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| 2. |
- Bridel, Claire, et al.
(author)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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In: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Research review (peer-reviewed)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 3. |
- Eklundh, Thomas, et al.
(author)
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Cerebrospinal fluid levels of monoamine compounds and cholecystokinin peptides after exposure to standardized barometric pressure
- 2000
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In: Aviation, Space and Environmental Medicine. - 0095-6562 .- 1943-4448. ; 71:11, s. 1131-1136
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Journal article (peer-reviewed)abstract
- BACKGROUND: Connections between mood changes and weather have been described throughout the ages, and in more recent years, there have been reports on a relationship between atmospheric pressure and neurotransmitter levels in cerebrospinal fluid.METHODS: To further investigate this issue under strictly standardized conditions, we have lumbar-punctured 8 healthy males under low (963 hPa) and high (1064 hPa) barometric pressure, using a pressure chamber.RESULTS: Under high pressure, the tyrosine concentrations in the cerebrospinal fluid (CSF) were lower, while the cholecystokinin tetrapeptide (CCK-4) levels were higher. No differences between low and high pressure were found for tryptophan, 5-hydroxyindolacetic acid (5-HIAA), dopamine (DA), and sulphated cholecystokinin octapeptide (CCK-8S). The serum level of CCK-8S was higher under high pressure. On comparing concentration ratios between the second and the first CSF fraction, we found significantly increased ratios for homovanillic acid (HVA) and 4-hydroxy-3-methoxyphenylglycol (HMPG), but a decreased ratio for tyrosine under high pressure. The difference in the concentration ratios of HVA between low and high pressure correlated negatively with age. Intraspinal pressure correlated negatively with tapping time at low pressure.CONCLUSION: Our results are in line with the hypothesis that atmospheric pressure influences CSF levels of monoamine compounds and cholecystokinin peptides.
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| 4. |
- Eklundh, Thomas, et al.
(author)
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Monoamine compounds in cerebrospinal fluid of healthy subjects punctured without preceding strict bed rest : A pilot study
- 2001
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In: Neuropsychobiology. - : S. Karger AG. - 0302-282X .- 1423-0224. ; 43:1
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Journal article (peer-reviewed)abstract
- The interpretation of data on compounds in the lumbar cerebrospinal fluid (CSF) is limited by several confounding factors, e.g. motor activity for which strict bed rest prior to lumbar puncture is recommended for standardisation. Now we report data from 14 healthy males employing the standardised procedure except for the requirement of strict bed rest. The levels of serotonin, noradrenaline, 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid and 4-hydroxy-3-methoxyphenylglycol in the second CSF fraction (7-12 ml) were significantly higher than those in the first fraction (0-6 ml), indicating the presence of concentration gradients. 5-HIAA was negatively influenced by age and the neuraxis distance in the lying position and positively by atmospheric pressure. Storage time and atmospheric pressure contributed to the variance in dopamine. Both tyrosine, tryptophan and dopamine were linearly correlated with storage time. We also found a significant curvilinear correlation between tapping time and atmospheric pressure. On comparing with previous studies, the results support the notion that the issue of strict bed rest or not prior to lumbar puncture might have to be taken into consideration when interpreting lumbar monoamine CSF data.
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| 6. |
- Gunnarsson, Tove, 1956-, et al.
(author)
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Acute Effects of Cholecystokinin Tetrapeptide on Brain Stem Auditory Evoked Potentials in Healthy Volunteers
- 2003
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In: Pharmacopsychiatry. - : Georg Thieme Verlag KG. - 0176-3679 .- 1439-0795. ; 36:5, s. 181-186
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Journal article (peer-reviewed)abstract
- This study investigated the effects of continuous slow intravenous infusion of cholecystokinin tetrapeptide (CCK-4) on brain stem auditory evoked potentials (BSAEP) in healthy subjects. Twenty-four subjects, 15 females and 9males, were assigned to infusion with either placebo or CCK-4 in a randomized, double-blind, parallel group design. BSAEPs, mood, physical symptoms, and vital signs were assessed once before infusion and at 10 min and 40 min after the onset of infusion. In the 16 subjects (N = 8, CCK-4; N = 8, placebo) CCK-4, compared to placebo, delayed peak I latency during early infusion, slowed the latencies of peaks III and V, and decreased the amplitude of peak III throughout the infusion. No significant treatment differences were observed with respect to symptoms, mood, or cardiovascular measures. These preliminary findings suggest that CCK-4 may interfere with information processing in the brain stem auditory pathways and that prolonged intravenous CCK-4 administration may be a useful challenge paradigm for investigating CCK's modulatory role on brain stem mechanisms mediating anxiety and panic in humans.
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| 7. |
- Gunnarsson, Tove, 1956-, et al.
(author)
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Cholecystokinin peptides in cerebrospinal fluid : a pilot study in hypothyroid patients
- 1999
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In: Human Psychopharmacology. - 0885-6222 .- 1099-1077. ; 14:2, s. 113-117
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Journal article (peer-reviewed)abstract
- The cholecystokinin tetrapeptide (CCK-4) and the sulphated octapeptide (CCK-8) were measured in cerebrospinal fluid obtained from nine hypothyroid patients before and during L-thyroxine treatment. Before treatment, CCK-4 and CCK-8S correlated negatively with S-TSH, whereas CCK-8S also showed a positive correlation with S-T3. During treatment, S-T4 correlated negatively with CCK-8S. CSF collection time was significantly shorter during treatment than prior to treatment for the first (0–6 ml) CSF fraction. On taking CSF collection time into account, the levels of both CCK-4 and CCK-8S in the first CSF fraction were significantly increased during medication. Our results are consistent with an impact of the hypothyroid disorder and L-thyroxine treatment on the disposition of CCK compounds in CSF. This might be due to an altered CSF circulation, but other mechanisms (e.g. metabolism or elimination) cannot be ruled out.
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| 8. |
- Gunnarsson, Tove, 1956-, et al.
(author)
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Cholecystokinin peptides in cerebrospinal fluid : a study in healthy male subjects lumbar-punctured without preceding strict bed-rest
- 1999
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In: Journal of neural transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 106:3-4, s. 275-282
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Journal article (peer-reviewed)abstract
- In a recent study we analysed the concentrations of two forms of cholecystokinin (CCK), CCK-8S (sulphated) and CCK-4 in cerebrospinal fluid (CSF) obtained from 14 healthy male volunteers lumbar-punctured after a minimum of eight hours of strict bed-rest.We have now lumbar-punctured another group of 14 healthy males, using the same procedure except for the requirement of strict bed-rest prior to puncture.In contrast to our previous study, the concentration of CCK-4 (but not CCK-8S) was significantly higher in the second CSF fraction (7–12 ml) than in the first one (0–6 ml). On using the concentration ratio between the second and first fraction, CCK-8S (but not CCK-4) correlated positively with the atmospheric pressure, which is in contrast to our previous study in which a significant negative correlation was found.When the lumbar CSF concentrations were expressed as the concentration per minute of tapping-time (an estimate of the mass flow), atmospheric pressure, age and the neuraxis distance in the lying position made significant contributions to the variance in CCK-8S. A significant positive correlation with atmospheric pressure was found for CCK-4.In conclusion, the results indicate that the question of strict bed-rest or not prior to lumbar puncture may have to be considered when interpreting data on lumbar CSF concentrations of CCK. A controlled study is warranted.
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| 9. |
- Gunnarsson, Tove, 1956-, et al.
(author)
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Depressive Symptoms in Hypothyroid Disorder with some Observations on Biochemical Correlates
- 2001
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In: Neuropsychobiology. - : S. Karger AG. - 0302-282X .- 1423-0224. ; 43:2, s. 70-74
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Journal article (peer-reviewed)abstract
- Lumbar punctures and ratings of depressive symptoms were done in hypothyroid patients before and during L-thyroxine therapy. Before treatment, the most prominent symptoms were concentration difficulties, lassitude, and reduced sexual interest. All patients suffered from sleep disturbances. Suicidal thoughts did not occur at all. Inner tension was negatively correlated with the anxiogenic cholecystokinin tetrapeptide (CCK-4) in the cerebrospinal fluid (CSF), while reduced sexual interest was negatively correlated with CSF tryptophan. Furthermore, failing memory correlated negatively with T3 as well as T4 in serum. A positive correlation was found between failing memory and serum TSH. All patients improved significantly during treatment. No biochemical correlates were found. In conclusion, hypothyroidism is associated with major depressive symptoms. CSF CCK-4 and tryptophan, as well as serum thyroid hormones, may constitute biochemical correlates for some of these symptoms.
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| 10. |
- Gunnarsson, Tove, 1956-
(author)
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On the cerebrospinal fluid disposition and neurobiological role of cholecystokinin in man
- 2000
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Doctoral thesis (other academic/artistic)abstract
- Cholecystokinin (CCK) is the most abundant neuropeptide in the brain, where it acts as a neurotransmitter and neuromodulator. The tetrapeptide CCK-4 and the octapeptide CCK-8 have been implicated in various behavioural and physiological functions, such as anxiety, pain and satiety. Analyses of the levels of CCK in plasma, CSF and brain tissue have been used in studies aimed at elucidating the pathophysiological mechanisms in psychiatric disorders, but the results have been inconsistent.Cerebrospinal fluid (CSF) levels of CCK-4 and CCK-8S were analysed in three groups of healthy subjects lumbar-punctured under different conditions, with the aim to provide reference values for studies on patients, and to investigate putative confounding factors. It was found that the concentrations of CCK-4 and CCK-8S were influenced by age, bedrest or not prior to lumbar puncture, neuraxis distance, position during lumbar puncture, height, atmospheric pressure and storage time. For a correct interpretation of data, these factors should be taken into account in future CSF studies in volunteers and patients.Hypothyroidism is associated with depression. Thyroid hormones have been assumed to affect neuronal functions in the CNS, and animal experiments have indicated a relationship between thyroid hormones and CCK. Depressive symptoms were assessed in hypothyroid patients who were also lumbar-punctured before and during L-thyroxine treatment. Thyroid stimulating hormone, tri-iodothyronine and thyroxine in serum correlated with both CCK peptides in the CSF. A negative correlation between CCK-4 and inner tension (anxiety) was found.Various studies implicate the involvement of brain-stem structures in the aetiology of panic attacks. Brain-stem auditory evoked potentials were recorded in healthy subjects before and during infusion with the panic-provoking agent CCK-4 or placebo. CCK-4 delayed the latencies of peak I, III and V, and decreased peak III amplitude. This suggests that exogenous CCK-4 affects stimulus processing in the brain stem.
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