-
S Neidert,
M Katan,
P Schuetz,
F Fluri,
A Ernst,
R Bingisser,
L Kappos,
S T Engelter, A Steck,
B Müller,
M Christ-Crain
[show abstract]
[hide abstract]
ABSTRACT: Early and accurate prediction of outcome in acute stroke is important and influences risk-optimized therapeutic strategies. Endocrine alterations of the hypothalamic-pituitary axis are amongst the first measurable alterations after cerebral ischaemia. We therefore evaluated the prognostic value of cortisol, triiodothyronine (T3), free thyroxine (fT4), thyroid-stimulating hormone (TSH) and growth hormone (GH) in patients with an acute ischaemic stroke.
In an observational study including 281 patients with ischaemic stroke, anterior pituitary axis hormones (i.e. cortisol, T3, fT4, TSH and GH) were simultaneously assessed to determine their value to predict functional outcome and mortality within 90 days and 1 year.
In receiver operating characteristic curve analysis, the prognostic accuracy of cortisol was higher compared to all measured hormones and was in the range of the National Institutes of Health Stroke Scale (NIHSS). Cortisol was an independent prognostic marker of functional outcome and death [odds ratio (OR) 1.0 (1.0-1.01) and 1.62 (1.37-1.92), respectively, P<0.0002 for both, adjusted for age and the NIHSS] in patients with ischaemic stroke, but added no significant additional predictive value to the clinical NIHSS score.
Cortisol is an independent prognostic marker for death and functional outcome within 90 days and 1 year in patients with ischaemic stroke. By contrast, other anterior pituitary axis hormones such as peripheral thyroid hormones and GH are only of minor value to predict outcome in stroke.
Journal of Internal Medicine 11/2010; 269(4):420-32. · 5.48 Impact Factor
-
Mira Katan,
Felix Fluri,
Philipp Schuetz,
Nils G Morgenthaler,
Christian Zweifel,
Roland Bingisser,
Ludwig Kappos, Andreas Steck,
Stefan T Engelter,
Beat Müller,
Mirjam Christ-Crain
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to examine the prognostic value of midregional pro-atrial natriuretic peptide (MR-proANP) in patients with acute ischemic stroke.
The rapid and reliable estimation of prognosis in acute ischemic stroke is pivotal to optimize clinical care. MR-proANP, a recently described, stable fragment of the ANP precursor hormone, may be useful in this setting.
In a prospective observational study, we measured MR-proANP on admission in plasma of 362 consecutive patients presenting with acute ischemic stroke. The prognostic value of MR-proANP to predict mortality within 90 days and functional outcome (defined as a modified Rankin Scale of ≤2 or ≥3) was evaluated and compared with the National Institutes of Health Stroke Scale (NIHSS) score.
The discriminatory accuracy, calculated with the area under the curve (AUC) of the receiver operating characteristics curve, of MR-proANP to predict death was comparable to the NIHSS (AUC: 0.86 [95% confidence interval (CI): 0.82 to 0.90] and 0.85 [95% CI: 0.81 to 0.89; p = 0.7]). Combined, the accuracy significantly improved (0.92 [95% CI: 0.88 to 0.96; p < 0.01]). The AUC of MR-proANP to predict functional outcome was 0.70 (95% CI: 0.65 to 0.75), similar to the NIHSS (0.75 [95% CI: 0.70 to 0.80]; p = 0.16). The prognostic value of MR-proANP for both outcomes was independent of the NIHSS. Higher MR-proANP concentrations were found in stroke of cardioembolic etiology.
MR-proANP is a prognostic marker in the acute phase of stroke, improving the discriminatory value of the NIHSS, independently predicting post-stroke mortality and functional outcome. (The "COSMOS"-Study [Copeptin in Osmoregulation and Stress Assessment]; NCT00390962).
Journal of the American College of Cardiology 09/2010; 56(13):1045-53. · 14.16 Impact Factor
-
Sandrine A Urwyler,
Philipp Schuetz,
Felix Fluri,
Nils G Morgenthaler,
Christian Zweifel,
Andreas Bergmann,
Roland Bingisser,
Ludwig Kappos, Andreas Steck,
Stefan Engelter,
Beat Müller,
Mirjam Christ-Crain,
Mira Katan
[show abstract]
[hide abstract]
ABSTRACT: An accurate long-term outcome prediction may improve management of stroke patients. We investigated the ability of copeptin to predict 1-year outcome in stroke patients.
In this preplanned post hoc analysis, the National Institutes of Health Stroke Scale score and copeptin levels were measured on admission in a cohort of patients with ischemic stroke. The primary end point was functional outcome (modified Rankin Scale score <3 or 3-6) after 1 year. The secondary end point was all-cause mortality.
Of 362 patients, 341 (94.2%) completed the 1-year follow-up, 146 (43%) patients had an unfavorable functional outcome, and 66 (20%) died. Multivariate logistic-regression analysis adjusted for age and National Institutes of Health Stroke Scale score showed that copeptin was an independent predictor of functional outcome (odds ratio=4.00; 95% CI, 1.94-8.19) and death (odds ratio=2.68; 95% CI, 1.24-5.82). The area under the receiver operating characteristic curve of copeptin was 0.72 (95% CI, 0.67-0.77) for functional outcome and 0.74 (95% CI, 0.69-0.78) for mortality. Copeptin improved the area under the receiver operating characteristic curve of the National Institutes of Health Stroke Scale score for functional outcome from 0.70 (95% CI, 0.64-0.74) to 0.76 (95% CI, 0.71-0.82; P=0.002) and for mortality from 0.74 (95% CI, 0.69-0.78) to 0.78 (95% CI, 0.71-0.85; P=0.04).
Copeptin levels are a useful, complementary tool to predict functional outcome and mortality 1 year after stroke.
ISCTRN 00390962; clinicaltrials.gov No. NCT00390962.
Stroke 07/2010; 41(7):1564-7. · 5.73 Impact Factor
-
Annals of Neurology 04/2010; 67(4):552; author reply 552-3. · 11.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Anti-myelin-associated glycoprotein (MAG) neuropathy is an antibody-mediated polyneuropathy. We correlated clinical features, immunoglobulin (Ig) M blood levels, IgM deposition and axonal degeneration in skin biopsies of anti-MAG neuropathy patients. By confocal microscopy, IgM deposits were found exclusively within perineurium-enclosed nerves; they were not found on single, non-perineurium-ensheathed myelinated axons. There was a linear correlation between IgM accumulation in nerve fascicles with IgM blood levels but not with anti-MAG antibody titer or disease duration. Axons with specific IgM deposits had signs of axonal damage, including neurofilament disintegration. Nodal structures were intact even at sites where the axons showed pathologic changes. Ultrastructural analysis revealed degeneration of myelinating Schwann cells. Taken together, these findings suggest that in anti-MAG neuropathy patients, IgM deposits are entrapped within cutaneous perineurium-ensheathed nerve bundles where they accumulate in the endoneurial space. High local IgM levels in the endoneurium may be required for IgM deposition on myelin and subsequent axonal injury and degeneration. This study underlines the importance of early, effective anti-B-cell treatments for preventing progression of this neuropathy.
Journal of Neuropathology and Experimental Neurology 02/2009; 68(2):148-58. · 4.26 Impact Factor
-
Journal of Neurology 03/2007; 254(2):253-4. · 3.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Acute porphyrias are inherited disorders caused by partial deficiency of specific heme biosynthesis enzymes. Clinically, porphyrias are manifested by a neuropsychiatric syndrome that includes peripheral neuropathy. Although much is known about the porphyrias’ enzyme defects and their biochemical consequences, the cause of the neurological manifestations remains unresolved. We have studied porphyric neuropathy in mice with a partial deficiency of porphobilinogen deaminase (PBGD). PBGD-deficient mice (PBGD–/–) imitate acute porphyria through massive induction of hepatic δ-aminolevulinic acid synthase by drugs such as phenobarbital. Here we show that PBGD–/– mice develop impairment of motor coordination and muscle weakness. Histologically femoral nerves of PBGD–/– mice exhibit a marked decrease in large-caliber (>8 μm) axons and ultrastructural changes consistent with primary motor axon degeneration, secondary Schwann cell reactions, and axonal regeneration. These findings resemble those found in studies of affected nerves of patients with acute porphyria and thus provide strong evidence that PBGD deficiency causes degeneration of motor axons without signs of primary demyelination, thereby resolving a long-standing controversy. Interestingly, the neuropathy in PBGD–/– mice developed chronically and progressively and in the presence of normal or only slightly (twofold) increased plasma and urinary levels of the putative neurotoxic heme precursor δ-aminolevulinic acid. These data suggest that heme deficiency and consequent dysfunction of hemeproteins can cause porphyric neuropathy.
Journal of Clinical Investigation 04/1999; · 15.39 Impact Factor
