Search

Objective: We aimed to compare long-term social outcomes in young adults with childhood-onset epilepsy (cases) with neurologically normal sibling controls., Methods: Long-term social outcomes were assessed at the 15-year follow-up of the Connecticut Study of Epilepsy, a community-based prospective cohort study of children with newly diagnosed epilepsy. Young adults with childhood-onset epilepsy with complicated (abnormal neurologic exam findings, abnormal brain imaging with lesion referable to epilepsy, intellectual disability (ID; IQ < 60) or informative history of neurologic insults to which the occurrence of epilepsy might be attributed), and uncomplicated epilepsy presentations were compared to healthy sibling controls. Age, gender, and matched-pair adjusted generalized linear models stratified by complicated epilepsy and 5-year seizure-free status estimated adjusted odds ratios (aORs) and 95% confidence intervals [CIs] for each outcome., Results: The 15-year follow-up included 361 individuals with epilepsy (59% of initial cases; N = 291 uncomplicated and N = 70 complicated epilepsy; mean age 22 years [standard deviation, SD 3.5]; mean epilepsy onset 6.2 years [SD 3.9]) and 173 controls. Social outcomes for cases with uncomplicated epilepsy with ≥5 years terminal remission were comparable to controls; cases with uncomplicated epilepsy <5 years seizure-free were more likely to be less productive (school/employment < 20 h/week) (aOR 3.63, 95% CI 1.83-7.20) and not to have a driver's license (aOR 6.25, 95% CI 2.85-13.72). Complicated cases with epilepsy <5 years seizure-free had worse outcomes across multiple domains; including not graduating high school (aOR 24.97, 95% CI 7.49-83.30), being un- or underemployed (<20 h/week) (aOR 11.06, 95% CI 4.44-27.57), being less productively engaged (aOR 15.71, 95% CI 6.88-35.88), and not living independently (aOR 10.24, 95% CI 3.98-26.36). Complicated cases without ID (N = 36) had worse outcomes with respect to productive engagement (aOR 6.02; 95% CI 2.48-14.58) compared to controls. Cases with complicated epilepsy were less likely to be driving compared to controls, irrespective of remission status or ID., Significance: In individuals with uncomplicated childhood-onset epilepsy presentations and 5-year terminal remission, young adult social outcomes are comparable to those of sibling controls. Complicated epilepsy, notable for intellectual disability, and seizure remission status are important prognostic indicators for long-term young adult social outcomes in childhood-onset epilepsy., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

Objective: This study identified items on the Child Behavior Checklist (CBCL) that predict those children and adolescents with epilepsy at highest risk for multiple psychiatric diagnoses., Methods: Three hundred twenty-eight children, ages 5-18 years, and their parents participated in separate structured psychiatric interviews about the children, which yielded Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision (DSM-IV-TR) diagnoses. Parents completed the CBCL. The sample was divided into a younger (≤12 years, n = 214) group and an older (>12-18 years, n = 114) group. This study identified a reduced set of parent-reported CBCL items associated with Multiple Diagnoses versus Single Diagnosis versus No Diagnosis using chi-square tests and stepwise logistic regression. We then performed a generalized logistic regression with Multiple Diagnoses versus Single Diagnosis versus No Diagnosis as the dependent variable and the reduced CBCL set of items as predictors. We calculated the area under the ROC (receiver operating characteristic) curve (AUC) as a measure of diagnostic accuracy for pairwise comparisons., Results: For the younger group, seven items (clingy, cruelty/bullying, perfectionist, nervous, poor school work, inattentive, and sulks) had high diagnostic accuracy (AUC = 0.88), and for the older group, three items (disobedient at school, loner, and lies/cheats) had high accuracy (AUC = 0.91) when comparing children with multiple psychiatric diagnoses to children with no diagnosis. For both age groups, there was less diagnostic accuracy in identifying children with a single versus no diagnosis (AUC = 0.75 [young]; 0.70 [older])., Significance: These findings suggest that responses to these two subsets of parent-reported CBCL items should alert clinicians to children and adolescents with epilepsy at risk for multiple psychiatric diagnoses and in need of a psychiatric referral., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

Objectives: We examined the associations of lifetime and current histories of psychiatric disorders and of suicidal thoughts and behaviors with childhood-onset epilepsies in a community-based cohort of young adults., Methods: Cases were neurotypical (normal neurologic, cognitive, and imaging examinations and no evidence of a brain insult responsible for the epilepsy) young adults with childhood-onset epilepsy followed since the onset of their epilepsy approximately 15 years earlier and recruited as part of a community-based study. They were compared to two different control groups: siblings and external controls from the National Comorbidity Survey-Replication (NCS-R). The Diagnostic Interview Survey assessed lifetime and current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnoses of mood disorders and anxiety disorders. Suicidal thoughts and suicide attempt were assessed using the Diagnostic Interview Survey for Children-IV and the Diagnostic Interview Survey (DIS-IV)., Results: Two hundred fifty-seven cases and 134 sibling controls participated in the DIS-IV portion of the young adult assessment. Comparing cases both to their sibling controls and to the controls drawn from the NCS-R, we did not find any evidence to suggest a higher prevalence of lifetime and current mood or anxiety disorders, suicidal thoughts, and suicide attempt in young adults with childhood-onset epilepsies., Significance: Our findings from a community-based sample of neurotypical young adults do not suggest a substantial or lasting association between childhood epilepsy and psychiatric disorders and suicidal behavior., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)

Objective: Psychogenic nonepileptic seizures (PNES) in youth are symptoms of a difficult to diagnose and treat conversion disorder. PNES is associated with high medical and psychiatric morbidity, but specific PNES risk factors in the pediatric population are not known. We examined if youth with PNES have a distinct biopsychosocial risk factor profile compared to their siblings and if the interrelationships between these risk factors differentiate the PNES probands from the sibling group., Methods: This multisite study included 55 youth with a confirmed diagnosis of PNES (age range 8.6-18.4 years) and their 35 sibling controls (age range 8.6-18.1 years). A video EEG and psychiatric assessment confirmed the PNES diagnosis. Parents reported on each child's past and present medical/epilepsy, psychiatric, family, and educational history. Each child underwent a structured psychiatric interview, standardized cognitive and academic achievement testing, and completed self-report coping, daily stress, adversities, and parental bonding questionnaires., Results: Compared to their siblings, the PNES probands had significantly more lifetime comorbid medical, neurological (including epilepsy), and psychiatric problems; used more medications and intensive medical services; had more higher anxiety sensitivity, practiced solitary emotional coping, and experienced more lifetime adversities. A principal components analysis of these variables identified a somatopsychiatric, adversity, epilepsy, and cognitive component. The somatopsychiatric and adversity components differentiated the probands from the siblings, and were highly significant predictors of PNES with odds ratios of 15.1 (95% CI [3.4, 67.3], and 9.5 (95% CI [2.0, 45.7]), respectively. The epilepsy and cognitive components did not differentiate between the PNES and sibling groups., Significance: These findings highlight the complex biopsychosocial and distinct vulnerability profile of pediatric PNES. They also underscore the need for screening the interrelated risk factors included in the somatopsychiatric and adversity components and subsequent mental health referral for confirmation of the diagnosis and treatment of youth with PNES., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)

Purpose: Neurobehavioral comorbidities are common in pediatric epilepsy with enduring adverse effects on functioning, but their neuroanatomic underpinning is unclear. Striatal and thalamic abnormalities have been associated with childhood-onset epilepsies, suggesting that epilepsy-related changes in the subcortical circuit might be associated with the comorbidities of children with epilepsy. We aimed to compare subcortical volumes and their relationship with age in children with complex partial seizures (CPS), childhood absence epilepsy (CAE), and healthy controls (HC). We examined the shared versus unique structural-functional relationships of these volumes with behavior problems, intelligence, language, peer interaction, and epilepsy variables in these two epilepsy syndromes., Methods: We investigated volumetric differences of caudate, putamen, pallidum, and thalamus in children with CPS (N = 21), CAE (N = 20), and HC (N = 27). Study subjects underwent structural magnetic resonance imaging (MRI), intelligence, and language testing. Parent-completed Child Behavior Checklists provided behavior problem and peer interaction scores. We examined the association of age, intelligence quotient (IQ), language, behavioral problems, and epilepsy variables with subcortical volumes that were significantly different between the children with epilepsy and HC., Key Findings: Both children with CPS and CAE exhibited significantly smaller left thalamic volume compared to HC. In terms of developmental trajectory, greater thalamic volume was significantly correlated with increasing age in children with CPS and CAE but not in HC. With regard to the comorbidities, reduced left thalamic volumes were related to more social problems in children with CPS and CAE. Smaller left thalamic volumes in children with CPS were also associated with poor attention, lower IQ and language scores, and impaired peer interaction., Significance: Our study is the first to directly compare and detect shared thalamic structural abnormalities in children with CPS and CAE. These findings highlight the vulnerability of the thalamus and provide important new insights on its possible role in the neurobehavioral comorbidities of childhood-onset epilepsy., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Purpose: The presence of specific neurocognitive deficits may help explain why school achievement and psychosocial functioning are often worse in children with epilepsy than would be predicted by their global intellectual functioning. This study compared children with two forms of epilepsy: localization-related epilepsy with complex partial seizures (CPS) and childhood absence epilepsy (CAE), to determine whether they display distinct neurocognitive profiles., Methods: Fifty-one children with CPS, 31 children with CAE, and 51 controls underwent neuropsychological testing assessing verbal memory, visual memory, and executive functioning. Groups were compared in these cognitive domains. Within-group analyses were also conducted to examine seizure-related factors that may be related to neuropsychological test performance., Key Findings: When compared to controls, children with CPS showed a mild generalized cognitive deficit, whereas children with CAE did not. When we controlled for intelligent quotient (IQ), both epilepsy groups showed poorer performance relative to controls in the domain of verbal memory. When the epilepsy groups were compared to one another, the CPS group performed significantly poorer than the CAE group on a test of generalized cognitive functioning. However, in the specific domains of executive functioning, verbal memory, and visual memory the epilepsy groups did not differ when compared to one another., Significance: Neurocognitive deficits present in the context of grossly intact global intellectual functioning highlight the importance of neuropsychological screening in both children with CPS and children with CAE., (Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.)

Purpose: To examine whether family history of unprovoked seizures is associated with behavioral disorders in epilepsy probands, thereby supporting the hypothesis of shared underlying genetic susceptibility to these disorders., Methods: We conducted an analysis of the 308 probands with childhood onset epilepsy from the Connecticut Study of Epilepsy with information on first-degree family history of unprovoked seizures and of febrile seizures whose parents completed the Child Behavior Checklist (CBCL) at the 9-year follow-up. Clinical cutoffs for CBCL problem and Diagnostic and Statistical Manual of Mental Disorders (DSM)-Oriented scales were examined. The association between first-degree family history of unprovoked seizure and behavioral disorders was assessed separately in uncomplicated and complicated epilepsy and separately for first-degree family history of febrile seizures. A subanalysis, accounting for the tendency for behavioral disorders to run in families, was adjusted for siblings with the same disorder as the proband. Prevalence ratios were used to describe the associations., Key Findings: In probands with uncomplicated epilepsy, first-degree family history of unprovoked seizure was significantly associated with clinical cutoffs for Total Problems and Internalizing Disorders. Among Internalizing Disorders, clinical cutoffs for Withdrawn/Depressed, and DSM-Oriented scales for Affective Disorder and Anxiety Disorder were significantly associated with family history of unprovoked seizures. Clinical cutoffs for Aggressive Behavior and Delinquent Behavior, and DSM-Oriented scales for Conduct Disorder and Oppositional Defiant Disorder were significantly associated with family history of unprovoked seizure. Adjustment for siblings with the same disorder revealed significant associations for the relationship between first-degree family history of unprovoked seizure and Total Problems and Aggressive Behavior in probands with uncomplicated epilepsy; marginally significant results were seen for Internalizing Disorder, Withdrawn/Depressed, and Anxiety Disorder. There was no association between family history of unprovoked seizure and behavioral problems in probands with complicated epilepsy. First-degree family history of febrile seizure was not associated with behavioral problems in probands with uncomplicated or in those with complicated epilepsy., Significance: Increased occurrence of behavioral disorders in probands with uncomplicated epilepsy and first degree family history of unprovoked seizure suggests familial clustering of these disorders. This supports the idea that behavioral disorders may be another manifestation of the underlying pathophysiology involved in epilepsy or closely related to it., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

Purpose: To investigate relationships between regional brain metabolites, social communication deficits, and seizure frequency in children and adolescents with cryptogenic epilepsy with complex partial seizures (CPS)., Methods: In 12 children and adolescents with CPS and 23 age- and gender-matched healthy controls, we acquired proton magnetic resonance spectroscopic imaging (MRSI) at 1.5 T and 30 ms echo-time from bilateral inferior frontal and superior temporal gyri, regions associated with social communication deficits. Videotaped speech samples of all the subjects were coded for social communication deficits and parents provided information on seizure frequency., Key Findings: Four MRSI findings emerged in right inferior frontal gyrus. N-acetyl-aspartate (NAA) plus N-acetyl-aspartyl-glutamate (NAAG)--together called "tNAA"--was 11.4% lower in patients with CPS than in controls. Choline-compounds (Cho) were 15.4% lower in CPS than in controls. Within CPS, higher tNAA was associated with more frequent seizures and abnormal social communication., Significance: Localization of findings to right inferior frontal cortex supports the involvement of this area in social communication deficits and may be related to atypical lateralization of expressive language in pediatric epilepsy. Lower levels of tNAA and Cho may indicate local neuronal or glial damage or underpopulation due to excitotoxicity or other causes. The sensitivity of tNAA to seizure frequency suggests effects of ongoing CPS on neuronal and glial function in this brain region., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

Purpose: This study compared frontotemporal brain volumes in children with childhood absence epilepsy (CAE) to age- and gender-matched children without epilepsy. It also examined the association of these volumes with seizure, demographic, perinatal, intelligence quotient (IQ), and psychopathology variables., Methods: Twenty-six children with CAE, aged 7.5-11.8 years, and 37 children without epilepsy underwent brain magnetic resonance imaging (MRI) scans at 1.5 Tesla. Tissue was segmented, and total brain, frontal lobe, frontal parcellations, and temporal lobe volumes were computed. All children had IQ testing and structured psychiatric interviews. Parents provided seizure, perinatal, and behavioral information on each child., Results: The CAE group had significantly smaller gray matter volumes of the left orbital frontal gyrus as well as both left and right temporal lobes compared to the age- and gender-matched children without epilepsy. In the CAE group these volumes were related to age, gender, ethnicity, and pregnancy complications but not to seizure, IQ, and psychopathology variables. In the group of children without epilepsy, however, the volumes were related to IQ., Conclusion: These findings suggest that CAE impacts brain development in regions implicated in behavior, cognition, and language. In addition to supporting the cortical focus theory of CAE, these findings also imply that CAE is not a benign disorder.

Purpose: This study examined the severity and range of linguistic impairments in young, intermediate, and adolescent youth with epilepsy and how these deficits were associated with illness effects, nonverbal intelligence, psychopathology, and reading., Methods: Tests of language, intelligence, achievement, and structured psychiatric interviews were administered to 182 epilepsy youth, aged 6.3-8.1, 9.1-11.7, and 13.0-15.2 years, as well as to 102 age- and gender-matched normal children. Parents provided demographic, seizure-related, and behavioral information on their children., Results: Significantly more epilepsy subjects had language scores 1 standard deviation (SD) below average than the age-matched control groups did. The intermediate and adolescent epilepsy groups also had significantly lower mean language scores compared to their matched controls. The older compared to the younger epilepsy groups had more language impairment and a wider range of linguistic deficits. Longer duration of illness, childhood absence epilepsy, psychiatric diagnosis, and socioeconomic status were associated with linguistic deficits in the young group. Prolonged seizures, lower Performance IQ, and minority status predicted low language scores in the intermediate epilepsy group. In the adolescent group, language impairment was associated with poor seizure control, decreased Performance IQ, and lower socioeconomic status. Linguistic and reading deficits were significantly related in each epilepsy group., Conclusions: The age-related increase in linguistic impairment, different profiles of predictors in each age group, and the relationship of linguistic deficits with poor reading skills have important clinical, developmental, theoretical, and academic implications.

Purpose: Evidence for a poor psychiatric, social, and vocational adult outcome in childhood absence epilepsy (CAE) suggests long-term unmet mental health, social, and vocational needs. This cross-sectional study examined behavioral/emotional, cognitive, and linguistic comorbidities as well as their correlates in children with CAE., Methods: Sixty-nine CAE children aged 9.6 (SD = 2.49) years and 103 age- and gender-matched normal children had semistructured psychiatric interviews, as well as cognitive and linguistic testing. Parents provided demographic, seizure-related, and behavioral information on their children through a semi-structured psychiatric interview and the child behavior checklist (CBCL)., Results: Compared to the normal group, 25% of the CAE children had subtle cognitive deficits, 43% linguistic difficulties, 61% a psychiatric diagnosis, particularly attention deficit hyperactivity disorder (ADHD) and anxiety disorders, and 30% clinically relevant CBCL broad band scores. The most frequent CBCL narrow band factor scores in the clinical/borderline range were attention and somatic complaints, followed by social and thought problems. Duration of illness, seizure frequency, and antiepileptic drug (AED) treatment were related to the severity of the cognitive, linguistic, and psychiatric comorbidities. Only 23% of the CAE subjects had intervention for these problems., Conclusions: The high rate of impaired behavior, emotions, cognition, and language and low intervention rate should alert clinicians to the need for early identification and treatment of children with CAE, particularly those with longer duration of illness, uncontrolled seizures, and AED treatment.

It is well recognized that children with epilepsy are at heightened risk for developing behavior problems and psychiatric disorders. Studies identifying factors associated with child behavior were reviewed and findings were placed into two broad categories for review and critique: illness-related variables and psychosocial variables. Illness-related variables were seizure frequency and seizure control, type of epilepsy, age of onset, duration of illness, and antiepileptic drugs. Psychosocial variables were reviewed using a family stress framework: stressors, perceptions, adaptive resources, coping, and family adjustment. After the literature on each category is reviewed, an integrated heuristic model that includes key illness-related and psychosocial variables is presented.

Purpose: This study examined affective disorders, anxiety disorders, and suicidality in children with epilepsy and their association with seizure-related, cognitive, linguistic, family history, social competence, and demographic variables., Methods: A structured psychiatric interview, mood self-report scales, as well as cognitive and language testing were administered to 100 children with complex partial seizures (CPSs), 71 children with childhood absence epilepsy (CAE), and 93 normal children, aged 5 to 16 years. Parents provided behavioral information on each child through a structured psychiatric interview and behavior checklist., Results: Significantly more patients had affective and anxiety disorder diagnoses (33%) as well as suicidal ideation (20%) than did the normal group, but none had made a suicide attempt. Anxiety disorder was the most frequent diagnosis among the patients with a diagnosis of affective or anxiety disorders, and combined affective/anxiety and disruptive disorder diagnoses, in those with suicidal ideation. Only 33% received some form of mental health service. Age, verbal IQ, school problems, and seizure type were related to the presence of a diagnosis of affective or anxiety disorder, and duration of illness, to suicidal ideation., Conclusions: These findings together with the high rate of unmet mental health underscore the importance of early detection and treatment of anxiety disorders and suicidal ideation children with CPSs and CAE.

Purpose: This study examined the role of cognition, language, seizure-related, and demographic variables in the psychopathology of children with complex partial seizure disorder (CPS) of average intelligence., Methods: One-hundred one CPS and 102 normal children, aged 5.1 to 16.9 years, had a structured psychiatric interview and cognitive and language testing. Parents provided demographic, perinatal, and seizure-related information, as well as behavioral information through the Child Behavior Checklist (CBCL) and a structured psychiatric interview about the child., Results: Significantly more CPS patients had psychopathology, cognitive deficits, and linguistic deficits than did those in the normal group. Among the patients, Verbal IQ predicted the presence of a psychiatric diagnosis, as well as CBCL scores in the borderline/clinical range. Seizure, linguistic, and demographic variables were unrelated to psychopathology. The cognitive and linguistic deficits of the CPS group, however, were predicted by seizure factors (e.g., prolonged seizures/febrile convulsions; seizure frequency/number of antiepileptic drugs) and demographic factors (e.g., minority status)., Conclusions: Because subtle verbal cognitive deficits predict behavioral disturbances in pediatric CPSs, the study's findings highlight the importance of assessing behavior, cognition, and language in these children. They also underscore the negative impact of prolonged seizures, febrile convulsions, seizure frequency, and antiepileptic drug polytherapy on cognition and language in pediatric CPSs.

Purpose: This study examined the relation between psychiatric diagnosis and mental health services in children with epilepsy and the associated demographic, cognitive, linguistic, behavioral, and seizure-related variables., Methods: The Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS), the Child Behavior Checklist, the Test of Language Development, and the Wechsler Intelligence Scale for Children-Revised (WISC-R) were administered to 114 children, aged 5 to 16 years, with either complex partial seizures (CPS) or primary generalized with absence (PGE, petit mal). A Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnosis and information regarding mental health services were derived from the K-SADS., Results: Although approximately 60% of the subjects had a DSM-IV psychiatric diagnosis, >60% received no mental health treatment. Absence of mental health care was associated with younger age, less parental education, limited number of antiepileptic drugs (AEDs; i.e., one or none), and higher verbal IQ. In addition, children with PGE and a single psychiatric diagnosis were less likely to have a history of mental health treatment., Conclusions: This is the first study to demonstrate unmet mental health need in a large sample of children with CPS and PGE. The study's findings suggest that parents and clinicians should be aware of the mental health needs of children with epilepsy, particularly if they have one or more of the identified risk factors.

A century ago, Dr William Osler was the best-known physician in the world. Although not yet Sir William, an honor bestowed in 1909, his encyclopedic Principles and Practice of Medicine of 1892 had been translated into many languages and was to see several further editions. Meanwhile, his fame as a teacher, speaker, essayist, educational administrator, clinical investigator, medical consultant par excellence, kind and wise mentor and friend, humanist, bibliophile and collector, practical joker, and loving family man had made him a legend when he was barely 40 years old. A native of Canada, who at the age of 35 came to the United States for 21 years and then moved to England for the final 14 years. Osler's stunning list of achievements continued until his death in 1919 and has since become a myth in its magnitude, aided substantially by the 1925 Pulitzer-prize-winning, huge, and adoring biography by his student and acolyte, Harvey Cushing. Today, dermatologists can recite the cutaneous signs of Cushing's disease, but may be less secure in stating (or, more importantly, identifying) a variety of lesions associated with Osler's name. This article reviews those lesions which commemorate the name and dermatologic contributions of this great physician. In addition, other contributions and important personal characteristics that justify keeping his memory alive are discussed.

In four groups of subjects free of thyroid disease, the following determinations were made: serum concentrations of thyroxine (T4), triiodothyronine (T3), reverse T3(rT3) and diiodothyronine (T2), and calculated indices of free thyroxine (FT4) and free triiodothyronine (FT3). Group A comprised healthy subjects aged 16-64; Group B, 24 healthy elderly subjects aged 68-95; Group C, 23 elderly patients with mild well-controlled chronic illnesses, aged 70-85; Group D, 40 nursing home residents aged 66-100. Serum T4 and T2 concentrations and the FT4 index were not affected by age; the rT3 concentration was slightly but significantly elevated only in Group D patients. Serum T3 concentration was significantly lower in all groups of elderly subjects and decreased FT3 index measurements were detected after age 75. It was concluded that old age, without complicating illness, is accompanied only by a decrease in the serum level of T3 and the FT3 index; values for other iodothyronines are unchanged. Clinicians should consider the age-related changes in T3 and FT3 values when interpreting thyroid function tests.

A 57-year-old man developed morphea while taking bromocriptine. This drug is a semisynthetic ergot alkaloid, one of a class of drugs that is associated with fibrotic disorders. Other agents known for such association are serotonin (5-hydroxytryptamine) and beta-adrenergic blockers. A common pathogenesis to link these agents to fibrosis remains uncertain.

Several tests of thyroid function were performed in 35 hyperthyroid patients over the age of 65 (elderly). The results were compared to those of similar tests in 48 hyperthyroid patients under the age of 65 (young). Total serum thyroxine (T4) was within the normal range in 14 percent of the elderly and 11 percent of the young hyperthyroid patients. The free thyroxine index (FTI) was within the normal range in 11 percent of both groups. The triiodothyronine uptake (T3U) proved to be a poor test in both groups. Although elevation of the triiodothyronine (T3) level allowed a diagnosis of "T3-toxicosis" in 2 elderly and 3 young hyperthyroid patients, the T3 level was normal in 34 percent of the elderly and 13 percent of the young subjects. Correction of the T3 range for age reduced the number of normal T3 values to 12.5 percent in the elderly hyperthyroid patients. The 24-hour uptake of radioactive iodine was normal in 12 percent of the young hyperthyroid patients, 27 percent of the elderly patients with Graves' disease, and 70 percent of the elderly patients with toxic nodular goiter, despite recent readjustment of the normal range for the test. It is concluded that the diagnosis of hyperthyroidism in the elderly may be difficult and that no single test can be relied upon to exclude the diagnosis.