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Background and Purpose: High blood pressure increases bleeding risk during treatment with antithrombotic medication. The association between blood pressure levels and the risk of recurrent stroke during long-term secondary stroke prevention with thienopyridines (particularly prasugrel) has not been well studied. Methods: This was a post hoc analysis of the randomized, double-blind, multicenter PRASTRO-I trial (Comparison of Prasugrel and Clopidogrel in Japanese Patients With Ischemic Stroke-I). Patients with noncardioembolic stroke were randomly assigned (1:1) to receive prasugrel 3.75 mg/day or clopidogrel 75 mg/day for 96 to 104 weeks. Risks of any ischemic or hemorrhagic stroke, combined ischemic events, and combined bleeding events were determined based on the mean level and visit-to-visit variability, including successive variation, of systolic blood pressure (SBP) throughout the observational period. These risks were also compared between quartiles of mean SBP level and successive variation of SBP. Results: A total of 3747 patients (age 62.1±8.5 years, 797 women), with a median average SBP level during the observational period of 132.5 mm Hg, were studied. All the risks of any stroke (146 events; hazard ratio, 1.318 [95% CI, 1.094–1.583] per 10-mm Hg increase), ischemic stroke (133 events, 1.219 [1.010–1.466]), hemorrhagic stroke (13 events, 3.247 [1.660–6.296]), ischemic events (142 events, 1.219 [1.020–1.466]), and bleeding events (47 events, 1.629 [1.172–2.261]) correlated with increasing mean SBP overall. Similarly, an increased risk of these events correlated with increasing successive variation of SBP (hazard ratio, 3.078 [95% CI, 2.220–4.225] per 10-mm Hg increase; 3.051 [2.179–4.262]; 3.276 [1.172–9.092]; 2.865 [2.042–4.011]; 2.764 [1.524–5.016], respectively). Event rates did not differ between the clopidogrel and prasugrel groups within each quartile of SBP or successive variation of SBP. Conclusions: Both high mean SBP level and high visit-to-visit variability in SBP were significantly associated with the risk of recurrent stroke during long-term medication with either prasugrel or clopidogrel after stroke. Control of hypertension would be important regardless of the type of antiplatelet drugs. Registration: URL: https://www.clinicaltrials.jp ; Unique identifier: JapicCTI-111582.

Clinicopathological studies were performed on the visceral organs and the sural nerve of a male patient with Churg-Strauss syndrome (CSS) in order to understand the mechanisms of peripheral nervous system damage. A 67-year-old man, with a 2-year history of bronchial asthma, developed acutely painful paraplegia and dyspnea. Laboratory data showed a leukocytosis, an elevated serum creatinine kinase (CK) and marked eosionophilia. Autoantibodies including p- and c-ANCA were negative. Electrophysiological studies revealed a severe sensory-motor neuropathy of multiple mononeuritis type. Steroid pulse therapy performed a day after biopsy of skin, muscle and sural nerve was effective in resolving his respiratory and neurological dysfunction but a perforation of an intestinal ulcer occurred which required surgical intervention. In the biopsied sural nerve and the surgically resected intestine and mesentery there was vasculitis with fibrinoid necrosis accompanied by numerous eosinophils and macrophages containing eosinophil cationic protein (ECP). These findings suggest that in addition to ischemic changes due to vasculitis some neurotoxic substances generated by the eosinophils may be involved in the development of neuropathy in CSS.

Adult T-cell lymphoma (ATL-L) developing initially in the meninges is rare. An autopsy case of ATL-L with an acute onset of meningitis and generalized lymphadenopathy in association with a cervical cord schwannoma is reported here. A 78-year-old woman with sensori-motor weakness of both arms over a 1-year period, developed febrile episodes and drowsiness with neck stiffness. Lumbar puncture revealed an increased protein content (161 mg/dL) and increased cell count (463/3) consisting of 99% of lymphocytes which contained atypical lymphocytes with multilobulated nuclei ('flower cells'), which are characteristic of ATL-L. Viral titers were positive only for HTLV-I antibodies (serum X 640: CSF X 16). Biopsy of an enlarged retroperitoneal lymph node revealed malignant lymphoma of the T-cell type. Brain MRI was negative, whereas an intradural extramedullary mass was found at the C4 level. With a diagnosis of ATL-L stage IV, chemotherapy was commenced, which was effective in reducing the generalized lymphadenopathy as well as the cervical mass and restoring the CSF findings to normality. The cervical cord mass was verified to be a solitary schwannoma, and ATL-L involvement was found not only in the leptomeninges, but also within the cervical cord schwannoma.

We review our 15 years of experience with patients with carotid artery stenosis to clarify the incidence of coronary artery disease. Of 197 patients who underwent carotid endarterectomy (CEA) since 1985, 16 (8.1%) had coronary artery disease that required treatment. Eleven patients could safely undergo staged treatments of CEA and coronary artery bypass graft (CABG)/percutaneous transluminal coronary angioplasty (PTCA). Four patients, however, underwent simultaneous CEA and CABG, because both carotid and coronary artery diseases were too serious for safe staged surgery. We present the detailed medical records of these 4 cases. All had tight (more than 90%) stenosis of the internal carotid artery (ICA) and 2 or 3 branches of the coronary artery. They experienced TIA or minor completed stroke as well as unstable angina. One patient also presented chronic heart failure due to severe myocardial ischemia. We performed CEA and then CABG. Would closure was done after all surgical procedures to avoid bleeding due to intraoperative heparinization. Postoperative courses were uneventful in all 4 patients. We performed carotid stenting preceding simultaneous surgery with contralateral CEA and CABG for 1 patient who had bilateral severe carotid stenosis.

非連続性に多発性脊椎損傷を認めた9例に対して,その臨床的な特徴や診断上の問題点について検討した。年齢は17～50(平均26.4)歳,男性7例,女性2例で受傷原因は交通外傷6例,転落3例,来院時の神経学的重症度は完全損傷(Frankel A)3例,不全損傷6(Frankel B: 1, C: 3, E: 2)例であった。6例で合併損傷を認め,その内訳は頭部外傷2例,胸部外傷4例,腹部外傷1例,四肢骨折2例,骨盤骨折1例であった。全例で頸椎損傷を伴っており,8例で損傷部位は2か所で,その組み合わせは,上位頸椎+下位頸椎:1例,上位頸椎+胸椎:1例,中下位頸椎+胸椎:6例であった。また,1例は3か所に損傷(頸椎に2か所と胸椎)を認めた。これらの結果から,脊椎・脊髄損傷例では多発性に脊椎損傷を有している可能性があり,全身の評価および全脊椎の検索が必要である。

An autopsy case of hypertrophic pachymeningitis and multiple cranial neuropathies is reported. A 53-year-old woman with paraplegia and various neurological signs which developed over a 2 year period was diagnosed as having an epidural mass with thickened dura mater extending from the lower cervical to the thoracic spinal cord. In addition, bilateral episcleritis, blephaloptosis, and blindness of the right eye with various cranial nerve deficits were found to be caused by the mass lesions involving the paranasal sinuses, orbit, and the cavernous sinus. Perinuclear antineutrophil cytoplasmic antibody (p-ANCA) was positive, but cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA) was negative by enzyme-linked immunosorbent assay. The partially removed epidural mass with hypertrophied dura mater and biopsy of the paranasal lesions showed chronic granulomatous inflammation with vasculitis. The remaining lesions resolved with steroid therapy with remarkable neurological improvement. The positive p-ANCA test, paranasal involvement, the report of a similar histopathological case and a review of the literature on granulomatous pachymeningitis suggest the presence of p-ANCA-positive Wegener's granulomatosis with central nervous system involvement characterized by hypertrophic pachymeningitis and/or multiple cranial neuropathies.

A 60-year-old female and a 40-year-old male underwent surgical revascularization for moyamoya disease and suffered small infarction in the ipsilateral frontal lobe 3 or 4 days postoperatively. Neuroimaging suggested that the bypass flow had caused rapid progression of occlusive changes in the carotid forks, a diminishing of moyamoya vessels, and flow reduction in the anterior cerebral artery ipsilateral to surgery, leading to critical ischemia in the frontal lobe. Surgical revascularization improves the outcome of patients with moyamoya disease, but postoperative management such as hydration is important to avoid ischemic complications due to frontal lobe infarction.

Adult onset Leigh syndrome with a nucleotide (nt) 8993 mutation in mitochondrial (mt) DNA is reported. A 43-year-old woman with a 6-year-history of insulin-resistant diabetes mellitus developed muscular weakness, intractable nausea and vomiting, and anemia. These were followed vertigo, blindness, and deafness with nystagmus. Magnetic resonance imaging (MRI) revealed abnormal high intensities in the bilateral medial regions of the thalamus and periaqueductal gray matters. Autopsy disclosed well-demarcated necrotizing lesions with prominent capillaries in the areas detected by MRI, which were sufficiently diagnostic for Leigh syndrome. MtDNA analysis performed on DNAs extracted from formalin-fixed tissues including liver, heart, brain, muscle, kidney and pancreas showed a T-->G mutation at nt 8993. This is the first case of adult Leigh syndrome demonstrating on mtDNA mutations.

A 57-year-old man who presented with leptomeningeal lymphoma was reported. The lymphoma cells in the cere-brospinal fluid were large in size, had atypical nuclei and contained many azurophilic granules in their pale cytoplasm, all of which were consistent with malignant lymphoma of large granular lymphocytes (LGL). Immunohistochemically, tumor cells were positive for cyto-plasmic CD3, UCHL-1, and CD56, markers of natural killer (NK)cells. Epstein-Barr virus encoded small RNA (EBER) was detected in tumor cells by in situ hybridization. No evidence of parenchymal central nervous system or systemic tumor was identified, although at autopsy microscopic lympuoma involvement was found in the pituitary gland and kidney. To our knowledge this is the first autopsy case report of primary meningeal LGL lymphoma.

This 75-year-old male who fell from a 1-m hight road shoulder subsequently suffered persistent neck pain. On admission to our institute he exhibited no neurological abnormalities. CT scan revealed an odontoid Anderson type III fracture. We selected conservative treatment with external fixation using a hard collar. No cervical deformity was recognized over the course of a month and he was transferred to another hospital for rehabilitation. As a cervical X-ray performed a month later disclosed a progressive kyphotic deformity, he was readmitted to our institute for surgery. He underwent internal fixation with a Ransford loop between the occipital bone and the C3 lamina. During the operation we noted that his bone was very fragile. His postoperative course was uneventful and he exhibited no neurological deficits; his cervical alignmen stabilized completely. At his 2nd admission, his bone mineral density was 0.767 g/cm2, 64% of the young adult mean and thus indicative of severe osteoporosis. We conclude that careful observation and appropriate internal fixation are necessary in osteoporotic patients who manifest deformity following an odontoid fracture.

The authors report 9 patients who presented with loss of consciousness (syncope) due to occlusive carotid artery diseases. All patients were males, and their age ranged from 59 to 83 years. The attack was associated with dehydration or hypotension in 5 patients. MRI demonstrated fresh cerebral infarction in the watershed zone. Cerebral angiography revealed occlusion of the unilateral internal carotid artery (ICA) in 7 patients, severe stenosis of the bilateral ICA in one, and occlusion of the unilateral ICA and severe stenosis of the contralateral ICA in one. Single photon emission tomography (SPECT) or positron emission tomography (PET) suggested reduced cerebral perfusion reserve because of inappropriate development of collateral circulation in 4 out of 9 patients. These 4 patients underwent superficial temporal artery to middle cerebral artery anastomosis and/or carotid endarterectomy. Other 5 patients were medically treated. No further episode of syncope occurred in all 9 patients during follow-up periods. The results suggest that occlusive carotid artery diseases should be taken in considerations as a cause of syncope attack.

The purpose of this study was to determine the incidence of mismanaged injury of the cervical spinal cord, to identify factors contributing to a failure to recognize such injury. Thirty-three patients with cervical spinal cord injury were transported to emergency department during the period from October, 1999 to March, 2001. Seven patients (21%) of them were transferred without cervical spine immobilization. Mechanism of injury in 7 patients was fall in 4, motor vehicle crash in 2, unknown in one. Clinical signs on admission revealed neck pain and/or back pain in 4 patients, altered mental status in 4 patients, numbness of extremities in 2 patients, paradoxical respiration in 2 patients, respiratory arrest in one. Neurological classification of Frankel grade was A in 2, B in 1, C in 2, D in 1 and E in 1. All trauma patients with a cervical spine injury or with a mechanism of injury having the potential to cause cervical spine injury should be immobilized at the scene, during transport and at the emergency room by using one of several available methods.

Clinicopathological studies were performed on the visceral organs and the sural nerve of a male patient with Churg-Strauss syndrome (CSS) in order to understand the mechanisms of peripheral nervous system damage. A 67-year-old man, with a 2-year history of bronchial asthma, developed acutely painful paraplegia and dyspnea. Laboratory data showed a leukocytosis, an elevated serum creatinine kinase (CK) and marked eosionophilia. Autoantibodies including p- and c-ANCA were negative. Electrophysiological studies revealed a severe sensory-motor neuropathy of multiple mononeuritis type. Steroid pulse therapy performed a day after biopsy of skin, muscle and sural nerve was effective in resolving his respiratory and neurological dysfunction but a perforation of an intestinal ulcer occurred which required surgical intervention. In the biopsied sural nerve and the surgically resected intestine and mesentery there was vasculitis with fibrinoid necrosis accompanied by numerous eosinophils and macrophages containing eosinophil cationic protein (ECP). These findings suggest that in addition to ischemic changes due to vasculitis some neurotoxic substances generated by the eosinophils may be involved in the development of neuropathy in CSS.

Intramedullary spinal cord metastasis was thought to be rare, but the advent of MR imaging and treatment for malignancy have revealed that it is more frequent than we previously thought. We report two cases of intramedullary spinal cord metastasis from lung and rectal colon carcinoma. Their symptoms were aggravated rapidly. We performed surgical treatment in both cases; one was grosstotal and the other was subtotal resection. After the operation, symptoms improved mildly in one patient and worsened in the other patient. Both died 3 months after surgery, because of respiratory disturbance due to brain stem compression and lung metastasis. In conclusion, MRI is highly useful for making a diagnosis of intramedullary spinal metastatic tumors. However, it is still difficult to treat such a patient by surgery alone. Further postoperative adjuvant therapy will be necessary to improve the prognosis of such patients.

Three cases of post-traumatic syringomyelia are presented and the mechanism of syrinx formation is discussed. Two cases were examined radiologically. Computed tomography and magnetic resonance images (MRI) showed an expansive syrinx with adhesive arachnoiditis in the thoracic levels below the injury site and a localized syrinx on the posterolateral gray matter in the cervical levels above the injury site. These syrinxes existed below the C2 level and had no communication with the fourth ventricle. The other was an autopsy case. Postmortem examination revealed that a syrinx existed from C2 to Th6 and had no communication with the fourth ventricle or the central canal. It is concluded that small traumatic cavities in the gray matter evolve to an extensive syrinx by cerebrospinal fluid (CSF) entering via the posterior root entry zone, and adhesive arachnoiditis is an important factor in increasing the CSF which is entering. MRI was useful for the diagnosis.

A 64-year-old female was admitted with chief complaints of paroxysmal hemifacial spasm and low-tone noise, which she experienced in the ipsilateral ear synchronously with the spasm. Impedance audiometry performed during spasms showed reduction or disappearance of the acoustic reflex (AR) and elevation of the AR threshold on the affected side. These phenomena could also be elicited by voluntary contraction of the affected side of the face. The patient underwent microvascular decompression of the facial nerve, which abolished both the facial spasm and the low-tone noise. The abnormal AR patterns revealed the spasm as well as synkinesis of the stapedius muscle. The abnormal contraction of the stapedius muscle is believed to have generated the low-tone noise.

Histopathological examination of cerebrovascular occlusive lesions with von Recklinghausen's disease has rarely been reported. The authors are presenting an autopsy case of von Recklinghausen's disease with the occlusion of bilateral proximal middle cerebral arteries (M1), basal moyamoya, and an anterior communicating artery aneurysm. A 60-year-old female suffered a subarachnoid hemorrhage with drowsiness and nuchal rigidity. Although the neck-clipping was performed without any trouble, the patient died of pneumonia 26 days after the operation. Histopathological examination revealed hypoplasia of bilateral M1 and extensive arteriosclerotic changes of the circle of Willis. The authors concluded that the primary hypoplasia of bilateral M1 induced basal moyamoya as collateral circulation and hemodynamic stresses facilitated the formation of the anterior communicating artery aneurysm. It is not clear whether there is any etiological relationship between hypoplasia of the bilateral M1 and von Recklinghausen's disease.