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Biomedical subjects

Michael H Silber

Publications and source records attributed to Michael H Silber.

At least 19 recordsLinked to original sources
PubMed2006

Hypersomnias of central origin.

Hypersomnia related to CNS disorders can be due to a variety of conditions. In this review, we discuss the diagnosis and treatment of narcolepsy with and without cataplexy, idiopathic hypersomnia, recurrent hypersomnia, and related illnesses. Research has provided insight into the underlying etiologies of these disorders, such as the genetic influences on disease development and the fundamental role of hypocretins in narcolepsy. We define the current utility of diagnostic testing, including sleep studies, neuroimaging techniques, and laboratory investigations. New treatment options for hypersomnia are discussed.

Central Nervous System↗
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

Complex nocturnal visual hallucinations.

BACKGROUND AND PURPOSE: To describe the clinical features and associations of complex nocturnal visual hallucinations. PATIENTS AND METHODS: We identified 12 patients seen between 1997 and 2004 with complex nocturnal visual hallucinations. Charts were reviewed and data analyzed. RESULTS: Of the 12 patients, 11 were women. Vivid, silent, often distorted images of people and animals occurred after waking, disappearing with increased light. Idiopathic hypersomnia, beta blocker use, dementia with Lewy bodies, macular degeneration and anxiety were associated factors. The hallucinations appeared to be a primary parasomnia in four patients with anxiety being the only associated feature. CONCLUSIONS: Complex nocturnal visual hallucinations represent a well-defined syndrome with diverse causes which should be differentiated from other parasomnias causing arousals.

Adolescent↗
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↗
PubMed2004

An update on the dopaminergic treatment of restless legs syndrome and periodic limb movement disorder.

This paper reviews evidence from April, 1998 through April 2002 for the dopaminergic treatment of the restless legs syndrome (RLS) and periodic limb movement disorder (PLMD). There has been increased study of dopaminergic agents for the treatment of these conditions since publication of a review paper and practice parameters that covered all types of medical treatment of RLS and PLMD in 1999. For this reason, the Restless Legs Syndrome Task Force and the Standards of Practice Committee decided to update the evidence on dopaminergic treatment of these conditions. This paper reviews the literature on levodopa, dopaminergic agonists (pergolide, pramipexole, ropinirole, talipexole, cabergoline, piribidel, DHEC), and other dopaminergic agents (amantadine, selegiline).

Dopamine Agonists↗
PubMed2004

Childhood-onset restless legs syndrome.

The clinical characteristics of childhood-onset restless legs syndrome are described. Thirty-two of 538 subjects (5.9%) examined in our sleep disorders center received diagnoses of restless legs syndrome. They were classified based on published criteria into probable (n = 9/32 or 28%) and definite (n = 23/32 or 78%) categories. Apart from an earlier age of diagnosis of the probable group, no differences were found between the two categories. Sleep onset or sleep maintenance insomnia was the most common symptoms, being present in 28 of 32 subjects (87.5%). Inattentiveness was seen in 8 of 32 subjects (25%). Serum ferritin levels were measured in 24 of 32 subjects and were below 50 microg/L in 20 of 24 subjects (83%). A family history of restless legs syndrome was present in 23 of 32 (72%) subjects, with mothers almost three times more likely to be affected than fathers (p = 0.02). We conclude that iron deficiency and a strong family history are characteristic of childhood-onset restless legs syndrome.

Adolescent↗
PubMed2004

REM sleep behavior disorder in Parkinson's disease and dementia with Lewy bodies.

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia manifested by vivid, often frightening dreams associated with simple or complex motor behavior during REM sleep. Patients appear to "act out their dreams," in which the exhibited behaviors mirror the content of the dreams. Management of RBD involves counseling about safety measures in the sleep environment; in those at risk for injury, clonazepam and/or melatonin is usually effective. In this article, the authors present a detailed review of the clinical and polysomnographic features, differential diagnosis, diagnostic criteria, management strategies, and pathophysiologic mechanisms of RBD. They then review the literature and their institutional experience of RBD associated with neurodegenerative disease, particularly Parkinson's disease and dementia with Lewy bodies. The evolving data suggests that RBD may have clinical diagnostic and pathophysiologic significance in isolation and when associated with neurodegenerative disease.

Diagnosis, Differential↗
PubMed2004

An algorithm for the management of restless legs syndrome.

Restless legs syndrome (RLS) is a common disorder with a prevalence of 5% to 15%. Primary care physicians must become familiar with management of this disorder. This algorithm for the management of RLS was written by members of the Medical Advisory Board of the Restless Legs Syndrome Foundation and is based on scientific evidence and expert opinion. Restless legs syndrome is divided into intermittent, daily, and refractory types. Nonpharmacological approaches, including mental alerting activities, avoiding substances or medications that may exacerbate RLS, and addressing the possibility of iron deficiency, are discussed. The role of carbidopa/levodopa, dopamine agonists, opioids, benzodiazepines, and anticonvulsants for the different types of the disorder is delineated.

Algorithms↗
PubMed2003

Pramipexole in the management of restless legs syndrome: an extended study.

STUDY OBJECTIVES: To determine whether pramipexole used over an extended time for restless legs syndrome (RLS) remains effective; whether the dose of the drug needs to be increased; whether augmentation develops; and whether side effects, especially sleepiness, are prominent. DESIGN: Retrospective review of the records of consecutive patients treated with pramipexole for RLS. SETTING: Sleep disorders center in an academic hospital. PATIENTS: 60 consecutive patients treated with pramipexole for RLS. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Pramipexole was completely effective in controlling RLS in 67%, partially effective in 27%, and ineffective in 7% of patients. Eleven patients (18%) discontinued pramipexole after less than 4 months; the remainder were followed for a mean of 27.2 months, during which only 4 others stopped the drug. The median daily dose increased from 0.38 mg after stabilization to 0.63 mg at the end of the study. Forty percent experienced mild side effects, most commonly insomnia, nausea or dyspepsia, and dizziness. Only 5% experienced sleepiness, and none experienced sleep attacks while driving. Augmentation developed in 33%, most in the first year and all by 30 months. Augmentation was not predictable by prior augmentation with other dopaminergic agents. Only 1 patient discontinued pramipexole because of augmentation. CONCLUSIONS: Pramipexole was effective for RLS with continued response with time. Modest escalations in dose occurred, partly due to additional doses prescribed for augmentation. Side effects were common, but generally mild and tolerated. Sleepiness while driving was not a problem. Augmentation occurred in 33% of patients but was treatable with increased doses earlier in the day.

Adult↗
PubMed2003

Melatonin for treatment of REM sleep behavior disorder in neurologic disorders: results in 14 patients.

OBJECTIVE: To describe the treatment response with melatonin for rapid eye movement (REM) sleep behavior disorder (RBD) associated with other neurologic disorders. BACKGROUND: Clonazepam has been considered the treatment of choice for RBD. However, an alternative treatment is desirable for those with RBD refractory to clonazepam, for those who experience intolerable side-effects with clonazepam, and for those in whom clonazepam precipitates or aggravates obstructive sleep apnea (OSA). To date, there is minimal published data and limited follow-up regarding the use of melatonin for patients with RBD associated with other neurologic syndromes and disorders. DESIGN/METHODS: The response to melatonin treatment for RBD was reviewed on consecutive patients the investigators treated with this agent at Mayo Clinic Rochester from January 2000 to June 2001. The coexisting neurologic disorders, reasons for using melatonin, effective doses, side-effects, and duration of follow-up were also reviewed on all patients. RESULTS: Fourteen patients were commenced on melatonin over the specified time period (13 male, median RBD onset age 56 years, range 20-77 years). The coexisting neurologic findings/disorders were dementia with Lewy bodies (n=7), mild cognitive impairment with mild parkinsonism (n=2), multiple system atrophy (n=2), narcolepsy (n=2), and Parkinson's disease (n=1). The reasons for using melatonin in these cases were incomplete response of RBD to clonazepam in six patients, existing cognitive impairment in five, intolerable side-effects with clonazepam in two, and presence of severe obstructive sleep apnea and narcolepsy in one. With seven patients continuing to use clonazepam at 0.5-1.0 mg/night, RBD was controlled in six patients, significantly improved in four, and initially improved but subsequently returned in two; no improvement occurred in one patient and increased RBD frequency/severity occurred in one patient. The effective melatonin doses were 3 mg in two cases, 6 mg in seven cases, 9 mg in one case, and 12 mg in two cases. Five patients reported side-effects, which included morning headaches (2), morning sleepiness (2), and delusions/hallucinations (1); these symptoms resolved with decreased dosage. The mean duration of follow-up was 14 months (range 9-25 months), with eight patients experiencing continued benefit with melatonin beyond 12 months of therapy. CONCLUSIONS: In this series, persistent benefit with melatonin beyond 1 year of therapy occurred in most but not all patients. Melatonin can be considered as a possible sole or add-on therapy in select patients with RBD. Prospective, long-term, controlled trials with melatonin are warranted in a larger number of patients with RBD associated with a variety of neurologic symptoms and disorders.

Adult↗
PubMed2003

Multiple blood donations associated with iron deficiency in patients with restless legs syndrome.

OBJECTIVE: To describe a series of patients with restless legs syndrome (RLS) and iron deficiency with and without anemia related to repeated blood donations. PATIENTS AND METHODS: Study patients were identified by asking consecutive patients with RLS seen at the Mayo Clinic in Rochester, Minn, from February 1 to December 31, 2001, whether they donated blood. All patients who fulfilled the International Restless Legs Syndrome Study Group criteria for RLS, had donated blood a minimum of 3 times a year the preceding 3 years, and had iron deficiency (serum ferritin concentration <20 microg/L) were included in the study. RESULTS: Eight patients met the study criteria. The mean +/- SD serum ferritin concentration was 8.1 +/- 3.5 microg/L, and 4 patients had anemia. In 6 of the 8 patients, RLS began at about the same time of or after blood donation. Patients had donated blood for 4.2 +/- 13 times a year (range, 3-6 times a year) for 15.2 +/- 83 years (range, 5-25 years). Hemoglobin concentrations were 12.8 +/- 1.8 g/dL (range, 10.6-15.5 g/dL). In 2 patients, RLS essentially resolved with correction of iron stores alone, and medications for RLS were successfully discontinued in 2 other patients. CONCLUSIONS: Repeated blood donation is associated with induction or perpetuation of RLS due to iron deficiency with or without coexisting anemia. Potential blood donors should be questioned about RLS, and donation should not be allowed until the serum ferritin concentration has been measured and iron stores replenished if necessary.

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↗
PubMed2002

The epidemiology of narcolepsy in Olmsted County, Minnesota: a population-based study.

STUDY OBJECTIVES: To determine the age- and sex-specific incidence rates and prevalence of narcolepsy in a United States community. DESIGN: The records-linkage system of the Rochester Epidemiology Project was utilized to ascertain all patients with narcolepsy seen in Olmsted County, Minnesota between 1960 and 1989. Age- and sex-specific incidence rates were calculated, using census data. Prevalence of narcolepsy on January 1,1985 was calculated. SETTING: N/A. PATIENTS OR PARTICIPANTS: Community patients diagnosed with narcolepsy by a validated set of diagnostic criteria. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The incidence rate per 100,000 persons per year was 1.37 (1.72 for men and 1.05 for women). The incidence rate was highest in the 2nd decade, followed in descending order by the 3rd, 4th and 1st decades. The prevalence on January 1, 1985 was 56.3 per 100,000 persons. Approximately 36% of prevalence cases did not have cataplexy. CONCLUSIONS: Narcolepsy is not a rare disorder. It appears to be commoner in men. It originates most commonly in the 2nd decade. Narcolepsy without cataplexy is an important subgroup, warranting further study.

Adolescent↗