Screening for Acromegaly in Patients with Carpal Tunnel Syndrome: A Prospective Study (ACROCARP).

Early diagnosis of acromegaly prevents irreversible comorbidities and facilitates surgical cure. Carpal tunnel syndrome (CTS) is common in acromegaly and patients have often undergone surgery for CTS prior to the diagnosis of acromegaly. We hypothesized that screening CTS-patients for acromegaly could facilitate active case-finding. We prospectively enrolled 196 patients [135 women, 56.9 (range 23-103) years] who presented with CTS for surgery. Patients were asked about 6 symptoms suggestive of acromegaly using a questionnaire calculating a symptom score (0-6 points), and insulin-like-growth factor 1 (IGF-1) was measured. If IGF-1 was increased, IGF-1 measurement was repeated, and random growth hormone (GH) and/or an oral glucose tolerance test (OGTT) with assessment of GH-suppression were performed. The mean symptom score was 1.7±1.3 points. Three patients reported the maximal symptom score of 6 points, but none of them had an increased IGF-1. There was no correlation between the symptom score and IGF-1-SDS (standard deviation score) (r=0.026; p=0.71). Four patients had an IGF-1>2 SDS. In 2 patients acromegaly was ruled out using random GH and OGTT. One patient had normal IGF-1 and random GH at follow-up. One patient refused further diagnostics. In this prospective cohort of patients with CTS, the observed frequency of acromegaly was at most 0.51% (95% CI 0.03 to 2.83%). In this prospective study, none of the 196 patients with CTS had proven acromegaly. Thus, we see no evidence to justify general screening of patients with CTS for acromegaly.

Exercise-induced cardioprotection: a role for eNOS uncoupling and NO metabolites.

Exercise is an efficient strategy for myocardial protection against ischemia-reperfusion (IR) injury. Although endothelial nitric oxide synthase (eNOS) is phosphorylated and activated during exercise, its role in exercise-induced cardioprotection remains unknown. This study investigated whether modulation of eNOS activation during IR could participate in the exercise-induced cardioprotection against IR injury. Hearts isolated from sedentary or exercised rats (5 weeks training) were perfused with a Langendorff apparatus and IR performed in the presence or absence of NOS inhibitors [N-nitro-L-arginine methyl ester, L-NAME or N5-(1-iminoethyl)-L-ornithine, L-NIO] or tetrahydrobiopterin (BH4). Exercise training protected hearts against IR injury and this effect was abolished by L-NAME or by L-NIO treatment, indicating that exercise-induced cardioprotection is eNOS dependent. However, a strong reduction of eNOS phosphorylation at Ser1177 (eNOS-PSer1177) and of eNOS coupling during early reperfusion was observed in hearts from exercised rats (which showed higher eNOS-PSer1177 and eNOS dimerization at baseline) in comparison to sedentary rats. Despite eNOS uncoupling, exercised hearts had more S-nitrosylated proteins after early reperfusion and also less nitro-oxidative stress, indexed by lower malondialdehyde content and protein nitrotyrosination compared to sedentary hearts. Moreover, in exercised hearts, stabilization of eNOS dimers by BH4 treatment increased nitro-oxidative stress and then abolished the exercise-induced cardioprotection, indicating that eNOS uncoupling during IR is required for exercise-induced myocardial cardioprotection. Based on these results, we hypothesize that in the hearts of exercised animals, eNOS uncoupling associated with the improved myocardial antioxidant capacity prevents excessive NO synthesis and limits the reaction between NO and O2·- to form peroxynitrite (ONOO⁻), which is cytotoxic.

Following brain trauma, copeptin, a stable peptide derived from the AVP precusor, does not reflect osmoregulation but correlates with injury severity.

The incidence of water and electrolyte disturbances following traumatic brain injury (TBI) is considerable and has been attributed to a dysregulation of the hypothalamic peptide arginine-vasopressin (AVP). Copeptin, the C-terminal part of the AVP prohormone, reflects AVP activity. In 71 TBI patients we measured copeptin in serum by a sandwich immunoassay. Injury severity was assessed by Glasgow Coma Score (GCS) and computed tomography, and recovery by Glasgow Outcome Score (GOS). Neuroendocrine and osmoregulation regulation were examined on day 0, 3 and 7, and 24 months post-injury. Copeptin was highest on admission (40.0 +/- 72.3 pmol/l), stabilized on day 3 and 7 (21.2 +/- 18.3 resp. 20.3 +/- 17.1 pmol/l), and normalized at follow-up (4.2 +/- 1.7 pmol/l). On admission, there was a correlation between serum sodium and urine excretion (p = 0.003), but the correlation got lost on day 3 and 7. Copeptin did not reflect the individual 24 h urine excretion or serum sodium levels indicating an uncoupling of copeptin/AVP release and renal water excretion. High copeptin level on day 3 were correlated with a low GCS (p < 0.001), midline shift (p = 0.019), intracerebral hemorrhage (p = 0.026), SAPS score (p = 0.001), as well as with a low GOS (p = 0.031). Copeptin was significantly decreased following skullbase fracture (p = 0.016).Our data reveal a loss of hypothalamic osmoregulation following TBI. The measurement of Copeptin/AVP release reveals a significant predictive function for the severity of TBI.

Dynamics of S100B release into serum and cerebrospinal fluid following acute brain injury.

High S100B serum levels are considered to reflect brain injury severity. However, the dynamics of S100B passage from the cerebral compartment into the blood remain unclear. We examined the temporal profile of S100B release into the cerebrospinal fluid (CSF) and blood in acute brain injury.In patients treated with ventricular drainage (subarachnoid hemorrhage, SAH, n = 23; traumatic brain injury, TBI, n = 19), we measured S100B levels in the serum and CSF. The Glasgow Coma Score (GCS) was assessed daily. Statistical analysis was performed by the Mann-Whitney rank sum test for group differences and by the Pearson correlation.In normal controls (n = 6), S100B levels in the serum (0.05 +/- 0.01 microg/L) comprised around 10% of the CSF concentration (0.66 +/- 0.08 microg/L). Following brain injury, S100B levels were significantly increased in the serum (p < 0.05 in SAH day 2-5, TBI day 1-8) and excessively increased in the CSF (p < 0.05 in SAH and TBI day 1-10). For the individual patient, there was no consistent correlation between S100B levels in serum or CSF and GCS. We therefore calculated the ratio of S100B serum/CSF. Following brain injury, the S100B passage from the CSF to the blood was significantly impaired. Further, higher ratios were correlated with better neurological function (p = 0.002).Because stimulated active S100B release may serve as a repair mechanism, a higher S100B serum/CSF ratio may contribute to neurological recovery.

Effect of dimethyl sulfoxide on blood-brain barrier integrity following middle cerebral artery occlusion in the rat.

Dimethyl sulfoxide (DMSO) is widely used as a solvent for other drugs, i.e., for the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) and the V1a receptor-antagonist SR49059, to reduce brain edema. We studied the effect of DMSO on blood-brain barrier (BBB) integrity following middle cerebral artery occlusion (MCAO) and the consequences on brain edema development. Male Sprague-Dawley rats were randomly assigned to sham procedure or infusion of 1% DMSO, PMA (230 microg/kg in 1% DMSO), or SR49059 (1 mg/kg in 1% DMSO) followed by MCAO (each group n = 10). After a 2-hour period of ischemia and 2 hours reperfusion, the animals were sacrificed for assessment of brain water content, sodium, and potassium concentration. BBB integrity was assessed by Evans blue extravasation. Statistical analysis was performed by ANOVA followed by a Tukey post hoc test. Low-dose DMSO treatment following MCAO significantly opened the BBB on the ischemic side (p < 0.037). PMA and SR49059 did not have any additional effect on BBB compromise compared to DMSO (p = 1.000, p < 0.957, respectively). We conclude that DMSO as a vehicle for drug administration may increase the drug concentration into the extracellular space, but since BBB permeability is increased, it may also provide an avenue for development of vasogenic edema.

Protective effect of the V1a receptor antagonist SR49059 on brain edema formation following middle cerebral artery occlusion in the rat.

There exists no pharmacological treatment for fulminating brain edema. Since evidence indicates that brain aquaporin-4 (AQP4) water channels are modulated by vasopressin V1a receptors, we examined the edema-reducing properties of the selective V1a receptor antagonist, SR49059, following middle cerebral artery occlusion (MCAO). Male Sprague-Dawley rats were randomly assigned to sham procedure, vehicle, or SR49059 infusion at different dosages (each n = 6,480 microL/hr, 640 microL/hr, 720 microL/hr) and starting 60 minutes before or after MCAO. After a 2-hour period of ischemia and 2 hours of reperfusion, the animals were sacrificed for assessment of brain water content, sodium, and potassium concentration. Statistics were performed using an ANOVA followed by a Tukey post hoc analysis. SR049059 treatment reduced brain water content in the infarcted area given at 640 microL/hr (p = 0.036), 720 microL/hr 60 minutes before (p = 0.002) or 60 minutes after (p = 0.005) MCAO. The consecutive sodium shift into the brain was prevented (p = 0.001), while the potassium loss was inhibited only by pre-treatment (p = 0.003). These findings imply that in ischemia-induced brain edema, the selective V1a receptor-antagonist SR49059 inhibits brain edema and the subsequent sodium shift into brain. This substance offers a new avenue in brain edema treatment and prompts further study into AQP4 modulation.

Modulation of AQP4 expression by the protein kinase C activator, phorbol myristate acetate, decreases ischemia-induced brain edema.

The protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), is known to interact with aquaporin-4 (AQP4), a water-selective transporting protein abundant in astrocytes and ependymal cells, that has been found to decrease osmotically-induced swelling. The purpose of this study was to examine whether PMA given at different time points following focal ischemia induced by middle cerebral artery occlusion (MCAO) reduces brain edema by AQP4 modulation. Male Sprague-Dawley rats were randomly assigned to sham procedure, vehicle, or PMA infusion (230 microg/kg), starting either 60 minutes before, or 30 or 60 minutes after MCAO (each group n = 12). After a 2-hour period of ischemia and 2 hours of reperfusion, the animals were sacrificed for assessment of brain water content, sodium, and potassium concentrations. AQP4 expression was assessed by immunoblotting. Statistical analysis was performed by ANOVA followed by Tukey's post hoc test. PMA treatment significantly reduced brain water content concentration in the infarcted area when started before or 30 minutes post-occlusion (p < 0.001, p = 0.022) and prevented the subsequent sodium shift (p < 0.05). Furthermore, PMA reduced ischemia-induced AQP4 up-regulation (p < 0.05). Attenuation of the ischemia-induced AQP4 up-regulation by PMA suggests that the reduction in brain edema formation following PMA treatment was at least in part mediated by AQP4 modulation.

Hypothalamic neuropeptide release after experimental subarachnoid hemorrhage: in vivo microdialysis study.

OBJECTIVES: As evidence exists about independent regulation of peripheral and central release of the vasoactive and natriuretic neuropeptides arginine-vasopressin (AVP) and oxytocin (OXT), we investigated their release patterns following subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: After injection of 0.1 ml arterial blood or saline into the great cistern of 33 Wistar rats, AVP and OXT levels were measured in blood and by microdialysis in the hypothalamic supraoptic (SON) and paraventricular nucleus (PVN). For statistical analysis, the analysis of variance (ANOVA) was used with Tukey HSD post hoc ANOVA tests to determine specific group differences. RESULTS: Plasma AVP and OXT peaked 2 h after SAH (P < 0.05), and normalized at 4 h. In the SON, both AVP and OXT peaked 4 h after SAH (P < 0.05). In the PVN, AVP increased in both groups (P < 0.05), while no OXT release occurred. By the sham group, any effect of experimental procedure was excluded. CONCLUSIONS: The SAH-specific central neuropeptide release, which exceeded peripheral release and continued longer, may contribute to pathophysiological events following SAH.

Early antithrombotic prophylaxis with low molecular weight heparin in neurosurgery.

BACKGROUND: Despite the high risk of venous thromboembolic events (VTE) in neuro-surgical patients, heparin prophylaxis has not been routinely established due to concern about bleeding complications. After initiating early low molecular weight heparin (LMWH) prophylaxis, we reviewed our patients in order to examine the viability of this practice. METHOD: Over a 3 year period, the records of patients admitted for elective neuro-surgery (ES), head injury (HI) or spontaneous intracranial haemorrhage (ICH) were analysed. Prophylaxis was performed with certoparin (3000 U anti-factor Xa s.c.) on the evening before ES and within 24 hours after surgery or admission whenever a CT did not show a progressive haematoma. Contraindications for LMWH were prothrombin time <70%, partial thrombo-plastin time >40 s, platelet count <100.000/ml, and platelet aggregation test sum <60%. The incidence of bleeding complications, VTE, and resulting morbidity/mortality was assessed. FINDINGS: 294 patients were admitted for ES, 344 for HI, and 302 for ICH. 155 of these were excluded because of contraindications. Intracranial bleeding was recorded in 1.5% (ES 1.1%, HI 3.5%, ICH 0%) and operative revision was performed in 1.1% (ES 0.7%, HI 2.8%) of patients. One case of moderate disability and no mortality occurred. The incidence of VTE and pulmonary embolism was documented in 0.2% and 0.1% of patients, with no associated mortality. No heparin induced thrombocytopenia was observed. INTERPRETATION: In neurosurgical patients, antithrombotic prophylaxis with certoparin was determined to be safe and efficacious when contraindications are carefully considered and a 12-hour time interval before and after surgery was guaranteed. This retrospective analysis should encourage a prospective trial of early LMWH prophylaxis.

Brain death and organ donation in Germany: analysis of procurement in a neurosurgical unit and review of press reports.

OBJECTIVE: A prospective study was undertaken to determine the number of potential organ donors in a neurosurgical intensive care unit and to record the actual number of organ donations. The reasons for refusal of organ donations were analysed with respect to the controversial public discussion of the brain death concept and the transplantation law in Germany. METHODS: From 1994 to 1997, the number of cases of brain death, and the number of cases in which relatives consented or refused to organ donation as well as the number of actual organ explantations was recorded. Over the same period, press reports of 5 German language newspapers were analysed with regard to the authors' position on brain death and transplantation law, their qualification, intention, and mode of presentation. RESULTS: Annually, about 70 deaths occurred on the department's intensive care unit of which almost 30% of the patients were determined to have suffered brain death without any obvious contraindications against organ donation. The refusal rate of relatives rose from 56% up to 78%, and the rate of organ donors thus decreased from 5% in 1994 to 4% presently in the department. About 100 reports were published each year in the analysed newspapers, of which about 90% voiced approval of organ transplantation. During the review period, the depiction became more objective (57% in 1994 to 82% in 1997) and the suspicious attitude toward the technique of brain death diagnosis declined. Whereas 50% of the articles rejected the brain death concept in 1994, this figure decreased to 39% in 1997 and conversely the concept of consent rose from 33% in 1994 to 56% in 1997. CONCLUSION: In Germany, the relatives refusal rate in organ donation is continuously high, presumable due to a depressing 39% of press reports rejecting the brain death concept, and resulting in a very low number of organ donations. There is hope that the transplantation law which has finally passed German parliament in 1997, confirming the brain death concept as well as the legal principle of prior consent by the donor or consent by the relatives will eventually result in an increase of organ donation especially when supported by an educational campaign which is embodied in the transplantation law.

Management of vein of Galen malformations. A review based on five neurosurgically treated cases and literature reports.

The high morbidity and mortality associated with the management of vein of Galen aneurysmal malformations (VGAM) continues to pose a tremendous challenge to the neurosurgeon as well as to the attending interventional radiologist. Since 1985, five patients with VGAM have been referred to the neurosurgical unit of the University of Cologne, two neonates, one infant and two adults. Four patients underwent direct operation and two patients received a shunt. The treatment was performed without mortality. A review of the literature reflects no substantial difference between neurosurgical treatment during the last 15 years (mortality 10%) and endovascular treatment (best series mortality 6%).

Carpal tunnel syndrome: staging of median nerve compression by MR imaging.

The purpose of this prospective study was to determine the potential of MR imaging to depict morphologic alterations of the median nerve correlating with the stage of carpal tunnel syndrome (CTS). Eighteen wrists of normal subjects and 81 wrists of patients with CTS were examined. MR imaging was performed with proton-density- and T2-weighted spin-echo sequences. Staging of CTS was done on the basis of clinical and electrophysiological testing, including evaluation of the number of previous steroid infiltrations in conservative treatment. Median nerve flattening, cross-sectional area, and signal intensity were measured from the distal radius to the end of the carpal tunnel. Delineation and structure of the median nerve were recorded qualitatively by two experienced radiologists in consensus. Three major MR imaging criteria of early CTS were (a) isolated prestenotic and intracarpal swelling of the median nerve (P < .01), (b) the absence of significant flattening, and (c) a generalized increase in signal intensity retrograde to the distal radius (P < .01). The nerve showed sharply delineated contours and a homogeneous signal pattern. Advanced CTS was characterized by retrograde swelling of the median nerve to the distal radius (P < .01) and decreased signal intensity (P < .05). Demarcation of the nerve became poorer, and its signal pattern appeared fasciculated. After steroid infiltration, the median nerve was difficult to delineate, showed an inhomogeneous structure, and swelling was less pronounced than without steroid infiltration (P < .05). MR imaging yields typical morphologic findings that correlate with the duration and severity of median nerve compression. Hence, MR imaging allows staging of median nerve compression in CTS and thus may contribute to therapeutic decision-making.

Spontaneous intracerebral hemorrhage. Prognostic factors in 896 cases.

To determine the prognostic value of etiology and localization in spontaneous intracerebral hemorrhage, 896 patients with spontaneous intracerebral hemorrhage, as proven by CT, operation or autopsy, were retrospectively studied using univariate data analysis. Etiologies were hypertension in 63.5%, cerebrovascular malformations in 8.5% and abnormal hemostasis in 15% of the patients. In 23% no etiology was determined. Main localizations were cerebral lobes in 49.2%, basal ganglia in 34.4%, brain stem in 6.9%, cerebellum in 6.7% and primary intraventricular in 2.3% of the patients. Ventricular extension was present in 47.0%. A higher case fatality correlated with: 1) ventricular extension (P < 0.00001), 2) increasing age (P = 0.00005), 3) surgical treatment (P = 0.00010), 4) localization in basal ganglia (P = 0.0108) and 5) hypertension as only etiology (P = 0.01471). A lower case fatality was found in patients with cerebrovascular malformations (P = 0.00006) and when the hemorrhage was localized to the cerebral lobes (P = 0.0050). We conclude that etiology and localization are of prognostic value in spontaneous intracerebral hemorrhage.

Diagnosis and staging of carpal tunnel syndrome: comparison of magnetic resonance imaging and intra-operative findings.

PURPOSE: In order to determine the reliability of magnetic resonance imaging (MRI) in the diagnosis and staging of carpal tunnel syndrome (CTS), the most common entrapment neuropathy, the following prospective study has been performed. METHODS: We compared clinical and electrophysiological studies in 58 cases of CTS with MRI investigations and confirmed the reliability by exact correspondence with intra-operative findings. RESULTS: Typical MRI characteristics of the median nerve in CTS have been established. There is a significant difference in flattening (p < 0.05), swelling (p < 0.01) and signal intensity (p < 0.05) of the median nerve between early and advanced CTS. Comparison of MRI and intra-operative findings revealed that median nerve compression was diagnosed correctly in 91% of cases. Additional lesions in the carpal tunnel, which are a primary cause of nerve compression, were established by MRI in 25 cases and confirmed by surgery. CONCLUSION: MRI is a reliable diagnostic tool for assessing as well as staging of CTS. Morphological changes following chronic nerve compression can be visualized. It is particularly useful in cases of suspected lesions within the carpal tunnel as a cause of CTS. The information provided may support the choice of adequate treatment modality.

The value of magnetic resonance imaging in carpal tunnel syndrome.

We examined 62 patients (72 hands) with carpal tunnel syndrome (CTS) by magnetic resonance imaging (MRI) of the carpal tunnel and latency measurements of the median nerve. In 32 of 72 hands a probable causative lesion of the CTS was identified by MRI, for example tenosynovitis, a cyst-like structure, or an aberrant muscle. The MRI findings were confirmed by surgery in 16 of 24 hands, slightly corrected in 5, and not substantiated in 3. In 65 of 72 hands, MRI disclosed pathology of the median nerve, most prominently an enlargement of the nerve at the level of the os pisiforme, a finding not seen during surgery. Oedema of the nerve was found in 14 of 72 hands. The distal latencies were prolonged in 62 of 72 hands. The sensory latencies correlated significantly with the MRI-determined cross-sectional area of the nerve at the level of the distal radius. The lack of other correlations suggests that partly independent features of the nerve lesion are demonstrated in each method or that the sensitivity and specificity of both methods are limited. Further experience with MRI in CTS is desirable. At present, the practical use of MRI in CTS should be restricted to special diagnostic problems such as carpal tunnel syndromes which do not respond adequately to conservative or surgical treatment.