Ramin Naraghi

Posterior fossa neurovascular anomalies in essential hypertension.

Intraoperative observations, necropsy, and angiographic studies support the presumption that neurovascular compression of the left ventrolateral medulla may cause neurogenic hypertension. Pulsatile irritation of the ventrolateral medulla at the root-entry zone of cranial nerves IX and X increases blood pressure in animals. To identify and assess the distribution of neurovascular compression at the ventrolateral medulla in human beings, we did a prospective single-blind study in 24 patients with essential hypertension, in 14 patients with renal hypertension, and in 14 normal subjects. To detect neurovascular compression, we used axial and coronal double-echo and magnetic-resonance angiography sequences. Blood pressure control and duration of hypertension were not different in the two groups of patients. 20 patients with essential hypertension had magnetic tomographic evidence of left-sided neurovascular compression at the ventrolateral medulla; 2 patients with renal hypertension and 1 of the normal subjects had a positive finding on the left. On the right side, we found signs of neurovascular compression in 4 patients with essential hypertension, in 4 with renal hypertension, and in 2 of the normal subjects. With magnetic resonance tomography, it is possible to evaluate the neurovascular relations in the posterior fossa and detect neurovascular compression at the ventrolateral medulla. These data in living subjects give further evidence of an association between neurovascular compression at the left ventrolateral medulla and essential hypertension.

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.

Severely Impaired Baroreflex-Buffering in Patients With Monogenic Hypertension and Neurovascular Contact

Background—We identified a family with a monogenic syndrome of hypertension, brachydactyly, and neurovascular contact of the brain stem. Neurovascular contact of the ventrolateral medulla may lead to arterial hypertension by interfering with baroreflex function. Methods and Results—In 5 patients with monogenic hypertension (18 to 34 years old), we conducted detailed autonomic function tests. Blood pressure during complete ganglionic blockade was 134±4.9/82±4.1 mm Hg and 90±6/49±2.4 mm Hg in patients and in control subjects, respectively. During ganglionic blockade, plasma vasopressin concentration increased 24-fold in control subjects and <2-fold in patients. In patients, cold pressor testing, hand-grip testing, and upright posture all increased blood pressure excessively. In contrast, muscle sympathetic nerve activity was not increased at rest or during cold pressor testing. The phenylephrine dose that increased systolic blood pressure 12.5 mm Hg was 8.0±2.0 &mgr;g in patients and 135±35 &mgr;g in control subjects before ganglionic blockade and 5.4±0.4 &mgr;g in patients and 13±4.8 &mgr;g in control subjects during ganglionic blockade. Conclusions—In patients with monogenic hypertension and neurovascular contact, basal blood pressure was increased even during sympathetic and parasympathetic nerve traffic interruption. However, sympathetic stimuli caused an excessive increase in blood pressure. This excessive response cannot be explained by increased sympathetic nerve traffic or increased vascular sensitivity. Instead, we suggest that baroreflex buffering and baroreflex-mediated vasopressin release are severely impaired.

PDE3A mutations cause autosomal dominant hypertension with brachydactyly

Cardiovascular disease is the most common cause of death worldwide, and hypertension is the major risk factor. Mendelian hypertension elucidates mechanisms of blood pressure regulation. Here we report six missense mutations in PDE3A (encoding phosphodiesterase 3A) in six unrelated families with mendelian hypertension and brachydactyly type E (HTNB). The syndrome features brachydactyly type E (BDE), severe salt-independent but age-dependent hypertension, an increased fibroblast growth rate, neurovascular contact at the rostral-ventrolateral medulla, altered baroreflex blood pressure regulation and death from stroke before age 50 years when untreated. In vitro analyses of mesenchymal stem cell–derived vascular smooth muscle cells (VSMCs) and chondrocytes provided insights into molecular pathogenesis. The mutations increased protein kinase A–mediated PDE3A phosphorylation and resulted in gain of function, with increased cAMP-hydrolytic activity and enhanced cell proliferation. Levels of phosphorylated VASP were diminished, and PTHrP levels were dysregulated. We suggest that the identified PDE3A mutations cause the syndrome. VSMC-expressed PDE3A deserves scrutiny as a therapeutic target for the treatment of hypertension.

Neurovascular Compression at the Ventrolateral Medulla in Autosomal Dominant Hypertension and Brachydactyly

BACKGROUND AND PURPOSE Autosomal dominant hypertension with brachydactyly features severe hypertension that causes stroke usually before the age of 50 years. We recently characterized the hypertension as featuring normal renin, aldosterone, and catecholamine responses and mapped the gene responsible to chromosome 12p. Since angiography in an affected subject had earlier shown tortuous vessels, we performed magnetic resonance tomography (MRT) angiography to look for possible neurovascular anomalies (NVA), which have been previously associated with hypertension. NVA can be caused by a looping posterior inferior cerebellar or vertebral artery. Experimental and clinical evidence suggests that NVA may cause hypertension by a compression of the ventrolateral medulla. METHODS We performed MRT in 15 hypertensive affected (aged 14 to 57 years) and 12 normotensive nonaffected (aged 12 to 59 years) family members. We then tested for linkage between the hypertension-brachydactyly phenotypes and the presence of NVA. RESULTS All 15 affected persons had MRT evidence for NVA. All had left-sided posterior inferior cerebellar artery or vertebral artery loops, while 6 had bilateral NVA. None of the nonaffected family members had NVA. The phenotypes were linked with an LOD score of 9.2 given a penetrance of 99%. CONCLUSIONS Autosomal dominant hypertension and brachydactyly regularly feature NVA, which is frequently bilateral. The early age at which NVA was identified suggests that the condition is primary. We suggest that NVA may be involved in the pathogenesis of this form of hypertension and perhaps essential hypertension as well. Further studies are necessary to address the question of causation.

Classification of neurovascular compression in typical hemifacial spasm: three-dimensional visualization of the facial and the vestibulocochlear nerves

OBJECT In this paper, the authors introduce a method of noninvasive anatomical analysis of the facial nerve-vestibulocochlear nerve complex and the depiction of the variable vascular relationships by using 3D volume visualization. With this technique, a detailed spatial representation of the facial and vestibulocochlear nerves was obtained. Patients with hemifacial spasm (HFS) resulting from neurovascular compression (NVC) were examined. METHODS A total of 25 patients (13 males and 12 females) with HFS underwent 3D visualization using magnetic resonance (MR) imaging with 3D constructive interference in a steady state (CISS). Each data set was segmented and visualized with respect to the individual neurovascular relationships by direct volume rendering. Segmentation and visualization of the facial and vestibulocochlear nerves were performed with reference to their root exit zone (REZ), as well as proximal and distal segments including corresponding blood vessels. The 3D visualizations were interactively compared with the intraoperative situation during microvascular decompression (MVD) to verify the results with the observed microneurosurgical anatomy. RESULTS Of the 25 patients, 20 underwent MVD (80%). Microvascular details were recorded on the affected and unaffected sides. On the affected sides, the anterior inferior cerebellar artery (AICA) was the most common causative vessel. The posterior inferior cerebellar artery, vertebral artery, internal auditory artery, and veins at the REZ of the facial nerve (the seventh cranial nerve) were also found to cause vascular contacts to the REZ of the facial nerve. In addition to this, the authors identified three distinct types of NVC within the REZ of the facial nerve at the affected sides. The authors analyzed the varying courses of the vessels on the unaffected sides. There were no bilateral clinical symptoms of HFS and no bilateral vascular compression of the REZ of the facial nerve. The authors discovered that the AICA is the most common vessel that interferes with the proximal and distal portions of the facial nerve without any contact between vessels and the REZ of the facial nerve on the unaffected sides. CONCLUSIONS Three-dimensional visualization by direct volume rendering of 3D CISS MR imaging data offers the opportunity of noninvasive exploration and anatomical categorization of the facial nerve-vestibulocochlear nerve complex. Furthermore, it proves to be advantageous in establishing the diagnosis and guiding neurosurgical procedures by representing original MR imaging patient data in a 3D fashion. This modality provides an excellent overview of the entire neurovascular relationship of the cerebellopontine angle in each case.

Neurovascular relationship at the trigeminal root entry zone in persistent idiopathic facial pain: findings from MRI 3D visualisation

Background: Patients with atypical neuralgia or atypical facial pain have been surgically treated with microvascular decompression (MVD) of the trigeminal root entry zone (TREZ). There are no data regarding the sensitivity and specificity of a vessel–TREZ relationship as a cause of pain in patients with persistent idiopathic facial pain (PIFP) according to the definition given by the International Headache Society (IHS). Methods: The TREZ was visualised by 3D CISS MRI in 12 patients with unilateral PIFP according to the IHS criteria. Results: The frequency of artery–TREZ, vein–TREZ, or vessel (artery/vein)–TREZ contacts on the symptomatic and asymptomatic sides did not differ significantly. On the symptomatic side, vessel–TREZ contact was found in 58% of patients (sensitivity). On the asymptomatic side, vessel–TREZ contact was absent in 33% of patients (specificity). Conclusions: On the basis of the low sensitivity and specificity found in the present study, PIFP cannot be attributed to a vessel–TREZ contact, and therefore, pain relief after MVD cannot be expected.

Contralateral hearing loss as an effect of venous congestion at the ipsilateral inferior colliculus after microvascular decompression: report of a case

Contralateral hearing loss after surgical procedures within the cerebellopontine angle is rarely seen and its pathophysiological background is not yet understood. A patient with contralateral hearing loss after microvascular decompression for trigeminal neuralgia is described. Ipsilateral brainstem auditory potential (BAEP) monitoring and facial nerve EMG did not show major abnormalities. During otherwise uneventful and successful surgery a branch of the petrosal vein was sacrificed to widen the access to the trigeminal root exit zone. On the third postoperative day the patient complained about contralateral hearing loss, which was verified by audiometry. Contralateral BAEPs showed low amplitudes and delayed interpeak latencies. Brain CT was normal. Brain MRI on the 8th postoperative day disclosed abnormal signals within the ipsilateral inferior colliculus. Intravenous heparinisation was performed and hearing slowly recovered over a 3 month period. Results from this patient offer a pathophysiological mechanism for contralateral hearing loss after cerebellopontine angle surgery, illustrate the importance of venous drainage preservation, gives evidence about the generation of BAEP components within the contralateral brainstem, and stresses the importance of intraoperative BAEP monitoring.

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.

Intraoperative three-dimensional visualization in microvascular decompression.

OBJECT The authors systematically analyzed 3D visualization of neurovascular compression (NVC) syndromes in the operating room (OR) during microvascular decompression (MVD). METHODS A total of 50 patients (26 women and 24 men) with trigeminal neuralgia (TN), hemifacial spasm (HFS), and glossopharyngeal neuralgia (GN) were examined and underwent MVD. Preoperative imaging of the neurovascular structures was performed using constructive interference in the steady state magnetic resonance (CISS MR) imaging, which consisted of 2D image slices. The 3D visualization of the neurovascular anatomy is generated after segmentaion of the CISS MR imaging in combination with direct volume rendering (DVR). The 3D representations were stored on a personal computer (PC) that was mounted on a mobile unit and transferred to the OR. During surgery, 3D visualization was applied by the surgeon with remotely controlled plasma-sterilized devices such as a wireless mouse and keyboard. The position of the 3D visualized neurovascular structures at the PC monitor was determined according to the intraoperative findings observed through the operating microscope. RESULTS The system was stable during all neurosurgical procedures, and there were no operative or technical complications. Interactive adjustment of the 3D visualization guided by the view through the microscope permitted observation of the neurovascular relationships at the brainstem. Vessels covered by the cranial nerves could be noninvasively viewed by intraoperative 3D visualization. Postoperatively, the patients with TN and GN experienced pain relief, and the patients with HFS attained resolution of their facial tics. Vascular compression of nerves was explored in all 50 patients during MVD. Intraoperative 3D visualization delineated the compressing vessels and respective cranial nerves in 49 (98%) of 50 patients. CONCLUSIONS Interactive 3D visualization by DVR of high-resolution MR imaging data offered the opportunity for noninvasive virtual exploration of the neurovascular structures during surgery. An extended global survey of the neurovascular relationships was provided during MVD in each case. The presented method proved to be extremely advantageous for optimizing microneurosurgical procedures, supporting superior safety and improving the operative results when compared with the conventional strategy. This modality proved to be a very valuable teaching instrument and ensured the improvement of neurosurgical quality.