Bjørn Sperling

Cgrp May Play A Causative Role in Migraine

Calcitonin gene-related peptide (CGRP) has been detected in increased amounts in external jugular venous blood during migraine attacks. However, it is unknown whether this is secondary to migraine or whether CGRP may cause headache. In a double-blind crossover study, the effect of human αCGRP (2 μg/min) or placebo infused intravenously for 20 min was studied in 12 patients suffering from migraine without aura. Headache intensity was scored on a scale from 0 to 10. Two patients were excluded due to severe hypotension and one because she had an infection. In the first hour median peak headache score was 1.0 in the hαCGRP group vs. 0 in the placebo group (P < 0.01). During the following 11 h all patients experienced headaches after hαCGRP vs. one patient after placebo (P = 0.0004). The median maximal headache score was 4 after CGRP and 0 after placebo (P = 0.006). In three patients after hαCGRP, but in no patients after placebo, the delayed headache fulfilled the IHS criteria for migraine without aura. As intravenous administration of hαCGRP causes headache and migraine in migraineurs, our study suggests that the increase in CGRP observed during spontaneous migraine attacks may play a causative role.

Migraine pain associated with middle cerebral artery dilatation: reversal by sumatriptan

The combination of measurements of regional cerebral blood flow (rCBF) and blood velocity in the middle cerebral arteries (MCA) by transcranial doppler sonography was used to investigate cerebrovascular involvement in migraine. Ten migraine patients with unilateral headache were studied during an attack and when they had been free of attacks for 5 days (non-attack). On both occasions they were given as intravenous infusion of sumatriptan (2 mg), a 5-HT1-like receptor agonist, which relieved the symptoms within 30 min without affecting rCBF. The MCA velocity was normal on both sides on the non-attack day and on the unaffected side during the attack. However, during the attack the MCA velocity on the headache side was significantly lower than that on the non-headache side (45 vs 61 cm/s:mean difference 16.3 [95% confidence interval 10.3-22.3]; p = 0.02). The MCA velocity on the headache side returned to normal after treatment with sumatriptan and recovery. Since rCBF in the MCA supply territory was unaffected, the lower velocity can be explained only by dilatation of the MCA. The mean MCA diameter increase was estimated to be 20%. Thus, headache was associated with intracranial large arterial dilatation on the headache side. Sumatriptan predominantly had effects on the distended artery, which suggests that the 5-HT receptor system has a role in the pathogenesis of migraine.

Incomplete Brain Infarction of Reperfused Cortex May Be Quantitated With Iomazenil

BACKGROUND AND PURPOSE [123I]Iomazenil is a specific radioligand for the central benzodiazepine receptor that may be useful as an indicator of the intactness of cortical neurons after focal cerebral ischemia. We evaluated the binding of this receptor in reperfused cortex among patients with ischemic stroke to detect viable neurons in cortex that appeared structurally intact on conventional neuroimaging studies. METHODS Fourteen patients were selected by (1) angiography within 24 hours of onset showing embolic occlusion of an intracranial artery, (2) cerebral blood flow showing ischemia of moderate severity in 12 cases and spontaneous reflow in 2 cases, and (3) thrombolysis with reperfusion within 24 hours in most cases. Thirty reperfused cortical areas that remained structurally intact, 7 infarcted cortical areas, and 6 contralateral cerebellar areas with reduced blood flow were selected as regions of interest to estimate receptor binding 5 days to 23 months after the stroke. A two-compartment model was used to compute the distribution volume (Vd) of iomazenil in relative units, with Vd proportional to benzodiazepine receptor concentration. The side-to-side asymmetry ratio of Vd was calculated. RESULTS The mean asymmetry ratio was 0.89 +/- 0.11 (range, 0.64 to 1.05), 0.50 +/- 0.15 (range, 0.23 to 0.67), and 0.97 +/- 0.05 (range, 0.90 to 1.04) in reperfused cortex, infarcted cortex, and contralateral cerebellum, respectively. Compared with unity, both reperfused cortex and infarcted cortex showed significant decrease of Vd (P < .001). Contralateral cerebellum showing diaschisis had no reduction of Vd. On MRI, obtained 3 or 6 months after the stroke, mild cortical atrophy was observed in two reperfused areas where the asymmetry ratio was moderately reduced (0.64 and 0.80). CONCLUSIONS The reduction of benzodiazepine receptor concentration in reperfused cortex that remained structurally intact is likely to be the result of injury involving only a limited number of neurons (ie, incomplete infarction). Our data suggest that the degree of viability of ischemic cortex apparently salvaged by early reperfusion can be quantified by iomazenil.

Reduced contralateral hemispheric flow measured by SPECT in cerebellar lesions: crossed cerebral diaschisis

Four patients with clinical signs of cerebellar stroke were studied twice by SPECT using ”“Tc-HMPAO as a tracer for cerebral blood flow (CBF). When first scanned 6 to 22 days after onset, all had a region of very low CBF in the symptomatic cerebellar hemisphere, and a mild to moderate CBF reduction (average 10 %) in contralateral hemispheric cortex. In all four cases clinical signs of unilateral cerebellar dysfunction were still present when rescanned 1 to 4 months later and the relative CBF decrease in the contralateral cortex of the forebrain also remained. The basal ganglia contralateral to the cerebellar lesion CBF showed variable alterations. A relative CBF decrease was seen in upper part of basal ganglia in all four cases, but it was not a constant phenomenon. A relative CBF increase in both early and late SPECT scans was seen at low levels of neostriatum in two cases. The remote CBF changes in cerebellar stroke seen in the forebrain are probably caused by reduced or abolished cerebellar output. The term “Crossed Cerebral Diaschisis” may be used to describe these CBF changes that would appear to reflect both decreased and increased neuronal 1 activity.

Interictal "patchy" regional cerebral blood flow patterns in migraine patients. A single photon emission computerized tomographic study.

In 92 migraine patients and 44 healthy control subjects we recorded regional cerebral blood flow (rCBF) with single photon emission computerized tomography and 133Xe inhalation or with i.v. 99mTc‐HMPAO. Migraine patients were studied interictally. A quantitated analysis of right‐left asymmetry indices in a fixed set of regions of interest was compared with the normal asymmetry indices in the healthy controls. An asymmetry index deviating more than ± 2.5 S.D.s in normals was defined as pathological asymmetry. By quantitated analysis 47% of images from patients with aura attacks and 48% of images from patients without aura attacks were established to contain higher rate of asymmetries, the difference being statistically significant (p < 0.05, Wilcoxon). A blinded visual analysis and scoring by a four level scale were done by four experienced observers. rCBF images from 18% of patients having attacks with aura and from 19% of patients without aura attacks was scored as containing abnormal right‐left asymmetries by the visual analysis. Images from healthy controls were all scored to be normal. In 37% of the images (all from patients) there was lack of consensus among observers (κ = 0.28). There was no correlation between visual or quantitated abnormalities and age, duration of migraine, frequency of attacks or prophylactic medication. No correlation could be established between asymmetries and the usual side of headache or aura symptoms. Two conclusions emerged: (1) visual evaluation of interictal migraine rCBF images is insufficient to pick up abnormalities; (2) almost 50% of the migraine sufferers had abnormal rCBF/asymmetries. However, these are discrete compared with those typically seen during the aura phase of a migraine attack. One explanation to the patchy rCBF patterns might be that they reflect interictal cerebrovascular dysregulation which might to be a common feature in both types of migraine.

The effect of i.v. L-NG methylarginine hydrochloride (L-NMMA: 546C88) on basal and acetazolamide (Diamox) induced changes of blood velocity in cerebral arteries and regional cerebral blood flow in man.

The aim of this study was to estimate the effect of Nitric Oxide synthase (NOS)-inhibition (L-NMMA) on the diameter of the middle cerebral artery (MCA) and on regional cerebral blood flow (rCBF). Furthermore, to assess the effect of L-NMMA on acetazolamide induced increases in MCA blood velocity (Vmean) and rCBF. In an open crossover design 12 healthy subjects attended the laboratory twice. The first day 6 mg/kg L-LNMMA i.v. over 15 min preceded 1 g acetazolamide iv over 5 min. Eight days later only acetazolamide was given. Vmean in MCA was determined with transcranial Doppler (TCD) and rCBF with Xe-133 inhalation SPECT at baseline, after L-NMMA and 25 and 55 min after acetazolamide infusion. After L-NMMA the decrease in rCBFMCA was 6.8% (± 7.4) (P < 0.019, n = 12), whereas Vmean was not affected (P = 0.83, n = 8). The change in MCA diameter was estimated to -1.3% (P = 0.44, n = 8). L-NMMA did not affect acetazolamide increases in Vmean (P = 0.67, n = 8) nor rCBF (P = 0.29, n = 12). The percentage increase of Vmean was 1.5 times that of rCBF (n = 8). Our data suggest that the basal tone of human cerebral arterioles but not of conduit arteries is NO-dependent. The action of acetazolamide in man is not NO-dependent.

MR-visible brain water content in human acute stroke

Quantification of metabolite concentrations by proton magnetic resonance spectroscopy (1H-MRS) in the human brain using water as an internal standard is based on the assumption that water content does not change significantly in pathologic brain tissue. To test this, we used 1H-MRS to estimate brain water content during the course of cerebral infarction. Measurements were performed serially in the acute, subacute, and chronic phase of infarction. Fourteen patients with acute cerebral infarction were examined as well as 9 healthy controls. To correlate with regional cerebral blood flow (rCBF) SPECT-scanning using 99mTc-HMPAO as flow tracer was performed in the patients. Mean water content (SD) in the infarct area was 37.7 (5.1); 41.8 (4.8); 35.2 (5.4); and 39.3 (5.1) mol x [kg wet weight](-1) at 0-3; 4-7; 8-21; and >180 days after stroke, respectively. Water content increased between Day 0-3 and Day 4-7 (p = 0.034) and decreased from Day 0-3 to Day 8-21 (p = 0.028). Water content at Day 4-7 was significantly higher than in controls (p < or = 0.05). At the same time intervals, mean rCBF (SD) was 76 (23); 94 (31); 106 (35); and 64 (26)%, respectively. There was a significant increase in rCBF from Day 0-3 to Day 4-7 (p = 0.050) and from Day 0-3 to Day 8-21 (p = 0.028). No correlation between rCBF and water content was found. Water content in ischemic brain tissue increased significantly between Day 4-7 after stroke. This should be considered when performing quantitative 1H-MRS using water as an internal standard in stroke patients.