Differential expression of heat shock proteins in normal and failing human hearts

OBJECTIVE: To predict spinal cord ischemia after endovascular stent graft repair of descending thoracic aortic aneurysms, temporary interruption of the intercostal arteries (including the aneurysm) was performed by placement of a novel retrievable stent graft (Retriever) in the aorta under evoked spinal cord potential monitoring. METHODS: From February 1995 to October 1997, endovascular stent graft repair of descending thoracic aortic aneurysms was performed in 49 patients after informed consent was obtained. In 16 patients with aneurysms located in the middle and distal segment of the descending aorta, the Retriever was placed temporarily before stent graft deployment. The Retriever consisted of two units of self-expanding zigzag stents connected in tandem with stainless steel struts. Each strut was collected in a bundle fixed to a pushing rod, and the stent framework was lined with an expanded polytetrafluoroethylene sheet. The Retriever was delivered beyond the aneurysm through a sheath and was retracted into the sheath 20 minutes later. A stent graft for permanent use was deployed in patients whose predeployment test results with the Retriever were favorable. Evoked spinal cord potential was monitored throughout placement of the Retriever and stent grafting until the next day. RESULTS: The Retriever was placed in 17 aneurysms in 16 patients. There were no changes in amplitude or latency of evoked spinal cord potential records obtained before or during Retriever placement. After withdrawal of the Retriever, all aneurysms were excluded from circulation immediately after permanent stent grafting. There were no changes in evoked spinal cord potential, nor were neurologic deficits seen after stent graft deployment in any patient. CONCLUSIONS: These results suggest that predeployment testing with the Retriever under evoked spinal cord potential monitoring is promising as a predictor of spinal cord ischemia in candidates for stent graft repair of thoracic aortic aneurysms.     

Subarachnoid hemorrhage secondary to spinal arteriovenous malformation and aneurysm. Report of a case and review of the literature

A patient with recurrent subarachnoid hemorrhage was seen initially with intermittent signs and symptoms of intracranial and spinal cord dysfunction. Myelography and spinal angiography revealed an arteriovenous malformation (AVM) and aneurysm of the spinal cord. Extensive investigation failed to reveal any intracranial lesion. The relationship of subarachnoid hemorrhage at a spinal level to the development of remote neurological abnormalities is discussed, and previous reports of aneurysms associated with spinal AVM are reviewed.     

Refractory giant cell arteritis with spinal cord infarction

We report an elderly patient with aggressive steroid-refractory giant cell arteritis manifesting as myelopathy and bilateral visual loss while on treatment. Pathologically, spinal cord infarction was observed and was due to extensive necrotizing granulomatous arteritis of spinal arteries. Spinal cord damage in giant cell arteritis is rare. One prior autopsy report of spinal cord infarction in giant cell arteritis did not identify vasculitic changes in the spinal arteries.     

Pathology of intravascular malignant lymphomatosis

On the basis of six necropsied cases of intravascular malignant lymphomatosis (IML), we elucidated its pathological characteristics. In the brain of IML, multiple softened areas of various size were observed, dominantly in the white matter of the cerebral hemisphere, which showed bilateral distribution with no relation to the supply area of the large vessels and intermingled fresh and old lesions. The spinal cord was one of the most often involved areas in IML, particularly at the lumbosacral segmental level. The origin of the tumor cells, based upon the findings that the tumor cell of all our cases were positive for SL-26, LN1, and LN2, were considered to be B-cell. We speculated that not only the circulatory failure due to the tumor cells which filled the vascular lumen, but also circulatory disturbances due to thrombosis, thickening of the intima and angiitis were significant findings for the necrosis in IML. IML is an important disease as the fourth type of central nervous system involvement due to malignant lymphoma, in addition to primary malignant lymphoma of the brain, meningeal lymphomatosis, compression of the spinal cord caused by extradural metastasis of lymphoma.     

Severe muscle weakness secondary to paraneoplastic hypophosphatemia in neuroblastoma

OBJECTIVES: To evaluate the influence of the use of a bypass on the results of thoracoabdominal aortic aneurysm surgery. METHODS: The results of the repair of 224 thoracoabdominal aortic aneurysms operated upon between 1981 and the end of 1996 were evaluated retrospectively. In 122 cases we used simple cross-clamping (clamp and sew technique) and in 102 cases a left heart bypass (atrio-femoral or aorto-femoral) was the preferred method. Except for the use of cerebrospinal fluid drainage over the last years, the methods of spinal protection were the same in both groups. Renal protection was also identical in both groups. All aneurysms were repaired using the inlay technique. RESULTS: Hospital mortality was 11.2%: 14.7% in cross-clamp group versus 6.8% in the bypass group (p = 0.04). Postoperative dialysis was necessary in 9.8%: 12.7% in the cross-clamp group versus 6.8% in the bypass group (p = 0.108). Paraplegia occurred in 8.4%: 7.4% in the cross-clamp group versus 9.8% in the bypass group (p = 0.517). Using the highly predictive model of Acher, there would have been 33% spinal cord lesions in the bypass group. CONCLUSIONS: Hospital mortality, postoperative dialysis and postoperative spinal cord problems are lowered by the use of a bypass during the repair of thoracoabdominal aortic aneurysms. These results evidence that the use of a bypass is indicated in this complex operation.     

False aneurysm of the left ventricle and coronary aneurysms in Beh?et disease

A false left ventricular aneurysm and coronary artery aneurysm were discovered in a 29 year old patient with Beh?et's syndrome. The operation under cardiopulmonary bypass consisted of closing the neck of the false aneurysm by an endo-aneurysmal approach with a Gore-Tex patch. The coronary artery aneurysms were respected. There were no postoperative complications. Cardiac involvement is rare in Beh?et's syndrome (6%). The originality of this case is the association of two aneurysmal pathologies: the coronary and ventricular aneurysms due to the angiitis and the myocardial fragility induced by ischaemia.     

Cerebral infarction associated with vasculitis due to varicella zoster virus in patients infected with the human immunodeficiency virus

Cases of herpes zoster ophtalmicus (HZO) with delayed contralateral hemiparesis caused by hemispheric stroke secondary to granulomatous angiitis have been reported and are a well-recognized complication of herpes zoster. Similar cases have been reported more recently during infection with human immunodeficiency virus (HIV). We describe two HIV+ patients without any clinical history of zoster dermatitis who developed a sudden hemiparesis followed 2 weeks later for one by an acute retinal necrosis. Computerized tomography (CT) scan, magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and digital subtraction angiography (DSA) were performed and showed a hemispheric stroke with evidence of a segmental arteritis of the carotid syphon. Varicella zoster virus (VZV) was found in the cerebro spinal fluid (CSF) in the two patients and after puncture of the vitreous fluid of the patient with the acute retinal necrosis. These two cases exemplify the difficulty of diagnosis of stroke in HIV+ patients, which seems to be more frequent than in similarly aged non-infected patients and demonstrates that VZV needs to be taken in consideration and identified even without any past history of zoster dermatitis.     

Segregation of germ granules in living Caenorhabditis elegans embryos: cell-type-specific mechanisms for cytoplasmic localisation

Extrinsic allergic alveolitis and pulmonary sarcoidosis are granulomatous diseases of the lung for which clinical presentation and anatomic site of granuloma formation differ. Extrinsic allergic alveolitis is caused by inhaled antigens, whereas the nature and source of the inciting antigen in sarcoidosis is unknown. To test the hypothesis that the route via which antigen is introduced to the lung contributes to the clinicopathological presentation of pulmonary granulomatous disease, rats immunized with intravenous (i.v.) Corynebacterium parvum were challenged after 2 weeks with either intratracheal (i.t.) or i.v. C. parvum. The granulomatous inflammation elicited by i.t. challenge predominantly involved alveolar spaces and histologically simulated extrinsic allergic alveolitis. In contrast, the inflammation induced by i.v. challenge was characterized by granulomatous angiitis and interstitial inflammation simulating sarcoidosis. Elevations of leukocyte counts and TNF levels in bronchoalveolar fluid, which reflect inflammation in the intra-alveolar compartment, were much more pronounced after i.t. than after i.v. challenge. Tumor necrosis factor, interleukin-6, CC chemokine, CXC chemokine, and adhesion molecule mRNA and protein expression occurred in each model. In conclusion, i.t. or i.v. challenge with C. parvum in sensitized rats caused pulmonary granulomatous inflammation that was histologically similar to human extrinsic allergic alveolitis and sarcoidosis, respectively. Although the soluble and cellular mediators of granulomatous inflammation were qualitatively similar in both disease models, the differing anatomic source of the same antigenic challenge was responsible for differing clinicopathological presentations.     

Surgical treatment of thoracoabdominal aortic aneurysms]

Between February, 1981, and April, 1989, 20 patients underwent surgical treatment of thoracoabdominal aortic aneurysms. Most of the patients were operated under temporary external bypass. For Group I and III aneurysms without reconstruction of renal arteries, a modified Crawford's graft inclusion technique was employed to shorten abdominal visceral ischemic time. This modification consists of (1) using adjuncts to perfuse the distal aorta during aortic clamp, (2) starting the first anasistomosis from the distal end of the graft, and (3) shifting the distal aortic clamp on the graft after completing the anastomosis in order to restore abdominal visceral circulation as soon as possible. For Group III and IV aneurysms with reconstruction of renal arteries as well as celiac and superior mesenteric arteries, a modified DeBakey's procedure was employed. This modification consists of (1) using the spiral opening method, (2) doing end-to-end anastomosis at the proximal aortic site, and (3) maintaining the circulation of abdominal organs and spinal cord by using adjuncts during the anastomosis of the proximal end. There were one operative death and two hospital deaths. Paraplegia developed in two cases, one of which was a ruptured case. Renal dysfunction was not found in any case. The survivors were followed from 5 to 103 months, and there was no late death. The results suggest that our modified procedures for thoracoabdominal aortic aneurysms are useful and reliable ones.     

Changes of NGF in injured spinal cord following treatment with a single large dose of methylprednisolone sodium succinate

Nerve growth factor (NGF) was detected by ABC-ELISA in rat normal spinal cord, spinal cord with mild contusion of 25gcm, and that with mild contusion plus a single intramuscular injection of large dose of methylprednisolone sodium succinate (MPSS) (80 mg/kg). The mean preinjury NGF level in spinal cord was 10.2 +/- 2.8ng/g. Following injury, NGF level in spinal cord began to increase progressively. NGF level in spinal cord without treatment was attenuated to 30.32 +/- 0.32, 89.51 +/- 2.14, 66.02 +/- 1.51, 50.32 +/- 1.23 and 46.23 +/- 1.42ng/g at 4, 7, 14, 21 and 28 days respectively, while in cord spinal with MPSS treatment it was 121.98 +/- 4.05, 119.56 +/- 1.45, 80.39 +/- 1.50, 68.31 +/- 0.77 and 59.86 +/- 0.97 ng/g at 4, 7, 14, 21 and 28 days, respectively. This result suggests that a single large dose of MPSS enhances NGF level in injured spinal cord with a peak at day 4. The implication of this article is that the changes of NGF level in spinal cord are relevant to spinal cord self-recovery.     

Middle lobe syndrome: apropos of 5 cases

The capacity of embryonic spinal cord tissue in the repair of injured structure of spinal cord has been noted for years. In order to investigate the embryonic spinal cord graft in the repair of motor function of injured spinal cord, the embryonic spinal cord tissue was transplanted to the hemisection cavity in spinal cord in adult rat. One hundred adult Wistar Rats were used to simulate the hemisectional injury of spinal cord by drilling 2-3 mm cavity in lumbar enlargement. Sixty rats were treated with rat embryonic spinal cord tissue grafting while the other forty were chosen as control. The outcome was evaluated according the combined behavioural score (CBS) and motor evoked potential (MEP) in the 1, 2, 4 and 12 weeks. The grafting group was superior to the control as assessed by CBS (P < 0.05), especially within 4 weeks. (P < 0.01). The restoration of the latent peak of early wave(P1, N1) was better in the grafting group, too. This suggested that embryonic spinal cord graft could improve the recovery of motor function of injured spinal cord in adult rat. The effect of the embryonic spinal cord tissue graft might be concerned with its secretion of several kinds of neurotrophic factors, nerve growth factor, nerve transmitted factor, or adjustment of hormone.     

Allergic granulomatous angiitis associated with cerebral infarction, myo-pericarditis and acute respiratory failure due to eosinophilic pneumonia

We encountered a 23-year-old woman with allergic granulomatous angiitis (AGA) associated with cerebral infarction, myo-pericarditis, and acute respiratory failure due to extended eosinophilic pneumonia. She underwent emergency treatment at our hospital because of right hemiparesis and impaired consciousness. AGA was suspected because the patient had a history of bronchial asthma accompanied by pulmonary infiltrations with eosinophilia, and presented with diffuse pulmonary infiltrates, pericardial effusion, diffuse hypokinesis of myocardium, cerebral infarction and marked peripheral eosinophlia. Pulmonary eosinophilia was confirmed by examination of broncho-alveolar lavage fluid. Myocardial tissue biopsy specimens revealed fibrous granulation indicative of myocarditis. The patient responded well to corticosteroid therapy.     

Multiple sclerosis of the spinal cord: magnetic resonance appearance

OBJECTIVE: To determine the MR appearance of spinal cord multiple sclerosis (MS) plaques in patients presenting with myelopathy by using a high-field (1.5 T) imager. MATERIALS AND METHODS: We studied 119 patients who underwent high-field (1.5 T) MR studies of the spinal cord for evaluation of myelopathy. All 119 patients were thought to have possible findings of spinal cord MS at the time of the MRI interpretation. RESULTS: Sixty-four plaques were studied in 47 patients with clinically definite MS and adequate quality MRI. Of these patients 68% had a single spinal cord plaque, 19% had two plaques, and 13% had three or more plaques. Sixty-two percent of the plaques occurred in the cervical spinal cord and most frequently involved the posterior (41%) and lateral (25%) aspects of the spinal cord. None of the 64 lesions involved the entire thickness of the spinal cord. The lesion length varied from 2 to 60 mm, with 84% of the lesions < 15 mm in length. The spinal cord diameter was unchanged in 84% of plaques, enlarged at the level of the lesion in 14%, and atrophic in 2%. Just over half (55%) of the plaques enhanced with intravenously administered gadolinium. Of the patients who received synchronous head and spinal cord examinations on the same day, 24% had normal findings on the MR study of the head. Follow-up spinal cord studies were available in nine patients. New lesions developed in two patients, while previously described lesions resolved. In three patients only new lesions developed. In four patients no change occurred in the existing number of cord plaques. CONCLUSION: Spinal cord demyelinating plaques present as well-circumscribed foci of increased T2 signal that asymmetrically involve the spinal cord parenchyma. Knowledge of their usual appearance may prevent unnecessary biopsy. An MR examination of the head may confirm the imaging suggestion of spinal cord demyelinating disease, because up to 76% of patients have abnormal intracranial findings. In the remaining 24% of cases in which the clinical diagnosis is not certain and MR findings in the head are negative, a follow-up spinal cord study is recommended, because these lesions evolve and change over time.     

Source and route of exposure influence infectivity of a molecular clone of human T cell leukemia virus type I

A 61-year-old woman presented with high fever, headache and left facial palsy with diplopia. Histopathological examination of the biopsied specimens taken from nasal mucosa and kidney revealed a granulomatous angiitis with giant cell infiltration. Ga-DTPA-enhanced magnetic resonance imaging (MRI) revealed a thickening of dura mater in the middle cranial fossa and tentorium cerebelli. The observed left facial and occulomotor palsy was considered to be caused by pachymeningitis associated with Wegener's granulomatosis (WG). Cyclophosphamide combined with prednisolone effectively improved the symptoms. However, the patient died of acute interstitial pneumonitis, presumably caused by cyclophosphamide. The pathohistology obtained in the autopsy revealed a fibrous thickening of the dura mater in the left meningen with a segmental scarring of the arteries and a necrotizing arteritis in the kidney.     

Spinal cord evoked potentials and edema in the pathophysiology of rat spinal cord injury. Involvement of nitric oxide

The possibility that nitric oxide is somehow involved in the early bioelectrical disturbances following spinal cord injury in relation to the later pathophysiology of the spinal cord was examined in a rat model of spinal cord trauma. A focal trauma to the rat spinal cord was produced by an incision of the right dorsal horn of the T 10-11 segments under urethane anaesthesia. The spinal cord evoked potentials (SCEP) were recorded using epidural electrodes placed over the T9 and T12 segments of the cord following supramaximal stimulation of the right tibial and sural nerves in the hind leg. Trauma to the spinal cord significantly attenuated the SCEP amplitude (about 60%) immediately after injury which persisted up to 1 h. However, a significant increase in SCEP latency was seen at the end of 5 h after trauma. These spinal cord segments exhibited profound upregulation of neuronal nitric oxide synthase (NOS) immunoreactivity, and the development of edema and cell injury. Pretreatment with a serotonin synthesis inhibitor drug p-chlorophenylalanine (p-CPA) or an anxiolytic drug diazepam significantly attenuated the decrease in SCEP amplitude, upregulation of NOS, edema and cell injury. On the other hand, no significant reduction in SCEP amplitude, NOS immunolabelling, edema or cell changes were seen after injury in rats pretreated with L-NAME. These observations suggest that nitric oxide is somehow involved in the early disturbances of SCEP and contribute to the later pathophysiology of spinal cord injury.     

Effect of xylitol and trehalose on dry resistance of yeasts

Nitric Oxide (NO) has been implicated as a mediator of neuronal injury in vascular stroke. On the other hand, NO is suggested to play a neuroprotective role by increasing blood flow during cerebral ischemia. In order to evaluate the role of NO in the spinal cord ischemia, effects of nitric oxide synthase (NOS) inhibition on the recovery of reflex potentials after a transient spinal cord ischemia were examined in urethane-chloralose anesthetized spinal cats. Spinal cord ischemia was produced by occlusion of the thoracic aorta and the both internal mammary arteries for 10 min. Regional blood flow (RBF) in the spinal cord was continuously measured with a laser-Doppler flow meter. The monosynaptic (MSR) and polysynaptic reflex (PSR) potentials elicited by electrical stimulation of the tibial nerve, were recorded from the L7 or S1 ventral root. The recovery process of spinal reflex potentials was reproducible when the oclusion was repeated twice at an interval of 120 min. Pretreatment with N(G)-monomethyl-L-arginine (L-NMMA, 10 mg/kg), a NOS inhibitor significantly accelerated the recovery of PSR potentials after spinal cord ischemia. The accelerating effect of L-NMMA on the recovery of PSR potentials was abolished by co-administration of L-arginine (1 mg/kg/min) but not by that of D-arginine (1 mg/kg/min). L-NMMA failed to improve RBF in the spinal cord during ischemia and reperfusion. Nitroprusside (10 microg/kg/min), a NO donor, retarded the recovery of PSR potentials after spinal cord ischemia. These results suggest that NO production has a significant influence on the functional recovery after transient spinal cord ischemia.     

Angiitis of the central nervous system in systemic diseases

PURPOSE: This review is aimed at presenting classification and diagnosis criteria of isolated central nervous system (CNS) angiitis, and at proposing guidelines for diagnosis and management of this disease. CURRENT KNOWLEDGE AND KEY POINTS: Isolated CNS angiitis are rare and most information has been provided by studies of very small series. Angiitis can be primitive or secondary to infectious, neoplastic diseases, or toxics. Clinical manifestations and radiologic abnormalities are not specific. A brain biopsy is therefore often required to confirm the diagnosis, as numerous non-inflammatory vascular diseases can mimic both clinically and radiologically isolated CNS angiitis. PERSPECTIVES AND PROJECTS: To help guide the diagnosis and therapeutical management of patients with CNS angiitis, strict classification criteria should be used: 1) rule out the various diseases that can mimic clinical and radiological CNS aspects related to isolated angiitis and differentiate "isolated CNS angiitis" from "CNS angiitis associated with systemic diseases"; 2) search for factors associated with the development of a "secondary CNS angiitis"; 3) check presumed mechanism at the origin of the cerebral vascular disease: "angiitis" versus "angiopathy"; 4) if the diagnosis of "primary CNS angiitis" is still suspected, it seems reasonable to perform cerebral and leptomeningeal biopsies. Treatment is still unknown and has to be discussed on a case by case basis according to the severity and progression of symptoms.     

Pharmacological characterization of N-methyl-D-aspartate receptors in spinal cord of rats with a chronic peripheral mononeuropathy

N-Methyl-D-aspartate (NMDA) receptor antagonists, acting in the spinal cord, are analgesic. However, the clinical utility of these antagonists is diminished by their adverse effects on cognition and behavior. To facilitate the development of spinal cord-selective NMDA receptor antagonists, we characterized ligand interactions at NMDA receptors in spinal cord of normal rats and rats with a chronic peripheral neuropathy. NMDA receptors in spinal cord were distinguished from those in cerebral cortex on the basis of differences in the potencies of competitive and noncompetitive antagonists and on the basis of differences in their response to spermidine. D(-)-2-Amino-5-phosphonopentanoic acid (AP-5) and (+)-(1-hydroxy-3-aminopyrrolidine-2-one) (HA-966) were more potent in inhibiting NMDA-dependent [3H]TCP binding in spinal cord while, conversely, MK-801 was more potent in inhibiting [3H]TCP binding to NMDA receptors in cerebral cortex. Spermidine increased [3H]TCP binding to NMDA receptors in cerebral cortex (39+/-8%) but not spinal cord (2+/-1%). Based on these properties, NMDA receptors in spinal cord more closely resembled those in cerebellum than those in cerebral cortex. Generation of a chronic neuropathy had no effect on the density of NMDA receptors in lumbar spinal cord. There were also no major changes in the potencies of competitive antagonists or channel blocking ligands, although there was a trend for kynurenic acid and D-CPP to be more potent in the spinal cords of neuropathic animals. These findings indicate that, in both normal and neuropathic pain states, NMDA receptors in spinal cord can be distinguished pharmacologically from those in cerebral cortex. These findings underscore the feasibility of developing spinal cord-selective NMDA receptor antagonists as novel analgesics.     

Cerebral amyloid angiopathy

Cerebral amyloid angiopathy affects the cerebral vasculature selectively, and there is no systemic amyloidosis. Amyloid is deposited in small and medium-sized vessels of the cortex and leptomeninges. Cerebral amyloid angiopathy is a common cause of spontaneous lobar haemorrhage in elderly patients. However, cerebral amyloid angiopathy may have atypical clinical and radiological presentations. We report on five patients (three males and two females, aged 43-77 years) with histologically verified cerebral amyloid angiopathy. One patient experienced an acute headache attack and classical lobar haemorrhage. The other patients had various neurological symptoms and signs, such as seizure, disturbed vision, pareses, aphasia, and dementia that were initially diagnosed as cerebral infarction or tumour. Two patients with cerebral amyloid angiopathy and granulomatous angiitis responded to immunosuppressive treatment.     

Intraoperative monitoring for spinal cord tumor by spinal cord evoked potential following unilateral spinal cord stimulation

We described our experiences with intraoperative spinal cord monitoring in 6 cases of spinal cord tumor. During the operation, spinal cord evoked potential following unilateral spinal cord stimulation was recorded from subdural monitoring electrodes. This series included two cases of intradural extramedullary tumor (one case each of neurinoma and of meningioma) and four cases of intramedullary tumor (2 cases of cavernous angioma, one case each of ependymoma, and of glioblastoma multiforme). Before the removal of the tumor, the spinal cord evoked potential showed lower amplitude or no response on the more affected side in all 6 cases. During the operation, the different intraoperative changes were shown on each side. The authors think that the detection of unilateral damage to the spinal cord is possible in spinal cord evoked potential using unilateral spinal cord stimulation.