[Cerebral vasculitis with delirium in neurosyphyllis]. / Lues-assoziierte zerebrale Vaskulitis mit delirantem Syndrom.

ANAMNESIS AND CLINICAL FINDINGS: In a 40-year-old man with delirium, right-sided facial palsy and anisocoria (right > left) were noticed. He had been suffering from headaches for four weeks prior to admission. The patient's HI-virus status was positive and he used illicit drugs regularly. Therefore, the symptoms were initially thought to be drug-induced. EXAMINATION AND DIAGNOSIS: Laboratory tests showed a pleocytosis of the cerebrospinal fluid (CSF) with 929 cells/µl. The MRI of the brain revealed several ischemic strokes in the territories of the middle cerebral artery and posterior cerebral artery in the left hemisphere. A highly positive IgG CSF/serum index confirmed the diagnosis of neurosyphilis. TREATMENT AND COURSE: An antibiotic regime with penicillin was administered, during which the clinical symptoms remitted and the liquor pleocytosis nearly normalized. The intracranial stenoses persisted for three months even after therapy with nimodipine, atorvastatin, and antibiotics. Therefore they are presumed to be a result of the lues-associated vasculitis. CONSEQUENCE: In patients with delirium the initially suspected underlying condition needs to be challenged. Early cerebral MRI, lumbar puncture and ultrasound of the cerebral arteries are mandatory to exclude menigoencephalitis.

[FEES in the stroke unit: recommendations for implementation in the clinical routine]. / FEES auf der Stroke-Unit : Empfehlungen zur Umsetzung im klinischen Alltag.

Dysphagia occurs in about 50 % of patients with acute stroke, is strongly related to early complications, such as aspiration pneumonia and is a major cause of increased morbidity and mortality in acute stroke. Flexible endoscopic evaluation of swallowing (FEES) has proven to be an easy to use, non-invasive tool for assessment of dysphagia in acute stroke, significantly adding accuracy to the clinical evaluation of dysphagia. With respect to the growing use of FEES in German stroke units this article summarizes recommendations for implementation and execution.A 3-step process is recommended to acquire the relevant knowledge and skills for carrying out FEES. After a systematic training (first step), swallowing endoscopy should be done under close supervision (second step) which is then followed by independent practice coupled with indirect supervision (third step). In principle, FEES should adopt a team approach involving both neurologists and speech language pathologists (SLP) or alternatively speech therapists. The allocation of responsibilities between these two professions should be kept flexible and should be adjusted to the individual level of education. Reducing the role of the SLP to mere assistance work in particular should be avoided. To enhance interprofessional communication and to allow for a smooth and efficient workflow, endoscopic grading of stroke-related dysphagia should adopt a standardized score that also includes protective and rehabilitative measures as well as nutritional recommendations. A major task for the future is to develop an educational curriculum for FEES that takes the specific needs of stroke unit care into account and is applicable to both physicians and SLPs.

[Billing based on a case-based lump sum for stroke. Did this lead to discharge of patients in a worse clinical condition?]. / Abrechnung mittels Fallpauschalen beim Hirninfarkt. Führte dies zu Entlassungen in klinisch schlechterem Zustand?

BACKGROUND: It has been supposed that the introduction of a new inpatient reimbursement system starting in 2004 in Germany using the German diagnosis-related groups (G-DRG) may lead to false incentives with encouragement of premature hospital discharge of patients. Exploring a large database on stroke patients, we addressed the question whether length of stay (LOS) and discharge in more severe condition were associated with the introduction of the G-DRG. We further examined other factors with probable effect on LOS such as variations of patient characteristics and treatment during the observation period. PATIENTS AND METHODS: All stroke patients treated in 2003-2006 in the German state of Hesse (6,100,000 inhabitants) were assessed with respect to stroke severity, symptoms on admission and discharge, LOS and stroke-related deficits on discharge. We compared LOS and outcome in 2003 (before introduction of the G-DRG) with 2004 when the G-DRG had recently been introduced and with 2006 when the G-DRG was already well established in the clinical routine. The effects of LOS and treatment year on outcome were assessed using a logistic regression model. RESULTS: During the observation period, we evaluated 37,396 stroke patients. The length of stay was reduced significantly from 12.2 to 10.4 days (p<0.001). Both severity of stroke on admission and outcome on discharge decreased during the observation period. A multivariate analysis revealed a minor but significant association [odds ratio (OR): 1.020 per day of hospital treatment; 95% confidence interval (CI): 1.016-1.024] of LOS on outcome. Treatment in 2006 compared to 2003 led to good outcome with an OR of 1.378 (95% CI: 1.279-1.485). Subgroup analysis limited to patients with severe stroke revealed that LOS was significantly lower in 2006 compared to 2003 also in this patient subgroup; moreover, the proportion of patients discharged with severe outcome was lower in 2006 compared to 2003. CONCLUSIONS: This study reveals a significant reduction of LOS during the years after introduction of the G-DRG. However, reduction of LOS was not associated with more severe outcome on discharge, possibly due to changes in stroke treatment implemented during the observational period. Our results do not support the conjecture that changes in the reimbursement system were associated with compromised patient care.

[Extradural lipomatosis after long-term treatment with steroids]. / Extradurale Lipomatose nach langjähriger Steroidbehandlung.

Epidural lipomatosis is a rare but severe complication of long-term corticoid treatment. A female who was treated with oral corticoids for more than 4 years developed progressive paraparesis over the course of 2 years. As causal for the clinical symptoms we found a massive epidural lipoma of the thoracic spine. Neurosurgical intervention was necessary.

[Cerebrovascular reserve capacity]. / Die zerebrovaskuläre Reservekapazität.

Cerebrovascular reserve capacity (CVR) describes how far cerebral perfusion can increase from a baseline value after stimulation. Measurement of cerebral blood flow (CBF) can be done by PET or SPECT. Noninvasive and easily performed transcranial Doppler sonography (TCD) is mostly used as indirect perfusion measurement. Stimulation of cerebral perfusion is often done by CO2 inhalation or acetazolamide injection. Alternative stimuli are breath holding or cerebral activation by hand-gripping. Normal values for these tests are presented. The hemodynamic effect of stenoses of the internal carotid artery (ICA) can be estimated using CVR. The relevance of CVR is discussed controversially, since cerebral infarction due to stenosis of arteries supplying the brain is probably mostly of embolic, not hemodynamic origin. The indication for carotid artery surgery according the NASCET and ECST investigations takes into account only the degree of the stenoses and not the CVR. According to recent studies, the risk of cerebral infarction in these patients is considerably higher with reduced CVR. Therefore, CVR can be used as an additional parameter if the indication for surgery is not defined, especially in asymptomatic carotid artery stenosis. It seems also possible to identify patients who might profit from an extra-intracranial bypass operation and high-risk patients for cerebral ischemia with cerebral microangiopathy. Furthermore, the risk of cerebral infarction during carotid artery surgery and also during heart surgery can be estimated using CVR. More studies with a higher number of patients are needed to confirm the potential predictive diagnostic value of CVR in order to establish CVR measurement as part of a routine diagnostic neuroangiologic program.

A gelatin in situ-overlay technique localizes brain matrix metalloproteinase activity in experimental focal cerebral ischemia.

To determine the activity of matrix metalloproteinases (MMP), especially MMP-2 and MMP-9, which play an important role in ischemic stroke and intracerebral hemorrhage, we adapted a simple and rapid method for localizing gelatinase activity to a gelatin film in situ-overlay technique previously used in cancer research. Ten micrometer cryosections of rat brain from controls and animals subjected to 3 h of ischemia and 48 h of reperfusion (suture model for transient cerebral ischemia) were used. After thawing, a gelatin film with a polyester base was put on the slide, incubated for 24 h at 37 degrees C, stained with Ponceau S, and then discolored in bi-distilled water. Non-staining areas on the film corresponded to lysis zones, caused by activated MMPs. This was proven by MMP incubation at various concentrations on the plain gelatin film and pretreatment with EDTA (an MMP inhibitor), which prevents lysis zones in normal and ischemic brains. As confirmatory tests, SDS-PAGE zymography was used to define MMP activity, and also MMP-2 immunohistochemistry to detect the possibly cellular origin of MMPs. Normal rat brain exhibited a low background activity, which was visible as a light halo-like lysis zone over and around the brain. Areas in normal brain with medium MMP activity were within the white matter (corpus callosum, anterior commissure, and cerebellum). Ischemic brain exhibited high activity lysis zones within the infarcted area (detected by microtubuli associated protein-2 staining). These zones consisted of microscopically small lysis holes with a diameter of about 10-20 microm. Immunohistochemistry showed that especially microvessels expressed MMP antigen. SDS-PAGE zymography differentiated between a high level of activated MMPs in the ischemic area and a low level in the non-ischemic basal ganglia. The gelatin film in situ-overlay technique is able to localize MMP activity in ischemic rat brain tissue on a microscopic level.

Reduced cerebrovascular CO(2) reactivity in CADASIL: A transcranial Doppler sonography study.

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukencephalopathy (CADASIL) is a hereditary angiopathy caused by mutations in Notch3. Cerebral microvessels show an accumulation of granular osmiophilic material in the vicinity of degenerating vascular smooth muscle cells. To study cerebrovascular function in CADASIL, we performed measurements on cerebral hemodynamics by using transcranial Doppler sonography. METHODS: Middle cerebral artery (MCA) mean blood flow velocity (MFV), cerebrovascular CO(2) reactivity, and the resistance index were measured by bilateral transcranial Doppler sonography in 29 CADASIL individuals (mean age, 49.0+/-2.4 years) and an equal number of age- and sex-matched control subjects. RESULTS: Compared with control subjects, CO(2) reactivity was reduced in CADASIL (33.4+/-2.7% versus 45.3+/-3.0%; P:<0.01). This difference remained significant when only nondisabled CADASIL individuals (Rankin=0, n=21) were included in the analysis (P:<0.05). CO(2) reactivity was significantly lower in disabled than in nondisabled CADASIL individuals (24.5+/-2.7% versus 36.8+/-3.4%; P:<0.05). MCA MFV was reduced in CADASIL (45.6+/-2.2 cm/s versus 54.2+/-2.4 cm/s; P:<0.05) and correlated negatively with age both in affected individuals (r=-0.314; P:<0.05) and control subjects (r=-0.339; P:<0.05). Resistance index was not significantly altered (59.0+/-1.0% versus 57.7+/-1.2%; P:=0.42). CONCLUSIONS: In CADASIL, there is a reduction of both CO(2) reactivity and basal MCA MFV. The reduced CO(2) reactivity suggests functional impairment of cerebral vasoreactivity probably related to vascular smooth muscle cell dysfunction. The reduction of CO(2) reactivity in nondisabled CADASIL individuals suggests an early role of impaired cerebral vasoreactivity in the evolution of the disease.

Intravenous immunoglobulins in the therapy of paraneoplastic neurological disorders.

The treatment of paraneoplastic neurological syndromes (e.g., tumor therapy, immunosuppressive therapy, plasmapheresis) rarely leads to an improvement in the neurological symptoms. We treated four patients suffering from paraneoplastic neurological syndromes with intravenous immunoglobulins. All four had high titers of antineuronal antibodies in serum and CSF. Two of the patients, one suffering from paraneoplastic cerebellar degeneration and the other from paraneoplastic brain stem encephalitis and polyneuropathy, received intravenous immunoglobulin treatment within 3 weeks of the onset of neurological symptoms. Both patients showed clinical improvement within 2 weeks after the initiation of therapy. They also showed a decline in the intrathecal antibody synthesis of the antineuronal antibody. Two other patients, who had suffered from paraneoplastic neuropathy for 3 and 6 months showed no improvement with the intravenous immunoglobulin therapy. In these cases there was no effect on intrathecal antibody synthesis. When started early, intravenous immunoglobulins may be of therapeutical value in treating paraneoplastic neurological syndromes. Specific intrathecal antibody synthesis may be a better measure of clinical course that autoantibody serum titers.

Integrin alphavbeta3 is expressed in selected microvessels after focal cerebral ischemia.

The endothelial and smooth muscle integrin alphaVbeta3, a receptor for vitronectin and fibrinogen, participates in angiogenesis associated with wound healing and tumorigenicity. The microvascular expression of alphavbeta3 and fibrin during experimental middle cerebral artery occlusion and reperfusion in a nonhuman primate model was examined by computer-assisted video imaging microscopy. No microvascular expression of alphavbeta3 was seen in the control subjects (n = 3) or the non-ischemic basal ganglia of subjects undergoing 2-hour MCA:O (middle cerebral artery occlusion) or 3-hour occlusion with 1-hour (n = 3), 4-hour (n = 3), and 24-hour (n = 3) reperfusion. In the ischemic territory, alphavbeta3 appeared initially at 2 hours of middle cerebral artery occlusion. Up-regulation of alphavbeta3 was confined to the media of 30.0- to 50.0-micron-diameter arterioles in the ischemic core and correlated significantly with fibrin deposition in those vessels (P < 0.0005). Integrin alphavbeta3 and its ligand fibrinogen appear in a subpopulation of microvessels after focal cerebral ischemia.

Somatostatin-like immunoreactivity, its molecular forms and monoaminergic metabolites in aged and demented patients with Parkinson's disease--effect of L-Dopa.

There is some evidence that Parkinson's disease (PD) seems to be a heterogenous and generalized brain disorder reflecting a degeneration of multiple neuronal networks, including somatostatinergic neurons. Somatostatin-like immunoreactivity (SLI) and its molecular forms, high molecular weight form (HMV-SST), somatostatin-14 (SST-14), somatostatin-25/28 (SST-25/28) and Des-ala-somatostatin (Des-ala-SST), as well as homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were estimated using HPLC and radioimmunoassay in the cerebrospinal fluid (CSF) of 35 aged parkinsonian patients with different stages of intellectual deterioration. The influence of L-dopa-treatment on these neurochemical parameters was evaluated. Without a correlation with dementia scores (p = 0.11), SLI was significantly reduced in PD in comparison to the control group (p < 0.05). The reduction was related to the progression of the disease. Correlations between SLI, HVA and 5-HIAA indicate a heterogenous brain disorder in PD with alterations of several transmitter systems and functions. Complex qualitative and quantitative changes in the molecular pattern of SLI are compatible with a dysregulated synthesis and/or posttranslational processing. L-dopa-treatment was associated with a significant increase of HVA (p < 0.05) and HMV-SST (p < 0.05) and a slight, but insignificant increase of SLI (p = 0.11).