Asymptomatic Relatives Of Patients Research Articles

Neurocysticercosis: The duration of its preclinical phase relies on the parasite location.

Neurocysticercosis (NC) is a heterogeneous disease particularly in terms of response to treatment and prognosis. Parasite localization is one of the main factors involved in this heterogeneity. In this study we aim to determine whether differences in the duration of the preclinical phase associated with parasite location, could contribute to said heterogeneity. Ninety-nine patients were included, 24 with parasites in the parenchyma (PAR), 56 in the subarachnoid (SA) space and 19 in the ventricular system (IV). A questionnaire designed to assess exposure to classic NC risk factors 5, 10, 15, 20 and more than 20 years prior to diagnosis was applied. The results were compared between the three groups. Also, asymptomatic relatives of patients who had shared their living conditions in childhood or more recently were included and underwent brain scan and blood testing for specific antibodies. Over the course of their lives, exposure to risk factors decreased significantly for all patients, although the decrease was more evident in patients with parasites in the SA space (p < 0.001) compared to patients with PAR (p = 0.011) or IV cysts (p = 0.020). Five years prior to diagnosis, exposure to risk factors was significantly higher in patients with PAR or IV NC than in patients with SA NC (p = 0.04). Furthermore, individuals in close contact with PAR or IV patients in the years preceding diagnosis were more likely to have asymptomatic NC, specific antibodies in sera, particularly IgM, compared to individuals in close contact with SA patients during the same period. All these findings are highly suggestive of the possibility of a more recent infection of patients affected by parenchymal and ventricular NC than of patients with subarachnoid NC. Consequently, subarachnoid disease could be considered a chronic disease, which, probably contributes to the severity of the disease as well as the minimal response to medical treatment.

Electroencephalographic findings in asymptomatic relatives of patients with juvenile myoclonic epilepsy: relationship with the degree of kinship.

A prevalence of 1 to 71% of electroencephalogram (EEG) abnormalities has been reported in asymptomatic relatives of patients with juvenile myoclonic epilepsy (JME). To determine the frequency of EEG abnormalities in asymptomatic relatives of patients with JME according to the degree of kinship. Prospective, analytical study. First-, second, and third-degree relatives of patients with JME who agreed to participate and signed informed consent were included. The analysis was descriptive, bivariate. 209 asymptomatic relatives were included, out of which 115 (55%) were females and 94 (45%) were males, with a mean age of 35.9 ± 16.9 (range between 6 and 73 years). Forty-four (21.1%) relatives had abnormal EEGs. First-degree relatives (12%) had abnormalities more frequently in comparison with second- and third-degree relatives (p = 0.007). EEG abnormalities were observed in one third of asymptomatic relatives. It is important to highlight that there were more alterations among first-degree relatives. In the future, these findings might enable for the risk of clinically developing the disease to be estimated and for genetic counseling to be provided.

Abnormal temporal lobe morphology in asymptomatic relatives of patients with hippocampal sclerosis: A replication study.

SummaryWe investigated gray and white matter morphology in patients with mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE+HS) and first‐degree asymptomatic relatives of patients with mTLE+HS. Using T1‐weighted magnetic resonance imaging (MRI), we sought to replicate previously reported findings of structural surface abnormalities of the anterior temporal lobe in asymptomatic relatives of patients with mTLE+HS in an independent cohort. We performed whole‐brain MRI in 19 patients with mTLE+HS, 14 first‐degree asymptomatic relatives of mTLE+HS patients, and 32 healthy control participants. Structural alterations in patients and relatives compared to controls were assessed using automated hippocampal volumetry and cortical surface–based morphometry. We replicated previously reported cortical surface area contractions in the ipsilateral anterior temporal lobe in both patients and relatives compared to healthy controls, with asymptomatic relatives showing similar but less extensive changes than patients. These findings suggest morphologic abnormality in asymptomatic relatives of mTLE+HS patients, suggesting an inherited brain structure endophenotype.

Abstract 11134: Subclinical Coronary Plaque Burden in Asymptomatic Relatives of Patients With Documented Premature Coronary Artery Disease

Introduction: A family history of premature coronary artery disease (CAD) is a well-known risk factor for adverse coronary events with age of onset being inversely related to the degree of heritability. Hypothesis: We hypothesized that asymptomatic first degree relatives, of patients with premature CAD, suffer a high burden of subclinical coronary atherosclerosis. Methods: First degree relatives, aged 30-65 years, of patients with a documented coronary revascularization procedure before the age of 40 years, were invited to participate in the study. Participants were matched by age, sex and absence of a family history, with patients referred for coronary CT angiography (CTA) because of atypical angina or non-anginal chest pain. A pooled blinded analysis was performed. The main outcome measure was the number of plaque-affected coronary segments. Results: 88 relatives and 88 symptomatic controls underwent CTA. Treatment of hypertension and dyslipidemia tended to be more common among controls (p=0.06). 4 relatives reported vague symptoms of which none had angiographic signs of obstructive CAD (any luminal stenosis above 50%). The calculated SCORE risk among relatives was generally low (85% having a 10-year risk of ≤1%). Relatives had significantly (p=0.006) more affected segments than controls (0 segments: 29,6% vs. 48,9%, 1-2 segments: 27,3% vs. 31,8%, 3-5 segments: 23,9% vs. 11,4% and ≥6 segments: 19,3% vs. 8,0%). In a multivariable logistic regression analysis, the presence of any CAD (OR 3.16 (1.50;6.70)) as well as non-calcified plaques (OR 2.2 (1.14;4.26)), mixed plaques (OR 6.77 (2.7;16.98)) and calcified plaques (OR 2.34 (1.01;5.43)) were more frequent. Although increased, the presence of obstructive plaques, however, did not differ statistically significantly between relatives and controls (OR 2.58 (0.85;7.83)). Conclusions: Asymptomatic relatives of patients with premature CAD suffer a high coronary plaque burden even when compared with symptomatic patients with an a priori higher risk of CAD. Our results indicate a strong genetic component in the genesis of coronary atherosclerosis and, moreover, underline the limitations of current guidelines on prevention of CAD.

EEG in asymptomatic relatives of idiopathic epilepsy; a prospective study

Introduction: The mainstay of diagnosis in Idiopathic Epilepsies (IE) is the electroencephalogram (EEG). The characteristic EEG of each syndrome is an electrographic endophenotype of the larger clinical phenotype of each and more directly associated with potential gene defects than the full phenotype. Endophenotypes represents primary abnormalities elicited by the gene defect, which, in some patients, blossom into full seizures. Revealing the percentage of abnormal EEGs in asymptomatic relative of patients with IE may help to describe the mode of inheritance that would help the ongoing genetics studies to discover the pathologic gene defect. Method: This is a prospective cohort study to identify the percentage of abnormal EEG in asymptomatic first-degree relatives of patients with IE Results: 20 out of 141 EEGs (14%) of first-degree relatives were abnormal. The abnormalities included generalized polyspikes and waves , generalized 3-Hz spike and waves or centro-temporal spikes in 50% of the abnormal EEGs. 50% of the abnormalities were nonspecific. Conclusion: These results may indicate that the EEG endophenotypes in IEs do not follow a Mendelian pattern of inheritance. Nevertheless, the EEG endophenotype is relatively common and thus genetically simpler than the full epilepsy, which will aid in gene identification

Extensive Phenotyping of Individuals at Risk for Familial Interstitial Pneumonia Reveals Clues to the Pathogenesis of Interstitial Lung Disease

Asymptomatic relatives of patients with familial interstitial pneumonia (FIP), the inherited form of idiopathic interstitial pneumonia, carry increased risk for developing interstitial lung disease. Studying these at-risk individuals provides a unique opportunity to investigate early stages of FIP pathogenesis and develop predictive models of disease onset. Seventy-five asymptomatic first-degree relatives of FIP patients (mean age, 50.8 yr) underwent blood sampling and high-resolution chest computed tomography (HRCT) scanning in an ongoing cohort study; 72 consented to bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsies. Twenty-seven healthy individuals were used as control subjects. Eleven of 75 at-risk subjects (14%) had evidence of interstitial changes by HRCT, whereas 35.2% had abnormalities on transbronchial biopsies. No differences were noted in inflammatory cells in BAL between at-risk individuals and control subjects. At-risk subjects had increased herpesvirus DNA in cell-free BAL and evidence of herpesvirus antigen expression in alveolar epithelial cells (AECs), which correlated with expression of endoplasmic reticulum stress markers in AECs. Peripheral blood mononuclear cell and AEC telomere length were shorter in at-risk individuals than healthy control subjects. The minor allele frequency of the Muc5B rs35705950 promoter polymorphism was increased in at-risk subjects. Levels of several plasma biomarkers differed between at-risk subjects and control subjects, and correlated with abnormal HRCT scans. Evidence of lung parenchymal remodeling and epithelial dysfunction was identified in asymptomatic individuals at risk for FIP. Together, these findings offer new insights into the early pathogenesis of idiopathic interstitial pneumonia and provide an ongoing opportunity to characterize presymptomatic abnormalities that predict progression to clinical disease.

Pilot study of A-FABP levels as a predictive factor of SPECT results in asymptomatic relatives of patients with cardiovascular disease.

A-FABP is a promising link between metabolic syndrome and atherosclerosis. It is not well known whether level of A-FABP predicts results of SPECT. In 82 subjects (53 males) with a median age of 54 years, who were first-degree relatives of patients with cardiovascular disease, the following tests and examinations were performed: A-FABP, calcium score (CS) and SPECT. Subjects with positive and negative SPECT results differed significantly in the noncategorized CS (p = 0.001), uric acid (p = 0.025) and the total cholesterol:high-density lipoprotein ratio (p = 0.043), but not in other parameters (including A-FABP). To predict SPECT results, the best model proved to be a logistic regression model with gender and noncategorized CS as predictors, with an area under the receiver operating characteristic curve of 0.89 (the sensitivity and specificity based on a CS cutoff of 11.1 were 77.78 and 75.34%, respectively). The serum level of A-FABP is not a predictor of a positive SPECT result.

A family study of asymptomatic small bowel Crohn's disease

Discrepancies between severity of lesions and symptoms may be observed in Crohn's disease. We prospectively assessed whether Crohn's disease may be diagnosed among asymptomatic relatives of patients, using Small Bowel Contrast Ultrasonography. Diagnosis of asymptomatic Crohn's disease relatives was defined ultrasonographically as: bowel wall thickness >3mm, bowel dilation/stricture, lumen diameter >2.5 cm. Diagnosis was confirmed by ileocolonoscopy. Subjects were also screened for the Leu3020insC mutation. Consent was given by 35 asymptomatic first-degree relatives of 18 Crohn's disease patients. Ultrasonography indicated increased bowel wall thickness (5mm) compatible with ileal Crohn's disease in 1 relative (2.8%), a 42 year-old male. Ileocolonoscopy, histology, and radiology confirmed the diagnosis of stricturing ileal Crohn's disease. Gallbladder stones were detected in 7/35 (20%) relatives and Leu3020insC mutation in 3/35 (8.5%). Small Bowel Contrast Ultrasonography may be a useful tool to diagnose asymptomatic small bowel Crohn's disease among first-degree relatives of patients.

Congenital Genetic Inborn Errors of Metabolism Presenting as an Adult or Persisting Into Adulthood: Neuroimaging in the More Common or Recognizable Disorders

Numerous congenital-genetic inborn errors of metabolism (CIEMs) have been identified and characterized in detail within recent decades, with promising therapeutic options. Neuroimaging is becoming increasingly utilized in earlier stages of CIEMs, and even in asymptomatic relatives of patients with a CIEM, so as to monitor disease progress and treatment response. This review attempts to summarize in a concise fashion the neuroimaging findings of various CIEMs that may present in adulthood, as well as those that may persist into adulthood, whether because of beneficial therapy or a delay in diagnosis. Notably, some of these disorders have neuroimaging findings that differ from their classic infantile or early childhood forms, whereas others are identical to their early pediatric forms. The focus of this review is their appearance on routine magnetic resonance imaging sequences, with some basic attention to the findings of such CIEMs on specialized neuroimaging, based on recent or preliminary research. The general classes of disorders covered in this complex review are: peroxisomal disorders (adrenoleukodystrophy), lysosomal storage disorders (including metachromatic leukodystrophy, Krabbe or globoid cell leukodystrophy, Fabry, Niemann-Pick, GM1, GM2, Gaucher, mucopolysaccharidoses, and Salla diseases), mitochondrial disorders (including mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes, myoclonic epilepsy with ragged red fibers, Leigh disease, and Kearns-Sayre syndrome), urea cycle disorders, several organic acidemias (including phenylketonuria, maple syrup urine disease, 3-hydroxy-3-methylglutaryl colyase deficiency, glutaric acidurias, methylmalonic academia, proprionic academia, 3-methylglucatonic aciduria, and 2-hydroxyglutaric acidurias), cytoskeletal or transporter molecule defects (including Alexander or fibrinoid leukodystrophy, proteolipid protein-1 defect or Pelizaeus Merzbacher, Wilson, and Huntington diseases), and several neurodegenerative disorders of brain iron accumulation. Additionally, an arbitrary "miscellaneous" category of 5 recognizable disorders that may present in or persist into adulthood is summarized, which include megalencephalic leukoencephalopathy with subcortical cysts (megancephalic leukoencephalopathy with subcortical cysts or van der Knaap disease), polymerase-III gene defect ("4H syndrome"), childhood ataxia with central nervous system hypomyelination ("vanishing white matter disease"), striopallidodentate calcinosis ("Fahr disease"), and Cockayne syndrome.

Combination of factor V Leiden and MTHFR mutations in myocardial infarction

Identifying patients who are at high risk of suffering myocardial infarction can be done by determining risk factors or by the adoption of molecular genetic testing for inherited thrombophilia. We report a case of myocardial infarction at a young age. The patient complained of dyspnea (stage III) and a burning pain of severe intensity that radiated to the left retrosternal side, but was not associated with palpitations or diaphoresis. A number of biochemical parameters were normal except for an elevated creatinine phosphokinase (CPK) level. Genetic testing revealed the subject to be heterozygous for both the factor V leiden and MTHFR C677T polymorphisms. The combination of these two mutations may be a high risk factor for myocardial infarction. Genetic screening for inherited thrombophilia in young patients, especially in the presence of a common risk factor, may be useful for primary thromboprophylaxis and in asymptomatic relatives of patients.

Nonbiopsy Diagnosis of Celiac Disease

See “Utility of the New ESPGHAN Criteria for the Diagnosis of Celiac Disease in At-risk Groups” by Kurppa et al on page 387. Recently, the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition released its updated guidelines on the diagnosis of celiac disease (CD) (1). These guidelines are timely, detailed, and thoughtful, and the recommendations reflect changes in our understanding of CD that have occurred since the guidelines of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition were published in 2005 (2). Although many of the recommendations are similar to those published previously, 2 new recommendations deserve mention. The first is a broader definition of CD that incorporates a “variable combination of gluten-dependent clinical manifestations, CD-specific antibodies, HLA-DQ2 and DQ8 haplotypes, and enteropathy.” This definition diminishes the relative diagnostic importance of the biopsy so as to include symptomatic individuals who may have positive serological tests that precede histological changes by up to 2 years (3–5). The definition will need to be tested over time, particularly in light of the emerging concept of non-CD gluten sensitivity (6). Distinguishing between CD and non-CD gluten sensitivity may have prognostic and therapeutic implications that have yet to be identified, and the distinction could be dependent on the presence or absence of an enteropathy. The second is the suggestion to omit a biopsy in symptomatic patients with tissue transglutaminase (tTG) antibody levels >10 times above the upper limit of normal provided they are also both endomysial antibody (EMA) positive and human leukocyte antigen (HLA)-DQ2 and/or -DQ8 heterodimer positive. To some these recommendations represent a radical change in thinking and will no doubt generate discussion. Although guidelines are helpful to the practicing clinician, the data upon which they are based are often generated in a research setting and may be subject to some bias. Therefore, the recommendations require testing in a real-world setting so that adjustments can be made if necessary. The article by Kurppa et al (7) in this issue of the Journal attempts to do just that. Their study involved >3000 family members and relatives of patients with CD. Subjects were screened for tTG and EMA antibodies and were grouped according to the level of red blood cell (RBC)-tTG2 antibodies into negative (<20 U), weakly positive (20–29 U), moderately positive (30–99 U), and strongly positive (>100 U). Seropositive subjects were tested for HLA-DQ alleles and offered intestinal biopsy. The strongly positive tTG correlated well with positive EMA and DQ2/8, and in 94% of those who underwent a biopsy, the diagnosis of CD was confirmed. These results support the suggestion that in certain circumstances, a biopsy is not necessary to diagnose CD. In contrast, the association between moderately or weakly positive tTG and positivity for EMA, celiac-type HLA, and biopsy evidence for CD was poor. It is noteworthy that the subjects in the present study were asymptomatic relatives of patients with CD, and a tTG level >5 times the upper limit of normal was designated strongly positive. This differs from the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines, which suggests omitting biopsies only in symptomatic individuals and uses a tTG >10 times the upper limit of normal (1). Does this study mean we are now ready to abandon biopsies in individuals who have “strongly” positive tTG levels together with EMA and CD-type HLA positivity? A diagnosis of CD should not be made lightly, given that it entails strict lifelong adherence to a burdensome dietary change. Although the ultimate goal is to confidently diagnose CD without the need for a biopsy, there are still some hurdles to overcome. Kurppa et al discuss some discrepancies with other studies that may be dependent on variables in age and pretest probability in the population under study. Additionally, in the United States, there is presently no standardization of CD tests, and wide interlaboratory variation in test results on the same serum samples of patients with known CD has been documented (8). The intestinal biopsy is an invasive procedure, the lesions can be patchy, proper orientation of the specimens is not standardized, and interpretation is subjective. Despite these limitations, intestinal biopsies will continue to play an important role in the diagnosis of CD in the majority of cases for the foreseeable future. Hopefully, there will be further improvements in the reliability of noninvasive tests, and additional studies will confirm the findings of Kurppa et al in other populations. Nonbiopsy diagnosis of CD can be likened to the young child who asks his parents shortly after starting a long journey “are we nearly there yet?” In both cases, the answer is “there is still a long way to go but we are headed in the right direction.”

Derivation and Validation of a Simple Exercise-Based Algorithm for Prediction of Genetic Testing in Relatives of LQTS Probands

Genetic testing can diagnose long-QT syndrome (LQTS) in asymptomatic relatives of patients with an identified mutation; however, it is costly and subject to availability. The accuracy of a simple algorithm that incorporates resting and exercise ECG parameters for screening LQTS in asymptomatic relatives was evaluated, with genetic testing as the gold standard. Asymptomatic first-degree relatives of genetically characterized probands were recruited from 5 centers. QT intervals were measured at rest, during exercise, and during recovery. Receiver operating characteristics were used to establish optimal cutoffs. An algorithm for identifying LQTS carriers was developed in a derivation cohort and validated in an independent cohort. The derivation cohort consisted of 69 relatives (28 with LQT1, 20 with LQT2, and 21 noncarriers). Mean age was 35±18 years, and resting corrected QT interval (QTc) was 466±39 ms. Abnormal resting QTc (females ≥480 ms; males ≥470 ms) was 100% specific for gene carrier status, but was observed in only 48% of patients; however, mutations were observed in 68% and 42% of patients with a borderline or normal resting QTc, respectively. Among these patients, 4-minute recovery QTc ≥445 ms correctly restratified 22 of 25 patients as having LQTS and 19 of 21 patients as being noncarriers. The combination of resting and 4-minute recovery QTc in a screening algorithm yielded a sensitivity of 0.94 and specificity of 0.90 for detecting LQTS carriers. When applied to the validation cohort (n=152; 58 with LQT1, 61 with LQT2, and 33 noncarriers; QTc=443±47 ms), sensitivity was 0.92 and specificity was 0.82. A simple algorithm that incorporates resting and exercise-recovery QTc is useful in identifying LQTS in asymptomatic relatives.

Section 5: Management of Asymptomatic Patients with Reduced Left Ventricular Ejection Fraction

Section 5: Management of Asymptomatic Patients with Reduced Left Ventricular Ejection Fraction

Evaluation of Corneal Topography With Orbscan II in First-degree Relatives of Patients With Keratoconus

To evaluate the corneal topographic characteristics of first-degree relatives of patients with keratoconus with corneal topography to determine the incidence of clinical keratoconus and topographic abnormalities. Between February and August 2006, Orbscan II analysis was done in 144 eyes of 72 cases who were first-degree relatives of patients diagnosed with clinical keratoconus. The findings were compared with preoperative Orbscan analyses of 52 clinically normal individuals who underwent laser in situ keratomileusis surgery and did not develop corneal ectasia in 3 years of follow-up. In 8 of the 72 first-degree relatives of patients with keratoconus, clinical keratoconus was diagnosed by the topographic pattern in Orbscan and clinical examination (group 1). The remaining 64 subjects (group 2) were compared with the control group (group 3). The central corneal thickness was 523.7 +/- 40.4 microm in group 2, whereas it was 546.3 +/- 33.1 microm in group 3 (P < 0.05). The central corneal thickness, thinnest pachymetric reading, posterior elevation value, distance between the greatest anterior/posterior elevation points, and corneal center, posterior best fit sphere (BFS) values, posterior BFS:anterior BFS ratio, and irregularity values were significantly different between group 2 and group 3 (P < 0.05). The keratoconus incidence was found to be 11% in first-degree relatives of patients with keratoconus as opposed to a reported incidence of keratoconus of 0.05% in the general population. In first-degree relatives of patients with keratoconus who did not have a topographic keratoconus pattern, abnormal corneal topographic values were detected. The asymptomatic relatives of patients with keratoconus should undergo a thorough preoperative analysis for subtle topographic abnormalities before any keratorefractive surgery.

Can antiheart autoantibodies predict disease risk in asymptomatic relatives of patients with dilated cardiomyopathy?

Can antiheart autoantibodies predict disease risk in asymptomatic relatives of patients with dilated cardiomyopathy?

Asymptomatic kindred of patients with coronary events have increased peripheral T-cell activities

T cells are involved in the pathogenesis of atherosclerosis. We aimed to search for any association between the peripheral T-cell activities and atherogenic risk factors in healthy subjects. Fifty male volunteers (age 22.0 +/- 2.4 years) were enrolled. No subject had any chronic disease or was under any drug treatment. Lymphocytes were isolated from heparinized venous blood and the proliferative responses to phytohemagglutinin (PHA) were measured from the amount of radioactive thymidine uptake by the lymphocyte DNA. T-cell activity responses of patients with a family history of coronary events were compared with others. The activity responses of smokers were compared with nonsmokers. Subjects with a positive family history of coronary events had higher PHA stimulated T-cell response and delta cpm (P < 0.05 for each). Total and low-density lipoprotein cholesterol levels of the subjects with a positive family history of cardiovascular events were positively correlated with the PHA-activated T-cell responses (P = 0.022, r = 0.604 and P = 0.015, r = 0.635, respectively). There was no significant difference between the T-cell activity responses of smokers and nonsmokers. No correlation was found between the biochemical parameters and T-cell activities in these groups. Peripheral T-cell activity responses to PHA are higher in the asymptomatic relatives of patients with coronary events. This may be a clue for the familial tendency of atherosclerotic diseases. Further follow-up studies are necessary to investigate the relationship.

Echocardiographic Evaluation in Asymptomatic Relatives of Patients With Dilated Cardiomyopathy Reveals Preclinical Disease

Echocardiographic Evaluation in Asymptomatic Relatives of Patients With Dilated Cardiomyopathy Reveals Preclinical Disease

Echocardiographic Evaluation in Asymptomatic Relatives of Patients with Dilated Cardiomyopathy Reveals Preclinical Disease

Idiopathic dilated cardiomyopathy is often familial, and apparently healthy relatives may have latent, early, or undiagnosed established disease. To determine the prevalence and natural history of asymptomatic cardiac abnormalities among sampled relatives of unselected patients referred for management of dilated cardio-myopathy. Prospective cohort study. 767 asymptomatic relatives of 189 consecutive unselected patients with dilated cardiomyopathy. Clinical evaluation, including history, physical examination, electrocardiography, and echocardiography, was performed. Participants were classified in accordance with published echocardiographic criteria. Sampled relatives who did not have evidence of dilated cardiomyopathy at the initial evaluation were followed for a median of 57 months (range, 1 to 133 months). Of the 767 patients evaluated, 592 (77.2%) were assessed as healthy, 35 (4.6% [95% CI, 3.7% to 7.6%]) had dilated cardiomyopathy, 119 (15.5% [CI, 12.5% to 18.8%]) had left ventricular enlargement without systolic dysfunction, and 21 (2.7% [CI, 1.9% to 4.9%]) had depressed fractional shortening without ventricular dilatation. At follow-up, progression to dilated cardiomyopathy occurred in 13 (10%) relatives with left ventricular enlargement or depressed fractional shortening versus 3 (1.3%) healthy relatives. In a multivariate model, only left ventricular enlargement or depressed fractional shortening independently predicted progression to dilated cardiomyopathy (hazard ratio, 10.0 [CI, 2.8 to 35.5]; P < 0.001). Because relatives had to be willing to participate and be available geographically, selection bias may have occurred. Treatable asymptomatic dilated cardiomyopathy was identified in 4.6% of asymptomatic relatives. In addition, left ventricular enlargement and depressed fractional shortening were common in asymptomatic relatives of patients with dilated cardiomyopathy and were associated with a statistically significant medium-term risk for disease progression. Evaluation of relatives of patients with cardiomyopathy is recommended.

Multidisciplinary Diagnostic Approach for Left Ventricular Hypertrabeculation/Noncompaction

The report on three patients with asymptomatic left ventricular hypertrabeculation/noncompaction (LVHT) by Koh et al.1 is stimulating but also raised the following concerns. In light of recent reports about patients in whom LVHT developed during their lifetimes,2,3 we regard discussing LVHT as a form of cardiomyopathy1 as unjustified. Though LVHT appears to be congenital in the majority of cases, particularly in cases involving children and young adults, it is verifiably acquired in single cases.2,3 Unfortunately, the pathomechanism of LVHT has neither been discovered for the acquired nor the congenital form. The most frequently presumed and discussed pathomechanisms for acquired LVHT are: (1) it is a compensatory mechanism of an impaired myocardium or (2) it results from destruction of the impaired myocardium by the intra-ventricular pressure. Congenital LVHT is most frequently attributed to an arrest of the physiologic intrauterine compaction process during embryonic heart development. Since long-term follow-up data about the diagnosis of LVHT are lacking, it is speculative to state that LVHT is associated with increased morbidity and mortality in the patients described by Koh et al. Since it is under debate if LVHT is an indication for oral anti-coagulation, we propose oral anti-coagulation only if decreased systolic function or atrial fibrillation is also present. This approach is substantiated by findings from a series of 62 patients of which thrombo-embolic events were found in only 10% of the patients with LVHT but in 15% of age-, sex- and left ventricular function-matched controls.4 LVHT is frequently found in patients with neuromuscular disorders. LVHT has been reported in association with Duchenne or Becker muscular dystrophy, myotonic dystrophy type 1, dystrobrevinopathy, Pompe's disease, myoadenylate-deaminase deficiency, mitochondriopathy, cypher gene mutations, centronuclear myopathy, Friedreich ataxia, Barth syndrome, or various other rare genetic disorders.5-10 Since atrio-ventricular block is a common feature of neuromuscular disorders with cardiac involvement, particularly in myotonic dystrophy, it appears essential to investigate each patient neurologically with appropriate examinations to exclude neuromuscular disorders as the underlying cause of LVHT. It is stated that LVHT is an extremely rare disorder.1 However, in our experience LVHT is more prevalent than previously thought particularly if asymptomatic relatives of patients with proven LVHT also undergo cardiac examinations. In an adult echocardiographic laboratory the prevalence of LVHT amounted to 0.25%/year.11 The true prevalence of LVHT among the general population is, however, unknown since no screening investigations have been carried out thus far. Establishing the diagnosis of LVHT is dependent on the echocardiographer's awareness and experience, the applied transducer frequencies, and the applied diagnostic criteria. So far, three different definitions of LVHT have been proposed.5,12,13 Since there is no consensus about the accuracy and applicability of these definitions, it is desirable to know if LVHT in the described patients also fulfils diagnostic criteria other than the applied. Furthermore, we cannot understand how the ratio between a non-compacted and a compacted layer can be easily calculated at endsystole, particularly in small, well-contracting left ventricles. Cardiac computed tomography represents a radiographic technique with a high radiation burden. An additionally supplied contrast medium is cost expensive. Cardiac MRI carries a much lower risk for side effects. Extensive trabeculations found at autopsy in 68% of normal hearts refers to a number of up to three trabeculations. More than three trabeculations were found in only 4% of the normal hearts.14 The following anatomical findings were the bases for Stollberger's LVHT definition: more than > 3 coarse, prominent trabeculations apically to the papillary muscles on echocardiography, which have the same echogenicity as the myocardium, move synchronously with it, are not connected to the papillary muscles, and are surrounded by intertrabecular spaces, which are perfused from the ventricular cavity.5 Finally, the diagnosis of a lumbar disc prolapse is questionable in a patient with bilateral radicular pain. Was there any indication for vertebral stenosis, discitis, or polyradiculitis? Did the patient's symptoms completely resolve after surgery? In conclusion, LVHT is a rare cardiac abnormality of which the underlying etiology and pathomechanism are poorly understood. LVHT requires special attention not only of the cardiologist but also of the neurologist. Furthermore, special consideration is also required of the pediatrician in childhood and juvenile cases.

Recognition memory abnormalities in asymptomatic biological parents of a patient with schizophrenia.

Recognition memory dysfunction has been frequently reported in schizophrenic populations, and has been linked with the development of delusions and thought disorder. A range of neuropsychological abnormalities have also been documented in the biological asymptomatic relatives of patients with schizophrenia; however, recognition memory has not been one of them. This study was carried out in order to investigate: (i) verbal and facial recognition memory in terms of accuracy and false alarm rates; and (ii) contributions from the episodic and semantic memory systems to recognition memory, in the biological asymptomatic parents of a reported schizophrenic patient and a set of male and female psychotic controls. Gender differences failed to emerge between the psychotic controls on any of the recognition measures (discrimination accuracy, response bias, hit and false alarm rates, 'remember' and 'know' recognition memory decisions). However, there was evidence of recognition dysfunction in the female relative, and to a lesser extent, in the male. Both parent's recognition memory performance profiles were marked by a pathologically elevated false alarm rate, and an increased dependence 'remember' judgements, i.e. input from the episodic memory system, to drive recognition memory decisions. These findings are discussed in the context of models of episodic and semantic memory impairment in schizophrenia.