Arteriovenous malformation hemodynamics: a transcranial Doppler study.

Congenital arteriovenous malformation (AVM) of the brain represents a defect in capillary development resulting in a high flow fistula between arterial and venous systems. In this study, AVM hemodynamics were related with clinical findings. Volume flow was calculated based on transcranial Doppler (TCD) and angiographic data. Forty patients admitted to the Massachusetts General Hospital for proton beam therapy (33 +/- 10 yr old; mean +/- SD) were studied. Four symptoms were considered: intracranial bleeding, progressive neurological deficit, seizures, and headache. Fourteen control subjects aged 30 +/- 7 years (mean +/- SD) were normal volunteers. Angiography with calibrated markers permitting magnification correction was available for all patients. Lateral and medial depth limits of the intracranial basal arteries in relation to the TCD temporal window were determined by TCD and angiogram with excellent correlation. Selected depth for data acquisition was determined independently in the angiogram and by TCD. The difference between the two techniques was less than 4 mm. Mean flow velocity, pulsatility index, and vessel diameter were studied. Flow volume was calculated from these data. Mean flow velocity, pulsatility index, vessel diameter, and flow volume were significantly different among AVM feeders, non-feeders, and control arteries. The non-feeding middle cerebral artery, anterior cerebral artery, and posterior cerebral artery flows were 254 +/- 13, 136 +/- 14, and 79 +/- 8 ml/min, respectively. Accordingly, the estimated cerebral flow volume was 938 ml/min. The feeding middle cerebral artery, anterior cerebral artery, and posterior cerebral artery flows were 552 +/- 47, 369 +/- 70, and 484 +/- 67 ml/min, respectively (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Pregnancy and the risk of hemorrhage from cerebral arteriovenous malformations.

We conducted a retrospective analysis of 451 women with an arteriovenous malformation (AVM) of the brain to determine whether pregnancy is a risk factor for cerebral hemorrhages. A total of 540 pregnancies occurred among our patient population, resulting in 438 live births and 102 abortions. There were 17 pregnancies complicated by a cerebral hemorrhage. The hemorrhage rate during pregnancy for women with an unruptured AVM was 0.035 +/- 0.005 per person-year. The hemorrhage rate for nonpregnant women of childbearing age with an unruptured AVM was 0.031 +/- 0.002 per person-year. Pregnancy did not increase significantly the rate of first cerebral hemorrhage from an AVM (P = 0.35). We found that women with an AVM face a 3.5% risk of hemorrhage during pregnancy. Pregnancy is not a risk factor for hemorrhage in women without a previous hemorrhage. This conclusion assumes no selection bias exists in our study population; a bias would be introduced if the risk of fatal outcome after a hemorrhage were greater in pregnant women than in nonpregnant women.

Cerebellar venous angioma associated with angiographically occult brain stem vascular malformation. Report of two cases.

We studied two patients with angiographically documented cerebellar venous angioma (malformation) and angiographically occult vascular malformation of the brain stem. One patient had recurrent hemorrhage in the pontine tegmentum. The second patient had recurrent hemorrhage in the midbrain. None had hemorrhage originating from the abnormal cerebellar venous channels. The more benign nature of angiographic venous malformations is supported by the cases we are presenting, as well as from a review of the literature, which includes an autopsy study of similar cases. The management of multiple vascular brain lesions is contingent on the verification of symptomatic pathological blood vessels. It is emphasized that angiographically occult vascular malformation could possibly exist in the vicinity of angiographic venous malformation when the patient with intracerebral hemorrhage, especially in the posterior fossa, was diagnosed as having venous malformation.

Intracerebral arteriovenous malformations: evaluation with selective MR angiography and venography.

Magnetic resonance (MR) angiography and spin-echo methods were used to evaluate intracerebral arteriovenous malformations (AVMs) in 10 patients. Spin-echo images obtained with flow presaturation demonstrated the nidus of the AVM in all cases, but it was difficult to determine feeding vessels. These vessels were directly visualized with three-dimensional MR angiography; their presence could be indirectly determined by means of selective presaturation of individual vessels, which resulted in a marked decrease in signal within the portion of the AVM supplied by that vessel. Vascular supplies from the internal carotid artery and anterior, middle, or posterior cerebral arteries were detected in all cases, but in three large malformations it was not possible to demonstrate small feeding vessels. MR angiograms were also helpful for further defining the nidus. The combination of MR angiographic and spin-echo methods provides information useful for therapeutic planning not provided by either technique alone.

Hypertension does not cause spontaneous hemorrhage of intracranial arteriovenous malformations.

The authors measured blood pressure changes non-invasively in 56 conscious, unpremedicated patients with cerebral arteriovenous malformations (AVMs) during preparation for proton beam therapy. The procedure requires six injections of local anesthetic and application of a stereotactic frame by fixation into the outer table of the skull, and has been used during the past 20 yr to treat over 1,000 patients with cerebral AVMs. No effort was made to control blood pressure. Blood pressure increased during administration of the local anesthetic and application of the frame. Maximum systolic and mean arterial pressures averaged 160 +/- 17 and 118 +/- 7 mmHg (mean +/- SD), respectively. This represented an average increase of 44 mmHg (38%) in systolic pressure and 32 mmHg (37%) in mean blood pressure at some point during the procedure (P less than 0.01 compared with pretreatment control pressures). Systolic pressure increased more than 60 mmHg in 21% of patients. Nevertheless, none of these 56 patients nor any of the more than 1,000 patients treated in similar fashion suffered a clinically evident AVM hemorrhage during the procedure. Since the treatment protocol has not changed materially during the past 20 yr, the authors assume that most patients treated in this fashion developed a similar degree of hypertension and conclude from this large clinical experience that moderate arterial hypertension does not precipitate spontaneous hemorrhage of intracranial AVMs.

Is the syndrome of pathological laughing and crying a manifestation of pseudobulbar palsy?

A case of angiographically occult brainstem vascular malformation presenting solely with pathological laughing and crying is reported. Although this emotional syndrome has been seen in association with several different pathological entities, review of the literature failed to identify its occurrence as the only clinical expression of angiographically occult brainstem vascular malformation, or as a solitary symptom in any disease. Our data suggest that pathological laughing and crying can occur without any other manifestation of pseudobulbar palsy. An attempt is made to correlate this patient's clinical and radiological findings. This case was treated by stereotactic Bragg-peak proton beam therapy.

Clinical presentations of vascular malformations of the brain stem: comparison of angiographically positive and negative types.

Clinical and radiographic features of 63 patients with a vascular malformation of the brain stem are described. On radiological grounds they were divided into two groups: one with angiographically visible lesions (AVAVMs), the other with lesions not seen angiographically, that is, occult (AOVMs). In the first group the initial clinical manifestation was due to haemorrhage in 20 of the 33 cases and consisted of a progressive neurological deficit in 12. In the second group 29 of the 30 initially presented with a brain stem haemorrhage. The latter was often characterised by development of symptoms over two days or more (16 cases), absence of headache (48 cases) and tendency to recurrence (20 cases). Clinical diagnosis was difficult in many cases especially in the AOVM group. Several of the patients were misdiagnosed as having multiple sclerosis. Clinical data in conjunction with magnetic resonance imaging were helpful in determining the nature of these lesions.

Transposition of target information from the magnetic resonance and computed tomography scan images to conventional X-ray stereotactic space.

A technique to apply reconstructed X-ray computed tomography (CT) and magnetic resonance imaging (MRI) for target determination in stereotactic Bragg peak proton beam therapy of intracranial lesions was developed. Twenty-one benign intracranial tumors and vascular abnormalities were managed using this technique. Clinical features of these lesions, as well as targeting problems associated with the MRI and CT image interpretation, are presented.

MR and CT of occult vascular malformations of the brain.

The need for improved specificity in the diagnosis of "occult" vascular malformations led to the use of MR in suspected cases in order to determine MR's potential for improved diagnostic accuracy. Six patients with six lesions histologically diagnosed as vascular malformation after partial (1) or complete (5) microsurgical excision were studied by CT, MR, and selective magnification subtraction angiography. In all cases, the cerebral lesions were apparently solitary and were visible as focal lesions on both CT and MR. Since angiography failed to reveal the pathologic blood vessels of the lesions, and no arteriovenous shunting was evident, these lesions were termed vascular malformations occult to angiography (VMOTA). Angiography revealed a mass effect in only two cases. MR did not reveal additional vascular malformations missed by CT. In each case, MR, which was performed in an attempt to support the diagnosis suggested by CT, did in fact do so by revealing signal abnormalities indicative of nonacute hemorrhage within the lesion on T1- and T2-weighted pulse sequences. Although, as on CT, MR features of these lesions were found to be nonspecific, the MR criteria reinforced the probable diagnosis of VMOTA in an additional 30 cases that had shown similar nonspecific CT features. In this second group, excluded from this study, in which histologic verification was not obtained because of perceived hazards of surgery, the increased assurance regarding the diagnosis led to proton-beam therapy without histologic verification in 18 cases. It is concluded that MR can provide significant improvement in the accuracy of diagnosing VMOTA beyond that obtainable just by plain and contrast-enhanced CT.

Stereotactic Bragg peak proton beam radiosurgery for cerebral arteriovenous malformations.

A series of 709 patients with inaccessible AVMs treated with the proton beam is reported. There is a follow-up time of over 2 years for 92% of the patients. AVMs have slightly lower thresholds for proton injury than does normal brain tissue. Proton beam therapy involves very low risk. However, the risks of treatment failure grow with inadequate therapeutic doses.

Bragg-peak proton-beam therapy for arteriovenous malformations of the brain.

Patients with arteriovenous malformations of the brain, who are subject to disabling or fatal recurrent hemorrhage, seizures, severe headache, and progressive neurologic deficits, may be considered unsuitable for conventional therapies (craniotomy with excision or embolization), usually because of the location, size, or operative risk of the lesion. We have treated such patients with stereotactic Bragg-peak proton-beam therapy and report the follow-up of 74 of the first 75, 2 to 16 years after treatment. Proton-beam therapy is intended to induce subendothelial deposition of collagen and hyaline substance, which narrows the lumens of small vessels and thickens the walls of the malformation during the first 12 to 24 months after the procedure. Two deaths from hemorrhage occurred in the first 12 months after treatment, but no lethal or disabling hemorrhages occurred after this interval. Seizures, headaches, and progressive neurologic deficits were in most cases arrested or improved. Bragg-peak proton-beam therapy appears to be a useful technique for treatment of intracranial arteriovenous malformations, especially those that are unsuitable for treatment by other methods.

Estradiol treatment of acromegaly. Reduction of immunoreactive somatomedin-C and improvement in metabolic status.

Administration of estrogens to acromegalic patients has been shown to reduce the serum concentrations of bioassayable somatomedin and to cause improvement in clinical status. These effects appear not to result from an effect on the secretion of growth hormone since growth hormone concentrations are not consistently reduced. Using a sensitive radioimmunoassay for somatomedin-C, we have assessed the relationship between the estrogen-induced reduction of somatomedin-C and changes in several indices of disease activity in five acromegalic patients. Statistically significant reductions in serum somatomedin-C (p < 0.02), urinary hydroxyproline (p < 0.05) and the phosphate clearance ratio (p < 0.01) occurred within three days of the institution of treatment with 1 mg ethynyl estradiol daily. Unlike the consistent reduction in serum somatomedin-C erratic changes in growth hormone were observed. The decline in serum somatomedin-C was not due to an estrogen-induced increase in somatomedin-binding proteins since total serum somatomedin-C concentrations measured after treatment of serum with acid also were reduced by estrogen therapy, and the magnitude of this reduction was equivalent to that observed in untreated serum. The study indicates that the reduction of immunoreactive somatomedin-C correlates with estrogen-induced improvement in the metabolic activity of acromegalic patients and suggests that measurement of somatomedin-C may be useful in monitoring the effects of other drugs on this disease.

Metrizamide sagittal tomography: adjunct to CT cisternography of the sellar region.

A total of 30 patients with pituitary adenoma was studied by sagittal polytomography en route to coronal and axial computed tomography (CT) cisternography after a low FDA-approved dose of 6 ml of 170 mg I/ml metrizamide via lumbar injection. The requirement for defining the relation of the optic nerves and chiasm to the intrasellar contents or suprasellar mass before proton beam irradiation or certain surgical approaches was satisfied. Pneumoencephalography as a supplemental procedure to CT and CT cisternography was replaced. The concomitant elimination of conventional sellar polytomography and pneumoencephalography results in decreased total radiation exposure and a more comfortable, expeditious workup.

Metabolic clearance and production rates of prolactin in man.

Metabolic clearance rates (MCR) and production rates (PR) of prolactin (PRL) have been determined by the constant infusion to equilibrium technique in 11 normal subjects, 6 patients with hyperthyroidism, 4 patients with hypothyroidism, and 9 patients with hyperprolactinemia. PRL MCR was also determined tin four patients during dopamine infusion. Mean PRL MCR was 46 +/- 1 ml/min per m2 in women and 44 +/- 3 ml/min per m2 in men, and was significantly correlated with body mass (r = 0.84, P less than 0.001). In contrast with controls, PRL MCR was higher in hyperthyroidism (MCR = 52 +/- 8 ml/min per m2, P less than 0.05), was slightly lower in hypothyroidism (MCR = 38 +/- 10 ml/min per m2, P = NS), and was significantly correlated with serum thyroxine (r = 0.46, P less than 0.02). PRL MCR was lower than controls in hyperprolactinemia (MCR = 40 +/- 5 ml/min per m2, P less than 0.01) and was inversely correlated with serum PRL (r = -0.72, P less than 0.001). PRL MCR was not significantly changed by dopamine infusion. Mean PRL PR for women and men was 211 +/- 74 and 187 +/- 44 micrograms/d per m2, respectively (P = NS). In hyperthyroidism the PRL PR was elevated (PR = 335 +/- 68 micrograms/d per m2, P less than 0.02), but in hypothyroidism the increase (PR = 233 +/- 159 micrograms/d per m2) was not significant. In hyperprolactinemia the PRL PR was extremely high (PR = 31,000 +/- 29,000 micrograms/d per m2). Dopamine infusion decreased RPL PR from 270 to 66 micrograms/d per m2 indicating that its effect was on pituitary PRL secretion and not PRL metabolism. To evaluate possible circulating PRL heterogeneity that might arise during infusion, gel filtration of infusate and serum obtained during the MCR procedure was performed. Labeled monomeric PRL (peak III, Kav (partition coefficient) = 0.4) was partially converted to two larger forms (peaks I and II) in vivo. Peak I (Kav = 0) was 30--40% immunoprecipitable, although peak II (Kav = 0.2) was not immunoprecipitable. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of peak I resulted in greater than or equal to 90% conversion to peak III and restoration of full immunoactivity. Thus, peak I is a noncovalently linked aggregate that is partially immunoactive, and therefore able to alter MCR determinations. These studies demonstrate the impact of hormone heterogeneity on MCR estimations and suggest that gel filtration of immunoprecipitable material be an integral part of future MCR measurements.

Evaluation of acromegaly by radioimmunoassay of somatomedin-C.

We measured serum concentrations of somatomedin-C by radioimmunoassay in 57 acromegalic patients and compared them with various indicators of disease activity. The mean fasting somatomedin-C concentration was 6.8 U per milliliter (range, 2.6 to 21.7) for the acromegalics and 0.67 U per milliliter (range, 0.31 to 1.4) for 48 normal, fasting adults. The somatomedin-C concentration correlated significantly with: heel-pad thickness (r = 0.73), fasting glucose (r = 0.74), and one-hour postprandial glucose (r = 0.77). In contrast, "glucose-suppressed" growth hormone correlated weakly (r = 0.34, 0.36, 0.34) with these clinical indexes of severity. Fasting growth hormone levels showed no correlation (r = 0.14). Five active acromegalics had "normal" growth hormone levels after glucose suppression, but they had elevated somatomedin-C. In 15 patients studied one year after treatment, changes in somatomedin-C concentrations paralleled the degree of clinical improvement. Measurement of somatomedin-C appears to provide a reliable means for confirming the diagnosis of acromegaly and of clinical disease activity than measurement of growth hormone concentrations.

Tension pneumocephalus of the cranial subdural space: a case report.

A case of subdural tension pneumocephalus is presented. Computerized cranial tomography permitted rapid diagnosis including localization of the air, thus facilitating prompt treatment. Tension pneumocephalus should be considered in a patient with a cerebrospinal fluid drainage device who deteriorates after craniotomy.