Individual risk and familial liability for suicide attempt and suicide in autism: a population-based study.

BACKGROUND: Studies on the individual gender-specific risk and familial co-aggregation of suicidal behaviour in autism spectrum disorder (ASD) are lacking. METHODS: We conducted a matched case-cohort study applying conditional logistic regression models on 54 168 individuals recorded in 1987-2013 with ASD in Swedish national registers: ASD without ID n = 43 570 (out of which n = 19035, 43.69% with ADHD); ASD + ID n = 10 598 (out of which n = 2894 individuals, 27.31% with ADHD), and 270 840 controls, as well as 347 155 relatives of individuals with ASD and 1 735 775 control relatives. RESULTS: The risk for suicidal behaviours [reported as odds ratio OR (95% confidence interval CI)] was most increased in the ASD without ID group with comorbid ADHD [suicide attempt 7.25 (6.79-7.73); most severe attempts i.e. requiring inpatient stay 12.37 (11.33-13.52); suicide 13.09 (8.54-20.08)]. The risk was also increased in ASD + ID group [all suicide attempts 2.60 (2.31-2.92); inpatient only 3.45 (2.96-4.02); suicide 2.31 (1.16-4.57)]. Females with ASD without ID had generally higher risk for suicidal behaviours than males, while both genders had highest risk in the case of comorbid ADHD [females, suicide attempts 10.27 (9.27-11.37); inpatient only 13.42 (11.87-15.18); suicide 14.26 (6.03-33.72); males, suicide attempts 5.55 (5.10-6.05); inpatient only 11.33 (9.98-12.86); suicide 12.72 (7.77-20.82)]. Adjustment for psychiatric comorbidity attenuated the risk estimates. In comparison to controls, relatives of individuals with ASD also had an increased risk of suicidal behaviour. CONCLUSIONS: Clinicians treating patients with ASD should be vigilant for suicidal behaviour and consider treatment of psychiatric comorbidity.

Perinatal risk factors in Tourette's and chronic tic disorders: a total population sibling comparison study.

Adverse perinatal events may increase the risk of Tourette's and chronic tic disorders (TD/CTD), but previous studies have been unable to control for unmeasured environmental and genetic confounding. We aimed to prospectively investigate potential perinatal risk factors for TD/CTD, taking unmeasured factors shared between full siblings into account. A population-based birth cohort, consisting of all singletons born in Sweden in 1973-2003, was followed until December 2013. A total of 3 026 861 individuals were identified, 5597 of which had a registered TD/CTD diagnosis. We then studied differentially exposed full siblings from 947 942 families; of these, 3563 families included siblings that were discordant for TD/CTD. Perinatal data were collected from the Medical Birth Register and TD/CTD diagnoses were collected from the National Patient Register, using a previously validated algorithm. In the fully adjusted models, impaired fetal growth, preterm birth, breech presentation and cesarean section were associated with a higher risk of TD/CTD, largely independent from shared family confounders and measured covariates. Maternal smoking during pregnancy was associated with risk of TD/CTD in a dose-response manner but the association was no longer statistically significant in the sibling comparison models or after the exclusion of comorbid attention-deficit/hyperactivity disorder. A dose-response relationship between the number of adverse perinatal events and increased risk for TD/CTD was also observed, with hazard ratios ranging from 1.41 (95% confidence interval (CI): 1.33-1.50) for one event to 2.42 (95% CI: 1.65-3.53) for five or more events. These results pave the way for future gene by environment interaction and epigenetic studies in TD/CTD.

Antidepressant prescription patterns and CNS polypharmacy with antidepressants among children, adolescents, and young adults: a population-based study in Sweden.

This study examines trends in antidepressant drug dispensations among young people aged 0-24 years in Sweden during the period 2006-2013, as well as prescription patterns and central nervous system (CNS) polypharmacy with antidepressants. Using linkage of Swedish national registers, we identified all Swedish residents aged 0-24 years that collected at least one antidepressant prescription (here defined as antidepressant users) between 1 January 2006 and 31 December 2013 (n = 174,237), and categorized them as children (0-11 years), adolescents (12-17 years), and young adults (18-24 years). Prevalence of antidepressant dispensation rose from 1.4 to 2.1% between 2006 and 2013, with the greatest relative increase in adolescents [by 97.8% in males (from 0.6 to 1.3%) and by 86.3% in females (from 1.1 to 2.1%)]. Most individuals across age categories were prescribed selective serotonin reuptake inhibitors, received their prescriptions from psychiatric specialist care, and had treatment periods of over 12 months. Prevalence of CNS polypharmacy (dispensation of other CNS drug classes in addition to antidepressants) increased across age categories, with an overall increase in prevalence from 52.4% in 2006 to 62.1% in 2013. Children experienced the largest increase in polypharmacy of three or more psychotropic drug classes (4.4-10.1%). Anxiolytics, hypnotics, and sedatives comprised the most common additional CNS drug class among persons who were prescribed antidepressants. These findings show that the dispensation of antidepressants among the young is prevalent and growing in Sweden. The substantial degree of CNS polypharmacy in young patients receiving antidepressants requires careful monitoring and further research into potential benefits and harms.

Suicide in obsessive-compulsive disorder: a population-based study of 36 788 Swedish patients.

The risk of death by suicide in individuals with obsessive-compulsive disorder (OCD) is largely unknown. Previous studies have been small and methodologically flawed. We analyzed data from the Swedish national registers to estimate the risk of suicide in OCD and identify the risk and protective factors associated with suicidal behavior in this group. We used a matched case-cohort design to estimate the risk of deaths by suicide and attempted suicide in individuals diagnosed with OCD, compared with matched general population controls (1:10). Cox regression models were used to study predictors of suicidal behavior. We identified 36 788 OCD patients in the Swedish National Patient Register between 1969 and 2013. Of these, 545 had died by suicide and 4297 had attempted suicide. In unadjusted models, individuals with OCD had an increased risk of both dying by suicide (odds ratio (OR)=9.83 (95% confidence interval (CI), 8.72-11.08)) and attempting suicide (OR=5.45 (95% CI, 5.24-5.67)), compared with matched controls. After adjusting for psychiatric comorbidities, the risk was reduced but remained substantial for both death by suicide and attempted suicide. Within the OCD cohort, a previous suicide attempt was the strongest predictor of death by suicide. Having a comorbid personality or substance use disorder also increased the risk of suicide. Being a woman, higher parental education and having a comorbid anxiety disorder were protective factors. We conclude that patients with OCD are at a substantial risk of suicide. Importantly, this risk remains substantial after adjusting for psychiatric comorbidities. Suicide risk should be carefully monitored in patients with OCD.

Paternal age at childbirth and eating disorders in offspring.

BACKGROUND: Advanced paternal age at childbirth is associated with psychiatric disorders in offspring, including schizophrenia, bipolar disorder and autism. However, few studies have investigated paternal age's relationship with eating disorders in offspring. In a large, population-based cohort, we examined the association between paternal age and offspring eating disorders, and whether that association remains after adjustment for potential confounders (e.g. parental education level) that may be related to late/early selection into fatherhood and to eating disorder incidence. METHOD: Data for 2 276 809 individuals born in Sweden 1979-2001 were extracted from Swedish population and healthcare registers. The authors used Cox proportional hazards models to examine the effect of paternal age on the first incidence of healthcare-recorded anorexia nervosa (AN) and all eating disorders (AED) occurring 1987-2009. Models were adjusted for sex, birth order, maternal age at childbirth, and maternal and paternal covariates including country of birth, highest education level, and lifetime psychiatric and criminal history. RESULTS: Even after adjustment for covariates including maternal age, advanced paternal age was associated with increased risk, and younger paternal age with decreased risk, of AN and AED. For example, the fully adjusted hazard ratio for the 45+ years (v. the 25-29 years) paternal age category was 1.32 [95% confidence interval (CI) 1.14-1.53] for AN and 1.26 (95% CI 1.13-1.40) for AED. CONCLUSIONS: In this large, population-based cohort, paternal age at childbirth was positively associated with eating disorders in offspring, even after adjustment for potential confounders. Future research should further explore potential explanations for the association, including de novo mutations in the paternal germline.

The association between childhood relocations and subsequent risk of suicide attempt, psychiatric problems, and low academic achievement.

BACKGROUND: Given the frequency with which families change residences, the effects of childhood relocations have gained increasing research attention. Many researchers have demonstrated that childhood relocations are associated with a variety of adverse outcomes. However, drawing strong causal claims remains problematic due to uncontrolled confounding factors. METHOD: We utilized longitudinal, population-based Swedish registers to generate a nationally representative sample of offspring born 1983-1997 (n = 1 510 463). Using Cox regression and logistic regression, we examined the risk for numerous adverse outcomes after childhood relocation while controlling for measured covariates. To account for unmeasured genetic and environmental confounds, we also compared differentially exposed cousins and siblings. RESULTS: In the cohort baseline model, each annual relocation was associated with risk for the adverse outcomes, including suicide attempt [hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.19-1.20]. However, when accounting for offspring and parental covariates (HR 1.08, 95% CI 1.07-1.09), as well as genetic and environmental confounds shared by cousins (HR 1.07, 95% CI 1.05-1.09) and siblings (HR 1.00, 95% CI 0.97-1.04), the risk for suicide attempt attenuated. We found a commensurate pattern of results for severe mental illness, substance abuse, criminal convictions, and low academic achievement. CONCLUSIONS: Previous research may have overemphasized the independent association between relocations and later adverse outcomes. The results suggest that the association between childhood relocations and suicide attempt, psychiatric problems, and low academic achievement is partially explained by genetic and environmental confounds correlated with relocations. This study demonstrates the importance of using family-based, quasi-experimental designs to test plausible alternate hypotheses when examining causality.

The heritability of clinically diagnosed attention deficit hyperactivity disorder across the lifespan.

BACKGROUND: No prior twin study has explored the heritability of clinically diagnosed attention deficit hyperactivity disorder (ADHD). Such studies are needed to resolve conflicting results regarding the importance of genetic effects for ADHD in adults. We aimed to estimate the relative contribution of genetic and environmental influences for clinically diagnosed ADHD across the lifespan with a specific focus on ADHD in adults. METHOD: Information on zygosity and sex was obtained from 59514 twins born between 1959 and 2001 included in the nationwide population-based Swedish Twin Registry. Clinical data for ADHD diagnoses (i.e. stimulant or non-stimulant medication for ADHD) were obtained from the Swedish Prescribed Drug Register (PDR) and from the National Patient Register (i.e. ICD-10 diagnosis of ADHD). Twin methods were applied to clinical data of ADHD diagnoses using structural equation modeling with monozygotic (MZ) and dizygotic (DZ) twins. RESULTS: The best-fitting model revealed a high heritability of ADHD [0.88, 95% confidence interval (CI) 0.83-0.92] for the entire sample. However, shared environmental effects were non-significant and of minimal importance. The heritability of ADHD in adults was also substantial (0.72, 95% CI 0.56-0.84). CONCLUSIONS: This study shows that the heritability of clinically diagnosed ADHD is high across the lifespan. Our finding of high heritability for clinically diagnosed ADHD in adults indicates that the previous reports of low heritability are best explained by rater effects, and that gene-identification studies of ADHD in adults need to consider pervasiveness (e.g. multiple raters) and developmentally (e.g. childhood-onset criteria) informative data.

Offspring psychopathology following preconception, prenatal and postnatal maternal bereavement stress.

BACKGROUND: Preconception, prenatal and postnatal maternal stress is associated with increased offspring psychopathology, but findings are inconsistent and need replication. We estimated associations between maternal bereavement stress and offspring autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), bipolar disorder, schizophrenia, suicide attempt and completed suicide. METHOD: Using Swedish registers, we conducted the largest population-based study to date examining associations between stress exposure in 738,144 offspring born 1992-2000 for childhood outcomes and 2,155,221 offspring born 1973-1997 for adult outcomes with follow-up to 2009. Maternal stress was defined as death of a first-degree relative during (a) the 6 months before conception, (b) pregnancy or (c) the first two postnatal years. Cox proportional survival analyses were used to obtain hazard ratios (HRs) in unadjusted and adjusted analyses. RESULTS: Marginal increased risk of bipolar disorder and schizophrenia following preconception bereavement stress was not significant. Third-trimester prenatal stress increased the risk of ASD [adjusted HR (aHR) 1.58, 95% confidence interval (CI) 1.15-2.17] and ADHD (aHR 1.31, 95% CI 1.04-1.66). First postnatal year stress increased the risk of offspring suicide attempt (aHR 1.13, 95% CI 1.02-1.25) and completed suicide (aHR 1.51, 95% CI 1.08-2.11). Bereavement stress during the second postnatal year increased the risk of ASD (aHR 1.30, 95% CI 1.09-1.55). CONCLUSIONS: Further research is needed regarding associations between preconception stress and psychopathological outcomes. Prenatal bereavement stress increases the risk of offspring ASD and ADHD. Postnatal bereavement stress moderately increases the risk of offspring suicide attempt, completed suicide and ASD. Smaller previous studies may have overestimated associations between early stress and psychopathological outcomes.

Disentangling the relationships between maternal smoking during pregnancy and co-occurring risk factors.

BACKGROUND: Maternal smoking during pregnancy (SDP) has been studied extensively as a risk factor for adverse offspring outcomes and is known to co-occur with other familial risk factors. Accounting for general familial risk factors has attenuated associations between SDP and adverse offspring outcomes, and identifying these confounds will be crucial to elucidating the relationship between SDP and its psychological correlates. METHOD: The current study aimed to disentangle the relationship between maternal SDP and co-occurring risk factors (maternal criminal activity, drug problems, teen pregnancy, educational attainment, and cohabitation at childbirth) using a population-based sample of full- (n=206 313) and half-sister pairs (n=19 363) from Sweden. Logistic regression models estimated the strength of association between SDP and co-occurring risk factors. Bivariate behavioral genetic models estimated the degree to which associations between SDP and co-occurring risk factors are attributable to genetic and environmental factors. RESULTS: Maternal SDP was associated with an increase in all co-occurring risk factors. Of the variance associated with SDP, 45% was attributed to genetic factors and 53% was attributed to unshared environmental factors. In bivariate models, genetic factors accounted for 21% (non-drug-, non-violence-related crimes) to 35% (drug-related crimes) of the covariance between SDP and co-occurring risk factors. Unshared environmental factors accounted for the remaining covariance. CONCLUSIONS: The genetic factors that influence a woman's criminal behavior, substance abuse and her offspring's rearing environment all influence SDP. Therefore, the intergenerational transmission of genes conferring risk for antisocial behavior and substance misuse may influence the associations between maternal SDP and adverse offspring outcomes.

Poor school performance in offspring of patients with schizophrenia: what are the mechanisms?

BACKGROUND: Offspring of patients with schizophrenia exhibit poorer school performance compared with offspring of non-schizophrenic parents. We aimed to elucidate the mechanisms behind this association. METHOD: We linked longitudinal national population registers in Sweden and compared school performance among offspring of schizophrenic parents with offspring of non-schizophrenic parents (1 439 215 individuals with final grades from compulsory school 1988-2006). To investigate the mechanisms, we studied offspring of schizophrenic patients and controls within the same extended families. We investigated genetic effects by stratifying analyses of parent-child associations according to genetic relatedness (half-cousins, full cousins and half-siblings). Environmental effects were investigated by comparing school performance of offspring of schizophrenic fathers and of schizophrenic mothers, respectively, and by stratifying the analyses according to environmental relatedness while controlling genetic relatedness (paternal and maternal half-cousins, paternal and maternal half-siblings). RESULTS: Offspring of parents with schizophrenia had poorer overall school performance than unrelated offspring of non-schizophrenic parents (-0.31 s.d.). Variability in genetic relatedness greatly moderated the strength of the within-family association (ß=-0.23 within exposure-discordant half-cousins, ß=-0.13 within exposure-discordant full cousins, ß=0.04 within exposure-discordant half-siblings), while no evidence was found that the environment affected offspring school performance. CONCLUSIONS: Genetic factors account for poorer school performance in children of parents with schizophrenia. This supports that cognitive deficits found in individuals with schizophrenia and their relatives might be genetically inherited. Early detection of prodromal signs and impaired functioning of offspring of patients with schizophrenia could lead to earlier and better tailored interventions.

Is maternal smoking during pregnancy a causal environmental risk factor for adolescent antisocial behavior? Testing etiological theories and assumptions.

BACKGROUND: Although many studies indicate that maternal smoking during pregnancy (SDP) is correlated with later offspring antisocial behavior (ASB), recent quasi-experimental studies suggest that background familial factors confound the association. The present study sought to test alternative etiological hypotheses using multiple indices of adolescent ASB, comparing differentially exposed siblings, and testing assumptions in the sibling-comparison design. METHOD: The study examined the association between maternal SDP and adolescent-reported ASB, criminal convictions and membership in a group of individuals with early-starting and chronic ASB among 6066 offspring of women from the National Longitudinal Survey of Youth, a representative sample of women in the USA. The analyses controlled for statistical covariates and examined associations while comparing differentially exposed siblings. RESULTS: At the population level, each additional pack of cigarettes per day predicted greater mean adolescent-reported ASB symptoms [ratio of means 1.15, 95% confidence interval (CI) 1.08-1.22], odds of being in the top 10% of ASB [odds ratio (OR) 1.34, 95% CI 1.10-1.65], hazard of a criminal conviction [hazard ratio (HR) 1.51, 95% CI 1.34-1.68] and odds of chronic ASB (OR 1.57, 95% CI 1.25-1.99). SDP robustly predicted most assessments of ASB while controlling for measured covariates. When siblings exposed to differing levels of SDP were compared, however, all of the associations were attenuated and were not statistically significant: adolescent-reported mean ASB (ratio of means 0.86, 95% CI 0.74-1.01), high ASB (OR 0.67, 95% CI 0.41-1.12), criminal conviction (HR 0.98, 95% CI 0.66-1.44) and chronic ASB (OR 0.80, 95% CI 0.46-1.38). CONCLUSIONS: The results strongly suggest that familial factors account for the correlation between SDP and offspring adolescent ASB, rather than a putative causal environmental influence of SDP.

Parental depression and offspring psychopathology: a children of twins study.

BACKGROUND: Associations between parental depression and offspring affective and disruptive disorders are well documented. Few genetically informed studies have explored the processes underlying intergenerational associations. METHOD: A semi-structured interview assessing DSM-III-R psychiatric disorders was administered to twins (n=1296) from the Australian Twin Register (ATR), their spouses (n=1046) and offspring (n=2555). We used the Children of Twins (CoT) design to delineate the extent to which intergenerational associations were consistent with a causal influence or due to genetic confounds. RESULTS: In between-family analyses, parental depression was associated significantly with offspring depression [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.20-1.93] and conduct disorder (CD; HR 2.27, CI 1.31-3.93). Survival analysis indicated that the intergenerational transmission of depression is consistent with a causal (environmental) inference, with a significant intergenerational association in offspring of discordant monozygotic (MZ) twin pairs (HR 1.39, CI 1.00-1.94). Logistic regression analysis suggested that the parental depression-offspring CD association was due to shared genetic liability in the parents and offspring. No intergenerational association was found when comparing the offspring of discordant MZ twins [odds ratio (OR) 1.41, CI 0.63-3.14], but offspring of discordant dizygotic (DZ) twins differed in their rates of CD (OR 2.53, CI 0.95-6.76). All findings remained after controlling for several measured covariates, including history of depression and CD in the twins' spouses. CONCLUSIONS: The mechanisms underlying associations between parental depression and offspring psychopathology seem to differ depending on the outcome. The results are consistent with a causal environmental role of parental depression in offspring depression whereas common genetic factors account for the association of parental depression and offspring CD.

Risk of eating disorders in international adoptees: a cohort study using Swedish national population registers.

AIMS: Compared to the general population, adoptees are more often referred to specialist psychiatric treatment, exhibit increased risk of suicide and display more symptoms of attention-deficit/hyperactivity-disorder. However, little is known about the impact of being an adoptee on the risk of developing an eating disorder. The aim of the present study was to assess whether international adoptees have a higher risk for eating disorders than native Swedes. METHODS: In the present retrospective cohort study, data from the Swedish total population registers on individuals born between 1979 and 2005 were used to assess whether international adoptees residing in Sweden (n = 25 287) have a higher risk for anorexia nervosa (AN) and other eating disorders (OED) than non-adoptees with Swedish-born parents from the general population (n = 2 046 835). The patterns of these results were compared to those for major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and anxiety disorders to determine whether any observed effects were unique to eating disorders or reflected a more general impact on mental health outcomes. RESULTS: A survival analysis adjusting for relevant demographic covariates revealed an elevated risk of all examined psychiatric disorders in international adoptees: hazard ratios (95% confidence intervals) are 1.21 (1.04-1.41) for AN, 1.60 (1.44-1.79) for OED, 1.90 (1.81-2.00) for MDD, 1.25 (1.09-1.44) for OCD, and 1.69 (1.60-1.78) for anxiety disorders. CONCLUSIONS: Elevated risk of eating disorders as well as of MDD, OCD, and anxiety disorders was found in international adoptees. A parallel pattern between AN and OCD was observed, which both display less elevated rates than the other diagnoses. A considerable number of biological, environmental, and societal factors have been suggested to explain the observed differences in mental health between adoptees and non-adoptees, but they remain primarily theoretical.

Schizophrenia and subsequent neighborhood deprivation: revisiting the social drift hypothesis using population, twin and molecular genetic data.

Neighborhood influences in the etiology of schizophrenia have been emphasized in a number of systematic reviews, but causality remains uncertain. To test the social drift hypothesis, we used three complementary genetically informed Swedish cohorts. First, we used nationwide Swedish data on approximately 760 000 full- and half-sibling pairs born between 1951 and 1974 and quantitative genetic models to study genetic and environmental influences on the overlap between schizophrenia in young adulthood and subsequent residence in socioeconomically deprived neighborhoods. Schizophrenia diagnoses were ascertained using the National Patient Registry. Second, we tested the overlap between childhood psychotic experiences and neighborhood deprivation in early adulthood in the longitudinal Twin Study of Child and Adolescent Development (TCHAD; n=2960). Third, we investigated to what extent polygenic risk scores for schizophrenia predicted residence in deprived neighborhoods during late adulthood using the TwinGene sample (n=6796). Sibling data suggested that living in deprived neighborhoods was substantially heritable; 65% (95% confidence interval (95% CI): 60-71%) of the variance was attributed to genetic influences. Although the correlation between schizophrenia and neighborhood deprivation was moderate in magnitude (r=0.22; 95% CI: 0.20-0.24), it was entirely explained by genetic influences. We replicated these findings in the TCHAD sample. Moreover, the association between polygenic risk for schizophrenia and neighborhood deprivation was statistically significant (R(2)=0.15%, P=0.002). Our findings are primarily consistent with a genetic selection interpretation where genetic liability for schizophrenia also predicts subsequent residence in socioeconomically deprived neighborhoods. Previous studies may have overemphasized the relative importance of environmental influences in the social drift of schizophrenia patients. Clinical and policy interventions will therefore benefit from the future identification of potentially causal pathways between different dimensions of cognitive functions and socioeconomic trajectories derived from studies adopting family-based research designs.

Comprehensive study of diagnosis and treatment of trigeminal neuralgia secondary to tumors.

Among 5,058 patients seen at the Mayo Clinic from 1976 through 1990 for face pain, we diagnosed trigeminal neuralgia in 2,972. Tumors were causing the face pain in 296 patients. Sex and pain distributions paralleled those in idiopathic trigeminal neuralgia; however, patients with tumors causing trigeminal neuralgia were younger than those with idiopathic pain. Meningiomas and posterior fossa tumors were the most common. Neurologic deficits developed on follow-up evaluation in 47% of the patients, often precipitating further study and eventual diagnosis of the tumor. Delay in tumor diagnosis averaged 6.3 years. CT with contrast was the most frequently used initial diagnostic radiographic technique, detecting a tumor in 40 of 43 examinations. MRI was subsequently used to confirm and better delineate the tumor in five of five cases. Carbamazepine was the most effective drug for relieving trigeminal neuralgia, but relief was usually temporary. Of the surgical treatment options, total removal of the tumor was the most effective in completely relieving tic pain. In patients at high surgical risk, however, temporarily or permanently blocking afferent impulses with radiofrequency ablation, glycerol rhizotomy, or alcohol blocks was a good alternative to craniotomy.

Central nervous system histoplasmosis with obstructive hydrocephalus.

A case of central nervous system histoplasmosis complicated by obstruction of the fourth ventricle is described. The patient rarely exhibited systemic symtoms of infection despite positive cultures for Histoplasma capsulatum from bone marrow, blood and urine. Infection recurred despite the administration of a total of 5 g of systemic amphotericin B. An additional course combined with intrathecal amphotericin B was terminated because of transverse myelitis.

Surgical treatment of chronic cluster headache.

Chronic cluster headache, also known as chronic migrainous neuralgia, is frequently unresponsive to medical management. Although neuronal factors may be involved in the pathogenesis of this form of recurrent hemicranial pain, vasodilatation within the distribution of the trigeminal nerve is believed to be important. Attempts to provide relief by surgical means have primarily involved interruption of the vasodilator pathways of the greater superficial petrosal nerve and the sphenopalatine ganglion. A more direct approach of interrupting the pain pathways of the trigeminal nerve has been attempted sporadically for more than 50 years. Recent interest in the role of substance P in the production of pain in cluster headache suggests that trigeminal ablative procedures might have a dual role in the relief of medically intractable cases. Among 26 patients who underwent posterior fossa trigeminal sensory rhizotomy or percutaneous radio-frequency trigeminal gangliorhizolysis at our institution, relief of pain was excellent in 14 (54%), fair to good in 4 (15%), and poor in 8 (31%).

An unusual compressive syndrome of the cauda equina.

An unusual case of a capillary hemangioma of the filum terminale is presented. The successful removal returned the patient to an asymptomatic state.

Brachial plexus injuries.

Brachial plexus injuries are uncommon. They are, however, complicated lesions because of the concomitant injury to adjacent structures and the imposing anatomy of the brachial plexus. Physicians who will be consulted in the management of such injuries should periodically consider the principles of management. Diagnosis of these injuries is based on clinical examination, myelography, axon reflex testing, and electrophysiologic studies. The lesion may be open or closed and supraclavicular or infraclavicular. It may be in continuity or there may be nerve disruption or root avulsion from the spinal cord. The anatomic relationships of the brachial plexus are reviewed, the pathophysiology of direct trauma, secondary trauma, and iatrogenic trauma is discussed, and the treatment of the various types of traumatic brachial palsy is surveyed.

Magnetic resonance imaging of the spine.

Magnetic resonance (MR) imaging offers the advantages of multiplanar capabilities, physiologic as well as anatomic imaging, and some tissue specificity. Since mid-1985, we have performed more than 2,800 MR examinations of the spine, and gadolinium has been used as a contrast agent in many MR studies since its release by the Food and Drug Administration last year. Although MR imaging has been promoted as the procedure of choice for all clinical indications, on the basis of our experience myelography still plays an important role in the imaging of many spinal disorders, including disk disease. Some pathologic conditions such as intraspinal vascular malformations and leptomeningeal metastatic lesions are best imaged by myelography. MR studies have been most useful in evaluating intraspinal neoplasms, spinal cord parenchymal lesions, infections, congenital abnormalities, and "postoperative failed back syndromes."