A systematic review on machine learning approaches in the diagnosis and prognosis of rare genetic diseases.

BACKGROUND: The diagnosis of rare genetic diseases is often challenging due to the complexity of the genetic underpinnings of these conditions and the limited availability of diagnostic tools. Machine learning (ML) algorithms have the potential to improve the accuracy and speed of diagnosis by analyzing large amounts of genomic data and identifying complex multiallelic patterns that may be associated with specific diseases. In this systematic review, we aimed to identify the methodological trends and the ML application areas in rare genetic diseases. METHODS: We performed a systematic review of the literature following the PRISMA guidelines to search studies that used ML approaches to enhance the diagnosis of rare genetic diseases. Studies that used DNA-based sequencing data and a variety of ML algorithms were included, summarized, and analyzed using bibliometric methods, visualization tools, and a feature co-occurrence analysis. FINDINGS: Our search identified 22 studies that met the inclusion criteria. We found that exome sequencing was the most frequently used sequencing technology (59%), and rare neoplastic diseases were the most prevalent disease scenario (59%). In rare neoplasms, the most frequent applications of ML models were the differential diagnosis or stratification of patients (38.5%) and the identification of somatic mutations (30.8%). In other rare diseases, the most frequent goals were the prioritization of rare variants or genes (55.5%) and the identification of biallelic or digenic inheritance (33.3%). The most employed method was the random forest algorithm (54.5%). In addition, the features of the datasets needed for training these algorithms were distinctive depending on the goal pursued, including the mutational load in each gene for the differential diagnosis of patients, or the combination of genotype features and sequence-derived features (such as GC-content) for the identification of somatic mutations. CONCLUSIONS: ML algorithms based on sequencing data are mainly used for the diagnosis of rare neoplastic diseases, with random forest being the most common approach. We identified key features in the datasets used for training these ML models according to the objective pursued. These features can support the development of future ML models in the diagnosis of rare genetic diseases.

Rare coding variants involving MYO7A and other genes encoding stereocilia link proteins in familial meniere disease.

The MYO7A gene encodes a motor protein with a key role in the organization of stereocilia in auditory and vestibular hair cells. Rare variants in the MYO7A (myosin VIIA) gene may cause autosomal dominant (AD) or autosomal recessive (AR) sensorineural hearing loss (SNHL) accompanied by vestibular dysfunction or retinitis pigmentosa (Usher syndrome type 1B). Familial Meniere's disease (MD) is a rare inner ear syndrome mainly characterized by low-frequency sensorineural hearing loss and episodic vertigo associated with tinnitus. Familial aggregation has been found in 6-8% of sporadic cases, and most of the reported genes were involved in single families. Thus, this study aimed to search for relevant genes not previously linked to familial MD. Through exome sequencing and segregation analysis in 62 MD families, we have found a total of 1 novel and 8 rare heterozygous variants in the MYO7A gene in 9 non-related families. Carriers of rare variants in MYO7A showed autosomal dominant or autosomal recessive SNHL in familial MD. Additionally, some novel and rare variants in other genes involved in the organization of the stereocilia links such as CDH23, PCDH15 or ADGRV1 co-segregated in the same patients. Our findings reveal a co-segregation of rare variants in the MYO7A gene and other structural myosin VIIA binding proteins involved in the tip and ankle links of the hair cell stereocilia. We suggest that recessive digenic inheritance involving these genes could affect the ultrastructure of the stereocilia links in familial MD.

[Diagnostic criteria for Menière's disease according to the Classification Committee of the Bárány Society]. / M. Menière: Diagnostische Kriterien des Internationalen Klassifikationskomitees der Bárány-Gesellschaft.

This paper presents diagnostic criteria for Menière's disease jointly formulated by the Classification Committee of the Bárány Society, The Japan Society for Equilibrium Research, the European Academy of Otology and Neurotology (EAONO), the Equilibrium Committee of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) and the Korean Balance Society. The classification includes two categories: definite Menière's disease and probable Menière's disease. The diagnosis of definite Menière's disease is based on clinical criteria and requires the observation of an episodic vertigo syndrome associated with low- to medium-frequency sensorineural hearing loss and fluctuating aural symptoms (hearing, tinnitus and/or fullness) in the affected ear. Duration of vertigo episodes is limited to a period between 20 min and 12 h. Probable Menière's disease is a broader concept defined by episodic vestibular symptoms (vertigo or dizziness) associated with fluctuating aural symptoms occurring in a period from 20 min to 24 h.

Extended phenotype and clinical subgroups in unilateral Meniere disease: A cross-sectional study with cluster analysis.

OBJECTIVES: To define clinical subgroups by cluster analysis in patients with unilateral Meniere disease (MD) and to compare them with the clinical subgroups found in bilateral MD. DESIGN: A cross-sectional study with a two-step cluster analysis. SETTINGS: A tertiary referral multicenter study. PARTICIPANTS: Nine hundred and eighty-eight adult patients with unilateral MD. MAIN OUTCOME MEASURES: best predictors to define clinical subgroups with potential different aetiologies. RESULTS: We established five clusters in unilateral MD. Group 1 is the most frequently found, includes 53% of patients, and it is defined as the sporadic, classic MD without migraine and without autoimmune disorder (AD). Group 2 is found in 8% of patients, and it is defined by hearing loss, which antedates the vertigo episodes by months or years (delayed MD), without migraine or AD in most of cases. Group 3 involves 13% of patients, and it is considered familial MD, while group 4, which includes 15% of patients, is linked to the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by a comorbid AD. We found significant differences in the distribution of AD in clusters 3, 4 and 5 between patients with uni- and bilateral MD. CONCLUSIONS: Cluster analysis defines clinical subgroups in MD, and it extends the phenotype beyond audiovestibular symptoms. This classification will help to improve the phenotyping in MD and facilitate the selection of patients for randomised clinical trials.

Menière's disease.

Menière's disease (MD) is a chronic multifactorial disorder of the inner ear characterized by episodic vestibular symptoms associated with sensorineural hearing loss, tinnitus, and aural pressure. Epidemiologic and genomic evidence supports a genetic susceptibility with multiple biochemical pathways involved, including the endocrine system, innate immune response, and autonomic nervous system. Allergens, infectious agents, vascular events, or genetic factors could modify inner-ear homeostasis and trigger MD. The diagnosis of MD is based on clinical criteria and requires the observation of an episodic vertigo syndrome associated with low- to medium-frequency sensorineural hearing loss and fluctuating aural symptoms (hearing loss, tinnitus, and/or fullness) in the affected ear. Headache is also found during the attacks and bilateral involvement is found in 25-40% of cases. Audiologic and vestibular assessment is recommended to monitor the clinical course. The treatment of MD is symptomatic to obtain relief of vestibular episodes and preventive to limit hearing loss progression. Treatment options include sodium restriction, betahistine, intratympanic gentamicin, or steroids and eventually surgery, such as cochlear implantation.

Caracterización de las alteraciones vestibulares en pacientes con síndrome de latigazo cervical / Vestibular disorders in patients with whiplash injury syndrome

Objetivo: Determinar la prevalencia de alteraciones vestibulares en pacientes con síndrome de latigazo cervical (SLC). Material y método: Estudio transversal en 24 pacientes consecutivos atendidos por presentar SLC con grado II o III de la Quebec Task Force y tiempo de evolución menor de seis meses. Se realizó exploración clínica vestibular completa y exploración instrumental con videonistagmografía (VNG), incluyendo prueba calórica bitérmica, registro de potenciales evocados miogénicos vestibulares (VEMPs), prueba de la vertical visual subjetiva (VVS) y posturografía dinámica. También fueron evaluados mediante los cuestionarios SF-36 (salud general), DHI-S (discapacidad vestibular) y SIMS (simulación). Resultados: La prevalencia de alteraciones vestibulares se situó en el 25%. El reflejo vestíbulo-cólico evaluado mediante VEMPs estaba alterado en el 25% de los pacientes con SLC. La VSV se encontraba alterada en el 17% de los casos. La posturografía dinámica identificó un patrón vestibular en el 25% de los casos. La estimación de simulación entre los pacientes con SLC se produjo, al menos, en el 25% de los casos. Conclusión: La alteración de varias pruebas vestibulares en pacientes con SLC sugiere una disfunción vestibular asociada a ILT prolongada. Las puntuaciones elevadas en los cuestionarios de discapacidad vestibular (DHI) y de simulación de síntomas (SIMS) podrían ser utilizadas como indicadores de percepción de trastorno vestibular grave e ILT prolongada (AU)

Objective: To determine the prevalence of vestibular dysfunction in patients with whiplash. Material and method: A cross-sectional study including 24 consecutive patients with grade II or III whiplash according to the Quebec Task Force scale and time course < 6 months. A complete vestibular examination with video-oculographic recording was performed including a bithermal caloric test, vestibular evoked myogenic potentials (VEMPs), subjective visual vertical (SVV) and dynamic posturography. We also used the questionnaires SF-36 (general health), DHI-S (vestibular handicap) and SIMS (malingering). Results: The prevalence of vestibular dysfunction is around 25%. The vestibulo-collic reflex evaluated by VEMPs was absent in 25% of patients with whiplash. SVV was abnormal in 17% of cases. Dynamic posturography showed a vestibular pattern in 25% of cases. Scores suggesting malingering in whiplash was observed in 25% of cases. Conclusion: The finding of several abnormal tests in patients with whiplash suggests a vestibular dysfunction associated with a long incapacity. High scores in the DHI and SIMS scales could be useful as predictors of severe vestibular disorder with long incapacity (AU)

Familial clustering and genetic heterogeneity in Meniere's disease.

The aims of this study were to estimate the prevalence of familial cases in patients with Meniere's disease (MD) and to identify clinical differences between sporadic and familial MD. We recruited 1375 patients with definite MD according to the American Academy of Otolaryngology-Head and Neck Surgery criteria, obtaining the familial history of hearing loss or episodic vertigo by direct interview or a postal survey in 1245 cases in a multicenter study. Familial clustering was estimated by the recurrence risk ratio in siblings (λs ) and offspring (λo ) using intermediate and high prevalence values for MD in European population. A total of 431 patients (34%) reported a familial history of hearing loss or recurrent vertigo and 133 patients had a relative with possible MD. After clinical reevaluation, 93 relatives in 76 families were diagnosed of definite MD (8.4%), including three pairs of monozygotic twins. λs and λo were 16-48 and 4-12, respectively. We observed genetic heterogeneity, but most families had an autosomal dominant inheritance with anticipation. No clinical differences were found between sporadic and familial MD, except for an early onset in familial cases. We may conclude that MD has a strong familial aggregation and that sporadic and familial MDs are clinically identical.

Hearing and vestibular disorders in patients with systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) is associated with several comorbidities, including hearing and vestibular disorders. We recently described an increase of SLE prevalence in patients with Menierés disease (MD). The aim of this study is to explore if a subset of SLE patients may have a common inner ear disorder and determine the potential relationship with migraine. METHODS; Eighty-nine patients with SLE (according to the American College of Rheumatology criteria for the diagnosis of SLE) were evaluated for audiovestibular symptoms by a telephone interview carried out by two experienced otoneurologists. Twenty-one patients with SLE were referred to the otoneurology clinic for a detailed clinical history for criteria assessment for MD and a complete audiovestibular examination (audiogram, oculomotor, and caloric testing with video-oculography). RESULTS: Recurrent headache was found in 50/89 patients, and 26 of them had diagnostic criteria for migraine. Twenty-four percent of patients reported sensorineural hearing loss (SNHL) or episodic vertigo. Among the eight patients (9%) with episodic vertigo, one had criteria for definite MD and another two patients had criteria for possible MD. SNHL was found to be associated with a history of episodic vertigo (Fisher's test, p=0.02), but not with headache or migraine. SLE and episodic vertigo were not associated with tinnitus, migraine, lupus nephritis, antinuclear antibodies or antiphospholipid syndrome. CONCLUSIONS: Migraine, SNHL and episodic vertigo are comorbid conditions in patients with SLE, but migraine is not associated with SNHL or vertigo in these patients. However, SNHL and vertigo are associated conditions in SLE, suggesting a common audiovestibular dysfunction.

[Oculomotor response to the vertical cephalic autorotatory test in patients with benign paroxistic positional vertigo of the posterior canal]. / Respuesta oculomotora al test de autorrotación cefálica vertical en pacientes con vértigo posicional paroxístico benigno del conducto posterior.

OBJECTIVE: To evaluate the eye movement response to the head auto-rotation test (HART) in the vertical plane in patients with benign paroxysmal positional vertigo. DESIGN: A transversal, descriptive study. SETTING UP: Outpatient clinic in a general Hospital. INDIVIDUALS: 34 posterior canal BPPV cases with a video-oculographic diagnosis, older than 18 years old, 7 of them were not able to perform the HART. INTERVENTION: HART was performed by a an electrooculographic system with simultaneous recording of head movement by an acelerometer in the vertical plane (Vorteq, Micromedical Instruments). The HART with eyes fixation was performed 3 times to determine its reliability. MAIN OUTCOME MEASURES: Gain, asymmetry and phase for the vertical VOR respectively. A statistical analysis was carried out to determine the test reliability and the number of individuals with an abnormal result. RESULTS: Gain is the only variable that showed a reproducible result in the HART for the active head movement at 1-2 Hz (test-retest reliability 0.83-0.89). The values of gain showed a moderate correlation at the frequencies 1-3 Hz (correlation 0.60-0.87). Asymmetry and phase were not reproducible variables (correlation < 0.55). Thirteen of 27 (48%) patients presented a decrease of the vertical gain, another 13 showed normal values and one case showed raised values. CONCLUSION: Gain is the only useful variable in the vertical HART. Forty-eight percent of patients with posterior canal BPPV have a reduced vertical gain, suggesting an impairment of inferior vestibular nerve function.

[Reference values for the vestibulo-ocular reflex response to the head shaking and the bithermal caloric tests]. / Valores poblacionales de referencia para video- oculografía en el test de agitación cefálica y la prueba calórica bitérmica.

OBJECTIVE: To obtain reference values for the vestibulo-ocular reflex response to the head-shaking nystagmus and the bithermal caloric test in the spanish population. DESIGN: A descriptive study. SET UP: General hospital. INDIVIDUALS: One hundred and seven healthy sex and age stratified voluntiers were included. The final sample included 97 individuals over 18 years of age. INTERVENTION: Spontaneous nystagmus (SN), head-shaking nystagmus (HSN) and caloric induced nystagmus were explored. The eyes movement was recorded by a video-oculographic system. The SN or HSN was considered significant when at least 6 consecutive beats with a slow phase velocity of 2 degrees/sec were detected. The caloric test was performed with water flow at 250mL/20 s at 30 degrees C and 44 degrees C with an interval of 10 minutes between irrigations. The percentage of canal paresis (CP) and directional preponderance (DP) was calculated using maximum slow phase velocity and the Jongkees index formula. MAIN OUTCOME MEASUREMENTS: Presence of SN, horizontal and vertical SHN, percentage of CP and DP. RESULTS: SN was found in 10,3% individuals (6 women and 4 men). Horizontal HSN was also observed in 9 women and 10 men (19,5%), and vertical HSN in 8 women and 10 men (18,6%). The mean and 95 percentil for CP were 13,10 and 28,60 in women and 11,02 and 27,30 in men. For DP, the mean and 95 percentil were 11,76 and 35,80 in women and 11,58 and 28,65 in men. The 5 percentils for slow phase velocity of nystagmus after each irrigation were 6,30; 5,14; 5,96; 4,02 degrees/s (left ear 44 degrees, right ear 44 degrees, left ear 30 degrees, right ear 30 degrees, respectively) in the group of women; and 5,82; 6,99; 5,67; 4,55 degrees/s in men (with the same irrigation sequence). CONCLUSION: Results presented should be considered as a population-based norms and may be useful as references for water bithermal test for VOG studies. The SN or HSN could be observed in subjects without vestibular pathology.

[Evaluation of scientific productivity at otorhinolaryngologic services in Spain in 1998-2002]. / Evaluación de la producción científica en los servicios de otorrinolaringología españoles durante el período 1998-2002.

OBJECTIVES: To count the scientific contributions that were carried out at the Otorhinolarngology Departments in Spain from 1998 to 2002 years and to measure their scientific relevance using different bibliometrics tools. METHOD: Abstracts of articles located on MedLine (http://www.ncbi.nih.gov/PubMed) that have been published by Otorhinolaryngology departments in Spain, by a specific designed search strategy. Papers were classified by journal type (national/international) and study design (original or clinical case). A rank of productivity per hospital was design according to the following variables: total number of articles, total number of originals and cummulative impact factor (according to the category assigned by the Journal of Citation Reports, 2000 from the Institute for Scientific Information). RESULTS: A total of 18,472 papers were located, being 703 papers from 116 Otorhinolaryngology departments in Spain. This represents a 4% of the world's scientific production. There were 196 international and 498 papers in Spanish journals; in addition, 439 were original articles and 265 clinical cases. The centers in Spain with the most relevant scientific productivity are: Hospital Central de Asturias, Hospital Virgen del Rocío de Sevilla, Hospital La Paz de Madrid, Hospital Santa Creu i San Pau de Barcelona, Clínica Universitaria de Navarra and Clínica Puerta de Hierro de Madrid (all of them with a cummulated impact factor in 5 years > 10).

[Tonsillectomy by electrical dissection: risk factors of postoperative hemorrhage in children]. / Amigdalectomía por electrodisección: marcadores de riesgo de hemorragia postoperatoria en niños.

OBJECTIVE: To identify pre or intraoperative risk factors that could indicate a higher risk for post-tonsillectomy hemorrhage (PTH) in children undergoing electrocautery dissection. SET-UP: Primary referral hospital. DESIGN: A retrospective study of 163 post-tonsillectomy children comparing 7 cases of PTH with 156 cases with no PTH. SAMPLE: This study includes children under the age of 18 that underwent tonsillectomy by dissection between 1997 and 2000. OUTCOME PARAMETERS: Age, sex, height, weight, body mass index, hemoglobin level, hematocrit, platelet count activated partial thromboplastin time (APTT), fibrinogen, ASA index (physical state classification of the American Society of Anesthesiology) and type of hemostasis. RESULTS: Prevalence of PTH was 4.29% in the cohort sample. The risk of PTH in children following tonsillectomy by electrodissection is significantly increased in patients over 15 years of age (OR = 8.46, p = 0.04) and when ligatures are used for hemostasis (OR = 8.62, p = 0.02). Activated partial thromboplastin time > or = 32 seconds is marginally significant (OR = 7.82, p = 0.05). CONCLUSIONS: Our findings show that tonsillectomy by electrodissection has an increased risk of bleeding in older children and when ligatures are used for hemostasis.

[Evaluation of the treatment of benign paroxysmal positional vertigo with the DHI-S questionnaire]. / Evaluación del tratamiento del vértigo posicional paroxístico benigno mediante el cuestionario DHI-S.

Benign paroxysmal positional vertigo (BPPV) is a recurrent chronic disease and its handicap is usually underestimated. The aim of this study is to determine the impact of the treatment by Epley maneuver on short-term BPPV-related quality of life. Forty-two individuals with BPPV were included: 39 with posterior canal affected, 2 with the lateral canal and one with the anterior canal. Diagnosis was established if a consistent clinical history was found and Dix-Hallpike test (DHT) in cases with canal posterior involvement. Subjects with positive DHT were treated by a single Epley maneuver and were recommended to avoid supine for the next 48 hours. The BPPV relapses were investigated at 7th and 30th day post-treatment. BPPV-associated quality of life was evaluated by the Dizzness Handicap Inventory Short-form (DHI-S) at days 1st and 30th post-treatment. Total and partial scores for emotional, physical and functional subscales were compared by Wilcoxon test for paired samples. Dix-Hallpike test was found positive in el 59% individuals (23/39), and 41% cases did not required any treatment. Among 23 patients treated with Epley maneuver, DHT was found negative in 90% at 30th day follow-up. Mean and standard deviation of the total scores obtained in the DHI-S at the first day were 19.22 +/- 9.66 in the DHT positive-patients and 19.79 +/- 10.14 in the whole group (DHT positive or negative). These scores significantly decreased to 10.84 +/- 10.99 at 30 days post-treatment (p = 0.002 and p = 0.001, respectively). In conclusion, the DHI-S is a specific health questionnaire able to assess BPPV-related health and the effectiveness of treatment.

[Prevalence of headaches and medication use in patients with recurrent vertigo]. / Prevalencia de cefalea y consumo de fármacos en pacientes con vértigo recurrente.

Headache and episodic vertigo are common symptoms in adults. Migraine-related dizziness and vertigo is a clinical process that is difficult to assess because specific diagnostic criteria are lacking. Although studies have demonstrated a relationship between migraine and dizziness, the prevalence of headache among patients with episodic vertigo is underestimated. A clinical inventory was used to determine the prevalence of headache among 150 patients with episodic vertigo and the impact that dizziness had on the quality of life using an ordinal scale for disability. Patients were questioned about drug use and self-perceived effectiveness. Twenty-three percent of the patients experienced a severe problem that disabled them for work. The prevalence of headache was 68.6% (71% of women and 64% of men). Forty-five percent of patients with episodic vertigo and 44% with headache did not obtain any benefit from symptomatic treatment. A subset of patients suffered from migraine-related dizziness and vertigo and were able to control their balance disorder with migraine therapy.

[Preoperative markers for risk of post-tonsillectomy bleeding in adults]. / Marcadores de riesgo preoperatorio en la hemorragia postamigdalectomía en adultos.

OBJECTIVE: To identify preoperative markers indicative of an increased risk of postoperative hemorrhage after tonsillectomy in adults. SETTING: Tertiary referral hospital. DESIGN: A retrospective 1:3 case-control study (19 post-tonsillectomy hemorrhage [PTH] cases versus a sample of 58 controls stratified by age and sex). SUBJECTS: Adults over 17 years of age who underwent tonsillectomy from 1989 to 1999 were included. MAIN OUTCOME MEASUREMENTS: Height, weight, percentage of excess weight, body area, systolic and diastolic blood pressure, smoking, drinking, hemoglobin and hematocrit levels, platelet count, partial thromboplastin time, prothrombin activity, fibrinogen, ASA index (physical state classification of the American Society of Anesthesiology), and history of peritonsillar abscess. RESULTS: The risk of PTH in adults was greater in patients with systolic blood pressure > or = 140 mm Hg (OR = 9.46, p = 0.01) and low hematocrit (< 37 for women and < 42 for men, OR = 3.46, p = 0.04). Hemoglobin levels < 12.5 also resulted in an increased risk of PTH in women (OR = 4.79, p = 0.058). CONCLUSIONS: Our findings show that systolic hypertension and anemia may be significant risk factors for PTH in adults.

[Diagnosis and treatment of sensorineural hearing deficits of autoimmune origin]. / Diagnóstico y tratamiento de la hipoacusia neurosensorial de origen autoinmune.

Sensorineural hearing loss (SHL) of autoimmune origin is characterized by a rapidly progressive onset. Diagnosis is difficult and the condition responds to corticoids or immunosuppressant agents. Two cases with an onset over weeks and progressive hearing loss are reported. Both patients had SHL associated with another autoimmune disease. Laboratory findings were abnormal (immunoglobulins and lymphocyte populations), suggesting an immune disorder. Treatment with 1 mg/kg/day of deflazacort restored hearing to normal. Both patients are currently asymptomatic. The clinical and laboratory response of patients to deflazacort supported the diagnosis of autoimmune SHL.

Un paciente con vértigo y mareo asociado a migraña

La cefalea y el mareo constituyen problemas de salud en la población española que originan millones La asociación de vértigo y migraña en un mismo individuo pueden disminuir considerablemente su calidad de vida, convirtiéndole en un usuario recuentador de consultas y un consumidor habitual de fármacos. El vértigo y el mareo asociado a migraña (VMAM) es una entidad caracterizada por un polimorfismo clínico, que cursa con un trastorno recurrente del equilibrio. La migraña no suele guardar relación con el mareo y puede incluso estar ausente. El VMAM requiere un abordaje terapéutico múltiple que debe incluir el control de los factores desencadenantes y el estrés, el ritmo de sueño, la rehabilitación vestibular y la farmacoterapia (AU)

[Diagnosis of common causes of vertigo using a structured clinical history]. / Diagnóstico de causas frecuentes de vértigo mediante historia clínica estructurada.

The structured clinical history is the most sensitive test for diagnosing vertigo. Its diagnostic effectiveness on the first visit was analyzed and key signs and symptoms with high predictive value for common causes of vertigo were identified. One hundred outpatients who complained of dizziness or loss of balance were evaluated using a structured clinical interview. Each questionnaire was examined independently by three blinded investigators, who assigned a diagnosis and identified the elements of the history that figured most prominently in the diagnosis. The gold standard was defined as independent selection of the same diagnostic category by all three investigators. A first-visit diagnosis was obtained in 40% of patients (95% confidence interval 30-50%): 38% women and 42% men. Causes included benign positional paroxysmal vertigo (BPPV, 13 patients), headache-associated vertigo (9), Meniere disease (7), cervical vertigo (3), psychiatric dizziness (2), post-traumatic vertigo (2), vertebro-basilar transient ischemic attack (1), vestibular neuritis (1), convulsive seizure (1), and presyncope (1). The best predictors of BPPV were the precipitating mechanism (specificity [SP] 100%), positional nystagmus (sensitivity [SE] 90%, SP 63%), and the Dix-Hallpike test (SE 82%, SP 71%). Elements predictive of headache-associated vertigo were duration of the attack (minutes) and a personal history of headache (both, SP 100%). Other predictors were facial hypoesthesia (SE 92%, SP 47%) and associated neurological disease (SE 82%, SP 58%).