Yoshinari Nakatsuka

Preventive effects of cilostazol against the development of shunt-dependent hydrocephalus after subarachnoid hemorrhage

OBJECTIVE Chronic hydrocephalus develops in association with the induction of tenascin-C (TNC), a matricellular protein, after aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to examine if cilostazol, a selective inhibitor of phosphodiesterase Type III, suppresses the development of chronic hydrocephalus by inhibiting TNC induction in aneurysmal SAH patients. METHODS The authors retrospectively reviewed the factors influencing the development of chronic shunt-dependent hydrocephalus in 87 patients with Fisher Grade 3 SAH using multivariate logistic regression analyses. Cilostazol (50 or 100 mg administered 2 or 3 times per day) was administered from the day following aneurysmal obliteration according to the preference of the attending neurosurgeon. As a separate study, the effects of different dosages of cilostazol on the serum TNC levels were chronologically examined from Days 1 to 12 in 38 SAH patients with Fisher Grade 3 SAH. RESULTS Chronic hydrocephalus occurred in 12 of 36 (33.3%), 5 of 39 (12.8%), and 1 of 12 (8.3%) patients in the 0 mg/day, 100 to 200 mg/day, and 300 mg/day cilostazol groups, respectively. The multivariate analyses showed that older age (OR 1.10, 95% CI 1.13-1.24; p = 0.012), acute hydrocephalus (OR 23.28, 95% CI 1.75-729.83; p = 0.016), and cilostazol (OR 0.23, 95% CI 0.05-0.93; p = 0.038) independently affected the development of chronic hydrocephalus. Higher dosages of cilostazol more effectively suppressed the serum TNC levels through Days 1 to 12 post-SAH. CONCLUSIONS Cilostazol may prevent the development of chronic hydrocephalus and reduce shunt surgery, possibly by the inhibition of TNC induction after SAH.

Tenascin-C in brain injuries and edema after subarachnoid hemorrhage: Findings from basic and clinical studies

Subarachnoid hemorrhage (SAH) by a rupture of cerebral aneurysms remains the most devastating cerebrovascular disease. Early brain injury (EBI) is increasingly recognized to be the primary determinant for poor outcomes, and also considered to cause delayed cerebral ischemia (DCI) after SAH. Both clinical and experimental literatures emphasize the impact of global cerebral edema in EBI as negative prognostic and direct pathological factors. The nature of the global cerebral edema is a mixture of cytotoxic and vasogenic edema, both of which may be caused by post‐SAH induction of tenascin‐C (TNC) that is an inducible, non‐structural, secreted and multifunctional matricellular protein. Experimental SAH induces TNC in brain parenchyma in rats and mice. TNC knockout suppressed EBI in terms of brain edema, blood‐brain barrier disruption, neuronal apoptosis and neuroinflammation, associated with the inhibition of post‐SAH activation of mitogen‐activated protein kinases and nuclear factor‐kappa B in mice. In a clinical setting, more severe SAH increases more TNC in cerebrospinal fluid and peripheral blood, which could be a surrogate marker of EBI and predict DCI development and outcomes. In addition, cilostazol, a selective inhibitor of phosphodiesterase type III that is a clinically available anti‐platelet agent and is known to suppress TNC induction, dose‐dependently inhibited delayed cerebral infarction and improved outcomes in a pilot clinical study. Thus, further studies may facilitate application of TNC as biomarkers for non‐invasive diagnosis or assessment of EBI and DCI, and lead to development of a molecular target drug against TNC, contributing to the improvement of post‐SAH outcomes.

Impact of Hypertriglyceridemia on Carotid Stenosis Progression under Normal Low-Density Lipoprotein Cholesterol Levels

BACKGROUND Dyslipidemia is a well-known risk factor for carotid stenosis progression, but triglycerides have attracted little attention. The aim of this study was to assess if serum triglycerides affect progression of carotid stenosis in patients with well-controlled low-density lipoprotein cholesterol (LDL-C) levels. METHODS This is a retrospective study in a single hospital consisting of 71 Japanese patients with internal carotid artery stenosis greater than or equal to 50% and normal serum LDL-C levels who underwent angiographic examination with or without the resultant carotid artery stenting or endarterectomy from 2007 to 2011, and were subsequently followed up for 4 years. Clinical factors including fasting serum triglyceride values were compared between the progression (≥10% increase in degree of carotid stenosis on ultrasonography) and the nonprogression groups. RESULTS During 4 years, 15 patients (21.1%) had carotid stenosis progression on either side. Cox regression analysis demonstrated that symptomatic cases (hazard ratio [HR], 4.327; P = .019), coexisting intracranial arteriosclerotic stenosis (HR, 5.341; P = .005), and hypertriglyceridemia (HR, 6.228; P = .011) were associated with subsequent progression of carotid stenosis. Kaplan-Meier plots demonstrated that the progression-free survival rate was significantly higher in patients without hypertriglyceridemia and intracranial arteriosclerotic stenosis at baseline. CONCLUSIONS Among patients with moderate to severe carotid stenosis and well-controlled LDL-C, hypertriglyceridemia was an important risk factor for progression of carotid stenosis irrespective of surgical treatments. It would be worthwhile to test if triglyceride-lowering medications suppress carotid stenosis progression.

A case of vertebral artery aneurysm presenting with dysphagia.

Here, we report a case of vertebral artery aneurysm causing dysphagia in a 56-year-old man who had no remarkable past history. Two months before the first visit, he developed posterior neck pain followed by difficulty swallowing 1 month later. He was referred to our clinic because of gradually worsening dysphagia. Physical examination showed paralysis of cranial nerves IX, X, and XII; therefore, he was hospitalized. Because enhanced CT and MRI showed a partially thrombosed right vertebral artery aneurysm, he was transferred to the care of the Department of Neurosurgery. Parent artery occlusion of the right vertebral artery aneurysm was performed and it improved his symptoms. After regaining his ability to take in liquid food, he was transferred to another hospital for further rehabilitation. In this case, we attributed the dysphagia to aneurysmal compression of the roots of cranial nerves IX, X, and XII. A partially thrombosed cerebral artery aneurysm may often rupture and cause worsening of neurologic symptoms. The prognosis is generally poor because the rupture rate is extremely high especially with large or giant aneurysms. However, this case had a good clinical course owing to treatment by parent artery occlusion.

Suspected Metallic Embolism following Endovascular Treatment of Intracranial Aneurysms

SUMMARY: We describe a case series of suspected metallic embolism after coil embolization for intracranial aneurysms. Between January 2012 and December 2014, 110 intracranial aneurysms had been treated by coil embolization in our institution. In 6 cases, the postprocedural MR imaging revealed abnormal spotty lesions not detected on the preprocedural MR imaging. The lesions were also undetectable on the postprocedural CT scan. They were demonstrated as low-intensity spots on T1WI, T2WI, DWI, and T2*-weighted imaging. On DWI, they were accompanied by bright “halo,” and on T2*-weighted imaging, they showed a “blooming” effect. In 3 of the 6 cases, follow-up MR imaging was available and all the lesions remained and demonstrated no signal changes. Although histologic examination had not been performed, these neuroradiologic findings strongly supported the lesions being from metallic fragments. No specific responsible device was detected after reviewing all the devices used for the neuroendovascular treatment in the 6 cases.