Effects of cilostazol on cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a multicenter prospective, randomized, open-label blinded end point trial.

OBJECT: Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) is a major cause of subsequent morbidity and mortality. Cilostazol, a selective inhibitor of phosphodiesterase 3, may attenuate cerebral vasospasm because of its antiplatelet and vasodilatory effects. A multicenter prospective randomized trial was conducted to investigate the effect of cilostazol on cerebral vasospasm. METHODS: Patients admitted with SAH caused by a ruptured anterior circulation aneurysm who were in Hunt and Kosnik Grades I to IV and were treated by clipping within 72 hours of SAH onset were enrolled at 7 neurosurgical sites in Japan. These patients were assigned to one of 2 groups: the usual therapy group (control group) or the add-on 100 mg cilostazol twice daily group (cilostazol group). The group assignments were done by a computer-generated randomization sequence. The primary study end point was the onset of symptomatic vasospasm. Secondary end points were the onset of angiographic vasospasm and new cerebral infarctions related to cerebral vasospasm, clinical outcome as assessed by the modified Rankin scale, and length of hospitalization. All end points were assessed for the intention-to-treat population. RESULTS: Between November 2009 and December 2010, 114 patients with SAH were treated by clipping within 72 hours from the onset of SAH and were screened. Five patients were excluded because no consent was given. Thus, 109 patients were randomly assigned to the cilostazol group (n = 54) or the control group (n = 55). Symptomatic vasospasm occurred in 13% (n = 7) of the cilostazol group and in 40% (n = 22) of the control group (p = 0.0021, Fisher exact test). The incidence of angiographic vasospasm was significantly lower in the cilostazol group than in the control group (50% vs 77%; p = 0.0055, Fisher exact test). Multiple logistic analyses demonstrated that nonuse of cilostazol is an independent factor for symptomatic and angiographic vasospasm. The incidence of new cerebral infarctions was also significantly lower in the cilostazol group than in the control group (11% vs 29%; p = 0.0304, Fisher exact test). Clinical outcomes at 1, 3, and 6 months after SAH in the cilostazol group were better than those in the control group, although a significant difference was not shown. There was also no significant difference in the length of hospitalization between the groups. No severe adverse event occurred during the study period. CONCLUSIONS: Oral administration of cilostazol is effective in preventing cerebral vasospasm with a low risk of severe adverse events. Clinical trial registration no. UMIN000004347, University Hospital Medical Information Network Clinical Trials Registry.

[The association of age and tracer clearance determined radionuclide cisternography].

We aimed to study tracer kinetics in radioisotope (RI) cisternography. For this purpose, we analyzed the RI images of 36 individuals in whom absence of cerebrospinal fluid (CSF) leakage was confirmed. For the semiquantitative assessment of tracer clearance, the geometric mean of the RI count in the anterior and posterior images was obtained for the entire head as well as for the whole spinal axis. After correcting for the radioactive decay of the tracer, tracer clearance was expressed as a ratio of the count in the range of the whole CSF space at different time points to that at the time of tracer delivery. Tracer clearance from the CSF space was not related to the degree of cranial transport of the tracer in 1 hour, but was significantly related with the age of the patients. At 24 hours after the injection, tracer clearance was significantly faster in the younger patients (Group I: age < 40 years) than in the older patients (Group II: age > or = 40 years). The cranial transport of the tracer appeared to be rapid in group I; however, the difference between these 2 groups was not significant. These results indicate that age should be taken in account while establishing the reference values for tracer kinetics in normal individuals.

Effectiveness of an epidural blood patch for patients with intracranial hypotension syndrome and persistent spinal epidural fluid collection after treatment.

OBJECT: Magnetic resonance imaging may show a fluid collection in the spinal epidural space of patients with spontaneous intracranial hypotension syndrome (SIHS), but the chronological changes remain unclear. METHODS: Brain and spine MR imaging findings were analyzed in 16 patients (9 women and 7 men, mean age 48.6 years) with SIHS before and after treatment. RESULTS: Diffuse dural enhancement was seen in 15 patients, and the epidural fluid collection in the spinal canal was clear in 15 and equivocal in 1. Symptoms disappeared after bed rest in 1 patient, and an epidural blood patch was performed in 15 patients, resulting in complete resolution of symptoms in 13. After the follow-up period (range 1-20 months, mean 5.0 months), 1 patient had persistent mild headache that gradually worsened in the afternoon, and another patient complained of heaviness of the eyes. Follow-up MR imaging demonstrated disappearance of the dural enhancement in all patients, but a fluid collection in the spinal canal remained in 4. Two of the 4 patients had persistent symptoms, but the other patients exhibited complete resolution of the symptoms. CONCLUSIONS: An epidural blood patch is effective for sealing of CSF leaks, but the resolution of SIHS-related symptoms does not always imply complete eradication of the leakage.

[Dilation of subarachnoid space around the optic nerve in a patient with subdural effusion: a case report].

A fifty-year-old man who had a history of minor head injury a month previously presented with headache, visual disturbance and papilloedema. Brain MR imaging showed bilateral subdural effusion and fat saturated orbital MR imaging demonstrated dilated subarachnoid space around the optic nerve. The diameter of the subarachnoid space behind the globe was 7.0 mm and that of the optic nerve was 3.5 mm. Bilateral simple drainage was performed to prevent deterioration of the visual disturbance. Light bloody fluid with a subdural pressure of 10.5 cmH2O was drained from the burr hole at the left side, and colorless fluid was drained from the right. Orbital MR imaging during continuous drainage revealed shrinkage of the subarachnoid space around the optic nerve. However, follow-up MR imaging 5 months after drainage showed disappearance of the subdural effusion and the reappearance of the subarachnoid space around the optic nerve, even though the size was smaller than before surgery. These findings suggest that the diameter of the optic subarachnoid space co-relates with the intracranial pressure, and may be an indication for increased intracranial pressure.

Internal carotid artery occlusion manifesting only as oculomotor nerve palsy.

Oculomotor nerve palsy is very rare as the only manifestation of internal carotid artery (ICA) occlusion, and the angiographic findings have not been described in detail. We present a case of ipsilateral ICA occlusion manifesting as only sudden onset of oculomotor nerve palsy. Cerebral angiography showed occlusion of the ICA from the cervical portion to the ophthalmic portion. Distal blood flow was compensated through an anastomosis from other arteries. Ischemia of the oculomotor nerve was thought to be caused by loss of supply from branches arising from the occluded cavernous portion of the ICA.

Effect of intracranial pressure on the diameter of the optic nerve sheath.

OBJECT: The subarachnoid space around the optic nerve in the orbit can be visualized using T2-weighted MR imaging with the fat-saturation pulse sequence. The optic nerve sheath (ONS) diameter can be estimated by measuring the outer diameter of the subarachnoid space. Dilated ONS is associated with idiopathic intracranial hypertension and hydrocephalus, and is believed to reflect increased intracranial pressure (ICP). The relationship between dilated ONS and ICP is unclear because of the difficulty in obtaining noninvasive measurements of ICP. The authors investigated the relationship between subdural pressure measured at the time of surgery and ONS diameter measured on MR images in patients with chronic subdural fluid collection. METHODS: Twelve patients underwent bur-hole craniostomy with continuous drainage for chronic subdural hematoma or hygroma in 2006. Orbital thin-slice fat-saturated MR images were obtained before and after surgery, and the ONS diameters were measured just behind the optic globe. Subdural pressure was measured using a manometer before opening of the dura mater. RESULTS: A significant correlation was found between the ONS diameter and the subdural pressure (correlation coefficient 0.879, p = 0.0036). The ONS diameter before surgery (6.1 +/- 0.7 mm) was significantly reduced after surgery (4.8 +/- 0.9 mm, p = 0.003; measurements are expressed as the mean +/- standard deviation). CONCLUSIONS: Increased ONS diameter measured on coronal orbital thin-slice fat-saturated T2-weighted MR images is a strong indicator of increased ICP, and helps to differentiate between passive subdural fluid collection due to brain atrophy and subdural hygroma with increased ICP.

Diffusion tensor tractography predicts motor functional outcome in patients with spontaneous intracerebral hemorrhage.

OBJECTIVE: We prospectively investigated the predictive value of diffusion tensor tractography for motor functional outcome in a case series of patients with intracerebral hemorrhage. METHODS: Diffusion tensor tractography was performed in 17 patients with intracerebral hemorrhage (putamen, nine patients; thalamus, seven patients; combined, one patient) within 5 days after onset. Mean fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values along the corticospinal tracts at the level of the hematoma were measured bilaterally, and the ratios of values (hematoma side/contralateral side) were determined as FA and ADC ratios, respectively. Patients were evaluated for motor function on admission and at 3 months after onset using the manual muscle test score and then divided into good (manual muscle test, 4-5) and poor (manual muscle test, 0-3) motor function groups. RESULTS: FA ratio measured shortly after the onset of intracerebral hemorrhage correlated well with motor functional outcome at 3 months (P < 0.05) but not with motor function on admission. FA ratios in the group with good motor functional outcome were significantly higher than those in the group with poor motor functional outcome (P < 0.01). The ADC ratio did not correlate with motor function either on admission or at 3 months. All patients with an FA ratio greater than 0.8 had a good motor functional outcome. In three patients, however, motor functional outcomes were favorable even though FA ratios were not high; in these patients, ADC ratios tended to be elevated. CONCLUSION: Motor functional outcome in patients with intracerebral hemorrhage can be predicted by measuring FA values using diffusion tensor tractography.

Patulous Eustachian tube in spontaneous intracranial hypotension syndrome.

A 48-year-old slender woman presented with a rare case of spontaneous intracranial hypotension syndrome manifesting as patulous Eustachian tube. The patient complained of sudden onset of ear fullness and nasal voice as well as typical orthostatic headache. Patulous Eustachian tube was identified by observation of synchronous movement of the tympanic membrane with respiration and swallowing. The diagnosis of spontaneous intracranial hypotension was confirmed by negative cerebrospinal fluid pressure, and typical magnetic resonance imaging and radioisotope cisternography findings. All symptoms completely resolved within a few days after epidural blood patch treatment. Changes in the venous blood distribution led by collapse of the dural sac of the cervical spine in the standing position presumably caused decreased size of the pterygoid venous plexus around the Eustachian tube.

Unsuccessful tracer injection in radionuclide cisternography revisited.

Since cerebrospinal fluid (CSF) leakage is highlighted as a cause of persistent headache, radionuclide cisternography has been increasingly performed in Japan to confirm the disorder, although the limited ability of the examination should be recognized. We present 3 cases in which failure of a tracer injection was strongly suspected. In 2 cases with chronic symptoms, the tracer appeared to be injected into the epidural space, because of irregular initial accumulation of the tracer and lack of diffusion along the CSF cavity. Another is a case with spontaneous CSF leakage confirmed by MRI, and the tracer was thought to be injected into the leaked fluid accumulated in the spinal epidural space. Tracer in the CSF space rapidly disappeared within several hours in all cases. As such cisternographic images may be misdiagnosed as severe CSF leakage, careful interpretation of images in patients especially with no typical MR findings of CSF leakage is necessary. Excessive tracer clearance from the body suggests such technical failure.

Subdural effusions in the posterior fossa associated with spontaneous intracranial hypotension.

BACKGROUND: Misdiagnosis of spontaneous intracranial hypotension remains a problem, despite increasing recognition. METHODS: Three patients with spontaneous intracranial hypotension presented with typical findings on lumbar puncture, magnetic resonance (MR) imaging, and radioisotope cisternography. All patients showed subdural effusions in the posterior fossa on axial T2-weighted MR imaging. Axial MR images of 112 patients with other conditions were also screened for this finding. RESULTS: One of three patients had typical orthostatic headache, and the other two had continuous headache. The finding of subdural effusions in the posterior fossa on axial T2-weighted MR imaging disappeared after treatment. Similar findings were found in 14 of 112 patients with other conditions. Most of the patients were over 60 years old or had dementia or previous radiation therapy. CONCLUSIONS: Subdural effusions in the posterior fossa can be identified by T2-weighted axial MR imaging, and are useful for the diagnosis of spontaneous intracranial hypotension and for verifying the effectiveness of treatment.

Atypical meningioma with large cyst. Case report.

A 29-year-old male presented with loss of consciousness and generalized seizure, followed by right hemiparesis and speech disturbance. Computed tomography and magnetic resonance imaging showed a solid, enhanced tumor with a cyst in the left frontal area with surrounding edema and mild mass effect. The cyst wall was also enhanced. The preoperative diagnosis was cystic falx meningioma. The tumor was totally resected, but most of the cyst wall adhered tightly to the surrounding brain and could not be removed. Histological examination revealed atypical meningioma and tumor cells in the cyst wall. The patient received local radiotherapy to the residual cyst wall with a total dose of 50 Gy.

[Semi-quantiative RI cisternographic patterns in patients with chronic headache: a resemblance to those of intracranial hypotension syndrome].

Semi-quantitative radionuclide cisternography was performed to evaluate CSF leakage for patients with long-lasting headache and/or neck pain or refractory dizziness which appeared to be related to posture as well as patients with spontaneous intracranial hypotension (SIH). Radioactivity in the whole CSF space was counted and was plotted against time. SIH cases showed rapid decrease of radioactivity in the CSF space. Chronic headache patients were divided into Group I (rapid decrease of activity similarly to those in patients with SIH, to less than 80% at 5h and 40% at 24h), Group II (gradual decrease to less than 40% at 24h), and Group III (activity remained more than 80% at 5h and 40% at 24h). Of 16 patients in Group I, epidural blood patch was attempted in 14, and improvement of symptoms was obtained in 10. In 3 patients who underwent post-treatment RI study, tracer kinetics was normalized. These findings may indicate that some of patients with chronic headache actually have CSF leakage that can be treated with epidural blood patch.

Jugular compression and radionuclide cisternographic patterns in patients with chronic headache.

OBJECTIVE: We investigated the value of the jugular compression test (JCT) in screening patients with chronic headache attributable to persistent cerebrospinal fluid (CSF) leakage. METHODS: Clinical records of 35 consecutive patients who underwent both 111In-diethylenetriamine pentaacetic acid radioisotope (RI) cisternography and JCT were retrospectively analyzed. RESULTS: A strong correlation was seen between JCT and RI cisternographic findings. Most patients who reported a feeling of fullness in the ear, hearing loss or headache during JCT had positive findings on RI cisternograms indicative of CSF leakage. In contrast, no RI study abnormalities were seen in patients reporting no symptoms in JCT. CONCLUSIONS: Among patients complaining of refractory headache and other miscellaneous symptoms, JCT may represent a simple, economic, and reliable technique in the screening of candidates for RI cisternography to evaluate CSF leakage. A subgroup of patients with chronic headache may have persistent CSF leakage.

Overexpression of bradykinin type 2 receptors on glioma cells enhances bradykinin-mediated blood-brain tumor barrier permeability increase.

Variations in the expression levels of bradykinin (BK) type 2 receptors (B2R) in different brain tumors may explain variable increases in BK-mediated blood-brain tumor barrier (BTB) permeability. This study investigated whether elevation of the B2R expression levels on glioma cells enhances BK-mediated BTB permeability increases. Stable transfectants of C6 rat glioma cells overexpressing B2R were established by transfection with recombinant vectors harboring rat B2R cDNA sequence. Elevated B2R expression levels in transfectants were confirmed by quantitative real-time PCR, Western blots, and [3H]-BK binding studies. BTB permeability was quantified with autoradiography and expressed as a unidirectional transport constant, Ki, for [14C]-alpha-aminoisobutyric acid (AIB: Mr 103), using a rat brain tumor model. Baseline Ki values in tumors overexpressing B2R were not significantly higher than in control tumors. Ki values after BK treatment in tumors overexpressing B2R, however, were significantly higher than in control tumors. Western blots confirmed that B2R expression levels in vivo in tumors overexpressing B2R remained higher than in control tumors. These results suggested that alteration of B2R expression levels on tumor cells could modulate BK-mediated BTB permeability. Therefore, B2R expression levels in human glioma could be used to analyze the treatment results of patients undergoing treatment involving BK-modulated BTB permeability.