[Chronic muscle dysfunction caused by whiplash trauma?].
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Biomedical subjects
Publications and source records attributed to P Marx.
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A patient suffering from a rare enzyme deficiency developed a malignant neuroleptic syndrome after having been treated with one single dose of haloperidol. We investigated the patient's serum for all frequent polymorphisms in cytochrome P450 2D6, assuming him to be a poor neuroleptic metabolizer. We will also discuss other potential mechanisms inducing this disturbance and its differential diagnoses.
BACKGROUND: Intracranial venous congestion is often caused by local venous thrombosis or brain arteriovenous fistulas. Hemodialysis shunts are known to cause venous enlargement in the arm or chest but have not been related to intracranial vascular pathology. Case Description- A 59-year-old woman who presented with increasing headache, gait instability, and memory loss was a renal transplant recipient who still carried a left upper arm shunt. Cranial CT scan showed enlarged veins in the posterior fossa with incipient hydrocephalus. Extracranial duplex sonography revealed reversed flow in the left internal jugular vein, which normalized on cuff inflation around the shunt-carrying arm. The reversed flow, intracranial venous congestion, and neurological status improved after surgical shunt ligation. CONCLUSIONS: To our knowledge, this is the first case description of an intracranial venous outflow obstruction caused by a peripheral arteriovenous shunt.
Administration of anticonvulsant drugs is clinically monitored by checking seizure frequency and by determining the serum concentration of the drug. In a few reports, drug concentrations in brain parenchyma have been determined using ex vivo techniques. Little is known about the in vivo concentration in the brain parenchyma. Our goals were to characterise the NMR spectra of the anticonvulsants at therapeutic concentrations, to determine the minimum detectable concentrations, and to quantify the drugs noninvasively. Volume-selective 1H-MR spectroscopy (MRS) was performed under standard clinical conditions using a single-voxel STEAM (stimulated-echo acquisition mode) sequence at 1.5 T. Spectra of the anticonvulsants carbamazepine, phenobarbital, phenytoin and valproate were acquired in vitro in hydrous solutions at increasing dilution. Phenytoin, phenobarbital and valproate were detectable below maximum therapeutic serum concentrations. Within therapeutic ranges, there was good agreement between concentrations determined by 1H-MRS and those by standard fluorescence polarisation immunoassay. Due to the absence of signals of brain metabolites, the aromatic protons of phenobarbital, phenytoin and carbamazepine, with resonance lines around 7.4 ppm, allow the drugs to be detected. Valproate, with two resonances around 1.2 ppm, should be differentiable from potential brain metabolites using nonlinear analysis of the brain spectrum. Volume-selective 1H-MRS is therefore expected to be able to monitor anticonvulsant therapy in vivo.
OBJECTIVE: A measurement protocol for magnetoneurography (MNG) is established which allows the non-invasive localization and tracing of evoked compound action currents propagating along cervical nerve roots in man. METHODS: Inside a magnetically shielded room either both median or both ulnar nerves of healthy subjects were conventionally electrostimulated in alternation. Evoked magnetic responses were recorded using a multichannel SQUID-detector with a planar measuring area centered over the neck. Simultaneously, electric surface potentials were recorded using cervical bipolar electrode montages. RESULTS: Upon median (ulnar) nerve stimulation somatosensory evoked magnetic fields up to 20 fT (10 fT) amplitude were detected propagating over the cervical transforaminal root entry zone, with corresponding electrical surface potentials of 1.5 microV (0.5 microV). Furthermore, the signal-to-noise ratio of the spatiotemporal magnetic field mappings in median nerve stimulation experiments allowed dipolar source reconstructions and tracing of the propagation of the compound action currents along nerve root fibers. CONCLUSION: Magnetoneurography allows tracing of the propagation of evoked compound action currents along cervical roots in healthy subjects with millisecond temporal and high spatial resolution. Thus, MNG offers a sensitivity appropriate to serve as a clinical diagnostic tool for localizing focal neuropathies of cervical nerve roots.
BACKGROUND AND PURPOSE: To evaluate prerequisites, safety, and efficacy of i.v.-thrombolysis of ischemic stroke with rtPA in an academic medical center. METHODS: Over a period of 2 years and 10 months all patients admitted with a diagnosis of stroke were recruited. Inclusion and exclusion criteria for i.v.-thrombolysis were combined from large scale randomized controlled trials, the time window, however, could be extended up to 4 hours in subjects with a negative CT-scan. Prespecified outcome parameters were the modified Rankin Scale (mRS) and the Barthel Index (BI) at 3 months, and symptomatic hemorrhagic complications. Additionally, time parameters, such as onset-admission-time, door-Ct-time, door-needle time, and onset-needle time were recorded. RESULTS: During the reported period 103 patients underwent i.v.-thrombolysis, corresponding to 14.9% of all patients with ischemic stroke, and 47% of patients with ischemic stroke arriving in < 3 hours after symptom onset. The mean baseline NIHSS was 14, the mean mRS 13 (3-34), the mean age 70 (+/- 12) years. The following time intervals were observed: Onset-admission-time 64 min., door-CT-time 27 min., admission-needle-time 80 min., and onset-needle-time 142 min. There were 4 symptomatic intracerebral hemorrhagic transformations, including 3 parenchymal hemorrhages, 2 of them lethal, and one with almost full recovery. According to the mRS, 39% of patients had a good (mRS 0-1), 72% a good to moderate recovery (mRS 0-2). The corresponding figures for the BI were 60% BI 95-100 and 72% BI > 90. The mortality was 15%. CONCLUSION: The i.v.-thrombolysis of ischemic stroke with rt-PA demands appropriate organisation of the pre- and in-hospital phase and can be performed safely and efficaciously in daily clinical routine if inclusion and exclusion criteria as well as all safety measures during the critical phase after therapy are strictly obeyed.
BACKGROUND AND PURPOSE: Infarct patterns on brain imaging contribute to the etiologic classification of ischemic stroke. However, the association of specific subtypes of infarcts and etiologic mechanisms is often weak, and acute lesions are frequently missed on initial computed tomography (CT). Diffusion-weighted imaging (DWI) is superior in visualizing acute ischemic lesions as compared to CT and conventional magnetic resonance imaging (MRI). In our prospective study, we addressed the question whether a distinct pattern of infarction on DWI is associated with infarct etiology and clinical outcome. METHODS: Sixty-two patients with clinical signs of acute ischemic stroke and negative acute CT upon admission underwent DWI within 10 days after the ictus. Neurological status was documented using the NIH stroke scale. A scattered lesion pattern was defined by at least 2 separate hyperintense DWI lesions within the territory of one of the major cerebral arteries. Ischemic lesions were defined as acute if the region was demarcated strongly hyperintense in all DW images, and if the apparent diffusion coefficient was below normal. RESULTS: In 32 patients, DWI revealed a scattered lesion pattern, while in 30 patients a single acute lesion was detected. In patients with scattered lesions, potential arterial or cardiac embolic sources were detected in 26 patients (81.3%), as compared to 5 patients (16.6%) in the group with single lesions (chi(2) test, p < 0.0001). The neurological status of patients with scattered lesions improved significantly more than among patients with single lesions (Mann-Whitney test, p < 0.0003). CONCLUSION: A scattered lesion pattern on DWI in patients with acute brain infarction and negative initial CT scan is associated with an embolic etiology and may indicate a favorable clinical outcome.
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BACKGROUND: Fatal cerebral herniation is a common complication of large ("malignant") middle cerebral artery infarcts but has not been reported in unilateral anterior cerebral artery (ACA) infarction. CASE DESCRIPTION: We report a 47-year-old woman who developed an acute left hemiparesis during an attack of migraine. Cranial CT (CCT) was normal but demonstrated narrow external cerebrospinal fluid compartments. Transcranial Doppler sonography was compatible with occlusion of the right ACA. Systemic thrombolytic therapy with tissue plasminogen activator was initiated 105 minutes after symptom onset. Follow-up CCT 24 hours after treatment revealed subtotal ACA infarction with hemorrhagic conversion. Two days later, the patient suddenly deteriorated with clinical signs of cerebral herniation, as confirmed by CCT. An extended right hemicraniectomy was immediately performed. Within 6 months, the patient regained her ability to walk but remained moderately disabled. CONCLUSIONS: This is the first reported case of unilateral ACA infarct leading to almost fatal cerebral herniation. Narrow external cerebrospinal fluid compartments in combination with early reperfusion, hemorrhagic transformation, and additional dysfunction of the blood-brain barrier promoted by tissue plasminogen activator and migraine may have contributed to this unusual course.
BACKGROUND AND PURPOSE: Safety and efficacy concerns toward thrombolysis for ischemic stroke prevail among many neurologists because of the risks of hemorrhage and the small proportion of suitable patients. We therefore prospectively assessed feasibility, safety, efficacy, and team performance in a single center to prove whether thrombolytic treatment is practical in daily clinical routine. METHODS: Patients were prospectively recruited over a 2-year period. Major inclusion and exclusion criteria from large, randomized controlled trials were combined. Prespecified outcome parameters were the modified Rankin scale (MRS) and the Barthel Index (BI) at 3 months and symptomatic hemorrhagic complications. In addition, certain time intervals during the diagnostic process preceding thrombolysis were prospectively recorded. RESULTS: Within 2 years a total of 75 patients underwent intravenous thrombolysis, corresponding to 9.4% of all admitted patients with stroke and 14.9% of patients with ischemic stroke. Mean+/-SD age was 68+/-13 (range 34 to 90) years; median baseline National Institutes of Health Stroke Scale score was 13+/-6 (range 2 to 34). Thrombolysis was started at an average time of 144 minutes after symptom onset, and 13 patients (17.3%) were treated beyond 3 hours. Two cerebral hemorrhages (2.7%) occurred. Outcome according to the MRS was good (MRS 0 to 1) in 40%, moderate (MRS 2 to 3) in 32%, and poor (MRS 4 to 5) in 13%; the corresponding results, as measured by the BI, were 61% (BI 95 to 100, good), 16% (BI 55 to 90, moderate), and 8% (BI 0 to 50, poor). The mortality rate was 15%. Over 2 years the median door-to-CT time decreased from 30 to 22 minutes (27%), and the door-to-needle time was shortened from 96 to 73 minutes (14%). The mean number of patients treated per month increased from 2 to 4. CONCLUSIONS: Thrombolytic therapy can be performed safely and efficaciously in daily clinical routine. More than a minority of acute stroke patients might be eligible for intravenous thrombolysis. The performance of a stroke team can be improved over time, subsequently increasing the proportion of eligible patients and thereby the efficiency of the method.
BACKGROUND AND PURPOSE: Compliance with pharmacological therapy is essential for the efficiency of secondary prevention of ischemic stroke. Few data exist regarding patient compliance with antithrombotic and risk factor treatment outside of controlled clinical trials. The aim of the present study was to assess the rate of and predictors for compliance with secondary stroke prevention 1 year after cerebral ischemia and to identify reasons for noncompliance. METHODS: Patients with a diagnosis of ischemic stroke or TIA and antithrombotic discharge medication were prospectively recruited. At 1 year, the proportion of patients compliant with antithrombotic treatment and with medication for risk factors (eg, hypertension, diabetes, hyperlipidemia) was evaluated through structured telephone interviews. In addition, the reasons for nontreatment with antithrombotic and risk factor medication were determined. Independent predictors for compliance were analyzed by logistic regression analyses. RESULTS: Of 588 consecutive patients admitted to our stroke unit, 470 had a discharge diagnosis of cerebral ischemia (TIA 26.2%, cerebral infarct 73.8%) and recommendations for antithrombotic therapy. At 1 year, 63 patients (13.4%) had died and 21 (4.5%) were lost to follow-up, thus, 386 could finally be evaluated. Of the patients, 87.6% were still on antithrombotic medication, and 70.2% were treated with the same agent prescribed on discharge. Of the patients with hypertension, diabetes, and hyperlipidemia, 90.8%, 84.9%, and 70.2% were still treated for their respective risk factors. Logistic regression analyses revealed age (OR 1.03, 95% CI 1.00 to 1.06), stroke severity on admission (OR 1.09, 95% CI 1.00 to 1.20), and cardioembolic cause (OR 4.13, 95% CI 1.23 to 13.83) as independent predictors of compliance. CONCLUSIONS: Compliance with secondary prevention in patients with ischemic stroke is rather good in the setting of our study. Higher age, a more severe neurological deficit on admission, and cardioembolic stroke cause are associated with better long-term compliance. Knowledge of these determinants may help to further improve the quality of stroke prevention.
OBJECTIVE: To evaluate the influence of 2 continuous combined estrogen-progestin replacement products, compared with unopposed estrogen and placebo, on cardiovascular risk markers in postmenopausal women in a randomized, double-blind, placebo-controlled trial. METHODS: Two hundred seventy healthy postmenopausal women were randomly assigned to 1 of 4 treatment groups: placebo, unopposed 17-beta estradiol (1 mg), 1 mg of 17-beta estradiol with 0.25 mg of norethindrone acetate, or 1 mg of 17-beta estradiol with 0.5 mg of norethindrone acetate. The primary outcome variable was change from baseline in low-density lipoprotein cholesterol concentration. Additional outcome variables included changes in other serum lipid levels, hemostatic variables, and indicators of carbohydrate metabolism. RESULTS: The low-density lipoprotein cholesterol level was reduced to a similar degree in all groups receiving active treatment (10%-14% from baseline; P =.001 for 17-beta estradiol with 0.5 mg of norethindrone acetate, P =.004 for 17-beta estradiol with 0.25 mg of norethindrone acetate, and P =. 001 for 1 mg of 17-beta estradiol vs placebo). Compared with unopposed 17-beta estradiol, 17-beta estradiol with 0.5 mg of norethindrone acetate enhanced the reductions in total cholesterol and apolipoprotein B levels (P<.01 vs 17-beta estradiol). 17-beta Estradiol plus norethindrone blunted or reversed the increases in levels of high-density lipoprotein cholesterol, apolipoprotein A-I, and triglycerides produced by 17-beta estradiol alone. Effects of 17-beta estradiol plus norethindrone on hemostatic variables were similar to those of 17-beta estradiol except for factor VII activity, which was significantly reduced with 17-beta estradiol combined with 0.25 mg (P<.01) and 0.5 mg (P<.05) of norethindrone acetate. 17-beta Estradiol plus norethindrone appeared to blunt reductions in C-peptide and insulin levels produced by unopposed 17-beta estradiol but did not elevate these values compared with placebo. CONCLUSIONS: 17-beta Estradiol plus norethindrone produced favorable changes in most cardiovascular risk markers evaluated and has a profile distinct from that of unopposed 17-beta estradiol. The impact of these differences on cardiovascular events warrants investigation. Arch Intern Med. 2000;160:3315-3325.
A predominance of small, dense low-density lipoprotein (LDL) particles (subclass pattern B) has been associated with a 2- to threefold increase in coronary heart disease risk. Recently, it has been reported that LDL subclass pattern B is associated with hyperfibrinogenemia, which is also a coronary heart disease risk factor. The present study examined the relation between hyperfibrinogenemia and LDL subclass pattern in 258 postmenopausal women. A significant univariate correlation was observed between the concentration of cholesterol carried in small, dense LDL particles and plasma fibrinogen concentration (r = 0.17, p = 0.01). The prevalence of LDL subclass pattern B was 41.9% in the highest fibrinogen tertile, compared with 27.9% and 24.4% in the first and second tertiles, respectively (global chi-square 6.8, p = 0.03). The crude odds ratio (OR) for LDL subclass pattern B among women in the highest fibrinogen tertile, compared with the lower tertiles, was 2.03 (95% confidence interval [CI] 1.18 to 3.51, p = 0.01). After adjustment for age and plasma lipids (log(e) triglycerides, LDL cholesterol, and high-density lipoprotein cholesterol), the OR was 2.14 (95% CI 1.17 to 3.96, p = 0.01). Further adjustment for hematocrit, indicators of carbohydrate homeostasis, body mass index, waist circumference, and several variables related to lifestyle did not attenuate this association (OR 2.56, 95% CI 1.27 to 5.27, p = 0.01). These data suggest that hyperfibrinogenemia and LDL subclass pattern B may be 2 components of a common syndrome and suggest that hyperfibrinogenemia may contribute to the increased coronary heart disease risk associated with LDL subclass pattern B.
OBJECTIVES: Randomized trials in North America (NASCET, ACAS) and Europe (ECST) have shown a beneficial effect of endarterectomy for patients with high grade carotid artery stenosis. The results of the NASCET and the ECST further suggest that the effect of endarterectomy differed by degree of stenosis, supporting the importance of stenosis measurement as a factor in the decision process regarding surgery. We investigated the interrater agreement for carotid artery stenosis measurements and treatment decision in a post hoc study on patients undergoing carotid surgery. METHODS: In a one-year series, 45 consecutive patients underwent preoperative conventional cerebral angiography followed by endarterectomy. Using a magnifying eyepiece and applying the two different measurement criteria of the randomized trials, angiograms were re-evaluated post hoc by three masked raters. Intra-class correlation coefficients (ICCs) with one-sided 95% confidence intervals (CIs) were calculated for the estimation of interrater agreement for degree of stenosis. Conger s kappa (k) statistics were used for the estimation of interrater agreement for a dichotomized stenosis evaluation, i.e. therapeutic decision on surgery (cut-off point for symptomatic stenosis: 70%, cut-off point for asymptomatic stenosis: 60%). RESULTS: ICCs were.74 (CI.63) for NASCET/ACAS criteria and.72 (CI. 59) for ECST criteria. k values were.55 (CI.42) for NASCET/ACAS criteria and.57 (CI.44) for ECST criteria. Disagreement for a therapeutic decision was seen in 6 of 23 symptomatic patients by NASCET criteria, in 2 of 23 symptomatic patients by ECST and in 4 of 22 asymptomatic patients by ACAS criteria. CONCLUSIONS: Overall, the interrater agreement for stenosis measurements was good. Agreement for therapeutic decisions on carotid surgery, however, was less strong. These findings suggest that accurate stenosis measurement may not suffice for reliable treatment decisions in patients with high grade carotid artery stenosis.
OBJECTIVE: We prospectively investigated the predictive value of clinical and CT-supported lacunar syndromes for lacunar infarcts on magnetic resonance (MR) brain imaging. PATIENTS AND METHODS: The 54 prospective, consecutive patients had clinical lacunar syndromes of acute onset and early computed tomography (CT; on admission day, i.e. < or =48 h after onset of symptoms) showing either a small deep infarct or no corresponding lesion. Taking MR (at day 2 to 4 after admission) as the gold standard, the positive predictive value of the CT-supported clinical syndrome for corresponding lacunar lesions was calculated. RESULTS: In 27 (50%) patients, early CT showed a lacunar infarct corresponding to the clinical syndrome, a further 27 (50%) patients had no fresh ischemic lesion. In 51 patients (94%), MR showed a recent lacunar infarct (hyperintense lacune in T2-weighted scans, no demarcation on T1-weighted scans and/or positive gadolinium-enhancement) corresponding to the clinical syndrome (positive predictive value 0.94, 95%, CI: 0.88 to 0.98). In 3 (6%) patients MR was normal. Aside from old unrelated ischemic (macro- and/or microangiopathic) lesions, MR revealed no acute non-lacunar infarct. CT and MR sites of lacunar lesions were matching. Compared to gold standard MR, the sensitivity of early CT for suspected lacunar lesions was 0.53 (95% CI: 0.38 to 0.67). CONCLUSION: Lacunar syndromes were highly predictive for small deep infarcts on MR. Magnetic resonance brain imaging may be redundant in the setting of a lacunar syndrome supported by a CT that excludes non-ischemic causes of stroke; it may therefore be abandoned in order to reduce costs in the health care system.
OBJECTIVE: A predominance of small, dense low-density lipoprotein (LDL) particles (subclass pattern B) is associated with increased risk for coronary heart disease and is characterized by elevated triglycerides and depressed high-density lipoprotein (HDL) cholesterol concentrations. The present analysis was undertaken to assess the impact of LDL subclass distribution pattern and adiposity on serum lipids in postmenopausal women. METHODS: Anthropometric measurements and fasting lipid data were obtained from 254 postmenopausal women 70 years of age or younger, not receiving sex hormone replacement, who were participating in a clinical trial designed to assess the influence of hormone replacement regimens on coronary heart disease risk markers. RESULTS: The prevalence of LDL subclass pattern B was 32%. Triglyceride levels were higher and HDL cholesterol lower (both p<0.001) in women with pattern B vs. pattern A, but total and LDL cholesterol levels did not differ. LDL subclass pattern contributed independently to the variance in HDL cholesterol (p<0.001) and log(e) triglyceride (p<0.001) concentrations explained by anthropometric variables (waist circumference or body mass index). Compared to women with LDL subclass pattern A and waist circumference below the median value of 83.0 centimeters, those with pattern B and waist > or =83.0 centimeters had markedly lower HDL cholesterol levels [44.0 (41.6-47.4) vs. 57.2 (54.1-60.3) mg/dL, mean (95% CI)] and increased triglyceride concentrations [geometric mean 147.8 (131.6-165.7) vs. 95.4 (88.2-102.5) mg/dL]. CONCLUSIONS: These data suggest that adiposity and LDL subclass distribution pattern are independent determinants of plasma triglyceride and HDL cholesterol concentrations in postmenopausal women.
Recently, biomagnetic fields below 0.1 Hz arising from nerve or muscle injury currents have been measured non-invasively using superconducting quantum interference devices (SQUIDs). Here we report first long-term recordings of cortical direct current (DC) fields in humans based on a horizontal modulation (0.4 Hz) of the body and, respectively, head position beneath the sensor array: near-DC fields with amplitudes between 90 and 540 fT were detected in 5/5 subjects over the auditory cortex throughout prolonged stimulation periods (here: 30 s) during which subjects were listening to concert music. These results prove the feasibility to record non-invasively low amplitude near-DC magnetic fields of the human brain and open the perspective for studies on DC-phenomena in stroke, such as anoxic depolarization or periinfarct depolarization, and in migraine patients.
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