The diagnostic test accuracy of a screening questionnaire and algorithm in the identification of adults with epilepsy.

OBJECTIVE: Accurate estimates of the incidence and prevalence of epilepsy allow us to better assess its societal impact. Prevalence and incidence studies often use unvalidated screening tools resulting in estimates of uncertain accuracy. We present the Canadian Longitudinal Study on Aging-Epilepsy Algorithm (CLSA-EA) as well as the results of our validation study designed to estimate the diagnostic accuracy of this epilepsy ascertainment algorithm. METHODS: We administered English or French-language versions of the CLSA-EA questionnaire to a consecutive sample of participants from a population-based cohort of 50,000 individuals aged between 45 and 85 years at baseline, as well as a consecutive sample of individuals from an epilepsy-enriched general neurology clinic. Every participant was also assessed by a study neurologist who, blinded to the results of the CLSA-EA, determined whether the person had epilepsy or not. RESULTS: We recruited 242 consecutive participants, 34 of whom were diagnosed with epilepsy by a study neurologist. The sensitivity and specificity of the CLSA-EA for a lifetime history of epilepsy were 97.1% and 98.1%, and for active epilepsy were 100% and 98.6%, when we defined a positive screening test result as a positive response to the antiepileptic drug question and either the single self-report diagnosis or any of the symptom-based questions. SIGNIFICANCE: The CLSA-EA was found to have a high sensitivity and specificity for the identification of adults with a lifetime history of epilepsy and active epilepsy. Although validation in other settings and age groups is required, the future application of this algorithm to population-based studies such as the CLSA should help to ensure more accurate estimates of the prevalence and incidence of epilepsy in the general population when a physician assessment is impossible.

Canadian epileptologists' counseling of drivers amidst guideline inconsistencies.

BACKGROUND: Epilepsy is a common medical condition for which physicians perform driver fitness assessments. The Canadian Medical association (CMA) and the Canadian Council of Motor transportation administrators (CCMTA) publish documents to guide Canadian physicians' driver fitness assessments. OBJECTIVES: We aimed to measure the consistency of driver fitness counseling among epileptologists in Canada, and to determine whether inconsistencies between national guidelines are associated with greater variability in counseling instructions. METHODS: We surveyed 35 epileptologists in Canada (response rate 71%) using a questionnaire that explored physicians' philosophies about driver fitness assessments and counseling practices of seizure patients in common clinical scenarios. Of the nine scenarios, CCMTA and CMA recommendations were concordant for only two. Cumulative agreement for all scenarios was calculated using Kappa statistic. Agreement for concordant (two) vs. discordant (seven) scenarios were split at the median and analyzed using the Wilcoxon signed rank sum test. RESULTS: Overall the agreement between respondents for the clinical scenarios was not acceptable (Kappa=0.28). For the two scenarios where CMa and CCMta guidelines were concordant, specialists had high levels of agreement with recommendations (89% each). A majority of specialists disagreed with CMa recommendations in three of seven discordant scenarios. The lack of consistency in respondents' agreement attained statistical significance (p<0.001). CONCLUSIONS: Canadian epileptologists have variable counseling practices about driving, and this may be attributable to inconsistencies between CMa and CCMta medical fitness guidelines. This study highlights the need to harmonize driving recommendations in order to prevent physician and patient confusion about driving fitness in Canada.

Genotype-phenotype correlation in interstitial 6q deletions: a report of 12 new cases.

Interstitial deletions of 6q are associated with variable phenotypes, including growth retardation, dysmorphic features, upper limb malformations, and Prader-Willi (PW)-like features. Only a minority of cases in the literature have been characterized with high resolution techniques, making genotype-phenotype correlations difficult. We report 12 individuals with overlapping, 200-kb to 16.4-Mb interstitial deletions within 6q15q22.33 characterized by microarray-based comparative genomic hybridization to better correlate deletion regions with specific phenotypes. Four individuals have a PW-like phenotype, though only two have deletion of SIM1, the candidate gene for this feature. Therefore, other genes on 6q may contribute to this phenotype including multiple genes on 6q16 and our newly proposed candidate, the transcription cofactor gene VGLL2 on 6q22.2. Two individuals present with movement disorders as a major feature, and ataxia is present in a third. The 4.1-Mb 6q22.1q22.2 critical region for movement disorders includes the cerebellar-expressed candidate gene GOPC. Observed brain malformations include thick corpus callosum in two subjects, cerebellar vermal hypoplasia in two subjects, and cerebellar atrophy in one subject. Seven subjects' deletions overlap a ~250-kb cluster of four genes on 6q22.1 including MARCKS, HDAC2, and HS3ST5, which are involved in neural development. Two subjects have only this gene cluster deleted, and one deletion was apparently de novo, suggesting at least one of these genes plays an important role in development. Although the phenotypes associated with 6q deletions can vary, using overlapping deletions to delineate critical regions improves genotype-phenotype correlation for interstitial 6q deletions.

Sanfilippo syndrome type D: natural history and identification of 3 novel mutations in the GNS Gene.

BACKGROUND: Mucopolysaccharidosis type IIID (MPS-IIID), or Sanfilippo syndrome type D, is a rare autosomal recessive lysosomal storage disorder caused by mutations in the N-acetylglucosamine-6-sulfatase (GNS) gene, leading to impaired degradation of heparan sulfate. OBJECTIVES: To report the natural history of MPS-IIID in 2 siblings described by Kaplan and Wolfe in 1987 and to study the phenotype in 2 other unrelated families with MPS-IIID. Design, Setting, and Patients Case series of 4 patients with MPS-IIID: 2 siblings followed up at the Montreal Neurological Hospital and Institute, 1 patient followed up at the UZ Brussel, and 1 patient recruited through the prenatal counseling program at the UZ Brussel. MAIN OUTCOME MEASURES: Clinical and molecular data collected from 3 families with enzyme-based diagnosis of MPS-IIID. RESULTS: The course of the disease was characteristic of MPS-IIID in all patients, although survival may be longer than was previously reported. In family 1, both siblings were homozygous for a novel nonsense mutation in the GNS gene (c.1168C>T). In family 2, the proband carried a heterozygous mutation occurring in a splice recognition site in the intron 7 boundary (c.876-2A>G). The second mutation in this patient remains to be identified. In family 3, the proband was homozygous for a novel frameshift mutation in GNS due to the insertion of 5 nucleotides (c.1138_1139insGTCCT). CONCLUSIONS: Major issues in the care of patients with MPS-IIID include behavioral problems, sleep problems, recurrent infections, dysphagia, and pain from orthopedic complications. To date, all mutations in GNS predict protein truncation, and there is no obvious genotype-phenotype correlation.

The Diagnostic Accuracy of Prolonged Ambulatory Versus Routine EEG.

Prolonged ambulatory electroencephalography (paEEG) is increasingly used in clinical practice but its diagnostic accuracy relative to that of routine EEG (rEEG) remains uncertain. We examined a consecutive sample of 72 individuals who had undergone 32-channel paEEG immediately after an rEEG, creating perfectly matched EEG samples. Each recording was prospectively assessed for epileptiform discharges (ED) and nonepileptiform abnormalities. The median paEEG duration was 22.5 hours (interquartile range: 22.0-23.0). The sensitivity of paEEG was 2.23 times greater than that of rEEG [sensitivity ratio: 2.23 (95% CI=1.49-3.34)] if a positive test was limited to the presence of epileptiform discharges. This benefit of paEEG versus rEEG was no longer evident if the definition of a positive test included nonepileptiform abnormalities (sensitivity ratio 1.26; 95% CI=1.02-1.55). The specificity of the 2 tests was not evidently different (specificity ratio 0.67; 95% CI=0.17-2.67). Twenty-six percent of paEEG recorded epileptic seizures while none of the rEEG did (absolute difference 26.0% (95% CI=11.8-40.2). Our findings quantify the benefit of 32-channel paEEG, relative to rEEG, and support its role in the diagnosis and characterization of epilepsy.

Post-ictal rage and aggression: a video-EEG study.

Post-ictal rage and aggression have been mentioned in the literature but have rarely been documented by video-EEG recording. We studied a patient with dramatic, episodic, seizure-related rage and violence. This mentally retarded man had a lifelong history of seizures. He developed increasing episodic rage and aggression. Caregivers were afraid of him, although there was no record of directed violence. In one of these episodes he fractured his tibia and fibula. Interictal discharges arose from both temporal areas independently. He had focal seizures with secondary generalization. Immediately after cessation of the ictal discharge he became greatly agitated, with undirected aggression, loud screaming, kicking and fighting against the restraints. A video sequence illustrates the behavior. Imaging studies showed bilateral, periventricular, nodular heterotopia in the lateral aspect of both temporal horns and the trigones. Increasingly frequent, severe bursts of rage and aggression were proven to be post-ictal. Documented attacks occurred while he was restrained and this may have been a factor in their severity. Such attacks however, have been described while he was not restrained and these increased in severity and frequency over time. Developmental abnormalities with periventricular, nodular heterotopia in the region of the trigones and inferomesial temporal areas are considered to be causally related to his retardation and epilepsy. [Published with video sequences].

Two-dimensional echocardiography estimation of right ventricular ejection fraction by wall motion score index.

BACKGROUND: Radionuclide angiography (RNA) and echocardiography (biplane Simpson method) are the most accepted methods for right ventricular ejection fraction (RVEF) evaluation. The authors tried to determine a new method to measure RVEF based on wall motion score index (WMSI). OBJECTIVES: One hundred forty-one patients with RV dysfunction had transthoracic echocardiography (TTE) evaluation of the right ventricle. In a first group of 54 patients, a correlation between RVEF using the biplane Simpson method (four chamber and two chamber [4C+2C]) and RV-WMSI was established from a polar map using an eight-segment model to find a regression equation. With the second group of 51 subsequent patients, this equation (RVEF=73.07-20.7 x WMSI), comparing the RVEF-WMSI with the biplane Simpson RVEF (4C+2C), was validated. In a third group of 36 consecutive patients with abnormal RV contractility, the RVEF was calculated by RNA and this RVEF was correlated to the RV-WMSI. RESULTS: The first group of 54 patients had a correlation coefficient of 0.84 between WMSI and RVEF (biplane Simpson method). The results from the second group of 51 patients with RVEF derived from the estimated regression equation correlated well with the biplane Simpson RVEF (r=0.84). The correlation coefficient for these two groups taken together (105 patients), that is, between WMSI and RVEF (biplane Simpson method), was 0.92. The third group of 36 patients with RNA-EF displayed a correlation coefficient of 0.83 with RV-WMSI. CONCLUSION: This new semiquantitative method for estimating RVEF from RV-WMSI is easy to use in routine TTE and shows an excellent correlation with the biplane Simpson method and RNA.

A new tool for estimating left ventricular ejection fraction derived from wall motion score index.

BACKGROUND: Radionuclide angiography (RNA) and echocardiography (biplane Simpson method) are the most accepted techniques for left ventricular ejection fraction (LVEF) assessment. A new method to evaluate LVEF based on the regional wall motion assessment of the LV was attempted. OBJECTIVE: To develop a simple method for LVEF estimation using wall motion score index (WMSI) with transthoracic echocardiography (TTE). METHODS: Two hundred and forty-three patients with abnormal LV contractility had TTE and RNA performed less than three days apart. The WMSI was calculated in all patients using the 16-segment model as proposed by the American Society of Echocardiography. For the first 150 patients, a correlation between LV WMSI and RNA EF was established to create a regression equation. This regression equation (RNA LVEF=92.8-25.8xWMSI) was used on 93 consecutive patients to compare this equation with RNA EF. From the total cohort (243 patients), three subgroups were studied specifically: atrial fibrillation (AF) (n=50 patients), dyskinesia (DK) (n=40 patients) and aneurysm (AN) (n=42 patients). RESULTS: Correlation between RNA EF and WMSI in the first 150 patients was r=0.82. In the second group of 93 consecutive patients, WMSI EF derived from the estimated regression equation correlated well with RNA EF (r=0.86). Correlation remained high in the three subgroups: AF (r=0.87), DK (r=0.87) and AN (r=0.80). In the 111 patients without DK, AN or AF correlation between RNA and the studied method was even higher (r=0.91). In a random subgroup of 54 patients, RNA was compared with the biplane Simpson method (49 of 54 patients, r=0.82). In the same subgroup of 54 patients, the score was modified to allow for mild hypokinesia (score=1.5) and severe hypokinesia (score=2.5) (54 of 54 patients, r=0.83). CONCLUSION: LVEF assessment by this new simple mathematical model using the WMSI is feasible and easy to use during routine TTE. It has excellent correlation with other methods such as biplane Simpson and RNA.