Effects of ameliorated haemorheology on clinical symptoms in cerebrovascular disease.

Cerebrovascular disease (CVD) is associated with high fibrinogen levels and lipid fractions leading to an increase of both plasma and whole blood viscosity as well as raised aggregability of blood cells. One important goal in the treatment of cerebral multiinfarct dementia (MID) therefore should be to reduce fibrinogen and lipoproteins and thereby to improve the haemorheological state. The effect of heparin-induced extracorporeal LDL precipitation (H.E.L.P.), a method for safe and immediate reduction of parameters relevant to haemorheology, such as plasma fibrinogen and the lipoproteins, was investigated in 98 patients with MID. All the patients underwent two H.E.L.P. applications within 8 days. The impact of H.E.L.P. on CVD was studied by changes of laboratory data and by evaluation of clinical symptoms before and after treatment. Each H.E.L.P. session caused an immediate, safe and significant reduction of important rheological parameters such as fibrinogen (P < 0.001), whole blood viscosity at high and low shear rate, plasma viscosity and red cell transit time (P < 0.01 each). Also total cholesterol and low density lipoprotein (P < 0.0001 each), lipoprotein (a) (P < 0.003) and the triglycerides (P < 0.0001) had been reduced. The results in laboratory measurement were followed by a statistically significant improved neurologic recovery, represented in the values of the Mathew Scale, the Mini Mental State Examination and the Activities-of-Daily-Living-Test. These results can indicate the importance and influence of haemorheology on clinical symptoms in CVD.

Heparin-induced extracorporeal fibrinogen/LDL precipitation (HELP): a promising regimen for the treatment of vascular diseases.

Current management of atherosclerotic diseases consists primarily of medical therapy designed to increase oxygen supply to the heart, the brain, retinal vessels, or lower limbs. The development of these diseases is based on atherosclerotic changes induced by risk factors such as elevated levels of fibrinogen and lipoproteins. These risk factors are related to a dramatic deterioration of the hemorrheologic pattern, which reduces perfusion. Consequently, attempts are now being made to treat ischemia via hemorrheological intervention. A new treatment modality utilizing the heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP), offers the possibility of obtaining therapeutic success not only in cases of severe hypercholesterolemia but also in the field of hemorheology. With HELP a safe and rapid reduction of fibrinogen and lipid fractions has become feasible, thus providing acute improvements of red cell aggregation, of the filterability of blood cells, of whole-blood and plasma viscosity, and thereby of microcirculation. Because cerebrovascular diseases are known to be related to disturbances of the hemorrheological situation, the HELP system is used in the Department of Electrobiology of Graz for the treatment of acute stroke, cerebral multi-infarct disease, and occlusions of retinal arteries.

Application of HELP in nonarteritic anterior ischemic optic neuropathy: a prospective, randomized, controlled study.

BACKGROUND: Heparin-induced extracorporeal LDL/fibrinogen precipitation (HELP) eliminates selectively fibrinogen, LDL, cholesterol, triglycerides and LP(a) from blood plasma using extracorporeal circulation. The reduction of fibrinogen and LDL by about 50% after only one procedure immediately improves the hemorheological situation. METHOD: In a prospective, randomized, controlled study over a period of 3 months, 40 patients with nonarteritic ischemic optic neuropathy (NAION) were randomly assigned to either HELP or hemodilution therapy to determine the efficacy of these two treatments on visual acuity and fields. RESULTS: After transformation of the Snellen acuity into logMAR units the statistical analysis did not show a significant difference between the two groups (P = 0.48). An increase of the visual acuity by two or more lines was obtained in 9 patients (47.4%) of the HELP group, 10 (52.6%) remained stable and none got worse. In the hemodilution group, visual acuity increased in patients (33.4%), 9 (42.8%) remained stable and 5 (23.8%) experienced a decrease. The calculated mean sensitivity of visual fields at baseline improved statistically significantly (P < 0.01) in the HELP group from 6.83 +/- 4.52 dB to 8.27 +/- 4.89 dB, but did not change significantly in the hemodilution group (6.25 +/- 4.12 dB to 6.12 +/- 3.92 dB). CONCLUSION: The HELP system seems to be safe and more effective than hemodilution in improving the hemorheological and the functional situation in NAION and could be a promising regimen in the treatment of NAION.

Influence of a single HELP application on hemorheology and retinal hemodynamics.

The heparin-induced extracorporeal low-density lipoprotein precipitation (HELP) eliminates selectively fibrinogen, total cholesterol, low-density lipoproteins (LDL) and triglycerides and improves hemorheology. We investigated the hemodynamic changes in 10 patients without ocular diseases performing a video fluorescein angiography after a single HELP procedure measuring the arm-retina time (ART) and the arteriovenous passage time (AVP). Laboratory parameters such as fibrinogen, cholesterol, LDL, triglycerides, red cell transit time, plasma and whole-blood viscosity were determined and retinal circulation was measured immediately before and after the HELP application. All of the laboratory parameters were lowered significantly. The ART was unaffected by the HELP procedure; however, there was a significant AVP reduction from 2.41 +/- 0.49 to 1.97 +/- 0.47 (p < 0.005). These results support the hemorheological and hemodynamic efficiency of the HELP system in microcirculatory diseases.

Increased cerebral perfusion following reduction of fibrinogen and lipid fractions.

High levels of plasma fibrinogen in cerebrovascular disease cause deterioration in the hemorheologic pattern, microcirculation and cerebral perfusion. We compared the value of heparin-induced extracorporeal LDL precipitation (HELP) which is a method that safely and effectively reduces plasma fibrinogen and lipoproteins and so improves the hemorheologic pattern and blood flow properties. Regional cerebral blood flow (rCBF) was measured by the 133Xe SPECT clearance method. After first measuring rCBF, 15 patients suffering from cerebral multi-infarct disease underwent a single HELP application. One hour later a second measurement of rCBF was performed. Fifteen other patients with similar clinical symptoms and findings on CAT scans who were not subjected to HELP served as controls. The HELP treatment produced an immediate and statistically significant reduction of all parameters relevant to hemorheology, such as plasma fibrinogen, whole blood viscosity at both high and low shear rate, plasma viscosity, and red cell transit time. Total cholesterol, low density lipoprotein, and triglycerides were also reduced. The treated group showed 9.7-19.9% increased rCBF in different vascular regions examined relative to the untreated controls. The results obtained indicate that HELP has a potent effect in a situation demanding rapid and significant improvement of the blood flow.

Extracorporeal fibrinogen and platelet precipitation as a new haemorheological treatment for acute stroke.

In thromboembolic brain infarctions high fibrinogen levels are associated with an increase of both plasma and whole blood viscosity as well as increased aggregability of blood cells. This decreases cerebral perfusion and might reduce blood flow in the penumbra surrounding infarction. An important goal in the treatment of acute cerebral infarction is to reduce fibrinogen and thereby improve the haemorheological state. Heparin-induced extracorporeal low-density lipoprotein/fibrinogen precipitation (HELP) appears to be successful in achieving this. Such treatment reduces lipid fractions, including total cholesterol, low-density lipoproteins (LDL) and triglycerides (p < 0.0001 each), as well as fibrinogen (p < 0.0001) in a safe and efficacious manner. Whole blood and plasma viscosity are also improved when measured by oscillo-rheometry. Furthermore, the number and aggregation tendency of blood cells is influenced positively as determined by Coulter counting and aggregometry. HELP improves the haemorheological profile to a degree which has not been achieved by haemorheologically active substances.

[Heparin-induced extracorporeal LDL precipitation (H.E.L.P.). A new therapeutic possibility in vascular occlusion of the retina--initial results]. / Heparin-induzierte extrakorporale LDL-Präzipitation (H.E.L.P.). Eine neue Therapiemöglichkeit bei Gefässverschlüssen der Netzhaut--Erste Ergebnisse.

Heparin-induced extracorporeal LDL precipitation (HELP) eliminates selectively fibrinogen, LDL cholesterol, cholesterol, triglycerides and LP(a) from the blood plasma using extracorporeal circulation. The reduction of fibrinogen and LDL about 50% after only one procedure immediately improves the hemorrheological situation, which has so far not been achieved by any hemorrheologically active substance. Five patients (1 central retinal vein occlusion, 3 branch vein occlusions, 1 central arterial occlusion) ranging from 59-76 years underwent HELP treatment six times over a 5-week period. After the first HELP procedure the fibrinogen was lowered from 278 +/- 57.8 to 157 +/- 22.2 mg/dl and LDL from 162.2 +/- 58 to 82.4 +/- 32.5 mg/dl. Plasma viscosity decreased from 1.3 +/- 0.07 to 1.1 +/- 0.05 mPa/s. At the end of the treatment an increase in visual acuity of 3 or more lines and an improvement in the visual field was seen in all patients. Measurements of the arteriovenous passage time with laser scan video fluorescein angiography before and at the end of the therapy showed a significant decrease from 3.5 +/- 1.59 to 2.88 +/- 1.54 s (P < 0.05) without influencing the arm-retina time. This first clinical and hemorrheological data on the HELP procedure in retinal vessel occlusion demonstrate a promising regimen in the treatment of acute retinal microcirculatory diseases.

EEG mapping--a new way of monitoring in epilepsy.

A method for comparison of EEG mapping findings on the basis of numeric data, i.e. the numeric power values measured at the electrode sites for each frequency band, is described. Examples for the clinical use of comparison studies in epileptic patients are given. The problems regarding methodological issues are discussed.

Role of long-term EEG monitoring in diagnosis and treatment of epilepsy.

The value of long-term EEG recordings for diagnosis and differential diagnosis of epilepsy is described. It is emphasized that long-term EEF monitoring increases the scope of EEG techniques and improves the diagnostic value of standard EEG recordings providing up to 90% positive diagnostic information. In particular, the value of ambulatory cassette recording is stressed. Allowing quantification of epileptic activity recorded in real-life situation, useful information not available by means of standard EEG recordings can be obtained. Recording and scoring all-night sleep, it enables studying abnormalities of sleep patterns. In addition the value of long-term EEG recordings in therapy and control of epileptic patients is pointed out and discussed.

A new type of database of antiepileptic medication for everyday use.

AED InfoBase, a first concept for a personal computer based database with an adequate design for everyday use is presented. AED InfoBase operates under a hypertext control program. At present it provides information about pharmacodynamics, pharmacokinetics, side effects and availability of drugs on the market of first choice anticonvulsives. A certain accent is put on drug interactions and drug therapy in epileptics.

Results of a two-month follow-up after single heparin-induced extracorporeal LDL precipitation in vascular dementia.

A trial was undertaken with 44 patients with the diagnosis of cerebral multi-infarct dementia. Of these, 24 had been exposed to single heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP) whereby an immediate, safe, and statistically significant reduction of total cholesterol, LDL, triglycerides, fibrinogen (<0.0001 each), lipoprotein (a) (p < 0.003), whole-blood viscosity (p < 0.005 at high shear and p < 0.007 at low shear rate), plasma viscosity (p < 0.0002) and red cell transit time (p < 0.0001) to between 17.9% and 58.8% could be obtained within 2 h. Even an amelioration in the neuropsychological state, objectified by the Mathew Scale (p < 0.01), the Mini-Mental State Examination (p < 0.03), and the Activities-of-Daily-Living Test (p < 0.05) was observed. Despite the fact that the laboratory parameters had reached their pretreatment values within 10 days after the HELP procedure, the scores of the test battery remained stable during a follow-up period of 2 months. Within a control group (n = 20), no changes in laboratory data or in test scoring could be observed.

[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)

Improved neurological recovery of cerebral infarctions after plasmapheretic reduction of lipids and fibrinogen.

BACKGROUND AND PURPOSE: High fibrinogen levels have been assessed in cerebrovascular disease with a direct relation to both plasma and whole-blood viscosity, as well as cerebral blood flow. Heparin-induced extracorporeal low density lipoprotein precipitation (HELP) is a new method that safely and effectively reduces fibrinogen and plasma lipoproteins and improves blood flow properties. METHODS: We studied 26 patients with acute embolic stroke and 22 with multi-infarct dementia. Each received two treatments with HELP within 8 days. Each patient had measurement of the important blood constituents and evaluation of changes in clinical signs and symptoms related to their cerebrovascular disease. RESULTS: Each HELP treatment safely produced an immediate and significant reduction in rheological measures, including fibrinogen (P < .001), whole-blood viscosity at high and low shear rates, plasma viscosity, and red cell transit time (P < .01 each). Total cholesterol, low density lipoprotein (P < .0001 each), lipoprotein(a) (P < .003), and triglycerides (P < .0001) were also reduced. The treated group in both the acute stroke group and the multi-infarct group showed improvement relative to the untreated control subjects in Mathew scale, Mini-Mental State Examination, and activities of daily living test scores. These uniform improvements persisted at least 3 days past the second HELP treatment. CONCLUSIONS: These results support the hypothesis that the improved hemorheologic property of blood is an important factor in clinical recovery as well as basic neurological function.

First experiences with the heparin-induced extracorporeal low-density lipoprotein precipitation in the treatment of critical limb ischaemia: a new therapeutical approach?

The heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP) system is based on the fact that besides lipoproteins even fibrinogen, which seems to be a very important factor in pathogenesis of peripheral arterial disease, is precipitated by high-dose heparin at acid pH values. The elimination of excess fibrinogen and lipoproteins, in particular LDL, leads to a markedly improved microcirculation. The restoration of the latter obviously enabled us to perform limb-saving surgical procedures instead of mutilating amputations. 12 patients suffering from peripheral arterial disease were submitted to 18 HELP treatments in each case instead of having their critically ischaemic legs removed. Surgery could be limited to necrosectomy only and the wounds were either primarily sutured or covered with skin grafts. We were able to avoid 13 amputations in these 12 patients who could finally walk out of the hospital. HELP treatment was free of side effects in all of them.

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)

[Heparin-induced extracorporeal LDL precipitation (HELP): a new therapeutic intervention in cerebrovascular diseases and peripheral arterial occlusive disease]. / Heparin-induzierte extrakorporale LDL-Präzipitation (HELP): eine neue therapeutische Intervention bei zerebrovaskulären Erkrankungen und peripherer arterieller Verschlusskrankheit.

Coronary heart disease, stroke and peripheral arterial disease are the major causes for death and disability in industrialized countries. These diseases have a common cause: Their development is based on atherosclerotic changes of blood vessels, induced by risk factors such as elevated values of lipoproteins and fibrinogen. There is no doubt that the risk factors mentioned above are even related to a dramatically deterioration of the hemorheologic pattern, thus reducing perfusion. Due to this massage there are attempts to treat ischemia via hemorheological intervention. Although a number of different methods is available--hemodilution, defibrinogenation or oral medication--it was not possible to improve the hemorheologic pattern fast, safe, and efficient to date. A new treatment modality, utilizing the heparin-induced extracorporeal LDL precipitation (HELP), now offers the possibility to obtain therapeutical success not only in cases of severe hypercholesterolemia but even in the field of hemorheology: Using HELP a safe and rapid reduction of lipid fractions and fibrinogen has become feasible, thus providing an acute improvement of red cell aggregation and filterability of blood cells, whole blood and plasma viscosity and thereby of microcirculation. As it is known that cerebrovascular diseases are related to disturbances of the hemorheological situation, the HELP system is used at the Department of Neurology, Karl-Franzens University of Graz, for the treatment of acute stroke, cerebral multi-infarct disease but even in cases of peripheral arterial disease.(ABSTRACT TRUNCATED AT 250 WORDS)

[Association between fibrinogen and blood sedimentation rate in combined extracorporal and fibrinogen reducing drug therapy]. / Die Assoziation zwischen Fibrinogen und Blutsenkungs-Geschwindigkeit bei kombinierter extrakorporaler und medikamentöser fibrinogensenkender Therapie.

Fibrinogen appears to play an important role in atherogenesis, whereby high levels of fibrinogen can lead to a disturbance of the haemorheologic pattern. To evaluate the association between fibrinogen and blood sedimentation rate (BSR) 40 patients suffering from cerebral multi-infarct disease underwent a single heparin-induced extracorporeal LDL < fibrinogen > precipitation (HELP). Subsequently they were randomly assigned to two groups, either receiving sustained-release bezafibrate 400 mg daily (n = 21) or placebo (n = 19) over a period of eight weeks. HELP led to a statistically significant reduction of fibrinogen (p < 0.0001). At the end of the trial the difference between the bezafibrate group and the controls became significant (p < 0.05). The BSR strictly followed the course of fibrinogen, indicating a significant reduction after HELP (p < 0.0001 for both BSR values) and a difference between both groups at the end of the study (p < 0.05 and p < 0.03, respectively). The correlation between fibrinogen and BSR remained significant during the whole trial.

Reopening of internal carotid artery occlusions during heparin-induced LDL precipitation (H.E.L.P.) associated with improved haemorheology: report of 2 cases.

As has already been reported, there is a direct relationship between the severity of cerebrovascular insufficiency and elevated plasma fibrinogen levels, as well as whole blood and plasma viscosity, Red Cell Transit Time (RCTT) and cerebral blood flow. By applying heparin-induced extracorporeal LDL < cholesterol, triglycerides, fibrinogen > precipitation (H.E.L.P.), a rapid reduction of fibrinogen has become possible which has proved to be very beneficial for the treatment of acute stroke and multi-infarct disease. The present report demonstrates the impact of H.E.L.P. in connection with Doppler and Duplex sonography: In one patient a complete occlusion at the origin of the right internal carotid artery was revealed by Doppler and Duplex sonography. In a second patient, a complete occlusion of the left internal carotid artery was verified. By applying H.E.L.P. once a week (seven times in patient #1, twelve times in patient #2), a consistent lowering of fibrinogen, whole blood and plasma viscosity, red cell transit time, total cholesterol, low density lipoprotein, lipoprotein (a) and triglycerides was achieved. After H.E.L.P. application, Doppler/Duplex sonography showed complete reopening of the previously occluded vessel in patient #1 and patency of the vessel of patient #2.