Search PubMed⌕ Search

Biomedical subjects

S Nevsimalova

Publications and source records attributed to S Nevsimalova.

11 recordsLinked to original sources
PubMed2001

CSF hypocretin/orexin levels in narcolepsy and other neurological conditions.

OBJECTIVE: To examine the specificity of low CSF hypocretin-1 levels in narcolepsy and explore the potential role of hypocretins in other neurologic disorders. METHODS: A method to measure hypocretin-1 in 100 microL of crude CSF sample was established and validated. CSF hypocretin-1 was measured in 42 narcolepsy patients (ages 16-70 years), 48 healthy controls (ages 22-77 years,) and 235 patients with various other neurologic conditions (ages 0-85 years). RESULTS: As previously reported, CSF hypocretin-1 levels were undetectably low (<100 pg/mL) in 37 of 42 narcolepsy subjects. Hypocretin-1 levels were detectable in all controls (224-653 pg/mL) and all neurologic patients (117-720 pg/mL), with the exception of three patients with Guillain-Barré syndrome (GBS). Hypocretin-1 was within the control range in most neurologic patients tested, including patients with AD, PD, and MS. Low but detectable levels (100-194 pg/mL) were found in a subset of patients with acute lymphocytic leukemia, intracranial tumors, craniocerebral trauma, CNS infections, and GBS. CONCLUSIONS: Undetectable CSF hypocretin-1 levels are highly specific to narcolepsy and rare cases of GBS. Measuring hypocretin-1 levels in the CSF of patients suspected of narcolepsy is a useful diagnostic procedure. Low hypocretin levels are also observed in a large range of neurologic conditions, most strikingly in subjects with head trauma. These alterations may reflect focal lesions in the hypothalamus, destruction of the blood brain barrier, or transient or chronic hypofunction of the hypothalamus. Future research in this area is needed to establish functional significance.

Carrier Proteins↗
PubMed2001

Low cerebrospinal fluid hypocretin (Orexin) and altered energy homeostasis in human narcolepsy.

Hypocretins (orexins) are hypothalamic neuropeptides involved in sleep and energy homeostasis. Hypocretin mutations produce narcolepsy in animal models. In humans, narcolepsy is rarely due to hypocretin mutations, but this system is deficient in the cerebrospinal fluid (CSF) and brain of a small number of patients. A recent study also indicates increased body mass index (BMI) in narcolepsy. The sensitivity of low CSF hypocretin was examined in 38 successive narcolepsy-cataplexy cases [36 human leukocyte antigen (HLA)-DQB1*0602-positive] and 34 matched controls (15 controls and 19 neurological patients). BMI and CSF leptin levels were also measured. Hypocretin-1 was measurable (169 to 376 pg/ml) in all controls. Levels were unaffected by freezing/thawing or prolonged storage and did not display any concentration gradient. Hypocretin-1 was dramatically decreased (<100 pg/ml) in 32 of 38 patients (all HLA-positive). Four patients had normal levels (2 HLA-negative). Two HLA-positive patients had high levels (609 and 637 pg/ml). CSF leptin and adjusted BMI were significantly higher in patients versus controls. We conclude that the hypocretin ligand is deficient in most cases of human narcolepsy, providing possible diagnostic applications. Increased BMI and leptin indicate altered energy homeostasis. Sleep and energy metabolism are likely to be functionally connected through the hypocretin system.

Adolescent↗
PubMed2000

A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains.

We explored the role of hypocretins in human narcolepsy through histopathology of six narcolepsy brains and mutation screening of Hcrt, Hcrtr1 and Hcrtr2 in 74 patients of various human leukocyte antigen and family history status. One Hcrt mutation, impairing peptide trafficking and processing, was found in a single case with early onset narcolepsy. In situ hybridization of the perifornical area and peptide radioimmunoassays indicated global loss of hypocretins, without gliosis or signs of inflammation in all human cases examined. Although hypocretin loci do not contribute significantly to genetic predisposition, most cases of human narcolepsy are associated with a deficient hypocretin system.

Adult↗
PubMed1994

Narcolepsy in children.

The clinical and polygraphic characteristics of narcolepsy in children were established on the analysis of 97 reported cases in children (including 12 personal cases). In idiopathic narcolepsies (77 cases) narcoleptic attacks occurred in 97% of the cases, cataplexy in 80.5%, hypnagogic hallucination in 39% and sleep paralysis in 29%; 13% of the children had the tetrad; dyssomnia was a prominent feature. Polygraphic data showed no significant differences between adults and children. In symptomatic narcolepsies (20 cases): cataplexy was the prominent feature occurring in 95% of the cases, 26% of the children had status cataplecticus; in these narcoleptic-cataplectic syndromes there was often an absence of polygraphic evidence of narcolepsy. Symptomatic narcolepsy should be suspected in cases where narcolepsy is detected in preteenage children, where cataplectic attacks are abnormally frequent, where there is an absence of polygraphic evidence of classical narcolepsy (although this criterion may not apply in the case of younger children) or where human leukocyte antigen typing for DR2 is negative. An association with a Niemann-Pick disease type C was found in 12 out of the 20 symptomatic cases, this association merits further study.

Catalepsy↗
PubMed1993

Excessive fragmentary myoclonus: time of night and sleep stage distributions.

Excessive fragmentary myoclonus during sleep consists of high amounts of brief twitch-like movements occurring asynchronously and asymmetrically in different body areas and has been reported to occur in association with a number of sleep disorders. It was analyzed using a new technique of quantification, the fragmentary myoclonus index (FMI). The FMI exhibited high rates in all stages of sleep but with a somewhat lower frequency in slow wave sleep explaining, as well, a significantly lower rate in the first hour after onset compared to later hours. There was no evidence for greater sleep fragmentation or lighter sleep compared to a matched patient group in whom it had not been noted.

Adult↗
PubMed1993

Event-related potentials in evaluation of metabolic encephalopathies.

Auditory event-related potentials (ERPs) were studied in 28 patients with chronic liver cirrhosis and in 34 patients on regular hemodialysis treatment for chronic renal failure. Prolongation of P3 wave latency was the earliest and most evident sign of brain cognitive dysfunction in both groups. The changes of ERPs well corresponded to the stage of metabolic affliction when, in addition, N1 and N2 wave latencies were delayed in patients with more advanced liver cirrhosis. In the group of hemodialyzed patients, ERPs reflected the effects of an individual treatment procedure as well.

Adult↗
PubMed1983

Life effects of narcolepsy: relationships to geographic origin (North American, Asian or European) and to other patient and illness variables.

A recent questionnaire survey of the life-effects of narcolepsy in 180 patients, 60 each from North American, Asian and European populations, compared to similarly distributed age and sex matched controls, documented multiple and marked effects on work, education, driving, accidents, recreation, personality, memory and other parameters. The data have now been further analysed according to the patients' geographic (culturo-genetic) origin and to a number of other patient and illness variables. The three different geographic populations showed few significant differences for the some 160 life-effects items in the questionnaire. This strongly indicates that these are an integral part of the disease or of the human reactions to it. Most of the few significant population differences appeared cultural in origin (e.g., concerning driving records, personality changes), although a few may possibly reflect genetic differences (e.g., visual problems). Analysis of the pooled data according to respondees' age, sex, age at illness onset, duration of illness and treatment led again to relatively few significant findings. It is concluded that, in general, once the disease has been diagnosed, all the major life effects are present and remain so. The results strongly support the contention that most life-effects are not related to the diagnostic 'tetrad' symptoms themselves but rather to excessive daytime sleepiness, the symptoms most resistant to ant-narcoleptic treatment.

Accidents, Traffic↗
PubMed1981

Life effects of narcolepsy in 180 patients from North America, Asia and Europe compared to matched controls.

A questionnaire survey has been made of the life effects of narcolepsy in 180 patients, 60 each from North American, Asian and European populations, with 180 similarly distributed age and sex matched controls. Life-effects were attributed by the patients to the primary symptoms of excessive daytime drowsiness, sleep attacks, cataplexy, vivid hypnagogic hallucinations and sleep paralysis, and also to other frequent symptoms such as visual problems (blurring, diplopia) and memory impairment. Occupational problems were prevalent (over 75%) and included statistically significant deleterious effects upon performance, promotion, earning capacity, fear of or actual job loss and increased disability insurance. Driving was greatly affected and patients fell asleep at the wheel more frequently (66%), had near or actual accidents from drowsiness or falling asleep at the wheel (67%), and could experience cataplexy (29%) or sleep paralysis (12%) while driving. Work or home accidents attributed to sleepiness or sleep (49%) or related to smoking (49%) were much more common in patients. There were also deleterious effects on education, recreation and personality related to disease. Narcolepsy can produce a variety of life-effects probably more serious and pervasive than, for instance, those of epilepsy, therefore emphasizing the importance of early diagnosis and treatment.

Accidents↗
PubMed1975

Depresssion in narcolepsy and hypersommia.

The authors studied the occurrence of depression in 100 randomly selected patients with narcolepsy and in 30 patients with hypersomnia. In the isolated form of idiopathic narcolepsy (without signs of cataplexy, sleep paralysis or hypnagogic hallucinations) depression occurred 28.6 per cent of cases. In idiopathic narcolepsy with cataplexy or other symptoms of sleep dissociation, depression was found in 17.2 per cent of cases. In idiopathic hypersomnia the occurrence of depression was 26.1 per cent. In the majority of cases the endogenous form of depression was observed. In the symptomatic form of narcolepsy and hypersomnia the occurence of depression has not been noted in any case. In most cases a parallel clincial course has been observed between the manifestation of depression and narcolepsy or hypersomnia. During a remission of the depressive state the hypersomniac symptoms decreased or disappeared totally. The authors furter discuss the possible pathophysiological mechanisms of the above mentioned symptoms. They are of the opinion that an important role is played by the secretion and metabolism of the cerebral monamines.

Cataplexy↗