Soluble and cell surface ICAM-3 in blood and cerebrospinal fluid of patients with multiple sclerosis: influence of methylprednisolone treatment and relevance as markers for disease activity.

OBJECTIVE: The expression of intercellular adhesion molecule-3 (ICAM-3), a member of the Ig supergene family, is restricted to immune competent cells. Expression of soluble and cell surface ICAM-3 (s- and c-ICAM-3) is preferentially seen in the state of low activation of the immune system. We studied the relevance of the expression levels of s- and c-ICAM-3 in cerebrospinal fluid (CSF) and blood as markers for disease activity as well as the influence of high-dose methylprednisolone (MP) treatment upon the expression of s- and c-ICAM-3 in blood of patients with multiple sclerosis (MS). MATERIALS AND METHODS: A total of 33 patients (relapses n = 25, remission n = 8) with relapsing-remitting MS were included into the study. CSF and blood were acquired from all of them. Of the patients 24 were treated with high-dose MP. In those, blood was additionally collected at the 10th day of the therapy and after 3 months. Expression of c-ICAM-3 was determined by two colour FACS analysis, whereas the concentration levels of s-ICAM-3 were measured by ELISA. RESULTS: In CSF we detected a significant decrease of the expression levels of c-ICAM-3 on CD3+ T cells in 25 patients suffering from an acute relapse in contrast to 8 patients with remission (P= 0.04). In comparison to the levels before treatment and after 3 months, at the 10th day of MP treatment we obtained highly significant changes of the expression values of c-ICAM-3 both on CD3+ T cells (P = 0.0004; P= 0.005) and CD14+ monocytes/macrophages (P =0.0006; P=0.008) on the 10th day of high-dose MP treatment from 24 MS patients. CONCLUSION: The increase of ICAM-3 levels might indicate the anti-inflammatory effect of the MP treatment. It could be interesting to search for similar effects investigating the new immune modulatoring therapy forms of MS.

Transcranial color-coded duplex sonography of intracranial veins and sinuses in adults. Reference data from 130 volunteers.

BACKGROUND AND PURPOSE: Transcranial color-coded duplex sonography (TCCS) of intracranial veins and sinuses in adults is a new, emerging application of ultrasonographic imaging. This study reports a standardized examination protocol for venous TCCS and provides reference data for clinical application. METHODS: In 130 healthy volunteers (mean age, 45.9+/-16.9 years; range, 14 to 77 years) the intracranial venous system was examined using frequency-based transtemporal TCCS. Identification rate, blood flow velocity, resistance index, and systolic/diastolic ratio were recorded for each examined venous vessel. RESULTS: Intracranial veins and sinuses show a low pulsatile forward flow with maximal systolic blood flow velocity up to 20 cm/s. Significant side differences of blood flow velocity in the paired venous structures could not be detected. Venous flow velocities decreased with age, whereas resistance indices and systolic/diastolic ratios increased. Women showed higher flow velocities than men. Mean identification rates for all age groups ranged from 70% to 90% for the deep middle cerebral vein, the basal cerebral vein, and the great cerebral vein of Galen. The straight sinus, the transverse sinus, and the rostral part of the superior sagittal sinus could be detected in 55% to 70% of cases. Detection rates were dependent on age and decreased as age increased. CONCLUSIONS: Venous TCCS can reliably image a significant part of the cerebral venous system. This method can provide information on venous hemodynamics in normal subjects and pathological cases.

Frontal bone windows for transcranial color-coded duplex sonography.

BACKGROUND AND PURPOSE: The use of the conventional temporal bone window for transcranial color-coded duplex sonography (TCCS) often results in difficulties in obtaining angle-corrected flow velocity measurements of the A2 segment of the anterior cerebral artery, the posterior communicating artery, and the midline venous vasculature because of the unfavorable insonation angle. The same applies to B-mode imaging of the frontal parenchyma. However, transorbital TCCS raises problems with the insonation of the orbital lens. To overcome these drawbacks, we studied the feasibility of frontal bone windows for TCCS examinations. METHODS: In 75 healthy volunteers (mean age, 45.3+/-17.0 years; age range, 17 to 77 years), the circle of Willis and the venous midline vasculature were insonated through a lateral and paramedian frontal bone window. Insonation quality of parenchymal structures (B-mode) was graded on a 3-point scale depending on the visibility of typical parenchymal landmarks. In a similar manner, the quality of the color-/Doppler-mode imaging of the arteries of the circle of Willis and the internal cerebral veins was assessed. In 15 patients (mean age, 62.7+/-13.7 years; age range, 33 to 83 years), the color-/Doppler-mode imaging quality of the intracranial vessels before and after application of an ultrasound contrast-enhancing agent was compared. RESULTS: B-mode insonation quality was optimal to fair in 73.3% of cases using the lateral and in 52.0% of cases using the paramedian frontal bone window, with defined parenchymal structures used as reference. Insonation quality decreased in those older than 60 years. In those younger than 60 years, angle-corrected flow velocity measurements of the A2 segment of the anterior cerebral artery and the internal cerebral vein were possible in 73.6% and 60.0%, respectively. Contrast enhancement resulted in a highly significant improvement in the imaging quality of the intracranial vessels. CONCLUSIONS: The transfrontal bone windows offer new possibilities for TCCS examinations, although the insonation quality is inferior to the conventional temporal bone window in terms of failure of an acoustic window. This can be compensated for by application of an ultrasound contrast-enhancing agent.

Assessment of intracranial venous hemodynamics in normal individuals and patients with cerebral venous thrombosis.

BACKGROUND AND PURPOSE: Despite ongoing improvements in noninvasive imaging techniques, transcranial color-coded duplex sonography (TCCS) has so far been used only on a limited basis in patients with cerebral venous thrombosis. We evaluated the diagnostic value of both noncontrast and contrast-enhanced TCCS by comparing normal volunteers and patients with acute cerebral venous thrombosis. METHODS: In 75 healthy volunteers (aged 45.8+/-17.4 years), normal values for the deep cerebral veins (DCVs) and the posterior fossa sinuses were established by transtemporal insonation. Eight patients with cerebral venous thrombosis were assessed by TCCS, through which the hemodynamics of the DCVs were measured, and the patients were followed-up over a period of between 33 and 387 days after examination. MR angiography served as the "gold standard" technique for confirming the venous status in all 8 patients. RESULTS: No side differences in flow velocities were detected in the paired venous structures in normal volunteers. As indirect signs of (and diagnostic criteria for) cerebral venous thrombosis, pathologically increased flow velocities or significant side differences in the DCVs were registered in 5 of the 8 patients; the other patients showed nonsignificant increases in flow velocity which decreased over time. During follow-up, the status of the posterior fossa sinuses could be diagnosed correctly in seven patients after contrast enhancement when these results were compared with those of venous MR angiography. In 1 patient, a partial recanalization was mistakenly diagnosed as an occlusion. CONCLUSIONS: TCCS allows a reliable evaluation of the major DCVs and posterior fossa sinuses. The anterior and mid portions of the superior sagittal sinus and cortical veins cannot be assessed. Increased venous blood flow velocity can be used as an indirect criterion for indicating a cerebral venous thrombosis. Clinical recovery coincided with decreases in blood flow velocity in the series of patients investigated in this study.

Soluble and cell surface ICAM-1 as markers for disease activity in multiple sclerosis.

OBJECTIVE: The intercellular adhesion molecule-1 (ICAM-1) is a member of the Ig supergene family. ICAM-1 is expressed on various cells like peripheral blood lymphocytes, endothelial cells or thymic cells and the cell surface form is supposed to be shed into a soluble form. The expression of ICAM-1 is induced by cytokines like Interleukin-1, TNF alpha or interferon gamma. The aim of the study was to investigate whether changes of cell surface and soluble ICAM-1 in the cerebrospinal fluid (CSF) and blood are indicative for disease activity in patients with multiple sclerosis (MS). MATERIAL AND METHODS: In all patients with relapsing-remitting MS (relapse: n=31, remission: n=11) and controls (n=13) the expression of cell surface ICAM-1 (c-ICAM-1) was determined by two colour flow cytometry. Soluble ICAM-1 (s-ICAM-1) was measured by ELISA. Follow-up examinations were done 3 months later. RESULTS: In 31 patients with a current relapse we found significantly decreased expression levels of c-ICAM-1 on leukocytes in CSF (P<0.001) and blood (P<0.10), when compared to those 11 individuals experiencing remission. In contrast we observed significantly (P<0.05) increased levels of s-ICAM-1 in CSF of patients with relapses. Comparing patients who had been in remission for more than 4 weeks (n=11) with remission lasting longer than 3 months (n=28) we detected stable c-ICAM-1 expression on CD3+ T cells in blood. CONCLUSION: Our results demonstrate for the first time that c-ICAM-1 on CD3+ T-cells in CSF and blood is an activity marker in MS.

Stages and syndromes of neuroborreliosis.

To ascertain the varieties of neuroborreliosis, 330 patients were identified at the Departments of Neurology in Würzburg and Giessen from 1979 to 1994. Patients who fullfilled at least one of three strict case definitions based on clinical and laboratory criteria were included in the study. Ninety-one per cent of the patients had second-stage neuroborreliosis (duration of symptoms < or = 6 months). The most common syndrome was a painful spinal meningoradiculitis, alone (37%) or in combination with a cranial radiculitis (29%). Meningoradiculitis cranialis (9%), isolated meningitis (4%) and erythema chronica migrans-associated mono/polyneuritis (3%) were further stage II features. Central nervous system involvement occurred either as an acute meningomyelitis or meningomyeloradiculitis (5%) and meningoencephalitis or meningenocephaloradiculitis (4%). Less than 9% of the patients ran a chronic course (stage III) with a disease duration between 6 months and 9 years, either as acrodermatitis chronica atrophicans associated mono- or polyneuritis (2%) or a chronic progressive encephalomyelitis (6%). Cerebrovascular neuroborreliosis (1%) occurred in both stages; however, the primary nature of the course was a chronic one. Involvement of other organs except the skin was rare (joints 3%, heart 1%) but elevated hepatic enzymes were frequent. Our study demonstrates that neuroborreliosis has to be considered in the differential diagnosis of a wide variety of neurological conditions. Cerebrospinal fluid analysis and the search for specific intrathecal antibody production are important diagnostic procedures.

Follow-up in carriers of the 'MELAS' mutation without strokes.

Eight carriers of the A3243G mutation of mitochondrial DNA without stroke-like episodes were monitored for up to 7 years in clinical and metabolic studies, by magnetic resonance imaging (MRI) and positron emission tomography (PET). None developed mitochondrial encephalopathy (MELAS), but 2 developed diabetes mellitus, 1 terminal kidney failure and 2 cardiomyopathy. One patient improved markedly under ubiquinone. Electroencephalography showed progressive slowing in 2 cases, but electrophysiological tests and MRI were otherwise noncontributary. PET showed widespread cortical and basal ganglion metabolic deficits in 6 cases. We conclude that internal medical complications are more common than MELAS in adult carriers of the mutation. PET findings, firstly reported in such patients, suggest that chronic subclinical encephalopathy is very frequent, and PET may play a role in monitoring in the future.

Relationship between the Borrelia burgdorferi specific immune response and different stages and syndromes in neuroborreliosis.

One hundred untreated neuroborreliosis patients were investigated by IgG/IgM immunoblot to find out if different stages and syndromes are characterized by different patterns of their Borrelia burgdorferi specific immune responses in CSF and serum. Stage III (n = 10) was characterized by a broad, highly specific intrathecal immune response (the mean number of IgM bands in CSF was 3.1 and of IgG bands 6.3). All patients recognized one or more of the following proteins (p35, p21, p18) or the 5 kd glycolipid. In contrast, the immune response in stage II (n = 90) was less restricted (28%) and heterogeneous (mean number of IgM bands 1.4 and of IgG bands 3.4). It was mainly directed against the highly crossreactive p41 antigen (91%). The different clinical features of stage II were comparable regarding the intrathecal immune response. However anti-glycolipid and anti-p35, -p21, -p18 IgG antibodies were detected in a small subset of patients, mainly corresponding to more severe courses of the disease. Our data are compatible with a direct agent-related pathomechanism in neuroborreliosis. Antibodies against certain proteins and the glycolipid of B. burgdorferi seem to have a prognostic value as to the development of more severe disease or transition to stage III.

Imaging of dopamine receptors with [123I]iodobenzamide single-photon emission-computed tomography in neuroleptic malignant syndrome.

With the tracer [123I]iodobenzamide ([123I]-IBZM), it is possible to image dopamine receptor occupancy with single-photon emission-computed tomography (SPECT). We report follow-up examinations with IBZM-SPECT in neuroleptic malignant syndrome (NMS) to display D2-receptor availability in the acute phase and during the course of remission. A 27-year-old man was admitted with severe akinesia, rigor, tachycardia, fever, and elevated creatine phosphokinase level (CK) after neuroleptic medication. NMS was diagnosed, and treatment was started with dantrolene, amantadine, and dopamine agonists. IBZM-SPECT examination was performed on days 6, 34, 90, 107, 131, and 201. In the acute state of NMS, there was no binding of IBZM to D2-receptors. SPECT reached almost normal values on day 131, but clinical examination still showed a mild parkinsonian syndrome. With SPECT, the D2-receptor occupancy in NMS could be successfully shown in correlation with extrapyramidal signs. IBZM-SPECT may therefore serve to monitor D2-receptor occupancy in patients at risk for NMS.

Specific cardiological evaluation after focal cerebral ischemia.

Purpose of this study was to define a subgroup of TIA/stroke patients who should be examined by transthoracal and transesophageal echocardiography or Holter-electrocardiography to identify those with cardiogenic brain embolism reliably; 300 consecutive patients with acute focal brain ischemia underwent a standardized diagnostic protocol for the evaluation of the etiology including, clinical examination by a cardiologist and routine electrocardiography, Holter-electrocardiography, transthoracal and transesophageal echocardiography. 188 patients had a potential cardiac source of embolism. In particular echocardiography was diagnostic in 163 patients, and Holter-electrocardiography 10; 159 of these 188 patients (84.6%) had competitive etiologies, predominantly large vessel atherosclerosis. In 136 patients cardiogenic brain embolism was assumed as quite definite or possible. To identify these patients reliably, transthoracal and transesophageal echocardiography would have been necessary in 89% of the entire group of patients (all with clinically cardiological abnormalities, pathological routine ECG, without vascular risk factors, or no atherosclerosis in duplex sonography), and Holter-electrocardiography in 54%.

VACTERL with the mitochondrial np 3243 point mutation.

The VACTERL association of vertebral, anal, cardiovascular, tracheo-esophageal, renal, and limb defects is one of the more common congenital disorders with limb deficiency arising during blastogenesis. The cause is probably heterogeneous; a molecular basis has not yet been defined. We report on a family in which a female infant with VACTERL was born in 1977 and died at age 1 month due to renal failure. Because her mother and sister later developed classical mitochondrial cytopathy associated with the A-G point mutation at nucleotide position (np) 3243 of mitochondrial (mt) DNA, we performed a molecular analysis of mt DNA in preserved kidney tissue from the VACTERL case. We discovered 100% mutant mt DNA in multicystic and 32% mutant mt DNA in normal kidney tissue. Mild deficiency of complex I respiratory chain enzyme activity was found in the mother's muscle biopsy. Other maternal relatives were healthy but had low levels of mutant mt DNA in blood. This is the first report to provide a precise molecular basis for a case of VACTERL. The differing tissue pathology depending on the percentage of mutant mt DNA suggests a causal connection between the mutation and symptoms. VACTERL, and this type of multicystic renal dysplasia, are new phenotypes for the np 3243 point mutation. The possibility of a mitochondrial disorder should be born in mind and also that VACTERL may occur as a first manifestation of a mutation that has been present for generations. This would have major implications for patient management and for genetic counselling regarding both the risk of recurrence and risk of other mitochondrial syndromes in affected families.

Clinical spectrum of the MELAS mutation in a large pedigree.

INTRODUCTION: MELAS is most often due to an mentally transmitted A-G transition mutation of mitochondrial DNA (mtDNA) at position 3243. In this study we report on the clinical spectrum associated with the mutation in the largest family reported so far. PATIENTS AND METHODS: In a family with three MELAS cases we identified 47 persons at risk for the mutation; sufficient data was available on 29. Mitochondrial disease was diagnosed in two of 9 deceased numbers (posthumous molecular analysis in one); 27 surviving family members underwent examination and 25 a molecular analysis of mt DNA from lymphoblasts. Then had a muscle biopsy and two were later autopsied. RESULTS: All 26 cases investigated by molecular analysis showed the mutation at position 3243. The 18 symptomatic patients without stroke-like episodes had sensorineural hearing loss in 15 cases, diabetes in 6, nephropathy in 7, mild myopathy in 4, cardiomyopathy in 2, cerebellar disease in 4 and mental retardation in 2 cases. Eight carriers were asymptomatic. Autopsy showed > 80% mutant mt DNA in all tissues except blood (20%) examined in a MELAS patients, but < 20 mutant mt DNA in all tissues except lever (40%) and kidney (70%) in a patient with hepatopathy, renal failure and diabetes. Histologic and biochemical studies of muscle biopsy were often non-informative. CONCLUSIONS: The mutation of mt DNA at position 3243 causes a multisystem disorder with a variable phenotype due to heteroplasmy. Most carriers are oligosymptomatic with hearing loss and a variety of neurological and internal medical symptoms. Diabetes, cardiomyopathy and renal disease, which is newly reported here for this mutation, are frequent. The blood test is a reliable screening tool in affected families, but is of prognostic value only combined with examination of other tissues.

[Myotonic dystrophy: magnetic resonance tomography and clinico-genetic correlations]. / Myotonische Dystrophie: Magnetresonanztomographie und klinisch-genetische Korrelationen.

Myotonic dystrophy (DM) is an autosomal dominant multisystem disorder involving muscle, brain, heart, eyes and endocrine organs, among others. The molecular basis is an unstable trinucleotide repeat at the 3'-untranslated end of the myotonin protein kinase gene on chromosome 19 q 13.3, and the number of repeats correlates with the severity of muscle weakness. We performed a clinical, psychometric and MRI study on 43 patients with DM and correlated findings with the molecular analysis. Nineteen patients had mild distal muscle weakness, 17 moderate und 7 severe weakness. Thirteen had marked cognitive deficits with reduced speed of cognition, low IQ, and apathy. MRI showed pathological muscle signal in 35 cases with a characteristic mosaic involving distal muscle groups, often sparing the posterior tibial muscle. Cerebral MRI showed significant subcortical white matter lesions in 20 cases and brain atrophy in 15 cases. Clinical and MRI findings of CNS and muscle both correlated with CTG repeat length, but did not parallel each other. DM is a significant disease of the brain as well as muscle, and several aspects of the disease correlate with molecular findings, with a threshold effect for repeats exceeding 1000 trinucleotides. The individual predominance of specific organ involvement probably depends on variable somatic mosaicism of the molecular defect.

[Therapy of Lyme borreliosis]. / Therapie der Lyme-Borreliose.

Lyme Borreliosis is an infectious disorder caused directly by Borrelia burgdorferi. Secondary immunological mechanisms might play an additional pathogenetic role. The natural course of the disease in stage I and II is in most cases benign, therefore the influence of antibiotic therapy is difficult to assess. Double-blind, placebo-controlled randomized studies were performed rarely. However, by comparing untreated and treated patient groups it seems, that antibiotic therapy shortens the disease duration and prevents late complications. In stage III the course of the disease is usually chronic progressive (central nervous system, joint, skin), if no antibiotic therapy is applied. Currently performed clinical trials were up to now unable to determine the optimal antimicrobial agent, route of application, dosage and optimal duration of therapy for the different manifestations of the disease. Susceptibility testing, antimicrobial pharmacokinetic considerations (e. g. CSF penetration, half-life) and clinical experiences are therefore the basis of our recommendations. Stage I: Doxycyclin 2 x 100 mg p. o. or if contraindicated Cefuroxim 2 x 500 mg, at least 14 days. In case of systemic symptoms (e. g. fever) a intravenous therapy is indicated. Stage II and III: Ceftriaxon 1 x 2--2 x 2 g i. v. or Cefotaxim 3 x 2 g i. v., at least 14 days. Corticosteroids can be given in defined cases (pain syndrome!) additionally. Therapy failure was described regarding all used antibiotics, therefore clinical and laboratory follow up is mandatory. Residual symptoms can disappear over months and are usually not due to refractory disease.(ABSTRACT TRUNCATED AT 250 WORDS)

[Current status of transcranial color duplex ultrasound in the adult]. / Aktueller Stand der transkraniellen Farbduplexsonographie beim Erwachsenen.

Technical improvements accomplished over the last few years allow imaging of intracranial parenchymal structures as well as of basal cerebral arteries by ultrasound. Low frequency probes (2-2.5 MHz) and colour Doppler technology are required for these examinations. Recent experience in clinical practice proves that perfusion patterns in basal cerebral arteries can be depicted more accurately and with better reproducibility compared to conventional transcranial Doppler sonography. Simultaneous B-Mode imaging allows detection of cerebral haemorrhage, brain tumours and ventricular enlargement. Preliminary data on the sensitivity and specificity are promising and encourage further prospective studies.

Brain disease and molecular analysis in myotonic dystrophy.

Abnormal amplification of a CTG repeat on chromosome 19 is the molecular basis of myotonic dystrophy (DM). Expansion of the repeat has been correlated with severity of several clinical features of the disease. We performed extensive cognitive testing, cerebral magnetic resonance imaging (MRI) and a molecular analysis in 28 cases of DM to determine the relationship between the molecular defect and brain disease. Performance in two or more cognitive tests was pathological in 10 cases. Fourteen patients had subcortical white matter lesions on MRI, 14 had cerebral atrophy. Amplification of the CTG repeat showed a strong correlation with cognitive test deficits when exceeding a length of over 1000 trinucleotides. MRI lesions were associated with impaired psychometric performance, but MRI and molecular findings were only weakly related. Disease duration influenced the appearance and amount of white matter lesions on MRI. Quantification of CTG repeat size may allow an early estimate on the probability of brain involvement in DM; cognitive dysfunction is associated with white matter lesions and cerebral atrophy later on in the course.

[Polyneuritis and myositis in Trypanosoma gambiense infection]. / Polyneuritis und Myositis bei Trypanosoma-gambiense-Infektion.

During a four-week trip to Nigeria a 54-year-old German developed a fever of 39 degrees C. Later on he had lymphadenopathy, pretibial oedema, dyspnoea and weight loss. After 16 weeks a wreath-like pale pink skin rash, increased pulse rate with pulse deficit and hepatosplenomegaly were noted. Abnormal laboratory findings were an increased blood sedimentation rate (95 mm), raised immunoglobulin M (483 mg/dl), haemoglobin of 12.0 g/dl, mean corpuscular volume of 76 fl and Borrelia IgM antibody titre of 1:512. The electrocardiogram was suggestive of myocarditis: the cardiac symptoms were controlled with digoxin and verapamil. The patient's general condition deteriorated while he was receiving antibiotic treatment with tetracycline and penicillin. Cerebrospinal fluid (CSF) showed an increased cell count (39/microliters) and albumin (0.98 g/dl). There was a mild, predominantly proximal, tetraplegia which--on the basis of electromyographic and biopsy findings--was thought to be due to polyneuritis and myositis. At this stage blood smear and CSF examination revealed Trypanosoma. He thereupon received suramin (1.0 g) and prednisolone (120 mg down to 40 mg) daily, to which melarsoprol was added after 6 days (0.5 ml up to 5.0 ml daily for 36 days). Almost all symptoms then regressed within 6 weeks.

White matter lesions and cognitive deficits: relevance of lesion pattern?

Magnetic resonance imaging (MRI) permits efficient visualization of white matter lesions (WML). A growing body of literature deals with the correlation of WML and cognitive dysfunction with conflicting results. We studied the influence of lesion pattern as well as size by analyzing MRI and psychometric test performance in 2 patient collectives with different WML patterns. 22 patients with myotonic dystrophy (MD) and mainly subcortical WML were compared with 39 patients with multiple sclerosis (MS) and mainly periventricular lesions. 73% of MD patients had WML, the extent of which correlated with cognitive deficits. Severely impaired patients had psychometric findings compatible with "subcortical" dementia. In MS the extent of WML alone did not correlate significantly with cognitive deficits. Significant cognitive dysfunction was observed with extension of WML to areas of white matter immediately underlying cortex, but not with exclusively periventricular lesions. Cerebral atrophy had less impact. Comparison of MD and MS indicates that WML immediately subjacent to cortex are likely to cause significant cognitive deficits, whereas extensive periventricular demyelination may cause no major dysfunction. This may relate to early disturbance of associative fibers by subcortical lesions. Our results emphasize the significance of pattern as well as total extent of WML. Myotonic dystrophy is a useful model to study the effect of subcortical lesions, due to a typical lesion pattern unusual in other conditions.

A comparison of transesophageal echocardiography and transcranial Doppler sonography with contrast medium for detection of patent foramen ovale.

BACKGROUND: Patent foramen ovale as a possible stroke risk factor can be diagnosed with transcranial Doppler sonography (TCD) by detecting intravenous contrast medium crossing from the right to the left atrium. The present study evaluates the reliability of this method. SUMMARY OF REPORT: We performed TCD and transesophageal echocardiography simultaneously in 50 patients using galactose microbubbles. We observed bubble signals passing the middle cerebral artery in 7 patients less than 20 seconds after injection; we found positive TCD tests in 14 patients using the Valsalva maneuver. With transesophageal echocardiography patent foramen ovale could be detected in 15 patients (sensitivity, 0.93; specificity, 1; P < .01). CONCLUSIONS: TCD with echo contrast is a reliable screening tool for patent foramen ovale. A standardized procedure including the Valsalva maneuver is essential to prevent false-negative results.

Meningeal carcinomatosis: CSF cytology, immunocytochemistry and biochemical tumor markers.

CSF cytology, immunocytochemistry and biochemical tumor markers were compared in 12 patients with a meningeal carcinomatosis regarding diagnostic significance and therapy control; 50 samples were investigated. Cytology was tumor-positive in 39 samples and immunocytochemistry in 45 samples. Intrathecally produced tumor markers were found in 47 samples. On initial examination only immunocytochemical testing correctly classified all cases. Cytology and biochemical tumor markers revealed positive results in 10 respectively 11 of 12 patients, combined use of these two methods would increase the sensitivity to 100%. On follow-up examination tumor markers correlated best with symptoms and were early indicators for clinical relapse. These results could be achieved only if several monoclonal antibodies and biochemical tumor marker tests were combined. It is concluded that immunocytochemistry and biochemical tumor markers are of major help regarding the problems of false-negative cytology and reliable therapy control in meningeal carcinomatosis.