Determinants of neurological disease: Synthesis of systematic reviews.

Systematic reviews were conducted to identify risk factors associated with the onset and progression of 14 neurological conditions, prioritized as a component of the National Population Health Study of Neurological Conditions. These systematic reviews provided a basis for evaluating the weight of evidence of evidence for risk factors for the onset and progression of the 14 individual neurological conditions considered. A number of risk factors associated with an increased risk of onset for more than one condition, including exposure to pesticides (associated with an increased risk of AD, amyotrophic lateral sclerosis, brain tumours, and PD; smoking (AD, MS); and infection (MS, Tourette syndrome). Coffee and tea intake was associated with a decreased risk of onset of both dystonia and PD. Further understanding of the etiology of priority neurological conditions will be helpful in focusing future research initiatives and in the development of interventions to reduce the burden associated with neurological conditions in Canada and internationally.

Risk factors for the onset and progression of Huntington disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by chorea, behavioural and psychiatric manifestations, and dementia, caused by a CAG triplet repeat expansion in the huntingtin gene. Systematic review of the literature was conducted to determine the risk factors for the onset and progression of HD. Multiple databases were searched, using terms specific to Huntington disease and to studies of aetiology, risk, prevention and genetics, limited to studies on human subjects published in English or French between 1950 and 2010. Two reviewers independently screened the abstracts and identified potentially relevant articles for full-text review using predetermined inclusion criteria. Three major categories of risk factors for onset of HD were identified: CAG repeat length in the huntingtin gene, CAG instability, and genetic modifiers. Of these, CAG repeat length in the huntingtin gene is the most important risk factor. For the progression of HD: genetic, demographic, past medical/clinical and environmental risk factors have been studied. Of these factors, genetic factors appear to play the most important role in the progression of HD. Among the potential risk factors, CAG repeat length in the mutant allele was found to be a relatively consistent and significant risk factor for the progression of HD, especially in motor, cognitive, and other neurological symptom deterioration. In addition, there were many consistent results in the literature indicating that a higher number of CAG repeats was associated with shorter survival, faster institutionalization, and earlier percutaneous endoscopic gastrostomy.

Impact of routine coronary catheterization in low extremity artery disease undergoing percutaneous transluminal angioplasty: study protocol for a multi-center randomized controlled trial.

BACKGROUND: The prevalence of significant obstructive coronary artery disease with complex lesions is high in patients who have low extremity artery disease (LEAD). However, intermediate- or long-term cardiovascular prognosis of LEAD patients undergoing percutaneous transluminal angioplasty (PTA) remains poor. Accordingly, prophylactic coronary revascularization may modify short- and long-term cardiovascular outcomes of LEAD patients receiving PTA. Because myocardial ischemic symptoms are often masked in LEAD and the accuracy of non-invasive stress tests is usually limited, a high-quality randomized controlled trial aimed at the investigation of the prognostic role of coronary evaluation strategies before PTA is warranted. METHODS/DESIGN: The proposed study is designed as a prospective, multi-center, open-label, superiority, randomized controlled trial. The study is conducted in high-volume centers for PTA and coronary revascularization in Taiwan. To meet the inclusion criteria, the patients must be at least 20 years old, have known LEAD, and have been admitted for elective PTA. We plan to enroll 450 participants who are randomly allocated to a routine group (routine coronary angiography without a previous non-invasive stress test before PTA) and a selective group (selective coronary angiography based on the results of non-invasive stress tests before PTA) with 1:1 ratio. Besides, we expect to enroll about 250 additional participants, who are not willing to be randomly assigned, in the registration group. The choice of revascularization procedure depends on the operator's or cardiovascular team's suggestion and the patient's decision. Clinical follow-up will be performed 30 days after PTA and every 6 months until the end of the 1-year follow-up for the last randomly assigned participant. The primary endpoint is the composite major adverse cardiac event on long-term follow-up. Pre-specified secondary and other endpoints are also evaluated. Those assessing biomarkers and clinical endpoints are all blinded after assignment to interventions. DISCUSSION: The results of the trial will, for the first time, support better decision-making for coronary evaluation before PTA in LEAD. If favorable, routine coronary angiography followed by revascularization will improve cardiovascular outcomes in LEAD patients undergoing PTA. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02169258 (registered on 21 June 2014); registry name: Routine Coronary Catheterization in Low Extremity Artery Disease Undergoing Percutaneous Transluminal Angioplasty (PIROUETTE-PTA).

Compressive Optic Neuropathy Caused by Cholesterol Gran- uloma in the Posterior Ethmoid Sinus.

PURPOSE: Cholesterol granuloma is usually associated with chronic middle ear disease. Involvement of the ethmoid sinus by cholesterol granuloma is rare. We describe a case with cholesterol granuloma of the posterior ethmoid sinus causing optic nerve compression. No previous reports were found in our review of the literature. CASE REPORT: A 48-year-old man had impaired visual acuity and a relative afferent pupillary defect in the right eye. Fundus fluorescein angiography showed a swollen optic nerve head and optic disc leakage. Automated perimetry revealed a severe peripheral visual field defect with tunnel vision. Computerized tomography demonstrated an expansile, isodense mass in the right posterior ethmoid sinus, remodeling of the bony walls of the right sphenoid sinus, and lateral displacement of the optic nerve in the right orbit. Compressive optic neuropathy caused by posterior ethmoid sinus lesion was diagnosed. A transnasal endoscopic exploration of the right ethmoid sinuses demonstrated a soft expansile cystic lesion with a thick yellow cap sule that filled the inside of the posterior ethmoid sinus. Brownish fluid with shiny crystals was drained by fine needle aspiration. The capsule was removed completely, and the mucociliary clearance of the sinus was reestablished. The pathologic pictures confirmed the diagnosis of cholesterol granuloma, which included typical cholesterol clefts surrounded by inflammatory cells with focal multi-nucleated giant cells. Visual function fully recovered without recurrent lesions after a three-year follow-up. CONCLUSION: Compressive optic neuropathy can be rarely caused by cholesterol granuloma in the posterior ethmoid sinus. The visual prognosis may be good after transnasal endoscopic decompression in such patients.

Prenatal risk factors for Tourette Syndrome: a systematic review.

BACKGROUND: Tourette Syndrome (TS) appears to be an inherited disorder, although genetic abnormalities have been identified in less than 1% of patients, and the mode of inheritance is uncertain. Many studies have investigated environmental factors that might contribute to the onset and severity of tics and associated comorbidities such as obsessive compulsive disorder (OCD) and attention deficit hyperactive disorder (ADHD). A systematic review and qualitative analysis were performed to provide a broad view of the association between pre- and perinatal factors and TS. METHODS: The Medline, Embase and PsycINFO databases were searched using terms specific to Tourette's syndrome and keywords such as "pregnancy", "prenatal", "perinatal", "birth" and "neonatal". Studies were limited to studies on human subjects published in English or French through October 2012. RESULTS: 22 studies were included. Studies were of limited methodological quality, with most samples derived from specialty clinics, and most exposures ascertained retrospectively. The majority of the results for demographic factors of parents, including age, education, socioeconomic status, and marital status, revealed no significant association with the onset of TS, or the presence of comorbidity. Many factors were reported to be significantly associated with the onset of TS, the presence of comorbidity and symptom severity, but the most consistently reported factors were maternal smoking and low birth weight. CONCLUSIONS: There are few studies evaluating the relationship between pre and perinatal events and TS, and existing studies have major limitations, including the use of clinic rather than epidemiologically derived samples, retrospective data collection on pre and perinatal events and multiple hypothesis testing without appropriate statistical correction. The mechanism by which prenatal and perinatal adversities could lead to TS onset or symptom severity is unknown, but may be related to changes in the dopaminergic system as a result of early brain injury.

Predictive model for improvement of idiopathic sudden sensorineural hearing loss.

OBJECTIVE: To establish a predictive model for evaluating improvement in patients with idiopathic sudden sensorineural hearing loss (ISSHL). STUDY DESIGN: Bayesian cure rate model. SETTING: Tertiary referral center. PATIENTS: Two hundred patients whose conditions were diagnosed as ISSHL from January 2001 to April 2007 were enrolled to build a model and to train relevant parameters for prediction. MAIN OUTCOME MEASURES: The time to improvement and potential predictive factors were collected for analysis. Established factors and significant variables in the univariate analysis were included in the final model. A Bayesian approach with the WinBUGS program was applied to predict the median and 95% confidence intervals (CIs) for the time to improvement, long-term probability of improvement, and improvement probabilities at specific days. RESULTS: The significant predictors in the final model include distortion product otoacoustic emission, auditory brainstem response, vestibular evoked myogenic potential, and audiometric types. The overall results predicted by the different combinations of covariates were summarized and organized in an Access program file that is convenient for clinical application. The results of area under the receiver operating characteristic curves at the 7th, 14th, and 30th days were 0.709 (95% CI, 0.692-0.717), 0.752 (95% CI, 0.737-0.753), and 0.807 (95% CI, 0.788-0.811), respectively. It showed that predictive validity, particularly at 1 month or so, is satisfactory. CONCLUSION: By using the cure rate model under the context of a Bayesian survival analysis, we first identified auditory objective factors as significant predictors of improvement of ISSHL patients and further predicted the time to improvement with these correlates. The model showed a satisfactory predictive validity, particularly for 1-month individual prediction, which prompted one to make an individual prediction with an available Access program.

Predictive model for progression of hearing loss: meta-analysis of multi-state outcome.

RATIONALE, AIMS AND OBJECTIVES: To develop a multi-state Markov model to predict multi-state progression of age-related hearing loss (ARHL). METHOD: A systematic searching of literature from Medline (1966-2005) was performed. The disease process for hearing loss was modelled as a four-state continuous-time Markov process. We estimated the progression rates for each study separately, then calculated weighted averages over all studies across age groups, weighting for each study by the inverse of variance. The pooled estimates were obtained and transition probabilities between states were illustrated. RESULTS: The progression of hearing loss increased with the ascending frequencies across all age groups. Men had significantly faster progression rates in all frequencies and age groups except for the age group of 90 years or older. In comparison between ears, the progression of hearing would be slightly faster in left ears initially in early elder life and did not show any difference in further ageing and later hearing declines. With the pooled estimates of progression rates, the probabilities of hearing deterioration could be obtained. CONCLUSIONS: The multi-state model can quantify the nature course of hearing progression in ARHL. Predictions of hearing status can be simulated either at population or individual level with this model.

Cost-effectiveness of hearing aids in the hearing-impaired elderly: a probabilistic approach.

OBJECTIVE: Hearing aids are the principal tool for rehabilitation of hearing loss, one of the most prevalent impairments among elderly adults, but cost-utility ratings for hearing aid use are limited. DESIGN: Cost-effectiveness analysis. SETTING AND PATIENTS: A multistate Markov model was constructed to model 50- to 80-year-old patients moving between states, including normal hearing, mild, moderate, or severe hearing loss. Parameters assigned in the model are partly derived from the Medline source (1966-2005) and partly from data on hearing-impaired elders (n = 96) in a tertiary care center in Taiwan. To address uncertainty, most of the parameters were specified by distributions, rather than base-case values. A probabilistic approach with Monte Carlo simulations was performed to produce an acceptability curve, showing the probabilities of being cost-effective given threshold values of willingness to pay (WTP). MAIN OUTCOME MEASURES: Hearing-related quality-adjusted life-years and cost in US dollars and Euros. RESULTS: The incremental costs for gaining an additional hearing-related quality-adjusted life-years in women and men were US $13,615 (Euro 10,826) and 9,702 (Euro 7,715), respectively. The probability of being cost-effective increased to 53% in women and 65% in men given a WTP of US $12,000 (Euro 9,542). The probabilities of being cost-effective to reach plateau were 67% for women and 78% for men given a WTP of US $20,000 (Euro 15,904). CONCLUSION: By modeling different degrees of hearing loss with a multistate model, hearing aid use was demonstrated to be a cost-effective strategy to rehabilitate the hearing-impaired elderly. These results can assist policy makers in allocating health resources appropriately and effectively.

Measurement of hearing aid outcome in the elderly: comparison between young and old elderly.

OBJECTIVE: To evaluate speech performance and subjective outcomes for older individuals who have hearing impairment and use digital hearing aids. The outcomes between young and old elderly users were compared. STUDY DESIGN: Prospective. SUBJECTS AND METHODS: Fifty-nine patients with hearing loss fitted with digital hearing aids were included. They were divided into two groups. Group A consisted of 32 subjects aged 65 to 80 years, whereas group B had 27 subjects older than 80 years. Speech performance and subjective outcomes were measured 4 months after fitting of hearing aids. Hearing Handicap Inventory for the Elderly-Screening Version (HHIE-S), Client Oriented Scale of Improvement (COSI), satisfaction, and usage questionnaires were used as subjective assessments. RESULTS: Improvements in speech performance were not significantly different between these two groups. There were no statistical differences in terms of HHIE-S score reduction, satisfaction rate, daily usage time, and COSI scores between both groups. CONCLUSION: Age by itself is not a limiting factor for older patients with hearing impairment to benefit from digital hearing aids.

Middle meatus bacteriology of acute rhinosinusitis in patients after irradiation of nasopharynx.

BACKGROUND: Patients who undergo radiotherapy for nasopharyngeal carcinoma (NPC) tend to suffer from rhinosinusitis because irradiation causes damage to sinonasal tissue; however, their bacteriology is lacking in the literature. The aim of this study was to determine the bacteriology and antibiotic resistance in acute rhinosinusitis (ARS) of these patients. METHODS: We collected nasal purulent discharge for bacteriology and antibiotic susceptibility tests in irradiated NPC patients with ARS. Middle meatus discharge was aspirated for culture with endoscopic assistance. RESULTS: A total of 33 episodes of ARS were documented in 25 patients. Staphylococcus aureus comprised 42% of all aerobes. Thirty-six percents of aerobic isolates were Gram-negative bacilli. Peptostreptococcus micros and Veillonella spp were the most frequently isolated anaerobes. CONCLUSION: The bacteriology in irradiated NPC patients with ARS was distinctive in the following: first, the most common pathogen was S. aureus; second, frequently isolated Gram-negative bacilli and anaerobes; and third, polymicrobial infections. The beta-lactamase-producing pathogens were highly prevalent.

Gauze-assisted technique in endoscopic removal of fungus balls of the maxillary sinus.

BACKGROUND: The aim of this study was to establish and evaluate a newly developed gauze-assisted technique in complete removal of fungus balls of the maxillary sinus with usual instruments of endoscopic sinus surgery. METHODS: Fifteen adults with fungus balls of the maxillary sinus were collected. A newly developed surgical technique that involves the replacement of the fungus balls with the gauze strip was applied. The number of course and duration of this procedure were recorded. RESULTS: The fungal material was removed with less than two courses of this procedure in these patients. The duration of this procedure ranged from 2 to 5 minutes with an average of 4 minutes. Postoperatively, these patients had been followed for 16-50 months with an average of 29 months. Neither recurrence nor complication was noted. CONCLUSION: With the excellent results, we strongly suggest this easy and timesaving technique in the management of such patients.

Distortion product otoacoustic emissions as a prognostic factor for idiopathic sudden sensorineural hearing loss.

We investigated distortion product otoacoustic emissions (DPOAE) as a prognostic factor in idiopathic sudden sensorineural hearing loss (ISSHL) patients with the time-dependent Cox proportional-hazards model. We also compared the importance of the prognostic factors that are reported in the literature. 108 patients with ISSHL were included. Both DPOAE and pure tone audiometry were performed everyday for a maximum of 7 days during admission and followed every other week or monthly after discharge. All DPOAE amplitudes were analyzed at 2f1-f2--namely 1093, 1375, 1750, 2187, 2781, 3500, 4375, and 5500 Hz. The average of two series of DPOAE intensity corrected for the noise level in eight frequencies was coded as dichotomous at > or =6 or <6 dB. We selected the most updated DPOAE at 3 days or more before the assessment of recovery into the analysis. The potential confounders including age, sex, history of vertigo at onset, history of hypertension, diabetes, coronary arterial disease, and stroke, configuration and severity of initial pure tone audiometry, the duration from onset to treatment, auditory brainstem response (ABR), vestibular evoked myogenic potential (VEMP), and plasma triglyceride and cholesterol levels, hemoglobin level, and erythrocyte sedimentation rate were collected for evaluation. The results showed that a better DPOAE amplitude was a significantly good prognostic indicator both in univariate analysis (recovery rate ratio = 3.626, 95% CI = 2.119-6.205, p < 0.0001) and multivariate analysis (recovery rate ratio = 2.94, 95% CI = 1.537-5.624, p = 0.0011). The Kaplan-Meier estimates showed that the younger age group (< or =40 years) with better initial pure tone audiometry (<65 dB) represented a better prognosis that was compatible with previous literature (log-rank test, p = 0.0297 and p = 0.0019 respectively). In the univariate analysis, normal ABR and VEMP waveforms were associated with a better prognosis (ABR: recovery rate ratio = 2.984, 95% CI = 1.742-5.112, p < 0.0001; VEMP: recovery rate ratio = 1.978, 95% CI = 1.183-3.305, p = 0.0093). The configuration of initial audiometry was also a significant prognostic factor that patients with scale-out type (recovery rate ratio = 0.228, 95% CI = 0.089-0.584, p = 0.002) and tent type (recovery rate ratio = 0.081, 95% CI = 0.008-0.778, p = 0.0295) were associated with a poorer prognosis than those with the flat type in the multivariate analysis. In this study, the time-dependent Cox proportional-hazards model established the prognostic value of DPOAE for ISSHL patients. This model can also be used for comparison of different treatment protocols. In addition, the further development of a predictive model based on this method is worthy of being investigated.

Cholesterol granuloma of the maxillary sinus.

Cholesterol granuloma (CG) of the maxillary sinus is very rare. In this study, the searching of the literature was performed with the keywords of cholesterol granuloma and maxillary sinus. All retrieved literature were reviewed throughout to identify and analyze all individual characteristics. Two additional cases in our hospital were also included. The result showed that, in the overall 37 cases, the ratio of male to female was about 3:1. Caucasian (14/37) and Turkish (10/37) were reported more frequently. CG of maxillary sinus had an opposite sex predilection compared with the fungus balls of the maxillary sinus. In addition, the comorbidity of these two diseases was found only in one patient in the literature. These results suggested that the different mechanisms other than poor aeration of the maxillary sinus played a role in the formation of CG of maxillary sinus. The diagnosis for CG of the maxillary sinus before operation is difficult, but the clear golden yellow rhinorrhea and hemorrhagic signs may provide a good diagnostic evidence. The symptoms were vague and about half of the patients presented with non-specific symptoms. Therefore, it seemed reasonable that CG of the maxillary sinus was under diagnosed in the clinical practice. Treatment consists of complete excision via Caldwell-Luc or endoscopic approach and provides a good prognosis. Bilateral involvements are rare but possible in this disease entity.

Dumbbell-shaped cervical spinal neurilemmoma presenting as neck mass.

Cervical neurilemmoma may originate from any nerve sheath tissue in the neck including the vagus nerve, glossopharyngeal nerve, brachial plexus, sympathetic trunk and cervical spine. We report an unusual case of a dumbbell-shaped neurilemmoma arising from the cervical spinal roots in a patient who complained of having had a neck mass for several months. Computed tomographic scan and magnetic resonance imaging revealed a dumbbell-shaped tumour extending from the C4 spinal level through the intervertebral foramen into the right parapharyngeal space. Decompression surgery was performed first via the cervical approach. Five months later, the patient received laminectomy and a complete tumour excision. The symptoms and signs were significantly relieved without neurological sequelae. No evidence of recurrence was noted after one-year follow up. This two-staged operation could offer an alternative surgical approach yielding ideal therapeutic results in such a rare disease.

Middle cranial fossa arachnoid cysts causing sensorineural hearing loss.

Arachnoid cyst of the middle cranial fossa has never been reported to present with sensorineural hearing impairment. We report the case of a 15-year-old girl who complained of progressive hearing loss on the right side for 4 years. The pure tone audiometry revealed sensorineural hearing loss with an average of 63 dB, and the auditory brain stem response demonstrated absence of all waves on the right side. Magnetic resonance imaging showed giant arachnoid cysts occupying the bilateral middle cranial fossa and extending to the parietal and prepontine areas with the atrophic change of the right facial-acoustic nerve cord and a decrease in signal intensity of the right cochlea and vestibule. The cystoperitoneal shunting procedure was suggested, but the parents hesitated about the surgical treatment. The patient has not received any surgical intervention, and her hearing has been stable for 1 year during the follow-up period. This case represents the first report that sensorineural hearing loss is a possible presenting symptom when arachnoid cysts of the middle cranial fossa are massive.

Uncommon anatomic variations in patients with chronic paranasal sinusitis.

OBJECTIVE: Some uncommon anatomic variations would be encountered with the increasing number of patients with chronic paranasal sinusitis who have undergone functional endoscopic sinus surgery. The correct identification and proper treatment for these variations are important. STUDY DESIGN AND SETTING: A retrospective study of serial computed tomography scan images was conducted in 100 patients collected randomly. Uncommon anatomic variations were recorded and clinical features were analyzed. RESULTS: Five (5%) cases with uncommon anatomic variations were found. These variations included bilateral pneumatization of uncinate process (1%), large uncinate process mimics the middle turbinate (1%), nontraumatic protrusion of orbital contents through dehiscence of lamina papyracea (1%), and nasal septal pneumatization (2%). Two of these 5 cases caused some modifications of routine functional endoscopic sinus surgery procedures and another 2 variants commanded further caution during routine uncinectomy. CONCLUSION AND SIGNIFICANCE: Uncommon anatomic variations, though unusual, are not rare in chronic paranasal sinusitis patients. Procedures should be tailored for most of these special conditions.

Leiomyoma of the external auditory canal--a case report and brief review of the literature.

Leiomyoma usually originates from the uterus and alimentary tract, but rarely from the soft tissue of the head and neck. It is extremely rare that leiomyoma appears in the external auditory canal. A 47-year-old male with left external auditory canal leiomyoma presented with conductive hearing impairment and post-auricular swelling. Tumor excision was successful via a retroauricular approach. The pathological examination demonstrated a vascular leiomyoma without malignant change. To date, including our case, only three cases of external auditory canal leiomyoma have been reported. The tumor occurs mainly in adult males aged around 50 and should be included in the differential diagnoses for external auditory canal tumor. The proper treatment of choice is complete excision. In case of an external auditory canal tumor, even if it is believed to be benign before surgery, precise pathologic examination is required to exclude the possibility of malignancy.

Triple discrete fungus balls of the paranasal sinuses.

Paranasal sinus fungus balls occur usually in single sinus, most frequently the maxillary sinus. Multisinus localization was found only 6% in the largest review of this disease entity. Even multiple sinuses involved, these sinuses were mostly contiguous. Bilateral involvement was rare in the literature. Nevertheless, there has never been a report of three discrete sinus fungus balls in the same patient. This report represents the first case of the paranasal sinus fungus balls presenting in triple discrete sinuses at once.

Hyalinizing clear cell carcinoma of the hard palate.

Hyalinizing clear cell carcinoma (HCCC) of the salivary gland is new disease only recognized in recent years. It is rare and the standard treatment is still under investigation. This is a report of a 42-year-old female with HCCC who presented with a painless submucosal hard palatal mass of three years duration. Wide excision of the tumour and the underlying palatal and maxillary bones was performed. Pathological examination revealed typical clear cells arranged in anastomosing trabeculae, cords, nests, or solid sheets with a hyalinizing stroma. These clear cells were positive for the periodic acid-Schiff (PAS) reaction but were negative for the mucin stain. Immunohistochemically, these neoplastic cells were positive for cytokeratin, but negative for actin. No recurrence nor distant metastasis was found during the eight-month follow-up period.