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Biomedical subjects

G J Lammers

Publications and source records attributed to G J Lammers.

At least 19 recordsLinked to original sources
PubMed2002

[Unwanted 'siesta'].

Explore the source record for details and available documents.

Diagnosis, Differential↗
PubMed2002

Reduction of plasma leptin levels and loss of its circadian rhythmicity in hypocretin (orexin)-deficient narcoleptic humans.

Recent observations have implicated hypocretin deficiency in the pathogenesis of narcolepsy. Hypocretin neurotransmission also affects energy balance, and narcoleptic patients tend to become obese. Because hypocretins appear to have important neuroendocrine effects, we hypothesized that the neuroendocrine systems that regulate energy balance might be distinctly set in narcolepsy. As leptin is a pivotal part of these systems, we explored the 24-h plasma leptin (20-min sampling interval) concentration profile in six narcoleptic males and six normal controls, matched for age, sex, body mass index, waist/hip ratio, and fat mass. We thus demonstrated a reduction of the mean 24-h leptin concentration in narcoleptics to 52% of that in controls (5.9 microg/liter in narcolepsy vs. 11.4 microg/liter in controls; P < 0.05). Further, a nocturnal acrophase (clock time of the highest concentration), which is typical of normal leptin secretion, was observed in controls (mean, 2335 h; 95% confidence interval, 2105-0205 h), but not in narcoleptic patients. The mechanisms that potentially disturb the circadian rhythm of leptin levels in hypocretin-deficient narcoleptic humans include anomalies of the sleep-wake cycle and/or disruption of the circadian distribution of autonomic activity. As leptin deficiency clearly leads to morbid obesity in experimental animals and humans, we infer that the observed reduction of plasma leptin levels may predispose narcoleptic humans to weight gain.

Adult↗
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↗
PubMed2001

Narcolepsy: clinical features, new pathophysiologic insights, and future perspectives.

Narcolepsy is characterized by excessive daytime sleepiness and abnormal manifestations of rapid eye movement sleep such as cataplexy. The authors review the clinical features of narcolepsy, including epidemiology, symptoms, diagnosis, and treatment, in detail. Recent findings show that a loss of hypocretin-producing neurons lies at the root of the signs and symptoms of narcolepsy. The authors review the current state of knowledge on hypocretin anatomy, physiology, and function with special emphasis on the research regarding the hypocretin deficiency in narcolepsy, which may also explain associated features of the disorder, such as obesity. Lastly, they discuss some future perspectives for research into the pathophysiology of sleep/wake disorders, and the potential impact of the established hypocretin deficiency on the diagnosis and treatment of narcolepsy.

Age of Onset↗
PubMed2000

Hypocretin (orexin) deficiency in human narcolepsy.

Alterations in the hypocretin receptor 2 and preprohypocretin genes produce narcolepsy in animal models. Hypocretin was undetectable in seven out of nine people with narcolepsy, indicating abnormal hypocretin transmission.

Adult↗
PubMed2000

Effects of startle and laughter in cataplectic subjects: a neurophysiological study between attacks.

OBJECTIVES: Cataplexy, when unequivocally present together with excessive daytime sleepiness, is diagnostic for narcolepsy. Unfortunately, it is difficult to induce cataplexy during consultation. In this study we tried to assess presumed subclinical expressions of cataplexy using neurophysiological tests. METHODS: In this controlled explorative study, we studied 14 patients with a clear history of cataplexy and 12 matched controls using standard H-reflex, H/M ratios, audiospinal reflex, H-reflexes modulated by emotions and startle reflexes. RESULTS: H-reflexes were attenuated during laughter in patients as well as controls. Startle reflexes were increased in patients. Audiospinal reflexes were not influenced. CONCLUSIONS: The patterns found add relevant knowledge concerning pathophysiological mechanisms and involved brain areas in cataplexy, and may reflect subclinical expressions of cataplexy. The presumed specificity of the abolishment of H-reflexes during cataplectic attacks is questioned by our findings. The exaggerated startle reflex is in line with recent findings concerning involved brain areas in narcolepsy.

Acoustic Stimulation↗
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↗
PubMed1999

Weak with laughter.

We found a marked reduction of H-reflex amplitude during laughter, suggesting that motor inhibition may underlie the feeling of being "weak with laughter". This effect may have a role in cataplexy, which is preferentially elicited by laughter.

Cataplexy↗
PubMed1999

An uncommon cause of stroke in young adults.

We describe a previously healthy 48-year-old man who presented with clinical characteristics suggestive of internal carotid artery dissection, confirmed by magnetic resonance imaging. He developed a massive infarction of the left cerebral hemisphere and died after 3 days of transtentorial herniation. Post-mortem examination identified a dissection of the thoracic aorta caused by Erdheim-Gsell cystic medionecrosis, with the characteristic degeneration of the elastic fibers of the lamina media. The dissection showed an unusually large extension not only distally into both iliac arteries, but also proximally into both carotid arteries. To our knowledge, such an extensive dissection has not been described previously. Underlying vessel wall disorders of the aorta, such as Erdheim Gsell cystic medionecrosis, should be considered in young patients with spontaneous arterial dissection.

Aortic Dissection↗
PubMed1999

Numerous and widespread alpha-synuclein-negative Lewy bodies in an asymptomatic patient.

Lewy bodies (LB) and pale bodies (PB), their putative precursors, can be found in a spectrum of diseases characterized by parkinsonism and/or dementia. Furthermore, LB are occasionally observed in some other neurodegenerative diseases and in normal aging. Classical LB are typically found in the brain stem, especially in the substantia nigra, where these inclusions are associated with neuronal loss and clinical signs of idiopathic Parkinson's disease (PD). The so-called cortical LB occur in the cerebral cortex, amygdala and claustrum with little or no neuronal loss and are clinically associated with dementia in dementia with LB (DLB). We describe a patient without apparent clinical signs of parkinsonism and/or dementia, whose brain contained numerous classical-like LB, pale inclusions with features of PB and transitions between these two. These inclusions had similar immunohistological (ubiquitin positive; neurofilament positive; tau negative) and ultrastructural features as the LB in PD and DLB except for the lack of immunoreactivity for alpha-synuclein. The pons and cerebral cortex showed the highest number of LB, up to 165/1.76 mm2. These numbers were contrasted by the lack of obvious neuronal loss or gliosis. The absence of alpha-synuclein reactivity in the LB in this symptomless patient corroborates the hypothesis that alpha-synuclein accumulation in LB is an important step in neurodegeneration in PD and DLB, but tones down the role of alpha-synuclein in LB formation in general. This patient seems to represent a new variant in the spectrum of diseases associated with LB.

Brain↗
PubMed1998

Prolonged coma and severely attenuated EEG after a single seizure.

A 63-year-old woman presented with a comatose state after a fall. Results of cranial computed tomography (CT) and magnetic resonance imaging (MRI) scans were normal. An EEG recorded 5 h after admission was very severely attenuated and slowed. Consciousness and EEG were improved the next day. No cause was detected initially. After sleep deprivation, the patient had a generalized seizure followed by a similar coma and EEG. Even a single seizure may cause a prolonged coma with a very severely attenuated and slowed EEG.

Accidental Falls↗
PubMed1997

Sleep scoring at a lower resolution.

Sleep scoring of whole-night polysomnograms is labor intensive. Scoring fewer epochs saves labor at the cost of accuracy; this study investigates the trade-off between the two. Whole-night sleep measures of 12 patients with sleep apnea syndrome, 10 patients with narcolepsy, and 35 controls were first computed using conventional successive 30-second epochs. Using the resulting list of sleep stages, a variable number of epochs was skipped among remaining epochs; the measures were recomputed for the reduced lists. The Bland-Altman analysis was used to define the agreements among the sleep measures at the conventional resolution and those at the lower resolutions. Scoring one-half to one-third of the number of epochs changes the duration of sleep stages only up to 2.5% and 5%, respectively, for all groups and sleep stages. In apnea patients, rapid eye movement (REM) latency deviates < 15 minutes when half of the epochs are scored. In controls and narcoleptics, much lower resolutions can be used before reaching the same level. Potential restrictions for the application of the method are discussed.

Adolescent↗