Prevalence of white matter lesions and stroke in children with migraine.

OBJECTIVES: To determine the prevalence of white matter lesions (WMLs) and infarcts in children with migraine and whether pediatric migraine could be a risk factor for silent ischemic lesions or stroke. METHODS: Prospectively collected data from 1,008 pediatric patients with headache were reviewed. The MRI data were collected and retrospectively reviewed. RESULTS: Of the 926 patients diagnosed with migraine, 375 patients had MRIs and 115 had abnormalities, of which 39 had WMLs. Among them, 24 (6% of migraine) patients had incidental white matter findings without known neurovascular disease, risk factors, or etiologies for WMLs. The prevalence of WMLs is more common in migraine with aura (10%) than without aura (4%) (p = 0.038), but it is not statistically significant compared with controls (4%) (p = 0.119). Deep WMLs are more prevalent than periventricular lesions; these are detected mainly in the frontal and parietal lobes. No lesions appeared to be infarct-like lesions. There was no association between the total lesion load and chronicity or the frequency of migraine. WMLs are nonprogressive. Pediatric migraineurs with aura do not develop stroke, based on the available follow-up data. CONCLUSION: WMLs in pediatric patients with migraine and aura are no more prevalent than in controls. They appear to be benign and are not associated with stroke.

A long-term follow-up study using IPMSSG criteria in children with CNS demyelination.

OBJECTIVE: To evaluate the practical application of International Pediatrics Multiple Sclerosis study group definitions in children with inflammatory demyelination of the central nervous system and to identify predictors of multiple sclerosis. METHODS: Baseline data on 123 children with a first episode of acute central nervous system demyelination were collected. The initial diagnosis according to the International Pediatrics Multiple Sclerosis study group was recorded and compared with final diagnosis. RESULTS: Forty-seven (38.2%) children met International Pediatrics Multiple Sclerosis study group criteria for acute disseminated encephalomyelitis and 67 (54.4%) had clinically isolated syndrome at the initial presentation. Four (3.2%) had the diagnosis of neuromyelitis optica and five (4%) did not meet any specific diagnosis per the study group criteria. Clinical follow-up was available on 118 of 123 children (95.9%), with a median of 61.5 months (quartile range 23, 110 months). Conversion from clinically isolated syndrome to multiple sclerosis occurred in 26 of 67 children (38.8%); acute disseminated encephalomyelitis to multiple sclerosis occurred in 4 of 47 children (8.5%). Adjusted multivariate logistic regression analysis for an outcome of future development of multiple sclerosis showed the following predictors: female gender (odds ratio 12.44; 95% confidence interval 1.03-149.3); initial diagnosis of monofocal brain stem or hemispheric dysfunction (odds ratio 24.57; 95% confidence interval 3.06-196.78); and Callen magnetic resonance imaging criteria if met (odds ratio 122.45; 95% confidence interval 16.57-904.57). CONCLUSION: International Pediatrics Multiple Sclerosis study group criteria affirm that children with initial clinically isolated syndrome are more likely to develop future multiple sclerosis compared with those with an acute disseminated encephalomyelitis initial diagnosis. In addition, female gender, brain stem or hemispheric involvement, and Callen magnetic resonance imaging criteria predict the diagnosis of multiple sclerosis.

Prevalence of Sleep Disturbances in Children With Neurofibromatosis Type 1.

Children with neurodevelopmental disorders are at increased risk for sleep issues, which affect quality of life, cognitive function, and behavior. To determine the prevalence of sleep problems in children with the common neurodevelopmental disorder neurofibromatosis type 1, a cross-sectional study was performed on 129 affected subjects and 89 unaffected siblings, age 2 to 17 years, using the Sleep Disturbance Scale for Children questionnaire. Children with neurofibromatosis type 1 were significantly more likely to have disturbances in initiating and maintaining sleep, arousal, sleep-wake transition, and hyperhidrosis, but not problems with abnormal sleep breathing, or excessive somnolence. Although the overall sleep scores were higher in children with neurofibromatosis type 1, this was not related to a coexisting attention deficit disorder, cognitive impairment, or stimulant medication use. Collectively, these results demonstrate that children with neurofibromatosis type 1 are more likely to have sleep disturbances, and support the use of appropriate interventions for this at-risk population.

Long-term prognosis of pediatric patients with relapsing acute disseminated encephalomyelitis.

Although long-term follow-up data are available for cases with acute disseminated encephalomyelitis, the findings range widely because of the lack of consistent definitions. Using the International Pediatric Multiple Sclerosis Study Group definitions strictly, we determined the long-term prognosis of children with acute disseminated encephalomyelitis, especially concerning relapsing cases. In our cohort of 86 children who presented with a first event of inflammatory demyelinating disease of central nervous system, 33 patients (38%) met the Study Group criteria for acute disseminated encephalomyelitis of which 9 patients had relapses. The mean follow-up duration was 12.8 years for relapsing cases and 9.2 years for all patients with acute disseminated encephalomyelitis. The risk of developing relapses is 27% but the risk of developing multiple sclerosis from acute disseminated encephalomyelitis is low at 6%. All relapsing cases had a benign course on prolonged follow-up, in spite of multiple relapses in the first 3 years.

Management of T3N1 glottic carcinoma: therapeutic outcomes.

OBJECTIVE: The aim of the current study was to determine the best total laryngectomy (TL) approach to the treatment of T3N1 glottic cancer, to study the impact of early nodal disease on stage III glottic cancers, and to describe the preliminary results in a group of patients recently treated for laryngeal preservation (LP). METHODS: A retrospective study of Tumor Research Project data were performed on previously untreated patients with T3N1 glottic squamous cell carcinoma who were treated with curative intent by TL and neck dissection (ND) with or without adjuvant radiation therapy (TL +/- RT) from April 1, 1955 to October 8, 1999 at Washington University School of Medicine/Barnes Jewish Hospital. A preliminary analysis of a similar group of patients more recently treated for LP (1-1-2000 to 1-1-2005) is reported. RESULTS: Forty-two patients with T3N1 glottic carcinoma were treated with TL and ND (TL/ND-16) and TL with ND and TL (TL/ND/RT-26). The 5 year observed survival (OS) and disease-specific survival (DSS) for TL/ND were similar at 62.5%. The 5 year OS and DSS for TL/ND/RT were 53.8% and 58.3%, respectively. There was no survival difference between the two methods. The overall local-regional control rate was 73.9% (11/42 recurrences). The overall recurrence rate was 38%, with 7.1% recurrence at both the primary site and neck. Recurrence was not related to treatment method. The overall salvage rate (5 year DSS after retreatment) was 20% with 50% salvage for patients with neck recurrence. No patients with local recurrence were survivors. The incidence of second primary cancers was 6.8%. More recently, 26 similar patients were treated with LP techniques. Preliminary results showed a 3 year OS of 63.5% and DSS of 76.8%. Local-regional control was 85.4%. LP was 88.5%. CONCLUSIONS: The two TL modalities had statistically similar results in terms of survival, recurrence, and complications. Decreased DSS was seen in older patients (>65 years) and in patients with involved resection margins, recurrent disease, and distant metastasis. Patients with T3N1 glottic cancer had an 8% decrease in DSS compared to patients with T3N0 disease. Previously patients with T3N1 disease have been treated with TL resulting in loss of natural voice in all patients. Preliminary results on 26 patients with T3N1 disease, treated between 2000 and 2005 with voice preservation intent, indicate that the OS, DSS, and local-regional control rates were similar to the TL group, whereas 88.5% of patients maintained natural voice and natural breathing. Use of LP techniques should be the initial therapeutic approach for patients with T3N1 glottic cancer.

Supraglottic laryngeal cancer: analysis of treatment results.

OBJECTIVE: This study reports the results of treatment for supraglottic laryngeal cancer with nine different treatment modalities with long-term follow-up. STUDY DESIGN: Retrospective study of 653 patients with supraglottic laryngeal squamous cell cancer treated from April 1955 to January 1999. METHODS: The study population included previously untreated patients with cancer of the supraglottic larynx treated with curative intent by one of nine treatment modalities and who were eligible for 5-year follow-up. The treatment modalities included subtotal supraglottic laryngectomy (SSL), SSL with neck dissection (SSL/ND), total laryngectomy (TL), TL/ND, radiation therapy (RT), SSL/RT, SSL/ND/RT, TL/RT, and TL/ND/RT. Multiple diagnostic, treatment, and follow-up parameters were studied using standard statistical analysis to determine significance. RESULTS: None of the nine treatment modalities produced a survival advantage, either overall or within the stages. Overall disease specific survival (DSS) by treatment modality included SSL 88.9%, SSL/ND 75.8%, TL 83.3%, TL/ND 66.7%, RT 47.2%, SSL/RT 68.9%, SSL/ND/RT 68.1%, TL/RT 59.3%, and TL/ND/RT 46.7%. Improved DSS and cumulative disease specific survival rates were associated with patients under the age of 65 years (P = .0001), early stage disease, N0 disease (P = .0001), clear resection margins (P = .0094), and no recurrence (P = .0001). Posttreatment function showed that 90% of patients were functional in everyday life, 90.7% were eating satisfactorily, 91.4% were breathing naturally, and 83% of SSL patients, 85.7% of RT patients, and 52.8% of TL patients had "good" voices. Laryngeal preservation was accomplished in 86.1% of SSL patients and 72.7% of RT patients (P = .0190). CONCLUSIONS: No treatment modality produced a survival advantage. Because SSL produced the best rate of laryngeal preservation, we recommend its use in treating the primary in eligible patients. The importance of clear resection margins is stressed. Patients with N+ disease should have the neck treated. Patients with N0 disease may be observed safely with no loss of survival advantage. Because of the pattern of recurrence and the high rates of distant metastasis and second primary cancers, follow-up for a period of not less than 8 years is recommended.

The influence of lymph node metastasis in the treatment of squamous cell carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx: N0 versus N+.

OBJECTIVES/HYPOTHESIS: Management of the N0 neck is a continuing controversy. The study compares the influence of N0 and N+ disease on the results of treating squamous cell carcinoma (SCCA) of the oral cavity (OC), oropharynx (OP), larynx (LX), and hypopharynx (HP) with five different treatment modalities. The study also compares the results of four different approaches to the treatment of the N0 neck. STUDY DESIGN: A retrospective study of 3887 patients. METHODS: Patients in the Tumor Research Project of the Department of Otolaryngology-Head and Neck Surgery of the Washington University School of Medicine (St. Louis, MO) with biopsy-proven previously untreated SCCA of one of the four above-mentioned regions who were treated with curative intent by one of five modalities and who were eligible for 5-year follow-up were included in the study. The treatment modalities included local resection of primary alone (LR), composite resection (primary with neck dissection) (CR), radiation therapy alone (RT), local resection with radiation therapy (LR/RT), and composite resection with radiation therapy (CR/RT). The N0 neck was treated with one of four approaches: observation with close follow-up reserving treatment only for subsequent neck disease, neck dissection, RT to the neck region, and a combination of neck dissection with RT. Multiple diagnostic, treatment, and follow-up parameters were studied using standard statistical analyses to determine statistical significance. RESULTS: The 5-year disease-specific survival (DSS) for the all-sites group (ASG) was 59%. The DSS for the subsites included the following: OC, 53%; OP, 47%; LX, 70%; and HP, 42%. Patients with N0 disease had significantly better DSS than patients with N+ disease at all sites. Occult neck disease in N0 patients was low with 4% pN1 for ASG, OC, and LX and with 11% pN1 for OP and HP. There was 3% pN2 for LX, 4% pN2 for ASG and OC, and 6% pN2 for OP and HP. The DSS for patients with occult neck disease was statistically similar to that of N+ patients. Prognostic survival indicators included age, decade of treatment, T stage, N stage, TN stage, treatment modality, and recurrence. Patients over 65 years of age had poorer DSS than younger patients. Staging T, N, and TN affected survival at all sites. Local resection produced better DSS for ASG, OC, LX, and HP patients. Local resection with radiation therapy produced increased DSS for ASG and OC patients. There was no survival advantage for HP patients related to treatment modality. Treatment of the N0 neck with observation and later treatment for subsequent neck disease produced a survival advantage for patients in the ASG. This advantage was specific for ASG and LX patients staged T1N0. For patients staged T2N0, T3N0, and T4N0 at all four subsites there was no survival advantage for any of the four neck approaches. CONCLUSION: Lymph node metastasis significantly and negatively affects DSS in patients with SCCA of the OC, OP, LX and HP. The rate of occult neck disease (pN+) in N0 patients receiving meticulous workup is low. When present, it produces DSS rates similar to those found in N+ patients. In the study series, there was decreased survival in patients older than 65 years of age, in patients with advanced tumor (T, N, TN), and in patients with recurrent disease. None of the four current approaches to treatment of the N0 neck produces a significant survival advantage. Close observation with later treatment reserved for subsequent neck disease produces statistically similar survival (DSS) to the three elective (prophylactic) treatments and is a valid form of treatment. It may preclude unnecessary treatment of the neck with its attendant risks and complications.

Management of stage IV glottic carcinoma: therapeutic outcomes.

OBJECTIVES/HYPOTHESIS: The best therapeutic approach for the treatment of stage IV glottic carcinoma is controversial. STUDY DESIGN: A retrospective study. METHODS: A retrospective study of Tumor Research Project data was performed using patients with stage IV glottic squamous cell carcinoma treated with curative intent by five different treatment modalities from 1955 to 1998 at Washington University School of Medicine and Barnes-Jewish Hospital (St. Louis, MO). RESULTS: Ninety-six patients with stage IV glottic carcinoma were treated by five modalities: total laryngectomy (TL) (n = 13), total laryngectomy with neck dissection (TL/ND) (n = 18), radiation therapy alone (RT) (n = 7) (median dose, 69.5 Gy), total laryngectomy combined with radiation therapy (TL/RT) (n = 10), and total laryngectomy and neck dissection combined with radiation therapy (TL/ND/RT) (n = 48). The overall 5-year observed survival (OS) rate was 39%, and the 5-year disease-specific survival (DSS) rate was 45%. The 5-year DSS rates for the individual treatment modalities included the following: TL, 58.3%; TL/ND, 42.9%; RT, 50.0%; TL/RT, 30.0%; and TL/ND/RT, 43.9%. There was no significant difference in DSS for any individual treatment modality (P =.759). The overall locoregional control rate was 69% (66 of 96). The overall recurrence rate was 39% with recurrence at the primary site and in the neck at 19% and 17%, respectively. Recurrence was not related to treatment modality. The 5-year DSS after treatment of locally recurrent cancer (salvage rate) was 30% (3 of 10) and for recurrent neck disease (28 of 67) was 42%. The incidence of delayed regional metastases was 28%; of distant metastasis, 12%; and of second primary cancers, 9%. There was no statistically significant difference in survival between node-negative (N0) necks initially treated (5-y DSS, 31%) versus N0 necks observed and later treated if necessary (5-y DSS, 44%) (P =.685). CONCLUSION: The five treatment modalities had statistically similar survival, recurrence, and complication rates. The overall 5-year DSS for patients with stage IV glottic carcinoma was 45%, and the OS was 39%. The cumulative disease-specific survival (CDSS) was 0.4770 with a mean survival of 10.1 years and a median survival of 3.9 years. Patients younger than age 55 years had better survival (DSS) than patients 56 years of age or older (P =.0002). Patients with early T stage had better survival than patients with more advanced T stage (P =.04). Tumor recurrence at the primary site (P =.0001) and in the neck (P =.014) and distant metastasis (P =.0001) had a deleterious effect on survival. Tumor recurrence was not related to treatment modality. Patients with clear margins of resection had a statistically significant improved survival (DSS and CDSS) compared with patients with close or involved margins (P =.0001). Post-treatment quality of life was not significantly related to treatment modality. Patients whose N0 neck was treated with observation and appropriate treatment for subsequent neck disease had statistically similar survival compared with patients whose N0 neck was treated prophylactically at the time of treatment of the primary. A minimum of 7 years of follow-up is recommended for early identification of recurrent disease, second primary tumors, and distant metastasis. None of the standard treatment modalities currently employed has a statistical advantage regarding survival, recurrence, complications, or quality of life.

Analysis of treatment results for base of tongue cancer.

OBJECTIVE: The study reported the results of treatment for base of tongue cancer with five different treatment modalities with long-term follow-up. STUDY DESIGN: This was a retrospective study of 262 patients with base of tongue cancer treated in the Departments of Otolaryngology-Head and Neck Surgery and Radiation Therapy at Washington University School of Medicine (St. Louis, MO) from July 1955 to January 1998. METHODS: The study population included previously untreated patients with biopsy-proven squamous cell carcinoma of the base of tongue who were treated with curative intent by one of five modalities and were all eligible for 5-year follow-up. The treatment modalities included local resection alone, composite resection alone, radiation therapy alone, local resection with radiation therapy, and composite resection with radiation therapy. Multiple diagnostic, treatment, and follow-up parameters were studied using standard statistical analysis to determine statistical significance. RESULTS: The overall 5-year disease-specific survival (DSS) was 49.6% with death due to tumor in 50.4%. The 5-year cumulative disease-specific survival probability (CDSS) was 0.526 (Kaplan-Meier) with a mean of 7.8 years and a median of 5.6 years. Patients with early disease had significantly improved DSS compared with patients with more advanced disease (stages I and II; TN stages T1N0, T2N0, and T2N1; and T stages T1 and T2.). Patients with N0 had better DSS than patients with positive lymph nodes (P =.010). The DSS for all stages by treatment modality included local resection (70.0%), composite resection (47.6%), radiation therapy (40.4%), local resection and radiation therapy (50.0%), and composite resection with radiation therapy (51.5%). Overall and within the stages there was no significant difference in either DSS or CDSS by treatment modality. Local-regional recurrence occurred in 26% of patients, and overall salvage was 10.5%. Patients with clear resection margins did better than patients with close or involved margins (DSS and CDSS). Patients treated with radiation therapy alone had improved capacity to swallow (P =.001), speak (P =.01), and work (P =.001) compared with patients treated with the other modalities. CONCLUSIONS: Cancer of the base of tongue is a lethal disease, and its treatment results in significant disability. No treatment produced a significantly improved survival advantage. Focus on improving local-regional control might improve overall survival. All treatment modalities were associated with major treatment-related complications. Radiation alone produced significantly improved post-treatment function and quality of life compared with the other modalities. Because of the recurrence rates at the primary and neck sites and the high rates of development of distant metastasis and second primary cancers, patients should be monitored for a minimum of at least 4 years.

Management of T3N0M0 glottic carcinoma: therapeutic outcomes.

BACKGROUND: The best therapeutic approach for the treatment of T3N0M0 (stage III) glottic carcinoma is controversial. METHOD: A retrospective study of Tumor Research Project data were performed using patients with T3N0M0 glottic squamous cell carcinoma treated with curative intent by seven different treatment modalities from January 1950 to December 1996 at Washington University School of Medicine/Barnes-Jewish Hospital. RESULTS: Two hundred patients with T3N0M0 glottic carcinoma were treated using seven modalities: total laryngectomy (TL, n = 30), TL with neck dissection (TL/ND, n = 40), conservation surgery alone (CS, n = 22), radiation therapy alone (RT, n = 29), TL combined with RT (TL/RT, n = 31), TL and ND combined with RT (TL/ND/RT, n = 36), and CS combined with RT (CS/RT, n = 12). The overall 5-year observed survival rate (OS) was 54% and the 5-year disease-specific survival rate (DSS) was 67%. The 5-year DSS for the individual treatment modalities included TL, 65.4%; TL/ND, 76.5%; CS, 71.4%; RT, 56.5%, TL/RT, 51.9%; TL/ND/RT, 71.4%; and CS/RT, 80%. There was no significant difference in DSS for any individual treatment modality (P =.375). The overall local and regional control rate was 74% (148 of 200). The overall recurrence rate was 37.5% with recurrence at the primary site and in the neck of 19.5% and 11%, respectively. Recurrence was not related to treatment modality. The 5-year DSS after treatment of recurrent cancer (salvage rate) was 35.8%. The incidence of distant metastasis was 11% and for second primary cancers it was 19.5%. There was no statistically significant difference in survival between necks initially treated (72%, 5-y DSS) versus necks observed and later treated if necessary (70%, 5-y DSS) (P =.797). CONCLUSIONS: The seven treatment modalities had statistically similar recurrence, complication, and survival rates. Patients with clear surgical margins have a significant survival advantage compared with patients with close and involved margins. Because postoperative radiation therapy in patients with positive margins did not improve survival, formal re-resection of the site of the positive margin should be considered. In patients whose N0 neck was not treated electively, close follow-up observation with meticulous examinations combined with appropriate treatment for subsequent neck disease resulted in a similar survival rate compared with those patients whose N0 necks were treated initially. Six-year minimum follow-up is recommended for early identification of primary and neck recurrence and for discovering expected second primary cancers. Patients treated with RT and CS had statistically similar rates of survival, maintenance of voice, and acquired permanent tracheal stoma. CS is a valid alternative to RT in treating highly selected patients with T3N0 glottic carcinoma.

Analysis of treatment results for oral tongue cancer.

OBJECTIVE: The study reports the results of treatment of oral tongue cancer with five different treatment modalities with long-term follow-up. STUDY DESIGN: Retrospective study of 332 patients with oral tongue cancer treated in the Departments of Otolaryngology-Head and Neck Surgery and Radiation Therapy at Washington University School of Medicine (St. Louis, MO) from 1957 to 1996. METHODS: Patients with biopsy-proven squamous cell carcinoma of the oral tongue who were previously untreated and were treated with curative intent by one of five modalities and who were eligible for 5-year follow-up were included. The treatment modalities included local resection alone, composite resection alone (with neck dissection), radiation therapy alone, local resection with radiation therapy, and composite resection with radiation therapy. Multiple diagnostic, treatment, and follow-up parameters were studied using standard statistical analysis to determine statistical significance. RESULTS: The overall 5-year disease-specific survival rate (DSS) was 57% with death due to tumor in 43%. The 5-year cumulative disease-specific survival probability (CDSS) was 0.61 (Kaplan-Meier) with a mean of 17.5 years and a median of 30.1 years. The DSS by treatment modality included local resection (73%), composite resection (61%), radiation therapy (46%), local resection and radiation therapy (65%), and composite resection with radiation therapy (CR/RT) (44%). Overall, local resection had a significantly improved DSS and CR/RT had a decreased DSS that was related to the stage of disease being treated. In treating stage IV disease, CR/RT produced a more significantly improved CDSS than the other treatment modalities. Recurrence at the primary site was as common as recurrence in the neck. Eighty-nine percent of recurrences occurred within the first 60 months. Recurrence significantly decreased survival. DSS was significantly improved in patients with clear margins of resection. Metastasis to a distant site occurred in 9.6% of patients. Twenty-one percent of patients had second primary cancers, and 54% of these patients died of their second primary cancer. CONCLUSIONS: Significant improvement in DSS was seen in patients with clear margins, early stage grouping and clinical (pretreatment) tumor stage, and negative nodes. Significant decrease in DSS was seen in patients with close or involved margins, advanced stage grouping and clinical (pretreatment) tumor staging, positive clinical (pretreatment) node staging, and tumor recurrence. Obtaining clear margins of resection is crucial because it significantly affects survival. A minimum of 5 years of close monitoring is recommended because of the high incidence of second primary cancers.