of children. The rationale lies on epidemiological observations that have noted a tenfold higher incidence of SUDEP in adults. We analyzed the video-EEG data of 105 GTCS events in 61 consecutive patients (12 children, 23 seizure events and 49 adults, 82 seizure events) recruited from the Epilepsy Monitoring Unit. Semiological, EEG, and 3-channel EKG features were studied. Periictal seizure phase durations were analyzed including tonic, clonic, total seizure, postictal EEG suppression (PGES), and recovery phases. Heart rate variability (HRV) measures including RMSSD (root mean square successive difference of RR intervals), SDNN (standard deviation of NN intervals), and SDSD (standard deviation of differences) were analyzed (including low frequency/high frequency power ratios) during preictal baseline and ictal and postictal phases. Generalized estimating equations (GEEs) were used to find associations between electroclinical features. Separate subgroup analyses were carried out on adult and pediatric age groups as well as medication groups (no antiepileptic medication cessation versus unchanged or reduced medication) during admission. Major differences were seen in adult and pediatric seizures with total seizure duration, tonic phase, PGES, and recovery phases being significantly shorter in children (p<0.01). Generalized estimating equation analysis, using tonic phase duration as the dependent variable, found age to correlate significantly (p<0.001), and this remained significant during subgroup analysis (adults and children) such that each 0.12-second increase in tonic phase duration correlated with a 1-second increase in PGES duration. Postictal EEG suppression durations were on average 28s shorter in children. With cessation of medication, total seizure duration was significantly increased by a mean value of 8s in children and 11s in adults (p<0.05). Tonic phase duration also significantly increased with medication cessation, and although PGES durations increased, this was not significant. Root mean square successive difference was negatively correlated with PGES duration (longer PGES durations were associated with decreased vagally mediated heart rate variability; p<0.05) but not with tonic phase duration. This study clearly points out identifiable electroclinical differences between adult and pediatric GTCSs that may be relevant in explaining lower SUDEP risk in children. The findings suggest that some prolonged seizure phases and prolonged PGES duration may be electroclinical markers of SUDEP risk and merit further study.

Migration from full-head mask to "open-face" mask for immobilization of patients with head and neck cancer.

To provide an alternative device for immobilization of the head while easing claustrophobia and improving comfort, an "open-face" thermoplastic mask was evaluated using video-based optical surface imaging (OSI) and kilovoltage (kV) X-ray radiography. A three-point thermoplastic head mask with a precut opening and reinforced strips was developed. After molding, it provided sufficient visible facial area as the region of interest for OSI. Using real-time OSI, the head motion of ten volunteers in the new mask was evaluated during mask locking and 15minutes lying on the treatment couch. Using a nose mark with reference to room lasers, forced head movement in open-face and full-head masks (with a nose hole) was compared. Five patients with claustrophobia were immobilized with open-face masks, set up using OSI and kV, and treated in 121 fractions, in which 61 fractions were monitored during treatment using real-time OSI. With the open-face mask, head motion was found to be 1.0 ± 0.6 mm and 0.4° ± 0.2° in volunteers during the experiment, and 0.8 ± 0.3 mm and 0.4° ± 0.2° in patients during treatment. These agree with patient motion calculated from pre-/post-treatment OSI and kV data using different anatomical landmarks. In volunteers, the head shift induced by mask-locking was 2.3 ± 1.7 mm and 1.8° ± 0.6°, and the range of forced movements in the open-face and full-head masks were found to be similar. Most (80%) of the volunteers preferred the open-face mask to the full-head mask, while claustrophobic patients could only tolerate the open-face mask. The open-face mask is characterized for its immobilization capability and can immobilize patients sufficiently (< 2 mm) during radiotherapy. It provides a clinical solution to the immobilization of patients with head and neck (HN) cancer undergoing radiotherapy, and is particularly beneficial for claustrophobic patients. This new open-face mask is readily adopted in radiotherapy clinic as a superior alternative to the standard full-head mask.