[Pathophysiology of cluster headache]. / Physiopathologie de l'algie vasculaire de la face (AVF).

The aetiology of cluster headache is partially unknown. Three areas are involved in the pathogenesis of cluster headache: the trigeminal nociceptive pathways, the autonomic system and the hypothalamus. The cluster headache attack involves activation of the trigeminal autonomic reflex. A dysfunction located in posterior hypothalamic gray matter is probably pivotal in the process. There is a probable association between smoke exposure, a possible genetic predisposition and the development of cluster headache.

Dural arteriovenous fistula (D-AVF): a rare cause of symmetrical bithalamic changes with free diffusivity changes.

We report a rare case of an encephalopathic presentation of a posterior fossa dural arteriovenous fistula with concomitant florid symmetrical bithalamic free diffusivity changes on MRI in a previously healthy individual. We describe the structural and functional imaging findings and the role of catheter angiography in diagnosis, prognostication and the timing and strategy in the management of this challenging vascular entity.

The 'headache tree' via umbellulone and TRPA1 activates the trigeminovascular system.

The California bay laurel or Umbellularia californica (Hook. & Arn.) Nutt., is known as the 'headache tree' because the inhalation of its vapours can cause severe headache crises. However, the underlying mechanism of the headache precipitating properties of Umbellularia californica is unknown. The monoterpene ketone umbellulone, the major volatile constituent of the leaves of Umbellularia californica, has irritating properties, and is a reactive molecule that rapidly binds thiols. Thus, we hypothesized that umbellulone stimulates the transient receptor potential ankyrin 1 channel in a subset of peptidergic, nocioceptive neurons, activating the trigeminovascular system via this mechanism. Umbellulone, from µM to sub-mM concentrations, selectively stimulated transient receptor potential ankyrin 1-expressing HEK293 cells and rat trigeminal ganglion neurons, but not untransfected cells or neurons in the presence of the selective transient receptor potential ankyrin 1 antagonist, HC-030031. Umbellulone evoked a calcium-dependent release of calcitonin gene-related peptide from rodent trigeminal nerve terminals in the dura mater. In wild-type mice, umbellulone elicited excitation of trigeminal neurons and released calcitonin gene-related peptide from sensory nerve terminals. These two responses were absent in transient receptor potential ankyrin 1 deficient mice. Umbellulone caused nocioceptive behaviour after stimulation of trigeminal nerve terminals in wild-type, but not transient receptor potential ankyrin 1 deficient mice. Intranasal application or intravenous injection of umbellulone increased rat meningeal blood flow in a dose-dependent manner; a response selectively inhibited by systemic administration of transient receptor potential ankyrin 1 or calcitonin gene-related peptide receptor antagonists. These data indicate that umbellulone activates, through a transient receptor potential ankyrin 1-dependent mechanism, the trigeminovascular system, thereby causing nocioceptive responses and calcitonin gene-related peptide release. Pharmacokinetics of umbellulone, given by either intravenous or intranasal administration, suggest that transient receptor potential ankyrin 1 stimulation, which eventually results in meningeal vasodilatation, may be produced via two different pathways, depending on the dose. Transient receptor potential ankyrin 1 activation may either be caused directly by umbellulone, which diffuses from the nasal mucosa to perivascular nerve terminals in meningeal vessels, or by stimulation of trigeminal endings within the nasal mucosa and activation of reflex pathways. Transient receptor potential ankyrin 1 activation represents a plausible mechanism for Umbellularia californica-induced headache. Present data also strengthen the hypothesis that a series of agents, including chlorine, cigarette smoke, formaldehyde and others that are known to be headache triggers and recently identified as transient receptor potential ankyrin 1 agonists, utilize the activation of this channel on trigeminal nerves to produce head pain.

Topiramate in the treatment of migraine: a kainate (glutamate) receptor antagonist within the trigeminothalamic pathway.

BACKGROUND: The development of new agents for the preventive treatment of migraine is the greatest unmet need in the therapeutics of primary headaches. Topiramate, an anticonvulsant drug, is an effective anti-migraine preventive whose mechanism of action is not fully elucidated. Since glutamate plays a major role in migraine pathophysiology, the potential action of topiramate through glutamatergic mechanisms is of considerable interest. METHODS: Recordings of neurons in the trigeminocervical complex (TCC) and the ventroposteromedial thalamic nucleus (VPM) of anesthetized rats were made using electrophysiological techniques. The effects of intravenous or microiontophorezed topiramate on trigeminovascular activation of second- and third-order neurons in the trigeminothalamic pathway were characterized. The potential interactions of topiramate with the ionotropic glutamate receptors were studied using microiontophoresis. RESULTS: Both intravenous and microiontophorized topiramate significantly inhibited trigeminovascular activity in the TCC and VPM. In both nuclei microiontophoretic application of topiramate significantly attenuated kainate receptor-evoked firing but had no effect on N-methyl-d-aspartic acid or α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor activation. CONCLUSION: The data demonstrate for the first time that topiramate modulates trigeminovascular transmission within the trigeminothalamic pathway with the kainate receptor being a potential target. Understanding the mechanism of action of topiramate may help in the design of new medications for migraine prevention, with the data pointing to glutamate-kainate receptors as a fruitful target to pursue.

[A case of dural arteriovenous fistula associated with bilateral thalamic lesions].

We report a 51-year-old man with a dural arteriovenous fistula (DAVF) associated with bilateral thalamic lesions. He was admitted to our hospital because of cognitive disorder. T2-weighted MRI and fluid-attenuated inversion recovery (FLAIR) sequence of the brain revealed symmetric hyperintense lesions of bilateral thalamus and abnormal flow void that represents the enlarged veins. Cerebral angiography demonstrated DAVF in the superior petrosal sinus (SPS). It was mainly supplied by the internal carotid arteries. The strait sinus was not revealed, and the venous drainage was retrograde into the internal cerebral vein. Therefore the mechanism of cognitive disorder in this case was considered to be vasogenic edema of the bilateral thalamus due to DAVF of SPS. We decided to treat the DAVF by embolization via the feeding arteries approach, because strait sinus was not revealed and venous approach was difficult. After embolization, the size of DAVF was remarkably reduced. His cognitive disorder was markedly improved and the hyperintense area on T2-weighted MRI and FLAIR sequence had disappeared. Cognitive disorder due to DAVF of SPS is very rare. It is also difficult to diagnose bilateral thalamic lesions as DAVF, but it may be reversible by DAVF treatment. Thus, early diagnosis and treatment is important. Like this case, abnormal flow void that represents the enlarged veins could help to diagnose bilateral thalamic lesions due to DAVF.

Role of BK(Ca) channels in cephalic vasodilation induced by CGRP, NO and transcranial electrical stimulation in the rat.

Both calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are potent vasodilators that have been shown to induce headache in migraine patients. Their antagonists are effective in the treatment of migraine attacks. In the present study, we hypothesize that vasodilation induced by the NO donor glyceryltrinitrate (GTN) or by CGRP is partially mediated via large conductance calcium-activated potassium (BK(Ca)) channels. The effects of the BK(Ca) channel selective inhibitor iberiotoxin on dural and pial vasodilation induced by CGRP, GTN and endogenously released CGRP by transcranial electrical stimulation (TES) were examined. Iberiotoxin significantly attenuated GTN-induced dural and pial artery dilation in vivo and in vitro, but had no effect on vasodilation induced by CGRP and TES. Our results show that GTN- but not CGRP-induced dural and pial vasodilation involves opening of BK(Ca) channels in rat.

Dural arteriovenous fistulas with aggressive course: clinical and angiographic correlations in two patients.

Cranial dural arteriovenous fistulas (DAVFs) usually present with non-aggressive symptoms. We here report two patients who presented a peculiar clinical picture related to DAVFs, with focal neurological signs and haemorrhagic (case 1) or ischaemic lesions (case 2) respectively. The clinical and angiographic findings and putative pathophysiological mechanisms are discussed.

The role of histamine in dural vessel dilation.

The pain of migraine is often throbbing suggesting an important role for the cranial blood vessels and their innervation by the trigeminal nerve. It is proposed that clinically effective anti-migraine compounds, such as 5-HT(1B/1D) agonists, have actions that include inhibiting calcitonin gene-related peptide (CGRP) release from trigeminal nerves. Human studies suggest that histamine can induce migraine possibly by activating nitric oxide (NO) synthase to promote endogenous NO production. The present studies investigated the effect of histamine and its antagonists on the cranial blood vessels using intravital microscopy to assess directly the diameter of dural arteries in sodium pentobarbitone anaesthetised rats. Electrical stimulation of a closed cranial window produces, by local depolarisation of nerves, dural vessel dilation that is monitored continuously on-line using video-microscopy and a video dimension analyser. Histamine infusion caused immediate and reproducible dilation of meningeal blood vessels (103.5+/-6%; n=40) that could be blocked by H(1)- (mepyramine) and H(2) (famotidine)-receptor antagonists (P<0.05), as well as a nitric oxide synthase inhibitor (N(G)-nitro-L-arginine methylester; P<0.05). Neurogenic dural vasodilation was not inhibited by H(2)-receptor antagonists, but was significantly inhibited by a H(1)-receptor antagonist at the high dose of 10 mg/kg. The present studies demonstrate that histamine is likely to activate NO synthase to promote NO production. There is also evidence that H(1)-receptors may be present on trigeminal neurones as the H(1)-receptor antagonist inhibited neurogenic vasodilation, albeit at a large dose.

Effect of quercetin on plasma extravasation in rat CNS and dura mater by ACE and NEP inhibition.

The effects of quercetin on substance P-induced plasma protein extravasation (PE) in the rat dura mater, cerebellum, olfactory bulb and cortex and also its modulation by endopeptidases, angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) were studied. PE was assessed by photometric measurement of extravasated Evans blue. Substance P (SP) and NEP or ACE inhibitors increased the PE in dura mater. Pretreatment with captopril or phosphoramidon potentiated PE induced by SP in the dura mater and cerebellum, respectively. Quercetin increased the PE in the dura mater, cerebellum and cortex. Further results suggested that the PE induced by SP in the dura mater was enhanced by pretreatment with quercetin, similar to that observed with selective peptidase inhibitors. Quercetin-stimulated extravasation in all tissues was abolished by NK-1 receptor blockade. These results suggest that quercetin increases PE in the dura mater and CNS tissues by inhibiting NEP and/or ACE, showing that the effect induced in the dura mater, cerebellum and cortex occurs through endogenous SP accumulation.

Study of an adenosine A1 receptor agonist on trigeminally evoked dural blood vessel dilation in the anaesthetized rat.

The purpose of this study was to use intravital microscopy to determine the effect of a selective adenosine A1 receptor agonist, GR79236 (1, 3 and 10 microg/kg i.v.), on neurogenic dural blood vessel dilation in anaesthetized rats. Vasodilation was evoked either by electrical stimulation of perivascular trigeminal nerves or by intravenous CGRP. GR79236 (1-10 microg/kg i.v.) caused a dose-dependent inhibition of neurogenic vasodilation, but had no significant effect on dural vasodilation caused by CGRP. GR79236 (1-3 microg/kg i.v.) had no effect on basal dural vessel diameter, but caused transient dose-dependant bradycardia and hypotension. Bradycardia was more prolonged following 10 microg/kg i.v. GR79236. Pre-treatment with the adenosine A1 receptor antagonist DPCPX (1 mg/kg i.v.) prevented the inhibitory effect of GR79236 (10 microg/kg i.v.) on neurogenic vasodilation as well as GR79236-induced bradycardia and hypotension. These data suggest that the inhibition of neurogenic vasodilation by GR79236 is mediated via the activation of prejunctional adenosine A1 receptors. Provided the systemic cardiovascular effects could be limited, such a mechanism may offer a novel approach to migraine therapy.

Histological demonstration of increased vascular permeability in the dura mater of the rat.

Neurogenic inflammation of the dura mater encephali has been suggested to play an important role in the pathophysiology of headaches. Although functional studies using extravasation techniques indicate an enhanced permeability of blood vessels after chemical or electrical stimulation of C-fibres supplying the dura mater, histological demonstration of leaky blood vessels is still a problem. We used the vascular labelling method combined with i.v. injection of colloidal silver solution to test the permeability increasing effect of intravenous administration of substance P, topical application of mustard oil or acidic phosphate buffer and local electrical stimulation of the exposed dura mater. Histological characteristics of increased vascular permeability were observed exclusively after mustard oil and acidic phosphate buffer. This observation may indicate different mechanisms of increased vascular permeability involving pinocytosis and formation of interendothelial gaps selectively visualized by the vascular labelling method.

Transarterial embolisation of complex cavernous sinus dural arteriovenous fistulae with low-concentration cyanoacrylate.

We report the effectiveness of low-concentration n-butyl-2-cyanoacrylate (NBCA)-Lipiodol-tungsten mixture (10-15 %) in the management of patients with aggressive or recurrent complex cavernous dural arteriovenous fistulae (CSDAVF). We treated five patients with complex CSDAVF with a low concentration of an NBCA-Lipiodol-tungsten mixture after catheterisation of the feeding arteries arising from the external carotid artery. Three had a recurrent CSDAVF after transarterial particulate embolisation. Three refused transvenous treatment or could not be treated in this way; two patients had also feeding dural branches of the internal carotid artery. All patients had complete resolution of symptoms and signs within a month of the procedure. No definite neurological complication was found during follow-up ranging from 12 to 36 months. Transarterial embolisation with low-concentration cyanoacrylate appears to be an effective alternative management of aggressive or recurrent CSDAVF.

[The effect of tropoxin on the neurogenic and vasogenic inflammation of the dura mater vessels]. / Vliianie tropoksina na neirogennoe i vazogennoe vospalenie sosudov tverdoi mozgovoi obolochki.

Subchronic administration of tropoxin (in doses of 7.5 and 10 mg/kg) caused dose-dependent blocking of 131I-albumin plasma transudation from the dura mater vessels, induced by electrical stimulation of the trigeminal ganglion and intravenous infusion of the agonist of 5-HT2B/2C receptors metachlorophenylpiperazine. The antimigraine agent metisergid produced a similar effect. A single injection of metisergid and tropoxin did not block albumin transudation. A 3 mg/kg dose of mianserin prevented the blocking effect of tropoxin and metisergid on plasma exudation into the dura mater. It is suggested that the mechanism of the tropoxin antimigraine effect is realized through the presynaptic 5-HT1 receptors of afferent endings of the trigeminal nerve and the postsynaptic 5-HT2B/2C receptors of the dura mater vessels.

Dural arteriovenous malformation manifesting as dementia due to ischemia in bilateral thalami. A case report.

BACKGROUND: Although dementia is one of the curable manifestations of a dural arteriovenous malformation (AVM), the pathophysiology remains unclear. CASE DESCRIPTION: We describe an elderly patient who had an AVM in the tentorium and manifested signs of dementia from ischemia, predominantly in the bilateral thalami. Intravascular embolization of the dural AVM resulted in amelioration of signs of dementia, and this improvement was consistent with that of neuroradiological and hemodynamic conditions in the thalami. CONCLUSION: The coincidental improvement of CBF in the thalami and signs of dementia after embolization of the AV shunt supports the concept of primary participation of the thalami in the pathophysiology of dementia of vascular origin in our patient.

Venous hypertension associated with a posterior fossa dural arteriovenous fistula: another cause of bithalamic lesions on MR images.

We report a case of a posterior fossa arteriovenous fistula (AVF) with bithalamic hyperintensity of MR images. The thalamic abnormality improved after surgery, suggesting reversible venous hypertension as the pathogenesis of the finding, as opposed to infarction. This manifestation of a posterior fossa AVF should be considered in the differential diagnosis of bilateral thalamic disease.

Massive bleeding during spine surgery in a patient with ankylosing spondylitis.

PURPOSE: Ankylosing spondylitis is associated with pathophysiology that has important anaesthetic implications. We report a case where the sequelae of ankylosing spondylitis may have been responsible for massive bleeding during emergency spine surgery. CLINICAL FEATURES: A 69 yr old man with long standing ankylosing spondylitis sustained a complex fracture of the lumbar spine in a fall, and was scheduled for stabilization of the spine. Under general anaesthesia, prone positioning was difficult because of the extreme spinal deformity. During exploration, dilatation of epidural veins was encountered and sustained haemorrhage was encountered throughout the surgical procedure. Estimated blood loss was 17,000 ml which was replaced with 31 units of packed red blood cells, 3200 ml of salvaged blood, 18 units of fresh frozen plasma, 26 units of platelets, 1,000 ml of albumin and 9,000 ml of crystalloid. CONCLUSIONS: Extreme deformity of the spine led to positioning difficulties that may have contributed to massive blood loss during complex spine surgery. Difficulties with placement in the prone position in-patients with advanced ankylosing spondylitis should be anticipated.

Reversible dural arteriovenous malformation-induced venous ischemia as a cause of dementia: treatment by surgical occlusion of draining dural sinus: case report.

We report a unique case of thalamic dementia caused by tentorial dural arteriovenous malformation (AVM), which was successfully treated by surgical occlusion of the straight sinus after attempts to occlude the dural AVM by endovascular procedures had failed. The tentorial dural AVM was fed by bilateral posterior meningeal arteries and occipital arteries, with early retrograde venous drainage into the straight sinus, inferior sagittal sinus, basal vein of Rosenthal, and dural veins in the falx cerebri. The venous ischemia in bilateral thalamus was revealed as low-density areas in computed tomographic scans, as high-intensity areas in T2-weighted magnetic resonance images, and as decreased cerebral blood flow and increased cerebral blood volume in single-photon positron emission computed tomography. Because this patient was not amenable to cure by endovascular embolization, an open surgical approach, surgical occlusion of the draining venous channel (the straight sinus), was performed. Postoperatively, dural AVM in angiography and venous ischemia in bilateral thalamus were resolved, as revealed by magnetic resonance imaging and single-photon positron emission computed tomography. Dementia caused by bilateral thalamic ischemia was also resolved. This case clearly illustrates the pathophysiological mechanism of venous ischemia in the bilateral thalamus to cause reversible dementia.

Spinal dural arteriovenous fistulas: evaluation with MR angiography.

PURPOSE: To show that postgadolinium three-dimensional time-of-flight MR angiography shows abnormal intradural vessels associated with spinal dural arteriovenous fistula better than routine MR imaging and provides screening information useful for subsequent diagnostic conventional angiography and/or posttreatment evaluation. METHODS: Precontrast and postcontrast MR imaging and MR angiograms, as well as subsequent digital subtraction angiograms, were obtained for eight patients with dural arteriovenous fistulas, diagnosed with digital subtraction angiography and verified with surgery. In four patients, MR studies also were obtained after surgery. RESULTS: All patients had cord hyperintensity of T2-weighted images and postgadolinium enhancement on T1-weighted images. Five had vessellike signal abnormalities in the subarachnoid space on MR. Abnormal intradural vessels were detected in all eight patients with MR angiography. Comparison with digital subtraction angiography revealed these vessels to be primarily enlarged veins of the coronal venous plexus on the cord surface. In six patients, the medullary vein draining the fistula was demonstrated, indicating the level of the fistula, later identified by digital subtraction angiography. After surgical obliteration of the fistula, the draining medullary vein and most or all of the abnormal coronal veins were no longer demonstrated, with decrease or resolution of cord hyperintensity on T2-weighted images. CONCLUSION: Postgadolinium, spinal MR angiography in cases of suspected dural arteriovenous fistula provides information about intradural veins that supplements the diagnostic value of the MR imaging results, facilitates the subsequent digital subtraction angiography study, and, in treated cases, reflects the success of surgery and/or embolization.

Anti-inflammatory effects of tianrong acupoint on blood vessels of dura mater.

Although Tianrong acupoint (SI 17) is used for migraine headache, its mechanism of action remains obscure. The effects of Tianrong acupoint therapy on neurogenically-mediated plasma protein extravasation (125I-BSA) in rat dura mater induced by electrical stimulation of the right trigeminal ganglion was studied. When the unilateral trigeminal ganglion was stimulated (5 Hz, 1.2 mA, 5 msec for 5 min), the ratio of stimulated side/unstimulated side (cpm/mg) was 1.6663 +/- 0.0217. The plasma extravasation was blocked by different kinds of treatment in different degrees. The order of the ratio was as follow: Tianrong acupoint therapy (1.0917 +/- 0.0266) and Tianrong electrical needle therapy (1.1281 +/- 0.0227) < Tianrong acupoint injection with normal saline (1.325 +/- 0.0444) < Quchi acupoint (LI 11) injection with prednisolonum (1.5284 +/- 1.1624). The results indicated that Tianrong acupoint therapy could inhibit the neurongenic inflammation on the affected side.