Robert Macfarlane

Chronic Trigeminal Ganglionectomy or Topical Capsaicin Application to Pial Vessels Attenuates Postocclusive Cortical Hyperemia but Does Not Influence Postischemic Hypoperfusion

Marked hyperemia accompanies reperfusion after ischemia in the brain, and may account for the propensity of cerebral hemorrhage to follow embolic stroke or carotid endarterectomy, and for the morbidity that follows head injury or the ligation of large arteriovenous malformations. To evaluate the contribution of trigeminal sensory fibers to the hyperemic response, CBF was determined in 12 symmetrical brain regions, using microspheres with up to five different isotopic labels, in four groups of cats. Measurements were made at 15-min intervals for up to 2 h of reperfusion after global cerebral ischemia induced by four-vessel occlusion combined with systemic hypotension of either 10- or 20-min duration. In normal animals, hyperemia in cortical gray matter 30 min after reperfusion was significantly greater after 20 min (n = 10) than after 10 min (n = 7) of ischemia (312 ml/100 g/min versus 245 ml/100 g/min; p < 0.01). CBF returned to preischemic levels ∼45 min after reperfusion and was reduced to ∼65% of basal CBF for the remaining 75 min. In cats subjected to chronic trigeminal ganglionectomy (n = 15), postocclusive hyperemia in cortical gray matter was attenuated by up to 48% on the denervated side (249 versus 150 ml/100 g/min; p < 0.01) after 10 min of ischemia. This effect was maximal in the middle cerebral artery (MCA) territory, and was confined to regions known to receive a trigeminal innervation. In these animals, substance P (SP) levels in the MCA were reduced by 64% (p < 0.01), and the density of nerve fibers containing calcitonin gene-related peptide (but not vasoactive intestinal polypeptide or neuropeptide Y) was decreased markedly on the lesioned side. Topical application of capsaicin (100 nM; 50 μl) to the middle or posterior temporal branch of the MCA 10–14 days before ischemia decreased SP levels by 36%. Postocclusive hyperemia in cortical gray matter was attenuated throughout the ipsilateral hemisphere by up to 58%, but the cerebral vascular response to hypercapnia (Paco2 = 60 mm Hg) was unimpaired. The duration of hyperemia and the severity of the delayed hypoperfusion were not influenced by trigeminalectomy, capsaicin application, or the intravenous administration of ATP. These data demonstrate the importance of neurogenic mechanisms in the development of postischemic hyperperfusion, and suggest the potential utility of strategies aimed at blocking axon reflex-like mechanisms to reduce severe cortical hyperemia.

Treatment of vasospasm with a 480-nm pulsed-dye laser

Laser energy at a wavelength of 480 nm was applied in 1-microseconds pulses of 3 to 10 mJ to two models of vasospasm. Rabbit common carotid arteries (CCAs) were constricted chronically by the application of human blood within a silicone sheath. Peak vasospasm developed 24 to 48 hours later, and persisted for up to 6 days. Endovascular laser treatment was delivered to 40 CCAs via a 200-microns diameter silica quartz fiber introduced through the femoral artery. The CCA caliber increased from 60% of the pre-vasospasm control diameter to a minimum post-laser diameter of 83% of control. No instances of laser-induced perforation or of arterial thrombosis were observed for up to 60 days after treatment. Prophylactic laser application to nine normal vessels was able to attenuate the development of vasospasm if blood was applied immediately thereafter (88% vs. 59% of control diameter, p less than 0.02), but not if blood was applied 7 days later. Studies in 16 normal CCAs established that there was a considerable margin between the laser energy required to induce dilatation and that which caused perforation, providing that the fiber remained relatively central within the artery. Morphological examination demonstrated focal loss of endothelial cells immediately after laser application, followed approximately 7 days later by the development of areas of intimal hyperplasia. Only minimal changes were observed in the medial or adventitial layers. In a second study, the basilar artery of seven dogs was constricted chronically by two intracisternal injections of autologous blood 3 days apart. Five dogs received endovascular laser treatment 7 or 10 days after the first injection, when basilar artery diameter was reduced to a mean of 61% and 77% of control, respectively. Immediately following treatment, basilar artery diameter increased to 104% and 102% of resting diameter, respectively. Both untreated and laser-treated arteries were smaller than the control diameter at 30 days (80% and 82%, respectively), but in each group the vasodilatory response to hypercapnia was preserved. These findings indicate that 1-microsecond laser pulses are well tolerated by systemic and cerebral arteries in two different animal models, and suggest that the 480-nm pulsed-dye laser may have an application for the treatment or prophylaxis of cerebral vasospasm.

Postischemic Cerebral Blood Flow and Neuroeffector Mechanisms

The influence of neuroeffector mechanisms in the regulation of postischemic cerebral blood flow was investigated by microsphere determination in 8 cats after chronic unilateral vascular deafferentation by trigeminal ganglionectomy. The animals were subjected to 90 min of reperfusion following 10 min of global ischemia induced by 4-vessel occlusion and systemic hypotension. Cortical hyperemia 30 min after reperfusion was attenuated by up to 48% in cortical gray matter ipsilateral to the side of trigeminal ganglionectomy (p less than 0.01). Axon reflex mechanisms involving the release of neuropeptides from peripheral sensory nerve fibers, such as substance P (SP), calcitonin gene-related peptide (CGRP) and neurokinin A (NKA), mediate this response. SP and NKA cause vasodilation by endothelium-dependent mechanisms (endothelium-dependent relaxing factor), whereas CGRP relaxes vascular smooth muscle by direct receptor interactions. Studies were therefore undertaken to determine the extent to which endothelium-dependent mechanisms mediate the hyperemia following global cerebral ischemia. In 7 intact cats, the postischemic response of pial arterioles to the topical application of acetylcholine (ACh; 10(-7) M), an endothelial-dependent vasodilator, was measured using a closed cranial window technique. Although ACh increased pial arteriolar caliber by 17% under resting conditions, the same dose elicited a vasoconstrictor response (87% of pre-ACh diameter 30 min after reperfusion) for the first 60 min of reperfusion after 10 min of ischemia. ACh-induced vasodilation was restored by 75 min (105%), but was less than control even at 120 min (109 vs. 117%; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Wound closure after acoustic neuroma surgery

Cerebrospinal fluid leakage from the wound or middle ear cavity remains a common cause of morbidity after acoustic neuroma surgery, regardless of the operative route employed. An incidence of around 15% is reported in most large series. The authors describe a method of wound closure which is applicable to both translabyrinthine and retrosigmoid tumour excision. Adoption of this technique in 188 consecutive patients has reduced the incidence of this complication in our unit from 13% to 1.6%.

Commentary on: ‘Cauda equina syndrome: The timing of surgery probably does influence outcome’, by N. V. Todd 1

Early studies on cauda equina syndrome (CES) reviewed patients who had lost executive control of bladder function. This forms part of Kostuik’s 1993 definition of CES. Dinning & Schaeffer, de facto and unwittingly, broadened the patient base by suggesting that the time of catheterization should be the landmark for defining urinary retention. However, this is not a satisfactory end-point because clinical experience tells us that the indications for catheterization are varied, including relief of discomfort or nursing convenience, whilst a few patients will come to surgery uncatheterized, having been in retention with overflow for several days. First, Ahn et al. and now Todd, have widened the base of CES still further to include some patients with urinary difficulty (CESI), rather than retention with overflow incontinence (CESR). Like others, we had excluded this group of patients for two reasons. First, we are not aware of anyone who proposes that a patient with deteriorating CESI requires anything other than urgent decompression. If surgery is carried out at the stage of CESI, bladder outcome is almost always favourable, whereas only about 50% of those who progress to CESR will have an acceptable recovery. The debate has been centred round whether urgent surgery confers advantage to patients who present in CESR. Secondly, if loss of bladder control is the endpoint for a study and patients who have not already reached this state are included, the results will be biased to show benefit from early surgery. This is because patients with CESI have the potential for bladder function to deteriorate in the interim, whilst those with CESR do not. In our opinion, a study that purports to claim advantage for emergency surgery in CESR, but includes any patients with CESI is flawed. There is another fundamental problem with this analysis. More than 100 articles have been published on CES in the last 40 years and, as Todd rightly points out, the conclusions that they have reached are discordant. The Ahn meta-analysis, of which he is rightly critical, at least made an attempt to sample that diversity by analysing 322 patients from 42 publications. In contrast, Todd evaluates data from just six papers and does not include any new cases of his own. Of the six, one was a review of just four patients whilst, of the remainder, all but one concluded that there was benefit from early surgery. Unfortunately, Todd does not balance this arm of the literature by including in his analysis any of the larger series that found no benefit from early surgery in CESR. Although describing meta-analysis as the next best evidence to a randomized controlled trial, his study represents neither a balanced sample of the literature nor does it address the specific question that has formed this debate. The whole premise upon which our argument is based is that surgery for CES can be a difficult operation, and it is important that surgery itself should not add to any existing neurodisability. If there is no benefit to be gained from emergency decompression in CESR then it is better for the procedure to be performed by an experienced surgeon in daylight hours, rather than to treat the condition as one would an extradural haematoma. For Todd to find that any delay in decompression is a potential cause of irreversible urinary incontinence, and yet still accept that it might be justifiable for the surgeon to wait and operate fresh after a night’s sleep is, to our mind, illogical.

The Innervation of Pial Blood Vessels and their Role in Cerebrovascular Regulation

Thomas Willis noted in his Cerebri Anatome (1664) that brain vessels were accompanied by fibers. Hovelaque (1927) and Sheehan (Northfield 1938) identified neural connections between the trigeminal ganglion and the internal carotid artery, but were unable to determine whether they represented sympathetic innervation of the trigeminal ganglion or a sensory innervation to the cerebral vessels. Levine and Wolff (1932) demonstrated that electrical stimulation of cat pial arteries increased galvanic skin responses, and that this effect was blocked by the application of procaine to the vessel. Motor end-plates were observed microscopically in the adventitia of pial arteries, and were thought to represent afferent nerve endings (McNaughton 1938). In primates, Wall and Pribram (1950) found that the hypertensive response to electrical stimulation of pial arteries was blocked by trigeminal neurotomy. In man, Fay (1932), Penfield and McNaughton (1940) and Ray and Wolff (1940) elicited forehead pain by electrical stimulation of the pial and dural arteries. However, it was not until the axonal tracing studies of Mayberg and colleagues (1981) that direct connections between the trigeminal nerve and the circle of Willis were documented.