Anti-Homer-3 antibodies in cerebrospinal fluid and serum samples from a 58-year-old woman with subacute cerebellar degeneration and diffuse breast adenocarcinoma.

INTRODUCTION: Subacute cerebellar ataxia combined with cerebrospinal fluid (CSF) pleocytosis is the result of an immune response that can occur due to viral infections, paraneoplastic diseases or autoimmune-mediated mechanisms. In the following we present the first description of a patient with anti-Homer-3 antibodies in serum and CSF who has been diagnosed with paraneoplastic subacute cerebellar degeneration due to a papillary adenocarcinoma of the breast. CASE PRESENTATION: A 58-year-old female was admitted to our clinical department because of increasing gait and visual disturbances starting nine months ago. The neurological examination revealed a downbeat nystagmus, oscillopsia, a severe standing and gait ataxia and a slight dysarthria. Cranial MRI showed no pathological findings. Examination of CSF showed a lymphocytic pleocytosis of 11 cells/µl and an intrathecal IgG synthesis of 26%. Initially, standard serological testing in serum and CSF did not indicate any autoimmune or paraneoplastic aetiology. However, an antigen-specific indirect immunofluorescence test (IIFT) revealed the presence of anti-Homer-3 antibodies (IgG) with a serum titer of 1: 32,000 and a titer of 1: 100 in CSF. Subsequent histological examination of a right axillary lymph node mass showed papillary adenocarcinoma cells. Breast MRI detected multiple bilateral lesions as a diffuse tumour manifestation indicative of adenocarcinoma of the breast. Treatment with high-dose methylprednisolone followed by five plasmaphereses and treatment with 4-aminopyridine resulted in a moderate decrease of the downbeat nystagmus and she was able to move independently with a wheeled walker after 3 weeks. The patient was subsequently treated with chemotherapy (epirubicin, cyclophosphamide) and two series of immunoglobulins (5 × 30 g each). This resulted in a moderate improvement of the cerebellar symptoms with a decrease of ataxia and disappearance of the downbeat nystagmus. CONCLUSION: The presented case of anti-Homer-3 antibody-associated cerebellar degeneration is the first that is clearly associated with the detection of a tumour. Interestingly, the Homer-3 protein interaction partner metabotropic glutamate receptor subtype 1A (mGluR1A) is predominantly expressed in Purkinje cells where its function is essential for motor coordination and motor learning. Based on our findings, in subacute cerebellar degeneration, we recommend considering serological testing for anti-Homer-3 antibodies in serum and cerebrospinal fluid together with tumor screening.

Seasonal patterns and associations in the incidence of acute ischemic stroke requiring mechanical thrombectomy.

BACKGROUND: In order to identify risk periods with an increased demand in technical and human resources, we tried to determine patterns and associations in the incidence of acute ischemic stroke due to embolic large vessel occlusions (eLVO) requiring mechanical thrombectomy (MT). METHODS: We conducted a time series analysis over a 9-year period (2010-2018) based on observational data in order to detect seasonal patterns in the incidence of MT due to eLVO (n = 2628 patients). In a series of sequential negative binominal regression models, we aimed to detect further associations (e.g., temperature, atmospheric pressure, air pollution). RESULTS: There was a 6-month seasonal pattern in the incidence of MT due to eLVO (p = 0.024) peaking in March and September. Colder overall temperature was associated with an increase in MT due to eLVO (average marginal effect [AME], [95% CI]: -0.15 [-0.30-0.0001]; p = 0.05; per °C). A current increase in the average monthly temperature was associated with a higher incidence of MT due to eLVO (0.34 [0.11-0.56]; p = 0.003). Atmospheric pressure was positively correlated with MT due to eLVO (0.38 [0.13-0.64]; p = 0.003; per hectopascal [hPa]). We could detect no causal correlation between air pollutants and MT due to eLVO. CONCLUSIONS: Our data suggest a 6-month seasonal pattern in the incidence of MT due to eLVO peaking in spring and early autumn. This might be attributed to two different factors: (1) a current temperature rise (comparing the average monthly temperature in consecutive months) and (2) colder overall temperature. These results could help to identify risk periods requiring an adaptation in local infrastructure.

Promotor polymorphisms of plasminogen activator inhibitor-1 and other thrombophilic genotypes in cerebral venous thrombosis: a case-control study in adults.

Plasminogen activator inhibitor 1 (PAI-1) is the main inhibitor of tissue-type and urokinase-type plasminogen activator. A 4G/5G polymorphism in the promoter region of the PAI-1 gene has been reported to enhance the plasma levels of PAI-1. In particular, the 4G allele (guanosine deletion) has been linked with increased plasma PAI-1 levels, which may lead to impaired activity of the fibrinolytic system, thus increasing the incidence of thrombotic events. The aim of this case-control study was to analyze whether variants of the PAI-1 promotor genotype 4G/4G, 4G/5G and 5G/5G, in particular the 4G/5G-variant, constitute an independent risk factor of cerebral venous thrombosis (CVT). A total of 136 consecutive patients with proven CVT were compared to 1,054 DNA specimens of healthy controls from a population-based cohort. PAI-1 promotor polymorphisms were evaluated using polymerase chain reaction. No significant association of CVT with PAI-1 4G/5G was found in either the additive (OR 1.04; 95 % CI 0.78-1.38) or in the dominant model (OR 1.24; 95 % CI 0.72-2.13). Also, the prevalence of the other genotypes (4G/4G and 5G/5G) in patients was not significantly different from controls. When considering the variants of the PAI-1 promoter genotype in combination with known genetical thrombophilias, no differences were found either. As was expected, the prothrombin (G20210A) genotype was confirmed as an independent risk factor for CVT. We conclude that the 4G allele of the PAI-1 polymorphism does not increase the risk of CVT in adults.

Extracranial and intracranial vertebral artery dissection: long-term clinical and duplex sonographic follow-up.

PURPOSE: To determine the value of color Doppler sonography (CDUS) in the diagnosis and follow-up of patients with extracranial and intracranial vertebral artery (VA) dissection. METHOD: Thirty-three patients aged 42 +/- 12 years with 40 VADS confirmed via digital subtraction angiography (DSA) (n = 37) and magnetic resonance angiography (MRA) (n = 3) were included in the study. All patients were investigated with extracranial CDUS and transcranial CDUS (TCCDUS) over a mean +/- SD follow-up period of 42 +/- 24 months and occurrence of new ischemic symptoms was assessed. Sonographic results were compared with initial and follow-up angiographic results. RESULTS: At presentation, 24/33 (73%) patients had suffered an ischemic stroke, 5/33 (15%) had a transient ischemic attack (TIA), and 4/33 (12%) were asymptomatic. Two patients had a recurrent vertebrobasilar TIA; there was no recurrent stroke. The initial DSA findings consisted of 14 stenoses, 20 tapered occlusions, and 6 pseudoaneurysms. During follow-up, 63% of the vessels recanalized. Sonographic findings were consistent with angiographic findings in 80% at the initial examination and in 86% during follow-up. The main reason for discordant results was the failure of CDUS to detect pseudoaneurysms. No recurrence occurred in the vertebral arteries (VA), but 1 patient had an asymptomatic carotid artery dissection during follow-up. CONCLUSION: Recurrent TIA or stroke after VAD appears to be extremely rare, independent of recanalization or persistent occlusion of the affected artery. CDUS and TCCDUS provide reliable follow-up of VAD in all patients presenting with stenosis or occlusion, but do not allow for detection of pseudoaneurysms of the VA.

The prognostic value of early transcranial Doppler ultrasound following cardiopulmonary resuscitation.

The aim of the presented study was to estimate the prognostic value of transcranial Doppler sonography (TCD) for the prediction of clinical outcome of patients after cardiopulmonary resuscitation (CPR) on the basis of the measured flow velocity changes in the basal cerebral arteries. Thirty-nine patients (27 men, 12 women) aged 66 +/- 15 y (+/-SD) who had undergone CPR were involved. Serial TCD examinations of the intracranial arteries were performed 1.5, 4, 8, 16, 24 and 72 h after CPR. Plasma neuron specific enolase (NSE), ventilation parameters (pH, paO(2), paCO(2)) and hemodynamic parameters were registered. Seventeen patients (group 1) survived with moderate or without neurologic deficits. Twenty-two patients (group 2) either died (n = 21) within 9 +/- 14 days or remained in vegetative state (n = 1). NSE levels ranged from 9 to 29 microg/L in group 1 and from 22 to 1242 microg/L in group 2 (p < 0.05). Four and 72 h after CPR, peak systolic flow velocities in the middle cerebral artery (MCA) were significantly higher in group 1 than in group 2 (p < 0.05). Twenty-four h after CPR, peak systolic and diastolic flow velocities in the ACA and PCA were also significantly higher in group 1 than in group 2 (p < 0.05). At this time, patients of group 2 showed significantly higher resistance index-values (RI = (sys-dia)/sys) in the anterior cerebral artery (ACA) and the posterior cerebral artery (PCA) (p < 0.05). A high correlation between peak systolic blood flow velocity in the MCA and systemic systolic blood pressure was observed in group 2 early 4 to 16 h after CPR (r = +0.52 to + 0.81, p < 0.05), while there was no such correlation in group 1. Using serial TCD examinations, patients with severely disabling or fatal outcome could be identified within the first 24 h. Besides established clinical and laboratory parameters, postanoxic myoclonus and NSE, serial TCD examinations following CPR may be helpful to predict the clinical outcome, but further studies with a larger number of patients are necessary to approve this hypothesis.

Cerebral aneurysms and arteriovenous malformations.

Cerebral aneurysms and arteriovenous malformations (AVMs), including arteriovenous fistulae, are rather seldom investigated by means of transcranial color-coded duplex sonography (TCCS). Nevertheless, the continuous improvements in high-quality scanners, ultrasound contrast enhancers, and special software, such as three-dimensional reconstruction tools, make these lesions assessable in a high number of patients. In particular, the possibility of investigating hemodynamics and hemodynamic changes in a noninvasive manner is a unique feature of TCCS, which is therefore particularly valuable for monitoring stepwise transcatheter treatment of these lesions. Limitations of the technique, mainly caused by restrictions of the insonated bone windows, render this method inadequate as a screening tool. However, TCCS has proven to be a highly useful technique for follow-up investigations of treated and untreated cerebral aneurysms and AVMs. This chapter explains the investigation of these lesions and gives an insight into the most important up-to-date literature.

Sonographic detection and follow up of an atypical pineal cyst: a comparison with magnetic resonance imaging. Case report.

The incidental ultrasonographic detection of an asymptomatic cystic pineal lesion in a young woman is described and compared with findings on magnetic resonance (MR) images. Follow-up studies obtained using both imaging modalities are presented. The results indicate that transcranial ultrasonography may represent an easy and cost-effective imaging technique for follow up of cystic lesions of the pineal gland, especially in patients unable to undergo MR imaging.

Assessment of dural arteriovenous fistulae by transcranial color-coded duplex sonography.

BACKGROUND AND PURPOSE: To study hemodynamic changes and to determine the value of contrast-enhanced transcranial color-coded sonography (TCCS) for the evaluation of dural arteriovenous fistulae (DAVF) before and after transcatheter embolization. METHODS: Twenty-four patients (mean age 61+/-11 years) with occipitally located DAVF were studied with contrast-enhanced TCCS using the transtemporal bone window in transverse-axial and coronal insonation planes. Blood flow velocity measurements of all depictable basal cerebral veins and sinuses were obtained before and after transcatheter embolization. Pretreatment and post-treatment flow velocity values were compared. RESULTS: Four of the 24 patients (17%) could not be studied because of an insufficient temporal bone window. In all remaining patients (n=20), draining veins/sinuses could be identified because of pathologically increased blood flow velocities with peak systolic flow velocities of >50 cm/s. Of the 27 draining vessels depicted by DSA, TCCS correctly identified 25 (93%): the basal vein (3 of 3), the straight sinus (3 of 3), the superior sagittal sinus (1 of 3), the transverse sinus (9), the sigmoid sinus (4), and the superior petrosal sinus (5/5). However, TCCS failed to depict supplementary drainage via cortical veins. After transcatheter embolization, mean reduction of blood flow velocity was 44+/-18% (P<0.01) compared with pretreatment values. CONCLUSIONS: Contrast-enhanced TCCS is a promising technique for monitoring embolization of DAVF, follow-up after complete fistula occlusion, and may even be useful as a screening tool in patients with pulsatile tinnitus.

Intracranial collateral pathways assessed by contrast-enhanced three-dimensional transcranial color-coded sonography.

Individual parameter settings of the duplex machine and limited insonation angles may influence the visualization of small intracranial vessels in 2-D transcranial color-coded sonography. The aim of our study was the morphologic assessment of intracranial collateral pathways (first auditory area celiac artery, A(1)CA; anterior communicating artery, AComA; first parental generation celiac artery P(1)CA; posterior communicating artery, PComA) using 3-D transcranial color-coded duplex sonography (3-D TCCS) and digital subtraction angiography (DSA). A total of 41 patients with large vessel disease and 30 patients who had suffered subarachnoidal hemorrhage (mean age 52 +/- 15 years) were involved. In all patients, angiography was performed within 10 days following 3-D sonography. The patients were investigated with a color-coded duplex system using the power mode. Contrast enhancement was achieved by continuous infusion of a galactose-based echo-enhancer using a perfusor pump. The 3-D system consists of an electromagnet that induces a low-intensity magnetic field near the head of the patient. A magnetic position sensor is attached to the ultrasound (US) probe and transmits the spatial orientation to a personal computer, which also receives the corresponding 2-D images from the video port of the duplex machine. Angiography revealed a "complete" circle of Willis in one third of the patients and, in the remaining patients at least one vessel was hypoplastic or absent. Sufficient temporal bone windows allowed the sonographic investigation of 466 (94%) of 497 expected arterial segments. The comparison of both techniques resulted in a weighted kappa value of 0.56 for the A(1)CA and 0.63 for the AComA. In the posterior circulation kappa values of 0.56 for the P(1)CA and 0.43 for the PComA were calculated. In 50 vessels (10%), 3-D sonography misdiagnosed the diameter of a collateral vessel as normal and angiography revealed hypoplasia or aplasia of this vessel. The main advantage of 3-D TCCS is that it enables the investigator to reconstruct virtually any arbitrary view angle. Compared with angiography or magnetic resonance (MR) angiography, 3-D sonography can be performed easily in critically ill patients on stroke units or intensive care units. The noninvasive assessment of the circle of Willis may be useful in patients who undergo carotid surgery without angiography. Combined with hemodynamic information, contrast-enhanced 3-D TCCS might increase the diagnostic impact of transcranial US.

Perfusion imaging of high-grade gliomas: a comparison between contrast harmonic and magnetic resonance imaging. Technical note.

Transcranial contrast harmonic (CH) imaging is emerging as a promising tool for the evaluation of brain perfusion. The authors report on two cases of histologically proven high-grade gliomas evaluated using CH imaging in comparison to perfusion magnetic resonance (pMR) imaging. In both cases, pMR imaging results demonstrated a massive decrease in signal intensity and an elevated regional cerebral blood volume (rCBV) in the tumor region; however, signal decrease was less prominent and rCBV was lower in healthy brain tissue. In one patient, the rCBV ratio of tumor/brain was 5.0 and the maximal signal decay occurred 3.1 times deeper in the tumor than in the healthy brain tissue. Results of an ultrasonography examination using CH imaging revealed similar data: the tumor/brain ratio for the area under the curve, a parameter corresponding to rCBV, was 4.1. The maximal signal intensity in the tumor was 3.3 times greater than in adjacent healthy brain. Comparable data were obtained in a second patient. Taken together, these findings indicate that CH imaging may be a valuable alternative to pMR imaging. This new, cost-effective bedside ultrasonic technique could be helpful not only as a means of noninvasive staging of gliomas but also as a follow-up imaging modality to evaluate postoperative tumor recurrence or response to antiangiogenic therapy.

Three-dimensional color-coded duplex sonography for assessment of the vertebral artery origin and vertebral artery stenoses.

OBJECTIVE: The aim of the study was to assess the potential of 3-dimensional (3D) color-coded duplex sonography (CDS) for evaluation of the vertebral artery origin and stenoses in this location. METHODS: To compare 2-dimensional (2D) and 3D CDS, both techniques were performed in 25 healthy volunteers and in 18 patients with 21 stenoses of the vertebral artery origin. Stenoses were graded in line with hemodynamic criteria on 2D CDS and according to North American Symptomatic Carotid Endarterectomy Trial criteria on 3D CDS. In 6 patients, digital subtraction angiography (DSA) was performed additionally. Stenoses were graded according to North American Symptomatic Carotid Endarterectomy Trial criteria and compared with 2D and 3D sonographic data. RESULTS: Overall correlation of both sonographic techniques concerning the grading of the stenoses was good (r = 0.69; P < .01). The interobserver correlation for assessment of stenoses by means of 3D CDS was high (r = 0.94; P < .01). Three-dimensional CDS correlated excellently with DSA in 3 of 6 patients but showed only intermediate or no correlation in the remaining 3 patients. In contrast, spatial information on the stenotic morphologic characteristics was always very comparable with the results obtained by DSA. CONCLUSIONS: Three-dimensional CDS represents a valuable tool for assessment of the origin of the vertebral artery, allowing important morphologic information on stenoses in this location. For grading of stenoses of the vertebral artery origin, 3D information should be combined with hemodynamic criteria obtained by spectral Doppler imaging in 2D CDS. Three-dimensional CDS could be a valuable tool before interventional procedures of the proximal vertebral artery, saving time and avoiding iodinated contrast agents.

Three-dimensional assessment of extracranial Doppler sonography in carotid artery stenosis compared with digital subtraction angiography.

BACKGROUND AND PURPOSE: Difficulties in data presentation, data storage, and a high interobserver variability may influence color-coded Duplex sonography assessment of internal carotid artery stenosis (ICAS). The aim of our study was to evaluate the between-method agreement of ICAS using 3D color Doppler sonography (CDS) compared with digital subtraction angiography (DSA). METHODS: Forty-nine patients with 64 ICASs (age 64+/-9 years) were involved. The patients were investigated with a color-coded duplex system using the power mode. The 3D system consists of an electromagnet that induces a low-intensity magnetic field near the patient's head. A magnetic position sensor is attached to the probe and transmits the spatial orientation to a personal computer. RESULTS: A total of 62 ICASs were reconstructed successfully with 3D CDS in 47 of 49 patients. High agreement for 2 independent observers was found in 3D CDS (weighted kappa coefficient of 0.88). Three-dimensional CDS slightly underestimated the mean stenotic degree (mean 3D CDS 68.47+/-10.5 versus DSA 71.3+/-10.0). The intermethod agreement comparing DSA with 3D CDS was analyzed with the Bland and Altman test, which showed good agreement. Mean sensitivity of 3D CDS was 93%, mean specificity 82.5%, mean positive predictive value 82%, and mean negative predictive value 98%. CONCLUSIONS: The 3D CDS findings demonstrated good agreement compared with the gold standard, DSA, yielding higher accuracy than CDS alone. Compared with angiography or magnetic resonance angiography, 3D CDS can be performed easily on critically ill patients in stroke or intensive care units and may therefore provide a useful tool for patients unable to undergo more invasive imaging techniques.

CT findings and clinical features as markers for patient outcome in primary pontine hemorrhage.

BACKGROUND AND PURPOSE: The overall mortality rate of primary pontine hemorrhage (PPH) in recent studies is 40-50%. The aim of the present study was to analyze the predictive value of clinical and neuroradiologic parameters concerning the outcome of patients with PPH. METHODS: We reviewed the clinical data of 29 consecutive patients (mean age, 59 +/- 13.5 years; 12 women, 17 men) with PPH. National Institutes of Health Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS) scores were assessed on admission, and NIHSS, GCS, and Glasgow Outcome Scale (GOS) scores were assessed on discharge. The hemorrhage volume was calculated by using a previously published formula. Clinical manifestations, outcome, and volume and location of the bleeding were correlated. RESULTS: The mean GCS score on admission was 6.8 +/- 3.9 and increased to 9.0 +/- 3.9 on discharge. The NIHSS score improved from 29.1 +/- 12.5 to 12.1 +/- 7.3. Nine patients (31%) died as a result of PPH after 5 +/- 3 days. The mean GOS score was 3.0 +/- 1.5 (3.9 +/- 0.8 for patients who survived). Arterial hypertension was the most common risk factor (90%); other causes were anticoagulation therapy (7%) and amyloid angiopathy (3%). A high correlation was observed between a poor outcome (GOS score < 4) and hematoma volume greater than 4 mL (P =.006), ventral hemorrhage (P <.001), and necessity for mechanical ventilation (P <.001). Patients with dorsally located hematomas less than 4 mL in volume had a significantly better outcome. CONCLUSION: The prognosis of PPH is better than commonly expected. Most patients with moderate neurologic deficits on admission and dorsally located small hematomas are able to survive PPH with minor neurologic deficits.

Second harmonic imaging of the human brain: the practicability of coronal insonation planes and alternative perfusion parameters.

BACKGROUND AND PURPOSE: Second harmonic imaging (SHI) is a novel ultrasound technique that allows the evaluation of brain tissue perfusion. The purpose of this study was to assess normal cerebral echo contrast characteristics in 3 regions of interest (ROIs) in the transverse axial and coronal insonation planes through the temporal bone window. Materials and Methods- SHI examinations were performed in 25 patients without cerebrovascular disease (aged 50+/-19 years) in a transverse axial and a coronal diencephalic insonation plane through the temporal bone window. After intravenous administration of 2.5 g (400 mg/mL) of a galactose-based echo contrast agent, 62 time-triggered images with a transmission rate of 1 frame per 2.5 seconds were recorded for offline analysis. Time-intensity curves, including peak intensity (PI) (dB) and positive gradient (PG) (dB/s), were calculated to quantify ultrasound intensity in 3 different ROIs in both planes of the following sections: the thalamus (ROI(thal)), the lentiform nucleus (ROI(ncl)), and the area supplied by the middle cerebral artery (ROI(mca)). RESULTS: Characteristic time-intensity curves with high PIs and steep PGs were recorded in each ROI. Statistical analysis of the aforementioned parameters showed no significant difference for comparison of the 3 ROIs in the transverse axial versus the coronal insonation plane. Comparison of different ROIs in the transverse axial insonation plane revealed that PI was significantly higher in ROI(thal) than in ROI(mca) (7.8 versus 5.5 dB; P<0.05) and significantly higher in ROI(ncl) than in ROI(thal) (9.3 versus 7.8 dB; P<0.05). In contrast, PG was comparable in ROI(thal) and in ROI(mca) (0.21 versus 0.25 dB/s; P=0.42). CONCLUSIONS: SHI is a promising technique for the evaluation of cerebral parenchymal perfusion. Comparison of the transverse axial and coronal insonation planes shows similar time-intensity curves with comparable values for PIs and PGs. Coronal insonation allows the evaluation of perfusion abnormalities near the vertex and skull base, areas that cannot be depicted in the transverse axial plane. Comparison of the different ROIs indicates that the PG is a more robust and reliable parameter than the PI.

Contrast-enhanced three-dimensional transcranial color-coded sonography of intracranial stenoses.

BACKGROUND AND PURPOSE: Intracranial stenoses are associated with a considerable number of strokes each year. The clinical value of a workstation-based three-dimensional (3D) reconstruction system for transcranial color-coded sonography was evaluated in patients with intracranial stenosis or occlusion. METHODS: Twenty-six patients (13 men, 13 women; mean age, 57 years +/- 12 [SD]) with 36 intracranial stenoses or occlusions, as detected at two-dimensional (2D) color Doppler imaging (CDI) and digital subtraction angiography (DSA), underwent Levovist-enhanced power Doppler imaging (PDI), with subsequent 3D reconstruction. A workstation connected to a magnetic sensor capable of spatial localization of the probe was used to reconstruct 3D images of the circle of Willis from serial PDI images. RESULTS: At DSA, seven (19%) stenoses were estimated to less than 50%, 24 (67%) were 50% or more, and five (14%) were occluded. DSA and 3D-PDI estimates of the degree of stenosis agreed in 33 cases (92%), with a weighted kappa value of 0.86. Disagreement occurred with two subtotal basilar artery stenoses and one subtotal middle cerebral artery stenosis, which were evaluated as being complete occlusions at 3D-PDI. Interobserver agreement between two experienced 3D investigators in estimating the percentage of stenosis was high (correlation coefficient,.98). CONCLUSION: 3D-PDI enables the investigator to reconstruct virtually any arbitrary viewing angle. Compared with conventional CDI, 3D-PDI offers easier spatial assessment of intracranial stenoses, and its findings are sufficiently correlated with angiographic findings. Because different investigators can postprocess the same 3D data, improving reproducibility and reducing investigator dependency in transcranial color-coded sonography may be possible.