Biomedical subjects
Publications and source records attributed to R Macfarlane.
A 75-year-old woman presented with symptoms related to a space occupying lesion in the cerebellum which histology showed to be a malignant lymphoma of prolymphocytic type. A diagnosis of chronic lymphocytic leukaemia (CLL) had been made over 1 year before. This form of lymphoma complicating CLL has not been described previously in the nervous system.
BACKGROUND AND PURPOSE: Hemodynamic changes associated with acute ischemia cannot be measured with conventional nuclear magnetic resonance imaging. In this study, we used dynamic susceptibility-contrast magnetic resonance imaging to measure the changes in vascular transit time and relative cerebral blood volume in a feline occlusion-reperfusion model. METHODS: Dynamic susceptibility-contrast measurements were obtained before and during 10 minutes of global cerebral ischemia and for up to 3 hours after the onset of reperfusion. A cerebral blood flow index was calculated from the vascular transit time and relative cerebral blood volume measurements. Functional maps were constructed to demonstrate the regional hemodynamic differences resulting from the induced ischemia. RESULTS: During the early phase after reperfusion, both the relative cerebral blood volume and blood flow index rose sharply, followed by a fall to near-basal levels at 45 minutes (1 x control and 1.3 x control, respectively). Thereafter, the volume rose slowly, whereas the flow index continued to drop. At 3 hours, cerebral blood volume had reached 1.6 times its control value, whereas the flow index had returned to its base value. CONCLUSIONS: The hemodynamic behavior we observed in our model reflects the independent responses of the cerebral blood volume and flow index to ischemic insult. Measurements acquired by our method were consistent with the temporal behavior reported in previous radionuclide studies. Susceptibility-contrast nuclear magnetic resonance tomographic imaging proved to be valuable in detecting and quantifying both immediate and subsequent changes in the hemodynamic state of the ischemic and hyperemic feline brain.
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%.
This chapter reviews the evidence that challenges traditional and unproven notions which perpetuate the singular importance of constriction and dilation to the genesis of migraine pain. New data in experimental laboratory models suggest that migraine headache may develop primarily from metabolic/neurophysiological events (as yet unidentified) within the cortical mantle, or from a disturbance in those regions of brain which closely approximate the distribution of trigeminovascular fibers innervating meningeal blood vessels. Accordingly, this chapter will review the consequences of trigeminovascular activation to pain and meningeal inflammation, and will summarize emerging molecular and pharmacological data suggesting that ergot alkaloids and sumatriptan alleviate pain primarily via activation of pre-junctional 5-HT1 heteroreceptors residing on primary afferent trigeminovascular fibers.
The 'vascular' aetiology of headache is questioned. An alternative hypothesis based on sensitisation of sensory nerve endings by neurogenic plasma extravasation is discussed. The development of drugs which selectively inhibit the release of vasoactive neuropeptides from perivascular sensory nerves may benefit patients with head pain from a variety of causes.
The relationship between pial arteriolar caliber and cerebral blood flow (CBF) was examined in 11 cats subjected to reperfusion for up to 120 min after 10 min of global cerebral ischemia induced by four-vessel occlusion and systemic hypotension. Thirty minutes after reperfusion CBF, as assessed by radiolabeled microsphere injection, had increased to 588% of control in middle cerebral artery (MSEC) cortical gray matter territory. The caliber of MSEC pial arterioles measured using the closed cranial window technique (greater than 33 to less than 213 microns) increased to 172% of baseline. By 60 min of reperfusion, CBF was 76% of basal levels, but pial arterioles remained 133% of baseline. After 120 min, CBF approximated baseline values, but pial dilatation persisted (115% of control). Intracranial pressure measurements did not differ significantly from resting values. At 45 min and beyond, total cerebrovascular resistance did not differ from resting values. The coexistence of vasodilatation within pial arterioles and normal blood flow in cortical gray matter indicates that pial vessels (greater than 33 microns) cannot be responsible for normal blood flow restoration following postocclusive hyperemia. Resistance during the posthyperemic phase must be increased selectively within parenchymal vessels to account for normal total cerebrovascular resistance, pial vessel dilatation, and normal-low parenchymal blood flow. Whether obstruction rather than vasoconstriction explains the resistance changes within intraparenchymal vessels remains for further study.
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 less than 0.01). CBF returned to preischemic levels approximately 45 min after reperfusion and was reduced to approximately 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 less than 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 less than 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 microliters) 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.
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)
Laser energy of 480 nm was applied in 1-microsecond pulses varying between 2.2 and 10 mJ to in vitro and in vivo models of cerebral vasospasm. First, the pulsed-dye laser was applied intravascularly via a 320-microns fiber to basilar artery segments from six dogs. The segments were mounted in a vessel-perfusion apparatus and constricted to, on average, 70% of resting diameter by superfusion with dog hemolysate. Immediate increase in basilar artery diameter occurred to a mean of 83% of control. In a second model, the basilar artery was exposed transclivally in the rabbit. In three normal animals, superfusion of the artery with rabbit hemolysate resulted in a reduction of mean vessel diameter to 81% of control. Following extravascular application of the laser, vessels returned to an average of 106% of the resting state. In six rabbits, the basilar artery was constricted by two intracisternal injections of autologous blood. 3 days apart. Two to 4 days after the second injection, the basilar artery was exposed. Extravascular laser treatment from a quartz fiber placed perpendicular to the vessel adventitia resulted in an immediate 53% average increase in caliber to an estimated 107% of control. No reconstriction was observed over a period of up to 5 hours. Morphologically, damage to the arterial wall was slight. This preliminary investigation suggests that the 1-microsecond pulsed-dye laser may be of benefit in the treatment of cerebral vasospasm.
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 (CCA's) 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 CCA's 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 CCA's 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.
Cerebral hyperperfusion, a state in which blood flow exceeds the metabolic needs of brain, may complicate a number of neurological and neurosurgical conditions. It may account for the propensity with which hemorrhage, cerebral edema, or seizures follow embolic stroke, carotid endarterectomy, or the excision of large arteriovenous malformations, and for some of the morbidity that accompanies acute severe head injury, prolonged seizures, and acute severe hypertension. Hyperperfusion syndromes have in common acute increases in blood pressure, vasodilatation, breakdown of the blood-brain barrier, and the development of cerebral edema. These common features suggest the possibility that they share the same pathogenic mechanisms. It was believed until recently that reactive hyperemia was caused primarily by the generation of vasoactive metabolites, which induced vasodilatation through relaxation of vascular smooth muscle. However, the authors have recently established that the release of vasoactive neuropeptides from perivascular sensory nerves via axon reflex-like mechanisms has a significant bearing upon a number of hyperperfusion syndromes. In this article, the authors summarize their data and discuss possible therapeutic implications for blockade of these nerves or their constituent neuropeptides.
The importance of trigeminal neuroeffector mechanisms in the regulation of postischemic cerebral blood flow (CBF) was evaluated in cats subjected to chronic unilateral denervation of cortical sensory nerve fibers by trigeminal ganglionectomy or by the topical application of capsaicin to a cortical branch of the middle cerebral artery. CBF was determined using isotopically labeled microspheres before and at intervals after reperfusion following 10 min of global cerebral ischemia induced by four vessel occlusion combined with systemic hypotension. Postocclusive hyperemia 30 min after reperfusion in cortical gray matter ipsilateral to the side of denervation was attenuated by up to 58% (176 vs. 91 ml/100 g per min; p less than 0.05), but resting CBF, the duration of hyperemia, and the cerebrovascular response to hypercapnia were unaffected. These data underline the influence of neurogenic mechanisms in the regulation of postischemic CBF. Blockade of this axon reflex-like mechanism may reduce the morbidity associated with several hyperperfusion syndromes.
The influence of the trigeminal nerve on the cerebral circulation was investigated in chronically denervated cats during and after reversible four-vessel occlusion for 10 minutes combined with controlled hypotension (50 mm Hg). Postocclusive hyperemia 30 minutes after reperfusion was attenuated by up to 48% in cortical gray matter of the anterior, middle, and posterior cerebral artery territories on the side of trigeminal ganglionectomy. Similar results were observed for denervation accomplished by direct surgical ablation and by the topical application of capsaicin to a cortical branch of the middle cerebral artery. Denervation did not alter basal cerebral blood flow or the duration of hyperemia, nor did it impair the cerebrovascular response to hypercapnia. These data demonstrate the importance of neurogenic mechanisms in the development of postischemic hyperperfusion and suggest that strategies directed at blocking axon reflex-like mechanisms may be beneficial in reducing the morbidity that follows severe cortical hyperemia.
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We present two patients with renovascular hypertension in association with neurofibromatosis. In both cases the diagnosis was established by angiography. The first patient suffered occlusion of the right renal artery combined with intrarenal arterial lesions. Treatment was by autotransplantation. The second patient suffered bilateral intrarenal arterial lesions alone and was treated medically. In both patients, control of the hypertension was established. We discuss the aetiology of renovascular hypertension in neurofibromatosis and consider its treatment.
A series of 76 consecutive patients undergoing unilateral acoustic neuroma excision is reported. Preoperative facial weaknesses and a tumour larger than 2.5 cm were predictive factors of poor facial nerve recovery, re-emphasising the need to detect and remove these tumours at an early stage. Electroneuronography performed around one week after surgery appears to be a good indicator of the likelihood of recovery in facial nerves which are anatomically intact, but which show no function at that stage. Multiple rehabilitative procedures are often required when inadequate function or poor cosmetic results are obtained. Primary nerve repair or facial-hypoglossal anastomosis provide better rehabilitative results than dynamic and static procedures.
A case of primary malignant melanoma of the dura mater occuring in a 10-year-old girl is reported. Surgical excision was complicated by the location of the lesion in the region of the torcular Herophili. The aetiology and treatment of melanoma in the central nervous system is discussed.
A consecutive series of 100 translabyrinthine operations for removal of acoustic neurinoma is reported. Complete tumor removal was achieved in 97% of cases. There were three perioperative deaths, and the postoperative morbidity rate was low. The facial nerve was preserved anatomically in 82% of patients. Preoperative facial weakness and tumor size larger than 2.5 cm were predictive of poor facial recovery. In patients with an intact nerve but complete facial palsy 1 week after surgery, electroneuronography was a good predictor of the final facial outcome and may influence the timing of rehabilitative procedures. With the exception of patients who have small tumors and good speech discrimination (where a suboccipital approach may preserve hearing acuity), the translabyrinthine operation is the procedure of choice for removal of acoustic neurinomas in patients who have normal hearing in the contralateral ear.