CXCL13 chemokine in pediatric and adult neuroborreliosis.

OBJECTIVES: Diagnosis of Lyme neuroborreliosis (NB) depends on the proof of intrathecal antibody production against Borrelia burgdorferi. CXCL13 has been seen to be elevated early in NB, before antibody production has started. In this study, we determined the diagnostic role of the CXCL13 chemokine in cerebrospinal fluid (CSF) and serum for the first time in pediatric NB patients as well as in adults, compared to controls and blood donors (BD). MATERIAL AND METHODS: CXCL13 levels were measured in CSF and serum of 33 children and 42 adult patients. Serum CXCL13 was measured in 300 BD. RESULTS: CSF CXCL13 levels were significantly elevated in definite and probable acute NB in children and adults compared to seropositive and seronegative neurological controls (P < 0.001). Serum CXCL13 levels showed great fluctuations and were not significantly elevated in NB patients. CONCLUSIONS: Our study suggests that CSF CXCL13 can be used as a diagnostic marker for NB in children as well. In contrast, CXCL13 serum levels show great variance even in the healthy population and are not indicative of active NB.

Radiosurgery/stereotactic radiotherapy in the therapeutical concept for skull base meningiomas.

OBJECTIVE: Microsurgical resection is still the treatment of choice for skull base meningiomas. But the risk of postoperative neurological deficits is high, and in many of these cases complete tumor removal cannot be achieved. Therefore recurrences are even more probable. Stereotactically guided radiation therapy - radiosurgery (RS) or stereotactic radiotherapy (SRT) - offers an additional or alternate treatment option for those patients. We evaluated local control rates, symptomatology, and toxicity. PATIENTS AND METHODS: 224 patients were treated with stereotactically guided radiation techniques in two departments between 1997 and 2003. 129 of 224 had recurrences after 1 to 3 prior tumor resections and 95 of 224 were treated with SRT/RS alone. 87.9% of cases had benign, 7.8% had atypical and 4.3% had malignant meningiomas. RS was only applied in 11 cases. Tumor volumes ranged from 0.16 ccm to 3.56 ccm. The other 213 patients had larger tumor volumes of up to 135 ccm or a meningioma close to optical structures. Therefore 183 cases were treated with SRT in normal fractions of 1.8-2 Gy in single doses up to 60 Gy. Hypofractionated SRT with single fraction doses of 5 or 4 Gy was applied in 30 cases. Follow-up data were available in 181 skull base meningiomas and the progression-free and overall survival rates, the toxicity and symptomatology were evaluated. RESULTS: The median follow-up was 36 months. The overall survival and the progression-free survival rates for 5 years were 92.9%, and 96.9%, respectively. Two tumor progressions have occurred to date but further follow up is required. Tumor volumes (TV) had shrunk about by 19.7% at 6 months (p<0.0001) and by 23.2% at 12 months (p<0.01) after SRT/RS. In 95.6% the symptoms had improved or were stable. Clinically significant acute toxicity (grade III) was seen in only 1 case (2.7%). Some patients developed late toxicity: 8.8% had grade I, 4.4% had grade II and 1.1% had grade III. No other neurological deficits occurred during follow-up. CONCLUSION: SRT and RS offer an additional or alternative treatment option with a high efficacy and few side effects for the tumor control of skull base meningiomas. An individual and interdisciplinary decision respecting treatment is needed for each patient. In cases of large TV (>4 ccm), tumors adjacent to critical structures (<2 mm) or in high-risk patients the use of SRT offers greater benefits.

Histopathologic analysis of foci of signal loss on gradient-echo T2*-weighted MR images in patients with spontaneous intracerebral hemorrhage: evidence of microangiopathy-related microbleeds.

BACKGROUND AND PURPOSE: Patients with spontaneous intracerebral hemorrhage (ICH) frequently have small areas of signal loss on gradient-echo T2*-weighted MR images, which have been suggested to represent remnants of previous microbleeds. Our aim was to provide histopathologic support for this assumption and to clarify whether the presence and location of microbleeds were associated with microangiopathy. METHODS: We performed MR imaging and correlative histopathologic examination in 11 formalin-fixed brains of patients who had died of an ICH (age range, 45-90 years). RESULTS: Focal areas of signal loss on MR images were noted in seven brains. They were seen in a corticosubcortical location in six brains, in the basal ganglia/thalami in five, and infratentorially in three specimens. Histopathologic examination showed focal hemosiderin deposition in 21 of 34 areas of MR signal loss. No other corresponding abnormalities were found; however, hemosiderin deposits were noted without MR signal changes in two brains. All specimens with MR foci of signal loss showed moderate to severe fibrohyalinosis, and there was additional evidence of amyloid angiopathy in two of those brains. CONCLUSION: Small areas of signal loss on gradient echo T2*-weighted images indicate previous extravasation of blood and are related to bleeding-prone microangiopathy of different origins.

[Indications of cerebral micro-hemorrhage in MRI. Comparative histological findings and possible clinical significance]. / Hinweis auf zerebrale Mikroblutungen in der MRT. Vergleichende histologische Befunde und mögliche klinische Bedeutung.

Increased use of gradient echo T2*-weighted gradient echo sequences in magnetic resonance imaging (MRI) of patients suffering from primary ICH called attention to foci of signal loss which were suggested to represent remnants of cerebral microbleeds. In a post mortem correlative MR and histopathological study we provide support for this notion. We found areas of signal loss on gradient echo T2*-weighted sequences in 7 out of 11 brains of patients who had died of intracerebral hematoma. Histopathologically, these areas represented hemosiderin deposits indicating previous extravasation of blood. To provide data about the prevalence of these MRI findings in a healthy elderly population a subgroup of participants of the Austrian Stroke Prevention Study was analyzed. We detected foci of signal loss on gradient echo T2*-weighted sequences in 18 out of 280 volunteers (6.4%). MR-based evidence of previous microbleeds may indicate a potentially higher risk of suffering from intracerebral bleeding which could have therapeutic implications for the treatment of acute stroke and for secondary prevention. This hypothesis will have to be tested in future prospective trials.

Is IgM of diagnostic value in case of delayed intrathecal production of IgG antibodies?

The neurological manifestations of Lyme borreliosis comprise a wide range of clinical signs. However, these symptoms might have other aetiologies. Therefore detection of intrathecal production of specific antibodies is necessary to confirm the clinical assumption of neuroborreliosis (NB). In case of delayed intrathecal production of specific IgG antibodies, detection of IgM could play a role in the early diagnosis of NB. To clarify whether IgM is of diagnostic value in such cases, paired CSF serum samples from 176 patients with suspected NB admitted to the department of Neurology, Karl Franzens University, Graz, Austria, were tested. Testing was performed with the IDEA Neuroborreliosis Kit (Dako, Denmark) and Enzygnost Borreliosis (Behring, Germany) and results of both methods were compared. According to well defined criteria 63 of the 176 patients had defined NB and 113 were regarded as possible NB. Twelve out of 63 patients with defined NB had delayed intrathecal IgG production. Only one patient with delayed IgG production had an intrathecal IgM production prior to IgG. In all patients with possible NB no intrathecal production of IgM was detected. At the time of the first lumbar puncture IgG intrathecal production could be detected with the IDEA seven times more often than with the Enzygnost Borreliosis. The determination of intrathecal production of IgM does not appear to be of diagnostic value in patients with delayed IgG antibody production. Therefore a consecutive lumbar puncture is more likely to confirm clinical assumption if there is strong clinical evidence of NB.

[Prevalence and risk factors in the population of Graz (Austrian Stroke Prevention Study)]. / Prävalenz von Risikofaktoren in der Grazer Bevölkerung (Austrian Stroke Prevention Study).

The Austrian Stroke Prevention Study recruited 1960 randomly selected subjects aged 50 to 75 years during a 3-year period of enrollment. The response rate of the study was 32.4%. A telephone interview with 200 randomly selected non-responders yielded no differences to responders regarding the frequency of major vascular risk factors known to the subjects. Besides demographics, the study assessed arterial hypertension, diabetes mellitus, cardiac disease, smoking, a complete lipid status including the apolipoprotein-E genotype, serum fibrinogen and anticardiolipin antibodies as well as various natural antioxidants such as vitamins A, C, E and beta-carotene. Arterial hypertension, diabetes mellitus, cardiac disease and hypercholesterolemia > 200 mg/dl were strikingly common and occurred in 38%, 7.6%, 32% and 76%, respectively. Suboptimal plasma concentrations of vitamin A, E, and beta-carotene were noted in 77.2%, 56.1% and in 53.2% of study participants. The rate of treatment of major risk factors known to the subjects prior to study entry were 60.3% and 70% for arterial hypertension and diabetes mellitus, but only 37.1% and 6.3% for cardiac disease and hypercholesterolemia > 250 mg/dl. Diet was commonly used to treat diabetes but was almost neglected in the treatment of other vascular risk factors. These data provide an orientation on the prevalence of risk factors and the use of primary preventive measures for stroke treatment in our community.

[Magnetic resonance tomography of the brain in amyotrophic lateral sclerosis]. / Magnetresonanztomographie des Gehirns bei amyotropher Lateralsklerose.

We compared the magnetic resonance imaging results of 15 patients suffering from amyotrophic lateral sclerosis (ALS) with those of 30 age-matched controls to search for disease specific cerebral abnormalities. Symmetric hyperintensity along the corticospinal tract on the proton density spin-echo sequence was exclusively found in 4 ALS patients. It was associated with younger age, rapid disease progression and evolution of symptoms starting in the lower extremities. Signal loss of the motor cortex on T2-weighted images was frequently seen in ALS (9 patients) but was also observed in controls. As MRI is capable of providing direct evidence for ALS besides excluding other diseases it should be included in the diagnostic work-up of these patients.

[Heparin-induced extracorporeal LDL precipitation (HELP). A new therapeutic possibility in cerebral multi-infarct dementia]. / Heparin-induzierte extrakorporale LDL-Präzipitation (HELP). Eine neue therapeutische Möglichkeit bei zerebraler Multiinfarktdemenz.

High fibrinogen levels have been assessed in cerebrovascular disease with a direct relationship to blood rheology. Heparin-induced extracorporeal LDL precipitation (HELP) is a method that effectively reduces fibrinogen and lipoproteins at the same time, thus improving the hemorheologic pattern. We studied 45 patients with cerebral multiinfarct dementia. After computer-randomization 30 patients received a HELP treatment, while the remaining 15 patients served as controls. HELP produced an immediate and statistically significant reduction on parameters relevant to hemorheology, such as fibrinogen (P < 0.001), total cholesterol, low-density lipoprotein, triglycerides (P < 0.0001 each) and whole blood viscosity (at high and low shear rate) as well as plasma viscosity and red cell transit time (P < 0.01 each). The treated group showed improvement after HELP (P < 0.05 for each test) on the Mathew Neurological Scale, Mini Mental State Examination and Activities-of-Daily-Living Test and also relative to the untreated controls (P < 0.05 each). These results may be regarded as a basis for some reflections about new hemorheological interventions in cases of cerebral multiinfarct dementia.

[Hemorrheology and quality of life in fibrinogen- and lipid-lowering therapy]. / Hämorheologie und Lebensqualität bei Fibrinogen- und Lipid-senkender Therapie.

Previous studies have demonstrated that heparin-induced extracorporeal LDL precipitation is able to reduce total cholesterol, LDL, triglycerides and plasma fibrinogen at the same time and thus improve the hemorheologic pattern. A combination of H.E.L.P. and bezafibrate, which also has a lipid- and fibrinogen-lowering potency, was applied in patients suffering from cerebral multi-infarct dementia and disturbances of the hemorheologic situation. In view of observations regarding improved quality of life after H.E.L.P., a prospective, randomized trial was conducted to determine possible interactions between improved hemorheology and better quality of life. To obtain a low baseline of laboratory parameters, all the patients underwent a single H.E.L.P. session and were then (double-blind) stratified into 2 groups: group 1 (16 males, 5 females, age 67.9 +/- 6.8 years) received sustained-release bezafibrate 400 mg (Bezalip) per day, while group 2 served as controls, and comprised 14 males and 5 females (age 69.2 +/- 6.8 years) who received placebo for a period of 56 days. After H.E.L.P. a statistically significant reduction of the following parameters relevant to hemorheology was obtained: fibrinogen (p < 0.0001), whole blood viscosity (low shear rate p < 0.007 and high shear rate p < 0.005), plasma viscosity (p < 0.002) and red cell transit time (p < 0.0001). Also, the metabolic parameters were influenced positively (p < 0.0001 for total cholesterol, LDL and triglycerides).(ABSTRACT TRUNCATED AT 250 WORDS)

Pathologic correlates of incidental MRI white matter signal hyperintensities.

We related the histopathologic changes associated with incidental white matter signal hyperintensities on MRIs from 11 elderly patients (age range, 52 to 82 years) to a descriptive classification for such abnormalities. Punctate, early confluent, and confluent white matter hyperintensities corresponded to increasing severity of ischemic tissue damage, ranging from mild perivascular alterations to large areas with variable loss of fibers, multiple small cavitations, and marked arteriolosclerosis. Microcystic infarcts and patchy rarefaction of myelin were also characteristic for irregular periventricular high signal intensity. Hyperintense periventricular caps and a smooth halo, however, were of nonischemic origin and constituted areas of demyelination associated with subependymal gliosis and discontinuity of the ependymal lining. Based on these findings, our classification appears to reflect both the different etiologies and severities of incidental MRI signal abnormalities, if it is modified to treat irregular periventricular and confluent deep white matter hyperintensities together.

First experience in application of heparin-induced extracorporeal LDL precipitation (H.E.L.P.) in acute thromboembolic stroke.

Heparin-induced Extracorporeal LDL < total cholesterol, triglycerides, fibrinogen > Precipitation (H.E.L.P.) was applied in cases of acute thromboembolic stroke within 48 to 96 hours after onset. 42 patients had been randomized for the trial. In Group A 12 patients underwent a single H.E.L.P. application, while remaining 10 patients formed a control group. In group B 10 patients had 10 H.E.L.P. applications, the other 10 patients firmed as controls. Results of group A: 4 days after H.E.L.P. an improvement in the Mathew Scale and in the Mini Mental State Examination could be obtained (p < 0.05 each). 10 days after H.E.L.P. all the tests showed significant changes (p < 0.05 in the Mathew Scale and in the Mini Mental State Examination and p < 0.01 in the Activities-of-Daily-Living Score). Relatet to the controls there appeared a statistically significant difference 4 days after H.E.L.P. in the Mini Mental State Examination and in the Activities-of-Daily-Living Score (p < 0.05 each). At day 10 all the tests showed a difference to the controls (p < 0.05 in the Mathew Scale and p < 0.01 in the other tests). Results of group B 10: One day after 1st H.E.L.P. a statistically significant difference could be observed in all the tests (p < 0.05 in the Mathew Scale and the Mini Mental State Examination and p < 0.01 in the Activities-of-Daily-Living Score). At that time even a difference to the controls became visible (p < 0.05 in the Mathew scale, p < 0.01 in the other tests).(ABSTRACT TRUNCATED AT 250 WORDS)

Bilateral medial medullary infarction: magnetic resonance imaging and correlative histopathologic findings.

Bilateral medial medullary infarction is a rare event which clinically presents with flaccid tetraplegia sparing the face, bilateral disturbance of deep sensation, hypoglossal nerve palsy and respiratory failure. We here report a patient with such symptoms in whom magnetic resonance imaging enabled the detection of signal abnormalities in the lower brainstem as soon as 9 h after onset. Results of a control study 3 weeks later correlated well with the extent of infarction that was seen at autopsy. Early lesion detection in the lower medulla by magnetic resonance imaging and the unfavorable prognosis of patients with ischemic damage at that location may provide the rationale for aggressive therapeutic strategies in such a condition.

Magnetic resonance imaging signal hyperintensities in the deep and subcortical white matter. A comparative study between stroke patients and normal volunteers.

Mixed population studies suggest a relationship between deep and subcortical white matter hyperintensities on magnetic resonance imaging and cerebrovascular disease. To further clarify this issue we compared the prevalence and extent of such signal abnormalities between a group of 133 consecutive stroke patients (mean age, 54.7 +/- 16.7 years) and 101 normal volunteers (mean age, 54.7 +/- 13.1 years). Diabetes and cardiac disease were significantly more common in patients than in normal subjects. Prevalence rates of clinically silent lesions were 44% and 47.5%, respectively. Beginning confluent and confluent foci were seen in 19.5% of patients, but in only 7.5% of normal subjects. Significant univariate correlations were found for the presence and extent of lesions with age, diabetes, cardiac disease, severity of extracranial carotid arteriosclerosis, and arterial hypertension, but not with the diagnosis of stroke or the type of brain infarction. Multivariate regression analysis established age and diabetes mellitus as the only independent predictors of white matter damage. We conclude that more extensive white matter abnormalities in stroke patients stem from their higher rate of cerebrovascular risk factors but are unrelated to the occurrence of ischemic attacks per se.

HELP application in multi-infarct dementia.

HELP is capable of lowering LDL, cholesterol, triglycerides, and fibrinogen. It has been proven that HELP application has an impact on MID by decreasing plasma fibrinogen, cholesterol, LDL, triglycerides, thus also reducing whole-blood plasma viscosity, plasma fibrinogen, and red cell transit time. It has been shown that a single HELP treatment in MID is followed by an improvement of the scores obtained from the rating scales employed (Mathew, Mini Mental State Examination, Activities of Daily Living) for as long as 10 days, which was supported by comparison with the scores of a control group. Repeated HELP application (up to five) within 40 days led to an improvement of the test battery values in comparison with base values and those of the respective control group. Further applications (up to 10) of plasmapheresis, however, remained without any remarkable effect on the rating scales employed, with the difference from the corresponding control groups remaining the same.

MRI in tuberculous meningoencephalitis: report of four cases and review of the neuroimaging literature.

The contribution of MRI is reported in four adult patients with tuberculous meningoencephalitis (TbM) and with autopsy correlation in one. Contrast-enhanced T1-weighted MRI revealed the characteristic basal meningeal inflammation of TbM and its focal spreading into adjacent brain. Mixed and T2-weighted pulse sequences delineated a plethora of parenchymal abnormalities. Their relation to TbM was established by a close matching of the patient's neurological findings, contrast enhancement or a change in lesion size. The latter accurately reflected the clinical course in all patients. It remained difficult, however, to distinguish between ischaemic and inflammatory changes, which in some locations were intermixed even histologically. From our experience and that of other groups, MRI provides more diagnostic information in TbM than CT. Moreover, MRI promises to be a useful tool for monitoring treatment response.

The morphologic correlate of incidental punctate white matter hyperintensities on MR images.

Postmortem examinations were made of the brains of six patients, 52-63 years old, who exhibited incidental punctate white matter hyperintensities on MR images before death. Our aim was to unravel the morphologic correlate of such lesions. By repeating the MR study after fixation on four specimens, cutting the brain parallel to the MR imaging plane, and examining whole-hemisphere microscopic sections, we optimized lesion identification. The white matter signal abnormalities were better delineated on pre- than postmortem scans, and visual inspection of the brain slices was normal in all but one location. Histologically, we found areas of reduced myelination with atrophy of the neuropil around fibrohyalinotic arteries as well as different stages of perivenous damage. The latter ranged from spongiform transformation of the neuropil and scattered foci of demyelination to large perivenous areas with marked rarefaction of myelinated fibers. Edematous glial swelling in foci of ganglion cell heterotopia caused subcortical white matter hyperintensities in one case. Our results suggest minor perivascular damage but not infarction as the most likely substrate of punctate MR white matter hyperintensities in elderly brains. Histologic correlations with MR images obtained during life or with studies of unfixed material are necessary to analyze such small lesions.

Chronic Lyme disease with an expansive granulomatous lesion in the cerebellopontine angle.

Expansive granulomatous lesions in the posterior cranial fossa are rare and have not been reported in conjunction with Lyme disease. We report a patient with verified Borrelia burgdorferi infection who developed a tumor in the cerebellopontine angle. Rapid growth of the tumor led to signs of cerebral compression and to hydrocephalus. Surgical intervention was required despite florid meningitis. The histological examination showed inflammatory, nonspecific granulation tissue. The origin of this tissue is almost certainly causally related to the B. burgdorferi infection. Signs of inflammation resolved rapidly after subtotal resection. The clinical, radiological, and biochemical course is documented. This is the first report of an expansive cerebral lesion in the chronic phase of Lyme disease.

[Percutaneous radiotherapy for thyroid gland carcinoma]. / Ergebnisse der perkutanen Strahlentherapie bei Schilddrüsenkarzinomen.

Prognostically relevant factors as well as indications for percutaneous radiotherapy are analysed by the hand of a retrospective analysis of therapeutic results in 86 patients that were exposed a percutaneous radiotherapy because of a thyroid carcinoma at the Clinic and Policlinic of the Medical Academy Erfurt during the period 1972 to 1982. The 5-years-survivals of 83% for patients with differentiated carcinoma and 22% for patients with dedifferentiated carcinoma prove the influence of tumor histology on prognosis of the disease. Next to it the locoregional tumor spreading at beginning of therapy rendered prognostically relevant. The 5-years-survival was 83% in tumor stages T1-3N0M0. With metastatic infiltration into lymph-nodes of the neck the 5-years-survival decreased to 57%, with spreading of the primary tumor beyond organ borders to 23.5%. The postoperative percutaneous radiotherapy should be applied in all cases of metastatic infiltration of lymph-nodes. In large, inoperable tumors the percutaneous radiotherapy is the solely possible palliative measure that should be applied both in differentiated and also in anaplastic carcinomas in spite of infaust prognosis.