Helga Frank

Decrease of blood pressure by ventrolateral medullary decompression in essential hypertension

BACKGROUND About 20% of adults worldwide will develop hypertension. Studies and clinical observations suggest an association between hypertension and pulsatile compression of the ventrolateral medulla oblongata by a looping artery. We investigated whether neurosurgical microvascular decompression substantially decreases blood pressure long-term in patients with severe essential hypertension. METHODS We included eight patients who had received three or more antihypertensive drugs without adequate control of blood pressure, intolerable side-effects, or both. All patients underwent microvascular decompression at the root-entry zone of cranial nerves IX and X after neurovascular compression of the ventrolateral medulla oblongata was seen on magnetic-resonance angiography. FINDINGS 3 months after surgery, blood pressure and antihypertensive regimens had decreased substantially in three patients. Four patients who were followed up for more than 1 year became normotensive, but their antihypertensive regimens remained the same as those at 3 months. One patient did not improve. No complications associated with decompression occurred. One patient experienced a transient vocal-cord paresis after the laryngeal part of the vagus nerve was manoeuvered during surgery. INTERPRETATION We showed a direct causal relation between raised blood pressure and irritation of cranial nerves IX and X. A subgroup of patients with essential hypertension may exist who have secondary forms of hypertension related to neurovascular compression at the ventrolateral medulla and who may be successfully treated with decompression.

Pregnancy‐induced sympathetic overactivity: a precursor of preeclampsia*

Background  Preeclampsia has been shown to constitute a state of sympathetic overactivity. However, it remains unclear if the sympathetic activity precedes preeclampsia or represents only a secondary phenomenon. To further investigate this issue, we performed a prospective study in pregnant women considered to be at increased risk for preeclampsia owing to preeclampsia during a preceding pregnancy.

Temporary Reduction of Blood Pressure and Sympathetic Nerve Activity in Hypertensive Patients After Microvascular Decompression

Background and Purpose— Experimental studies suggested neurovascular compression of the brain stem as a cause of hypertension. The aim of our prospective study was to investigate the effect of microvascular decompression in patients with severe hypertension with neurovascular compression on blood pressure and central sympathetic nerve activity in the long-term. Methods— Fourteen patients (4 males; mean age, 46±8 years) with essential hypertension underwent microvascular decompression of the brain stem. Vasoconstrictor muscle sympathetic nerve activity (recorded by microneurography: burst frequency, bursts/min) and blood pressure (24-hour profiles) were investigated before surgery and 7 days, 3 months, and every 6 months postoperatively. Results— Muscle sympathetic nerve activity was preoperatively elevated and decreased significantly postoperatively (35±13 bursts/min vs 20±9 bursts/min; P<0.01). Sympathetic activity remained reduced 3 months (19±8bursts/min; P<0.01), 6 months (19±7 bursts/min; P<0.01), and 12 months (23±9 bursts/min; P<0.01) postoperatively. However, in the long-term, sympathetic nerve activity increased again (18 months after surgery: 28±10 bursts, not significant; 24 months postoperatively: 34±12 bursts/min, not significant). Systolic and diastolic blood pressure decreased from 162±6/98±5 mm Hg preoperatively to 133±6/85±4 mm Hg (7 days postoperatively; P<0.01); 136±5/86±4 mm Hg (3 months postoperatively; P<0.01); 132±4/85±4 mm Hg (6 months postoperatively; P<0.01); 132±3/85±5 mm Hg (12 months postoperatively; P<0.01); 132±5/84±5 mm Hg; P<0.01). Twenty-four months after microvascular decompression, blood pressure increased again up to 158±7/96±6 mm Hg, corresponding to the sympathetic nerve activity course. Conclusion— Sympathetic nerve activity and blood pressure are temporary reduced by microvascular decompression in patients with severe hypertension with neurovascular compression. The data are a hint for sympathetic overactivity as a pathomechanism in this subgroup of patients.

Cardiovascular Effects of Beta-Blockers with and without Intrinsic Sympathomimetic Activity

Background: Celiprolol, a newer beta-blocking agent, has been reported to have vasodilatory capacity which may be due to partial beta-2-receptor agonistic activity or to alpha-receptor antagonistic or central sympathoinhibitory effects. Methods: To more critically assess the physiologic effects of celiprolol, we measured sympathetic nerve activity to muscle (MSNA), forearm blood flow (FBF), blood pressure (BP), central venous pressure, and heart rate (HR) in 10 normal volunteers at rest, during unloading of cardiopulmonary baroreceptors with lower body negative pressure (LBNP), and during a cold pressor test (CPT). Responses were compared with those seen with metoprolol and with placebo, i.e. each subject was studied three times. Results: Celiprolol did not alter resting levels of hemodynamics, FBF, and MSNA nor did it alter responses to LBNP or the CPT. In contrast, metoprolol produced significant decreases of FBF and HR, and increases of forearm vascular resistance and BP, but had also no effect on responses to the applied stress tests. Conclusions: The lack of peripheral vasoconstriction seen after acute administration of celiprolol is most likely due to its partial beta-2-receptor agonistic effect and does not seem to be due to a central or reflex action or to an alpha-blocking effect. Both beta-blockers do not impair fundamental neural mechanisms involved in circulatory homeostasis.

Ungewöhnliche Ursache einer hepatorenalen Symptomatik

Zusammenfassung□ FallbeschreibungBei einem 65jährigen normotensiven Patienten besteht seit August 1994 eine isolierte Erhöhung der Cholestaseparameter (alkalische Phosphatase 297 U/1, γ-GT 315 U/l) und des Serumbilirubins (1,4 mg/dl). Im März 1995 erfolgte eine Leberbiopsie, die einen Verdacht auf eine subakute virusinduzierte Hepatitis (Serologie: HBs-Antigen negativ, Anti-HBs und Anti-HBc positiv) ergab; differentialdiagnostisch wurde eine medikamentös-toxische Läsion angenommen. In einer ER CP vom April 1995 wurde ein Verdacht auf eine Papillitis stenosans geäußert, die in einer Kontroll-ER CP vom Mai 1995 nicht bestätigt wurde; es zeigte sich sonographisch kein Hinweis auf gestaute intra- oder extrahepatische Gallenwege. Im November 1995 kam es zu einem Anstieg des Serumkreatinins auf 1,7 mg/dl (März 1995 1,1 mg/dl) mit einer Proteinurie von 2,1 g/die. Wegen progredienter Erhöhung des Serumkreatinins auf 2,8 mg/dl und einer unselektiven Proteinurie von 3,5 g/die führten wir eine Nierenbiopsie durch. Hierbei gelang der histologische Nachweis einer ausgeprägten glomerulären, vaskulären und geringer ausgeprägt auch peritubulären Aλ-Amyloidose. Auch aus Biopsaten der Magen- und Duodenalschleimhaut zeigten sich deutliche Amyloidablagerungen. Aufgrund dieser Befunde erfolgte eine Nachfärbung des Leberbiopsats vom März 1995 mit Kongorot, wobei sich hier ebenfalls Ablagerungen von Amyloid nachweisen ließen. Mittels einer Beckenkammbiopsie konnte schließlich ein niedrigmalignes Non-Hodgkin-Lymphom (Immunozytom) als Ursache für diese generalisierte Amyloidose verifiziert werden.□ DiskussionDie Beteiligung von Leber und Nieren bei systemischer Amyloidose ist bekannt. Im vorliegenden Fall eines Patienten mit länger bestehender intrahepatischer Cholestase ungeklärter Ursache und einer im Verlauf progredienten Niereninsuffizienz ließ sich durch Nierenbiopsie und retrograde Aufarbeitung der ein Jahr zuvor durchgeführten Leberbiopsie die Diagnose einer systemischen Amyloidose stellen und damit die Genese einer ungewöhnlichen hepatorenalen Symptomatik klären. Ursächlich liegt ein niedrigmalignes Non-Hodgkin-Lymphom vor, wobei die Produktion monoklonaler Immunglobulin-Leichtketten zu einer generalisierten Amyloidose vom Typ Aλ führte.□ SchlußfolgerungBei diesem Patienten führte die ungewöhnliche Erstmanifestation einer Cholestase erst durch die nachfolgende Entwicklung einer Nierenfunktionsstörung zur Diagnosestellung einer Amyloidose. Daher sollte bei unklarer hepatorenaler Symptomatik eine Amyloidose in die Differential-diagnostik einbezogen werden.Abstract□ Case ReportA 65-year-old patient with normal blood pressure had an exclusive elevation of the cholestasis enzymes (alkaline phosphatase 297 U/l, γ-GT 315 U/l) and elevated bilirubin levels (1.4 mg/dl) since August 1994. A biopsy of the liver in March 1995 showed features of a “subacute viral hepatitis”; DD drug-induced or toxic lesions. Serological tests gave no support for an acute hepatitis. Intra-or extrahepatic cholestasis could not be proved neither by ultrasound nor by an endoscopic retrograde cholangiopancreatography. Since November 1995 serum creatinine increased up to 1.7 mg/dl (March 1995 1.1 mg/dl) and proteinuria (2.1 g/d) developed. Due to worsening of renal function (serum creatinine 2.8 mg/dl) and increasing proteinuria (3.5 g/d) without nephrotic syndrome, a kidney biopsy was performed. Histologically an amyloidosis (type Aλ) was proven, involving glomerula, kidney vessels and tubules. Further biopsies from the stomach and the duodenum showed profound infiltration of the mucosa and submucosa with amyloid. Therefore, staining of the liver biopsy of March 1995 with congo red proved the diagnosis of liver amyloidosis. By a punch biopsy of the iliac crest a low-grade non-Hodgkin’s lymphoma could be identified as the cause for this generalized amyloidosis.□ DiscussionIn the present case, the reason for these unusual hepatorenal symptoms with unclear cholestasis over years as the first clinical symptom and a succeeding progressive renal insufficiency with proteinuria could be found by the use of kidney biopsy and extending the analysis of a liver sample taken by Hodgkin’s lymphoma caused a generalized amyloidosis type Aλ.□ ConclusionAs a consequence, by an occurrence of unusual hepatorenal symptoms with cholestasis and progressive renal failure, amyloidosis should be considered as a pathogenetic factor.