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Biomedical subjects

Lois E Krahn

Publications and source records attributed to Lois E Krahn.

At least 19 recordsLinked to original sources
PubMed2006

A preliminary fluorodeoxyglucose positron emission tomography study in healthy adults reporting dream-enactment behavior.

STUDY OBJECTIVES: To test the hypothesis that healthy adults reporting dream-enactment behavior (DEB+) have reduced cerebral metabolic rate for glucose (CMRgl) in regions preferentially affected in patients with dementia with Lewy bodies (DLB). DESIGN: Automated brain-mapping algorithms were used to compare regional fluorodeoxyglucose (FDG) positron emission tomography (PET) measurements from previously evaluated DEB cases and controls. SETTING: Tertiary-care academic medical centers. PARTICIPANTS: Seventeen cognitively normal patients with DEB+ and 17 control subjects (DEB-) who were individually matched for age (59 +/- 11 years), education level (16 +/- 4 years), sex (67% women), body mass index (26 +/- 4.8 kg/m2), first-degree relative with dementia (85%), and proportion of apolipoprotein E (APOE) e4 carriers (13 e4 carriers, 4 noncarriers). INTERVENTIONS: FDG-PET. MEASUREMENTS AND RESULTS: DEB was associated with significantly lower CMRgl in several brain regions known to be preferentially affected in both DLB and Alzheimer disease (parietal, temporal, and posterior cingulate cortexes) and in several other regions, including the anterior cingulate cortex (p < .001, uncorrected for multiple comparisons). The DEB-associated CMRgl reductions were significantly greater in the APOE e4 noncarriers than in the carriers. CONCLUSIONS: These preliminary findings suggest that cognitively normal persons with DEB have reduced CMRgl in brain regions known to be metabolically affected by DLB, supporting further study of DEB as a possible risk factor for the development of DLB.

Adult↗
PubMed2005

Studies of humoral immunity to preprohypocretin in human leukocyte antigen DQB1*0602-positive narcoleptic subjects with cataplexy.

BACKGROUND: Canine models for narcolepsy have mutations of the hypocretin receptor 2 gene, and preprohypocretin knockout murine lines exhibit narcoleptic-like behaviors. Human narcolepsy with cataplexy is associated with human leukocyte antigen DQB1*0602 and reduced hypocretin levels in cerebrospinal fluid, suggesting an autoimmune diathesis. We tested the hypothesis that DQB1*0602-positive narcoleptic subjects with cataplexy have immunoglobulin (Ig)G reactive to human preprohypocretin and its cleavage products. METHODS: Serum samples of 41 DQB1*0602-positive narcoleptic subjects with cataplexy and 55 control subjects were studied, as were 19 narcoleptic and 13 control samples of cerebrospinal fluid. We tested for IgG reactive to preprohypocretin and its major cleavage products (including hypocretin 1 and 2), using immunoprecipitation assays (IP), immunofluorescence microscopy (IF) of Chinese hamster ovarian cells expressing preprohypocretin, and Western blots. RESULTS: There was no evidence for IgG reactive to preprohypocretin or its cleavage products in CSF of subjects with narcolepsy as measured by IPs, Western blots, and IF. Although the IP with CSF and the C-terminal peptide showed significant differences by two methods of comparison, the control subjects had higher counts per minute than narcoleptic subjects, which was opposite to our hypothesis. CONCLUSIONS: The hypothesis that DQB1*0602-positive narcoleptic subjects with cataplexy have IgG reactive to preprohypocretin or its cleavage products was not supported.

Adult↗
PubMed2005

Reevaluating spells initially identified as cataplexy.

BACKGROUND AND PURPOSE: Cataplexy, transient episodes of bilateral muscle weakness with areflexia provoked by emotions, is a state highly specific to narcolepsy. Cataplexy is diagnosed based on clinical interview. Two screening tools have been developed recently but their usefulness has been limited because of length or current lack of psychometric data. Used effectively even these screening tests require the interpreting physician to have an understanding of the typical features of cataplexy. Most physicians encounter patients with cataplexy fairly infrequently, making it difficult to gain proficiency in detecting cataplexy based on clinical interview alone. Relatively little attention has been given to the differential diagnosis of cataplexy, which increases the likelihood of unnecessary sleep testing or false positive diagnosis. PATIENTS AND METHODS: This case series describes six cases where cataplexy was initially diagnosed. In all cases the weakness spells were eventually not attributed to cataplexy. The presentation and characteristics of these cases will be presented as a means to discuss the differential diagnosis of cataplexy. RESULTS: These cases represent a diverse set of medical disorders including bradycardia, migraine, delayed sleep phase syndrome, conversion disorder, malingering and a chronic psychotic disorder. CONCLUSIONS: A more in-depth understanding of the classic features of cataplexy should improve recognition of this fascinating state. Improved cataplexy recognition will enhance the appropriate usage of sleep tests and eventually increase the timeliness and accuracy of the diagnosis of narcolepsy with cataplexy.

Adolescent↗
PubMed2005

Psychiatric disorders associated with disturbed sleep.

Disturbed sleep is a feature of many psychiatric disorders. When clinicians are investigating insomnia, excessive daytime sleepiness, as well as parasomnia, they need to consider whether these complaints might be secondary to a psychiatric process. The association that is best supported by scientific evidence is between insomnia and mood disorders. Nonetheless, other psychiatric conditions including anxiety, psychosis, chemical dependency, and attention deficit hyperactivity disorder are closely linked with alteration in sleep quality and quantity. Treatment plans should take into account the nature of sleep symptomatology as well as the effect of medications on sleep. Ideally, management should include a combination of medications and behavioral treatment.

Antidepressive Agents↗
PubMed2005

Analysis of hypocretin (orexin) antibodies in patients with narcolepsy.

STUDY OBJECTIVES: We tested the hypothesis that patients with narcolepsy have serum antibodies specific for preprohypocretin and its derivatives. DESIGN: We tested sera from strictly diagnosed HLA DQB1*0602-positive narcoleptic patients with cataplexy for evidence of autoantibodies against human preprohypocretin, hypocretin 1 and 2, N-terminal leader and C-terminal peptides of preprohypocretin using enzyme-linked immunosorbent assays (ELISA). These results were compared to samples from nonnarcoleptic psychiatric and sleep apnea controls. Laboratory personnel were blinded to subject status. SETTING: Narcoleptic patients and nonnarcoleptic controls were recruited from the Mayo Clinic facilities in Rochester, Minnesota; Scottsdale, Arizona; and Jacksonville, Florida. Laboratory testing was conducted in the Mayo Psychogenomic Laboratory at the Rochester Mayo Clinic. PARTICIPANTS: A sample of 34 narcoleptic patients and 49 nonnarcoleptic controls. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: ELISA measurements were in optical density. Primary analyses were of the entire narcoleptic and control groups for each potential antigen, and none of the differences reached P values required for significance after Bonferroni adjustment. Secondary analyses by age and sex yielded P values that were significant after Bonferroni adjustment in only 2 cases, but further statistical analyses cast doubt on the veracity of these differences. In all cases where a significant difference was recorded, the hypothesis was not supported because the control optical density reading was higher than the narcoleptic values. CONCLUSIONS: These ELISA assay results do not support the hypothesis that HLA DQB1*0602-positive narcolepsy with cataplexy is associated with serum antibodies against preprohypocretin or its cleavage products.

Autoantibodies↗
PubMed2005

Risks of high-dose stimulants in the treatment of disorders of excessive somnolence: a case-control study.

STUDY OBJECTIVES: To ascertain complications associated with high-dose stimulant therapy in patients with narcolepsy or idiopathic hypersomnia. DESIGN: Case-control, retrospective chart review. SETTING: Sleep center in an academic hospital. PATIENTS: 116 patients with narcolepsy or idiopathic hypersomnia were individually matched by sex, diagnosis, age of onset, and duration of follow-up from both onset and diagnosis. Members of the high-dose group (n = 58) had received at least 1 stimulant at a dosage > or = 120% of the maximum recommended by the American Academy of Sleep Medicine Standards of Practice Committee. The standard-dose control group (n = 58) had received stimulants at a dosage < or = 100% of the American Academy of Sleep Medicine guidelines. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The prevalence of psychosis (odds ratio = 12.0 [1.6-92.0]), alcohol or polysubstance misuse (odds ratio = 4.3 [1.2-15.2]), and psychiatric hospitalization (odds ratio = 3.2 [1.1-10.0]) was significantly increased in the high-dose group. More high-dose patients also experienced tachyarrhythmias (odds ratio = 3.3 [0.92-12.1] and anorexia or weight loss (odds ratio = 11.0 [1.4-85.2]). The frequency of physician-diagnosed depression, drug-seeking and suicide-related behaviors, hypertension, and cardiovascular disease did not differ significantly between the groups. CONCLUSIONS: This study demonstrated a significantly higher occurrence of psychosis, substance misuse, and psychiatric hospitalizations in patients using high-dose stimulants compared to those using standard doses. Tachyarrhythmias and anorexia or weight loss were also more common in this group as compared with controls. Clinicians should be very cautious in prescribing dosages that exceed maximum guidelines.

Adult↗
PubMed2005

Characterizing the emotions that trigger cataplexy.

Cataplexy is an intriguing example of how emotions can trigger muscle weakness by activating neural pathways. When associated with excessive daytime sleepiness, cataplexy is considered pathognomonic of narcolepsy. A questionnaire was administered to 55 patients with narcolepsy-cataplexy and 47 comparison subjects with obstructive sleep apnea. The area under the receiver-operating curve was 0.94 for the combination of muscle weakness with laughter and ability to hear during the episode. A 51-item questionnaire succeeds in identifying cataplexy in narcolepsy-cataplexy patients measured up against a comparison group. In the future, an abbreviated survey with these two questions should identify cataplexy with high sensitivity and specificity. These selected questions could subsequently be included into screening tools for use with different patient populations.

Adult↗
PubMed2005

Psychiatric manifestations of Creutzfeldt-Jakob disease: a 25-year analysis.

This study characterizes the type and timing of psychiatric manifestations in sporadic Creutzfeldt-Jakob disease (sCJD). Historically, sCJD has been characterized by prominent neurological symptoms, while the variant form (vCJD) is described as primarily psychiatric in presentation and course: A retrospective review of 126 sCJD patients evaluated at the Mayo Clinic from 1976-2001 was conducted. Cases were reviewed for symptoms of depression, anxiety, psychosis, behavior dyscontrol, sleep disturbances, and neurological signs during the disease course. Eighty percent of the cases demonstrated psychiatric symptoms within the first 100 days of illness, with 26% occurring at presentation. The most commonly reported symptoms in this population included sleep disturbances, psychotic symptoms, and depression. Psychiatric manifestations are an early and prominent feature of sporadic CJD, often occurring prior to formal diagnosis.

Adult↗
PubMed2004

A putative link between childhood narcolepsy and obesity.

BACKGROUND AND PURPOSE: While there have been anecdotal observations of binge eating in childhood-onset narcolepsy, the possible relationship between increased weight gain and childhood-onset narcolepsy has not been evaluated. PATIENTS AND METHODS: A retrospective, case-control design was used to compare the body mass index (BMI) of 31 narcolepsy children at the time of diagnosis with that of healthy, age- and gender-matched controls. RESULTS: The median BMI in the narcolepsy subjects was 22.93 as compared to that in controls of 20.36 (P=0.001). BMI did not differ significantly between narcolepsy subjects who had received prior psychotropic medications and those who had not. The mean BMI of 22 of 31 narcolepsy subjects who had not received psychotropic medications prior to diagnosis was also significantly higher than that of controls (25.1, SEM 1.53 versus 21.1, SEM 0.56; P=0.008 ). CONCLUSION: The tendency for increased weight gain is intrinsic to childhood narcolepsy and is manifested relatively early in the course of the disorder. Correlation of this finding with hypocretin and leptin metabolism may further understanding of the pathogenesis of narcolepsy.

Adolescent↗
PubMed2003

Sleep disorders.

Patients with sleep disorders present with a variety of complaints including excessive daytime sleepiness, daytime spells, inability to sleep, uncomfortable sensation in the extremities, and unusual night time behaviors. This article provides eight vignettes on patients with sleep disorders including narcolepsy, idiopathic hypersomnia, obstructive sleep apnea, restless legs syndrome, and rapid eye movement behavior disorder. The discussion provides data regarding the epidemiology, pathophysiology, and diagnostic approach for these conditions. The various treatment options for these sleep disorders are also identified.

Adjuvants, Anesthesia↗
PubMed2003

Patients who strive to be ill: factitious disorder with physical symptoms.

OBJECTIVE: Factitious disorder with physical symptoms characterizes patients who strive to appear medically ill and assume the sick role. Clinical suspicion is highest for female health care workers in the fourth decade of life. This study was designed to analyze the diagnosis of factitious disorder, the demographics of affected patients, and intervention and treatment. METHOD: Retrospective examination was of 93 patients diagnosed during 21 years. Two raters agreed on subject eligibility on the basis of DSM-IV criteria and absence of a somatoform disorder and a plausible medical explanation. RESULTS: The group included 67 women (72.0%); mean age was 30.7 years (SD=8.0) for women and 40.0 years (SD=13.3) for men. Mean age at onset was 25.0 years (SD=7.4). Health care training or jobs were more common for women (65.7%) than men (11.5%). Most often, inexplicable laboratory results established the diagnosis. Eighty had psychiatric consultations; 71 were confronted about their role in the illness. Only 16 acknowledged factitious behavior. Follow-up data were available for only 28 patients (30.1%); maximum duration of follow-up was 156 months. Two patients were known to have died. Few patients pursued psychiatric treatment. Eighteen left the hospital against medical advice. CONCLUSIONS: Factitious disorder affects men and women with different demographic profiles. Diagnosis must be based on careful examination of behavior, motivation, and medical history and not on a stereotype. Laboratory data and outside medical records help identify suspicious circumstances and inconsistencies. Confrontation does not appear to lead to patient acknowledgment and should not be considered necessary for management.

Adult↗
PubMed2003

The effect of nicotine patch therapy on depression in nonsmokers: a preliminary study.

Prior uncontrolled studies of nonsmokers with major depressive disorder (MDD) indicate rapid reduction in depressive symptoms with nicotine patch therapy. This randomized, double-blind, placebo-controlled pilot study examined the effect of nicotine patch therapy on depressive symptoms in non-medicated nonsmokers with current MDD. Due to recruitment difficulties, only 7 were enrolled and of these 6 (5 females, 1 male) completed the study. Participants received either placebo (n = 4) or active (n = 2) patch therapy for 8 days. They completed daily clinic visits during patch therapy and a final visit on Day 12. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression (HRSD). The mean change in HRSD scores of all participants decreased (p = 0.021) from baseline by Day 1 of patch use. Similar decreases in HRSD scores were observed for placebo and active patch groups. Among the placebo participants, the mean HRSD score decreased (p = 0.038) by Day 2. The study needs replication with a larger sample and utilizing novel recruitment strategies.

Administration, Cutaneous↗
PubMed2003

Long-term survival of patients with anorexia nervosa: a population-based study in Rochester, Minn.

OBJECTIVE: To estimate long-term survival of unselected patients with anorexia nervosa from Rochester, Minn. PATIENTS AND METHODS: In this population-based retrospective cohort study, all 208 Rochester residents who presented with anorexia nervosa (193 women and 15 men) for the first time from 1935 through 1989 were monitored for up to 63 years. Subsequent survival was compared with that expected for Minnesota white residents of similar age and sex, and standardized mortality ratios were determined on the basis of age- and sex-specific death rates for the US population in 1987. RESULTS: Survival was not worse than expected in this cohort (P = .16). The estimated survival 30 years after the initial diagnosis of anorexia nervosa was 93% (95% confidence interval, 88%-97%) compared with an expected 94%. During 5646 person-years of follow-up (median, 22 years per patient), 17 deaths occurred (14 women and 3 men) compared with an expected 23.7 deaths (standardized mortality ratio, 0.71; 95% confidence interval, 0.42-1.09). One woman died of complications of anorexia nervosa, 2 women committed suicide, and 6 patients (5 women and 1 man) died of complications of alcoholism. Other causes of death were not increased. CONCLUSIONS: Long-term survival of Rochester patients with anorexia nervosa did not differ from that expected. This finding suggests that overall mortality was not increased among the spectrum of cases representative of the community.

Adolescent↗
PubMed2002

Search for neuron-specific and nonneuron-specific antibodies in narcoleptic patients with and without HLA DQB1*0602.

STUDY OBJECTIVES: Narcolepsy is strongly associated with the presence of HLA DQB1*0602. This and other evidence suggests that human narcolepsy is an autoimmune disease. This is in distinction to that found in canine models where hypocretin receptor 2 mutations are etiologic. We decided to test for the presence of several neuron-specific and organ-specific autoantibodies to see if they were present in HLA DQB1*0602-associated or cataplexy-associated narcolepsy or could serve as a serologic marker of the illness. DESIGN: We tested for N-type and P/Q-type voltage-gated calcium-channel antibodies, neuronal nicotinic acetylcholine receptor alpha3 subunit, acetylcholine receptor-binding antibodies, striated muscle antibodies, Type 1 Purkinje cell cytoplasmic antibodies, types 1 and 2 antineuronal nuclear antibodies and amphiphysin antibodies, GAD-65 antibody, and thyroid microsomal and thyroglobulin antibodies in the serum of 43 patients with or without cataplexy, 41 with known HLA status. SETTING: Narcoleptic subjects were recruited from the Mayo Sleep Disorders Center. PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: No antibody test yielded significantly positive results for the group as a whole or for subgroups of patients with cataplexy or positive HLA DQB1*0602 status. CONCLUSIONS: These results do not support the hypothesis that narcolepsy is an autoimmune disease. However, it is possible that the autoimmune attack is very selective and does not involve the epitopes measured in this study. Recent findings that the hypocretin neurotransmission system is involved in animal models of narcolepsy should lead to research to look for antibodies directed against components of the hypocretin neurotransmission system in narcolepsy.

Adult↗
PubMed2002

Hypocretin (orexin) levels in cerebrospinal fluid of patients with narcolepsy: relationship to cataplexy and HLA DQB1*0602 status.

STUDY OBJECTIVES: Hypocretin (orexin) deficiency (< 40 pg/ml) is highly associated with narcolepsy with cataplexy (89.5%) and more specifically with patients with cataplexy who are HLA DQB1*0602 positive (95.7%). The relationship between hypocretin-1 levels and narcolepsy without cataplexy or the DQB1*0602 allele is less clear. METHODS/DESIGN: This study compared cerebrospinal (CSF) hypocretin-1 in 13 patients with HLA DQB1*0602 allele and cataplexy to 4 HLA negative patients with cataplexy, 3 HLA positive patients without cataplexy, and 6 HLA negative patients without cataplexy, plus 15 neurologic controls. SETTING: Data were collected at a sleep disorders center. PATIENTS/PARTICIPANTS: Twenty-six patients with narcolepsy, with and without HLA DQB1*0602 and with and without cataplexy, as well as 15 neurologic controls. INTERVENTIONS: N/A. MEASUREMENT & RESULTS: Using analysis of variance techniques, statistically significant differences were found between the CSF hypocretin-1 levels in HLA positive patients and all other groups (P < 0.01). Although the sample size was small, subjects with the DQB1*0602 allele without cataplexy had lower hypocretin-1 levels than did other groups (other than the HLA and cataplexy positive group). Hypocretin-1 levels were not associated with age at diagnosis, age at lumbar puncture, body mass index at time of diagnosis, or body mass index at time of lumbar puncture. CONCLUSION: This data confirms the previous finding that undetectable hypocretin-1 levels are highly specific for HLA positive narcolepsy with cataplexy. The data suggests that the pathophysiology and, by extension, etiology of this disorder are distinctly different from the other conditions studied. The relationship of the DQB1*0602 allele and reduced hypocretin-1 levels needs further study.

Adolescent↗