Fatal familial insomnia: a new Austrian family.
We present clinical, pathological and molecular features of the first Austrian family with fatal familial insomnia. Detailed clinical data are available in five patients and autopsy in four patients. Age at onset of disease ranged between 20 and 60 years, and disease duration between 8 and 20 months. Severe loss of weight was an early symptom in all five patients. Four patients developed insomnia and/or autonomic dysfunction, and all five patients developed motor abnormalities. Analysis of the prion protein (PrP) gene revealed the codon 178 point mutation and methionine homozygosity at position 129. In all brains, neuropathology showed widespread cortical astrogliosis, widespread brainstem nuclei and tract degeneration, and olivary 'pseudohypertrophy' with vacuolated neurons, in addition to neuropathological features described previously, such as thalamic and olivary degeneration. Western blotting of one brain and immunocytochemistry in four brains revealed quantitative and regional dissociation between PrP(res)(the protease resistant form of PrP) deposition and histopathology. In the cerebellar cortex of one patient, PrP(res) deposits were prominent in the molecular layer and displayed a peculiar patchy and strip-like pattern with perpendicular orientation to the surface. In another patient, a single vacuolated neuron in the inferior olivary nuclei contained prominent intravacuolar granular PrP(res) deposits, resembling changes of brainstem neurons in bovine spongiform encephalopathy. (+info
Ethanol as a hypnotic in insomniacs: self administration and effects on sleep and mood.
The purpose of this study was to assess the effects of low ethanol doses on sleep and mood and to assess its reinforcing effects used as a hypnotic. Twenty healthy adults, aged 21-45 yrs, all moderate social drinkers, were studied: eleven subjects had insomnia and nine were normal sleepers, as documented by clinical polysomnography. On two sampling nights each, ethanol (0.5 g/kg) or placebo was administered before sleep in color-coded cups presented in three doses (0.2, 0.2, and 0.1 g/kg) separated by 15 min. On three subsequent nights subjects chose their preferred presleep beverage (0.2 g/kg ethanol or placebo) based on cup color and were given an opportunity for 3 additional refills (0.2 g/kg each) of the chosen beverage at 15 min intervals, yielding a total possible dose of 0.8 g/kg. Insomniacs chose ethanol 67% of nights and normals 22%. Insomniacs chose significantly more ethanol refills than normals for an average nightly dose of 0.45 g/kg and normals took significantly more placebo refills. On the sampling nights 0.5 g/kg ethanol reduced REM sleep for both groups for the 8-hr sleep period and in insomniacs increased stage 3-4 sleep and reduced stage 1 sleep during the first half of the night to the level seen in the normals. Other sleep variables were not altered in either group or halves of the night. Presleep improvements in the Profile of Mood States tension and concentration factors were also associated with ethanol administration. Thus, acutely, both sleep and mood effects appear to be associated with the reinforcing effects of ethanol as a hypnotic for insomniacs. (+info
Prevalence of insomnia: a survey of the enrollees at five managed care organizations.
The purpose of the study was to assess the prevalence of and factors associated with insomnia among enrollees of managed care organizations (MCOs). A survey was distributed either by mail or during a clinic visit to 7,500 enrollees of five MCOs in the United States. The survey included a sleep questionnaire, demographic questions, and questions about medical encounters and prescription drug use. Three levels of insomnia (none; level I--difficulty initiating or maintaining sleep; level II--insomnia with daytime dysfunction) were defined from the responses. Comorbidities were determined by proxy from prescription drug use reported by respondents. A total of 3,447 survey responses were received, yielding a response rate of 46%. Level I and level II insomnia was reported by 13.5% and 32.5% of the respondents, respectively. Level II insomnia increased with decreasing education, income, and age and was more prevalent in women and non-Caucasians. Insomnia was significantly correlated with all daytime sleepiness and most nighttime disturbances factors. Fifty-two percent of all respondents reported at least one comorbid condition. Respondents with multiple comorbidities reported level II insomnia more frequently than those with no comorbidities. Only 0.9% of clinic visitors were seeing a physician specifically for sleep problems. Of those with level I and level II insomnia, only 5.5% and 11.6%, respectively, were taking prescription medications specifically for sleep problems; 11.2% and 21.4%, respectively, were taking over-the-counter medications for sleep. Insomnia occurs in MCO enrollees at rates comparable to those found in the general population. However, few patients with insomnia are actually being treated for their condition. Proper evaluation, diagnosis, and treatment of insomnia are warranted. (+info
Insomnia is a common complaint with potentially significant medical and psychologic complications. In some cases insomnia presents as a symptom of another underlying medical, psychiatric or environmental condition. In these cases, management of insomnia depends on accurate diagnosis and successful treatment of the underlying condition. In other cases, insomnia is a primary disorder requiring direct treatment. Pharmacologic treatments include nonprescription medications, sedating tricyclic antidepressants, benzodiazepines and related drugs. Behavior management methods that may be administered in the office setting include stimulus control therapy, sleep restriction therapy and sleep hygiene education. Although prescription medications and behavior therapy have similar short-term efficacy, behavior interventions are recommended as the first line of treatment for primary insomnia because of their greater safety and long-term efficacy. (+info
Insomnia: assessment and management in primary care. National Heart, Lung, and Blood Institute Working Group on Insomnia.
Patients with insomnia may experience one or more of the following problems: difficulty falling asleep, difficulty maintaining sleep, waking up too early in the morning and nonrefreshing sleep. In addition, daytime consequences such as fatigue, lack of energy, difficulty concentrating and irritability are often present. Approximately 10 percent of adults experience persistent insomnia, although most patients do not mention it during routine office visits. Asking sleep-related questions during the general review of systems and asking patients with sleep complaints to keep a sleep diary are helpful approaches in detecting insomnia. Behavior and pharmacologic therapies are used in treating insomnia. Behavior approaches take a few weeks to improve sleep but continue to provide relief even after training sessions have ended. Hypnotic medications are safe and effective in inducing, maintaining and consolidating sleep. Effective treatment of insomnia may improve the quality of life for many patients. (+info
Sleep and serotonin: an unfinished story.
Serotonin (5-HT) was first believed to be a true neuromodulator of sleep because the destruction of 5-HT neurons of the raphe system or the inhibition of 5-HT synthesis with p-chlorophenylalanine induced a severe insomnia which could be reversed by restoring 5-HT synthesis. However the demonstration that the electrical activity of 5-HT perikarya and the release of 5-HT are increased during waking and decreased during sleep was in direct contradiction to this hypothesis. More recent experiments suggest that the release of 5-HT during waking may initiate a cascade of genomic events in some hypnogenic neurons located in the preoptic area. Thus, when 5-HT is released during waking, it leads to an homeostatic regulation of slow-wave sleep. (+info
Chronic insomnia: a practical review.
Insomnia has numerous, often concurrent etiologies, including medical conditions, medications, psychiatric disorders and poor sleep hygiene. In the elderly, insomnia is complex and often difficult to relieve because the physiologic parameters of sleep normally change with age. In most cases, however, a practical management approach is to first consider depression, medications, or both, as potential causes. Sleep apnea also should be considered in the differential assessment. Regardless of the cause of insomnia, most patients benefit from behavioral approaches that focus on good sleep habits. Exposure to bright light at appropriate times can help realign the circadian rhythm in patients whose sleep-wake cycle has shifted to undesirable times. Periodic limb movements during sleep are very common in the elderly and may merit treatment if the movements cause frequent arousals from sleep. When medication is deemed necessary for relief of insomnia, a low-dose sedating antidepressant or a nonbenzodiazepine anxiolytic may offer advantages over traditional sedative-hypnotics. Longterm use of long-acting benzodiazepines should, in particular, be avoided. Melatonin may be helpful when insomnia is related to shift work and jet lag; however, its use remains controversial. (+info
Peripheral blood stem cell mobilization and apheresis: analysis of adverse events in 94 normal donors.
Adverse events were analyzed in 94 normal donors who underwent PBSC harvest with G-CSF. The median dose of G-CSF was 9.7 microg/kg/day (range, 2.0-16.7), and the duration of administration was 4-6 days. Frequent symptoms were bone pain (71%), general fatigue (33%), headache (28%), insomnia (14%), anorexia (11%), nausea and/or vomiting (11%). One donor (1%) developed grade 3 toxicity bone pain (WHO criteria). WBC counts and ANC increased during G-CSF administration. After leukapheresis, three donors (3%) developed grade 3 toxicity neutropenia. Platelet counts decreased after leukapheresis. Three donors (3%) developed grade 3 thrombocytopenia. The means of both ALP and LDH increased approximately 1.9-fold compared with pretreatment levels. In one pediatric donor (1%), ALP was elevated to the grade 3 toxicity level. From multivariate analysis, the incidence of bone pain increased when G-CSF was given at a dose of 8.8 microg/kg/day or more, headaches were frequent in donors younger than 35 years, and the incidence of nausea and/or vomiting was high in female donors. The peak levels of WBC counts and ANC and post-treatment level of LDH increased in correspondence with the escalation of G-CSF dose. All adverse events normalized on follow-up evaluation. In conclusion, although PBSC harvest for normal donors is acceptable, care must be taken for all donors in terms of their sex and age as well as the G-CSF dose. We recommend less than 8.8 microg/kg/day as the G-CSF dose for PBSC mobilization in normal donors. (+info