Kenichi Uemura

Plasma Concentrations of Brain Natriuretic Peptide in Patients With Subarachnoid Hemorrhage

BACKGROUND AND PURPOSE Hyponatremia after subarachnoid hemorrhage (SAH) is commonly associated with diuresis and natriuresis, but the causes are still controversial. We investigated whether brain natriuretic peptide (BNP) was related to such hyponatremia. METHODS Plasma BNP concentrations were measured by immunoradiometric assay in 18 patients at 0 to 2 days (period 1), 7 to 9 days (period 2), and > 14 days (period 3) after SAH. Plasma concentrations of antidiuretic hormone (ADH), atrial natriuretic peptide (ANP), and noradrenaline were also measured during period 2. RESULTS The 11 patients with hyponatremia (serum sodium concentration of < 135 mEq/L) had much higher plasma BNP concentrations during each period than did healthy controls (P < 0.05), whereas the 7 patients with normonatremia did not show statistically higher values. In the patients with hyponatremia, the plasma BNP concentration during period 2 was statistically higher than that during periods 1 and 3 (P < 0.05). The plasma noradrenaline concentration during period 2 was higher in patients with hyponatremia than in those with normonatremia (P < 0.05), whereas the plasma concentrations of ADH and ANP during period 2 were not statistically different between the hyponatremic and normonatremic patients. CONCLUSIONS We conclude that BNP may be related to hyponatremia associated with natriuresis following SAH. The increase of noradrenaline may promote the secretion of BNP.

Subthalamic nucleus stimulation for gait disturbance in Parkinson's disease.

OBJECTIVE A preliminary study of subthalamic nucleus (STN) stimulation was performed to determine its applicability for the treatment of gait and postural disturbances in Parkinsons disease. METHODS Five Parkinsons disease patients with freezing gait and postural instability were selected for this study. Their ages ranged from 60 to 73 years (mean+/-standard deviation, 65.6+/-4.8 years). Semi-microelectrode recording was used to identify the STN and to place a chronic electrical stimulation electrode within the right STN in all patients. The Unified Parkinsons Disease Rating Scale and the modified Hoehn and Yahr Staging Scale were used to assess patients in on- and off-drug conditions before surgery and 3 months after surgery. RESULTS The scores on the Hoehn and Yahr Staging Scale and the total Unified Parkinsons Disease Rating Scale for akinesia (P < 0.05), gait (P < 0.05), and gait and posture (P < 0.01) in off-drug on-stimulation conditions significantly improved over the preoperative and postoperative off-drug off-stimulation conditions (analysis of variance [ANOVA], P < 0.01). Improvement over the preoperative scores was 24% on the Hoehn and Yahr Staging Scale, 43.6% on the total Unified Parkinsons Disease Rating Scale, 33.4% for akinesia, 36.6% for gait, and 38.7% for gait and posture. However, stimulation in the on-drug phase did not show a significant difference compared with pre- and postoperative conditions (ANOVA, P > 0.05). Comparisons between preoperative on-drug and postoperative off-drug on-stimulation conditions revealed that there were no significant differences in the scores, except for gait (ANOVA, P < 0.05). The scores on subscales for falling, freezing, walking, and gait in off-drug on-stimulation conditions were significantly improved over the scores for preoperative and postoperative off-stimulation (ANOVA, P < 0.05), but the score for postural stability remained unchanged. CONCLUSION Our findings showed that STN stimulation effectively alleviates freezing gait and improves walking to its status during the preoperative on-drug phase and can be applied for treatment of Parkinsons disease patients with these symptoms.

MRI of Intracranial Neurovascular Compression

Twelve patients with clinical indications of intracranial neurovascular compression (6, hemifacial spasm; 4, trigeminal neuralgia; 2, vertigo and tinnitus) were studied by MRI. Axial 1 mm thick slices were obtained in a 1.5 T unit using a three-dimensional (3D) fast low angle shot data set of 32 contiguous slices. The data were postprocessed with multiplanar reconstruction algorithms to obtain oblique sagittal (along the long axis of a nerve) images or coronal images with a slice thickness of 0.8 mm. The MR angiographic images were also obtained from the same 3D data set with maximum intensity projection algorithms. The MR studies showed that 9 of 12 patients had neurovascular compression caused by one or two arteries. These findings were verified at surgery. In two of the remaining three patients, MRI failed to delineate the affected nerves compressed by a vein in one, and a previously applied prosthesis in the other. In the last patient no neurovascular compression was found by MRI or at surgery.

Chronological Changes of Arterial Diameter, cGMP, and Protein Kinase C in the Development of Vasospasm

BACKGROUND AND PURPOSE We hypothesized that nitric oxide exerts a negative feedback control on protein kinase C (PKC) activation, and the disturbance of the feedback control after subarachnoid hemorrhage results in vasospasm due to PKC activation. This study was undertaken to verify this hypothesis. METHODS Different dogs were prepared for three separate experiments: measurement of the angiographic diameter of the basilar artery and determination of cGMP and PKC activity in vascular smooth muscle cells. In each experiment, two models were used: the single-hemorrhage model for mild vasospasm and the two-hemorrhage model for severe vasospasm. In both models, chronological changes of these three parameters were examined from day 1 until day 7. RESULTS In the single-hemorrhage model, mild vasospasm and a slight decrease of the cGMP level were noted on day 4, then both returned to the baseline levels on day 7. PKC activity was slightly enhanced throughout the study period. In the two-hemorrhage model, severe vasospasm and a significant decrease of the cGMP level were observed on day 5 and persisted until day 7. PKC activity was remarkably enhanced from day 5 until day 7. The differences between the two models with regard to the three parameters were statistically significant. CONCLUSIONS The decrease of cGMP level and the enhancement of PKC activity were obviously associated with the development of severe vasospasm. We conclude that subarachnoid hemorrhage disturbed the feedback control exerted by nitric oxide on PKC activation, leading to PKC-dependent vasospasm.

CT classification of small thalamic hemorrhages and their clinical implications

Thirty-seven small thalamic hemorrhages (less than 2 cm) were classified into four types depending on topographic location. Patients with posterolateral lesions had severe sensory and motor disability as well as the worst prognosis. Anterolateral lesions resulted in mild prefrontal signs with milder sensory and motor impairment. Medial hematomas disturbed consciousness in the acute stage, followed by impaired prefrontal signs of long duration. Dorsal hematomas were associated with ipsilateral parieto-occipital signs (aphasia on the left and topographic memory disturbance on the right).

Relation between protein kinase C and calmodulin systems in cerebrovascular contraction: investigation of the pathogenesis of vasospasm after subarachnoid hemorrhage.

The protein kinase C (PKC) and calmodulin systems each play a role in vascular contraction. However, the correlation of these two systems in producing contraction has been unclear. To clarify the pathophysiology of vasospasm after subarachnoid hemorrhage, the authors demonstrated tonic contraction of the cerebral artery in a study of isometric tension, and investigated the correlation of the PKC and calmodulin systems in producing the contraction. To develop better management for vasospasm, they also examined the effect of calmodulin antagonists on tonic contraction. The development of isometric tension in canine basilar arteries was measured, with the following results: 1) tonic contraction was dependent on the PKC system, but initiation of the contraction by the calmodulin system was necessary for the subsequent PKC-dependent tonic contraction; 2) specific calmodulin antagonists like chlorpromazine and pimozide partially inhibited the tonic contraction associated with PKC activation; 3) another calmodulin antagonist, trifluoperazine, inhibited the PKC system as well. On the basis of these results, the authors conclude that the PKC system plays a role in the development of vasospasm. In the early phase of contraction, the calmodulin system contributes to the subsequent fully-activated, PKC-induced tonic contraction. To manage vasospasm, a specific calmodulin antagonist would therefore not be sufficient. Suppression of both the calmodulin and PKC systems with trifluoperazine in the earliest stage of vasospasm is recommended.

Cerebral blood flow autoregulation following subarachnoid hemorrhage in rats: Chronic vasospasm shifts the upper and lower limits of the autoregulatory range toward higher blood pressures

We sought to determine whether chronic vasospasm following subarachnoid hemorrhage (SAH) would abolish the cerebral blood flow (CBF) autoregulation in anesthetized Sprague-Dawley rats. SAH was induced by intracisternal injection of autologous blood; in control animals saline was injected instead. CBF was measured 48 h after SAH, that is during chronic vasospasm, by laser-Doppler flowmetry over the frontal cortex under condition of hypertension (SAH, n = 6; control, n = 8) or hypotension (SAH, n = 6; control, n = 6). Hyper- and hypotension were induced by increasing mean arterial blood pressure (MABP) stepwise from 90 to 180 mmHg with phenylephrine (0.1-10 micrograms/min i.v.), or by decreasing it from 90 to 40 mmHg by controlled hemorrhage. An autoregulatory index (AI) expressed as delta CBF (%) per 10 mmHg increase or decrease in MABP was employed to analyze CBF response. CBF remained constant (-7 < AI < 7) at MABPs ranging from 60 to 130 mmHg in the control group and from 70 to 140 mmHg in the SAH group, showing CBF autoregulation. In the SAH group, that is, the upper and the lower limits of autoregulatory range were increased by 10 mmHg (p < 0.05). SAH did not increase intracranial pressure significantly (control 9.2 +/- 0.67 vs. SAH 10.0 +/- 1.05 mmHg, n = 5) 48 h after SAH was induced. These results indicate that, during chronic vasospasm, SAH does not abolish the autoregulation process but raises its lower and upper blood pressure limits. The capacity of spastic cerebral arteries to dilate in case of hypotension decreased, while their tolerance to hypertension increased.

Low frequency stimulation induces an increase in after-discharge thresholds in hippocampal and amygdaloid kindling

In rats with electrodes implanted in the hippocampus or amygdala, the effect was studied of a single episode of low frequency stimulation (125 msec, biphasic 4 Hz, for 1 min at a current 50% of threshold for after-discharge), LFS, on the after-discharge thresholds (ADTs) during the course of hippocampal and amygdaloid kindling. ADTs were significantly increased following the LFS. The effect lasted longer (hippocampus, 12 days; amygdala, 5 days) when the LFS was given on day 1 of kindling than when kindling was fully established (less than 24 h).

Therapeutic Effect of a New Immunosuppressant, FK-506, on Vasospasm after Subarachnoid Hemorrhage

We hypothesized that the immunological reaction against extravasated blood might play a role in the development of vasospasm after subarachnoid hemorrhage. Under the hypothesis, we had reported significant therapeutic efficacy of cyclosporin A on vasospasm in canine models. We here investigated the efficacy of a new, potent immunosuppressant, FK-506, on vasospasm in animal models. Dogs were randomly classified into sham operated, subarachnoid hemorrhage treated-1 group, (FK-506, 0.3 mg/kg-d, intramuscular injection), and treated-2 group (FK-506, 0.15 mg/kg-d, intramuscular injection). Levels of the third factor of complement (C3) and the activity of serum complement inducing 50% hemolysis of sheep erythrocytes (CH50) in serum were also determined. In the treated groups, the levels of FK-506 in serum were monitored. As for C3 and CH50, there were no statistically significant differences among the groups and there were no changes between Day 1 and Day 7 in any group. Angiographical diameters of a basilar artery on Days 1 and 7 were measured with a computed image analyzer, and the extent of vasospasm was compared among the groups. Statistically significant differences between the sham-operated group and the other three groups were noted. However, under sufficient levels of FK-506 in serum, the extent of vasospasm in either treated group was the same as that in the subarachnoid hemorrhage group. These results indicate a significant discrepancy in the therapeutic mechanism for vasospasm between cyclosporin A and FK-506. They have common aspects in the immunosuppressive mechanism. However, in T-cell suppression, the different mechanism in situ between the two drugs is also postulated.(ABSTRACT TRUNCATED AT 250 WORDS)

Magnetic resonance angiography of extracranial carotid and vertebral arteries, including their origins: comparison with digital subtraction angiography

SummaryAlthough carotid bifurcation stenoses are not the only lesions of the extracranial cerebral arteries, magnetic resonance angiographic (MRA) studies to date have concentrated on the carotid bifurcation. We compared digital subtraction angiography of the extracranial portions of the cerebral arteries with MRA using an ordinary body coil, the time-of-flight method, and multiple transverse slabs which covered the arteries down to the aortic arch. Twenty-two patients (15 with arteriosclerotic diseases, 4 with aortitis, and 3 with tumours) had MRA using a 1.5 T magnet system with a three-dimensional fast imaging with steady state precession (FISP) technique. Thirty-nine carotid and 39 vertebral arteries were assessed by three radiologists with regard to stenoses or occlusions, graded as normal, mild (<30%), moderate (30–60%) or severe (>60%) stenosis, or occluded. Grading corresponded well in 81%; stenoses appeared more marked on MRA in 14% and were seen less clearly on MRA in 5%. When 26 carotid bifurcations were assessed separately, grading corresponded well in 95%. MRA is the only method which can display the whole course of the extracranial carotid and vertebral arteries non-invasively and satisfactorily.