Correlative angiographic and pathologic findings in the diagnosis of ulcerated plaques in the carotid artery.

We determined the accuracy of angiography in the diagnosis of internal carotid ulcers by comparing the angiographic reports with the pathologic findings in 36 endarterectomy specimens. Eighteen of these specimens had microscopic ulcerations, and the observer with the highest accuracy rate read 12, of which ten were ulcerated. These results revealed a sensitivity of 56%, a specificity of 89%, and an overall accuracy of 61% for angiography. The ulcers were classified into types A, B, and C to assess the interobserver agreement rate among three readers. This resulted in a 4% interobserver agreement among a total of 75 ulcers. Because of the high interobserver disagreement and the poor correlation between angiographic and pathologic findings in the surgical specimens, we conclude that the diagnosis of carotid artery ulceration by angiography is not reliable.

Computed tomography--but not magnetic resonance imaging--identified periventricular white-matter lesions predict symptomatic cerebrovascular disease in probable Alzheimer's disease.

OBJECTIVE: To examine the clinical consequences of periventricular white-matter lesions on computed tomography (CT) and magnetic resonance imaging (MRI) scans in probable Alzheimer's disease. DESIGN: Case series, 12-month follow-up. SETTING: Multidisciplinary behavioral neurology research clinic. PATIENTS: We longitudinally evaluated the clinical characteristics of 27 patients with probable AD for whom both CT and MRI scans had been performed at baseline. INTERVENTIONS: None. MAIN OUTCOME MEASURE: The presence of abnormal neurological signs was examined at baseline and at a 12-month examination. RESULTS: Periventricular white-matter lesions were observed with CT in 12 patients (44%) and with MRI in 21 patients (78%). Computed tomography did not detect lesions of 1 to 3 mm, as were seen on MRI scans, and CT also did not detect lesions of 4 to 10 mm when they occurred in the deep subcortical white matter and were not part of a greater confluent lesion. There was no relationship between the severity of periventricular white-matter lesions with either neuroimaging method and the presence of abnormal neurological signs. However, there was a greater frequency of periventricular white-matter lesions shown on CT scans than on MRI scans at baseline in patients in whom abnormal neurological signs (eg, abnormal gait, asymmetric deep tendon reflexes, focal motor deficits, abnormal plantar response) developed at 12-month follow-up. CONCLUSION: Although MRI may be more sensitive in detecting periventricular white-matter lesions, CT is more specific in predicting subsequent symptomatic cerebrovascular disease.

Cerebrovascular complications after orthotopic liver transplantation: a clinicopathologic study.

We analyzed 55 autopsy cases in 1,357 patients undergoing orthotopic liver transplantation at the University of Pittsburgh and found that 13 (23.6%) patients had intracranial bleeding, and five (9%) had infarcts. Eight patients had bleeding localized to one intracranial compartment: intracerebral hemorrhage (three patients); subarachnoid hemorrhage (three patients); and subdural hematoma (two patients). Five patients had combinations of multiple sites of bleeding: three with subarachnoid hemorrhage-intracerebral hemorrhage, one with subarachnoid hemorrhage-intracerebral hemorrhage-subdural hematoma, and one with subdural hematoma-intracerebral hemorrhage. Coexistent CNS infections (fungal or bacterial) were associated with hemorrhagic infarcts and intracerebral hemorrhage in four patients. Cerebral embolism and hemorrhagic infarction from bacterial endocarditis occurred in one patient. Five patients died of intracranial bleeding. Severe coagulopathy was the major cause of intracranial bleeding and was associated with systemic bleeding in 12 patients. Significant systemic or metabolic complications were present in all patients and masked the focal signs of the intracranial process in more than one half.

Safety of anticoagulation after hemorrhagic infarction.

Cerebral hemorrhagic infarction visualized on CT, secondary to embolic stroke in an anticoagulated individual, is usually associated with clinically stable or improving neurologic signs; fear of transforming the hemorrhagic infarction into a hematoma, however, usually prompts cessation of anticoagulation until the blood has cleared on CT, despite the recognized risk of recurrent embolism during this non-anticoagulated period. We now report our experience with 12 patients with hemorrhagic infarction who remained anticoagulated. Eleven men and one woman, ages 33 to 77, developed hemorrhagic infarction while on heparin, warfarin, or both, for prevention of recurrent embolism. Patients were either continued on uninterrupted anticoagulation from stroke onset (n = 6), or anticoagulation was withheld for several days and then resumed (n = 4), or it was withheld for 5 and 14 days (n = 2) after stroke onset and then continued uninterrupted despite the CT appearance of hemorrhagic infarction. Eleven patients had a definite cardioembolic source for stroke (atrial fibrillation, seven; ventricular thrombus, two; and ventricular dyskinesia, two). One patient had carotid occlusion with local intra-arterial embolism. Hemorrhagic infarcts varied in size and were located in the middle cerebral artery territory in 11 patients and posterior cerebral artery territory in one. All patients remained clinically stable or improved on anticoagulation. Serial CTs showed fading hemorrhagic areas. When the risk of recurrent embolism is high, anticoagulation may be safely used in some patients with hemorrhagic infarction.

Seizures after liver transplantation: a clinicopathologic study.

We reviewed the clinical and neuropathologic findings in 21 patients who had seizures after orthotopic liver transplants. Tonic-clonic seizures were the most common seizure type. Six patients developed status epilepticus. In 9 patients, seizures occurred within 1 week following transplantation. We found CNS lesions that were probably responsible for the occurrence of seizures in most patients; some had more than 1 finding. Neuropathologic examination revealed ischemic or hemorrhagic strokes in 18 patients, central pontine myelinolysis in 5, and CNS infections in 5. Multiple metabolic abnormalities were a contributing factor to the onset of seizures in some patients.

Central pontine myelinolysis after liver transplantation.

Eight adults and 3 children out of 85 patients who had neuropathologic examination after death following orthotopic liver transplantation showed central pontine myelinolysis (CPM). Four patients also had extrapontine myelinolysis. Eight patients had significant serum sodium changes. In 5, the fluctuation occurred perioperatively and 4 had a clinical picture consistent with CPM, although no patient had this as an antemortem diagnosis. We emphasize the role of hepatic dysfunction as a cause of CPM and recommend careful monitoring of electrolytes in the perioperative period of patients undergoing liver transplantation.

Cerebellar infarcts in the New England Medical Center Posterior Circulation Stroke Registry.

We report the clinical findings and stroke mechanisms of 63 patients with cerebellar infarcts. We divided the intracranial vertebrobasilar circulation into the proximal territory (P), fed by the intracranial vertebral arteries and their branches; the middle territory (M), fed by the proximal and middle basilar artery and its branches; and the distal territory (D), fed by the rostral basilar artery and its branches. Cerebellar infarcts were classified by vascular territories P, M, D, P&D, and middle-plus (P&M, M&D, and P&M&D). Patients with P infarcts (11 patients) frequently had vertigo, gait instability, limb ataxia, and headache, whereas patients with D infarcts (15 patients) most often had limb ataxia, gait instability, and dysarthria. Patients with P&D infarcts (17 patients) had signs and symptoms of both groups combined. Infarcts in which the middle territory was involved, either alone (three patients) or combined with other territories (17 patients) were dominated by brainstem signs and symptoms. The predominant stroke mechanisms in the P, D, and P&D groups were embolic due to intra-arterial or cardiac embolism. When the M territory was involved, either alone or with P, D, or P&D territories, stroke mechanisms were more varied, and there was often large-artery occlusion with hemodynamic ischemia.

Postoperative brainstem and cerebellar infarcts.

OBJECTIVE: To study the clinical features and causes of postoperative brainstem and cerebellar infarcts. METHODS: Two groups were studied. The 10 group 1 patients had cardiac (eight) or aortic (two) surgery. The 12 group 2 patients had noncardiac-nonvascular surgery, including orthopedic (five), gynecologic (four), and general (three). Patients were studied by stroke services at university hospitals in Boston (13), Charlottesville (three), Baltimore (three), and Mainz (three) during 2 consecutive years. RESULTS: Onset of strokes was immediately postoperative (six), during the first 48 postoperative hours (nine), and delayed 3 days or more (seven). Clinical syndromes were altered level of consciousness or cognition (15), vestibulocerebellar (four), and hemiparesis with focal brainstem signs (three). Infarction involved the brainstem (13), cerebellum (13), and posterior cerebral artery hemispheric territory (10). Causes: In group 1, five infarcts were due to cardiogenic embolism and three to embolism from the aorta. One patient had a postoperative pontine lacunar infarct and one developed an infarct in the territory of a known stenotic basilar artery. In group 2, one patient had vertebral artery injury from instrumentation, one had medical complications with severe hemorrhage and hypotension, and 10 most likely had position-related vertebral artery thromboses. CONCLUSIONS: Patients with postoperative brainstem and cerebellar infarcts present with altered consciousness or vestibulocerebellar syndromes. The major cause of brain infarcts after cardiac surgery is embolism from the heart and aorta. The causes of infarction after general surgery are less clear, but neck positioning during or after surgery may play an important role by promoting thrombi in compressed arteries that later embolize intracranially when neck motion becomes free.

Reliability of the NINDS Myotatic Reflex Scale.

The assessment of deep tendon reflexes is useful for localization and diagnosis of neurologic disorders, but only a few studies have evaluated their reliability. We assessed the reliability of four neurologists, instructed in two different countries, in using the National Institute of Neurological Disorders and Stroke (NINDS) Myotatic Reflex Scale. To evaluate the role of training in using the scale, the neurologists randomly and blindly evaluated a total of 80 patients, 40 before and 40 after a training session. Inter- and intraobserver reliability were measured with kappa statistics. Our results showed substantial to near-perfect intraobserver reliability, and moderate-to-substantial interobserver reliability of the NINDS Myotatic Reflex Scale. The reproducibility was better for reflexes in the lower than in the upper extremities. Neither educational background nor the training session influenced the reliability of our results. The NINDS Myotatic Reflex Scale has sufficient reliability to be adopted as a universal scale.

Neurologic complications of liver transplantation.

The clinical and neuropathologic findings of 55 adults and 30 children who received liver transplants were reviewed. Encephalopathy was the most common clinical neurologic syndrome and was usually caused by metabolic or anoxic causes. (Alzheimer type astrocytes were present in 73 per cent of patients, and evidence of diffuse hypoxic damage was present in 40 per cent of children and 25 per cent of adults.) Cerebrovascular lesions were a common finding with infarcts or hemorrhages present in 30 per cent of patients. CNS infections were documented in 34 per cent of patients. Seizures were present in a third of patients. Central pontine myelinolysis was present in 12 per cent of patients and was more common in adults than in children. Antemortem diagnosis of neurologic complications was more often based on clinical presentation rather than specific radiologic or laboratory tests.

Effects of diet composition on the metabolic and heart rate responses to cold water exposure in men.

The reaction to immersion in cold water (22 degrees C) was studied in ten healthy male volunteers successively receiving balanced (C), hypercarbohydrate (HC), hyperprotein (HP), and hyperlipid (HL) normocaloric diets with a three week equilibration period on each diet. Oxygen consumption (ml min-1 m-2) increased from 149 to 224 during C, from 160 to 196 during HL, from 154 to 178 during HP, and from 166 to 187 during HL. Only the first two differences were significant. Pulmonary ventilation (ml min-1 m-2) increased from 4.08 to 6.24 during C, from 4.01 to 5.48 during HC, from 3.41 to 3.83 during HP, and from 3.77 to 5.48 during HL. The difference was statistically significant only for C. Heart rate (beats/min) decreased from 73 to 64 during C, from 74 to 61 during HC, from 73 to 60 during HP and from 72 to 64 during HL. The differences were statistically significant for all diets except HL. Oral temperature decreased in all groups (range 0.4 to 1.6 degrees C). Respiratory rate changes were not statistically significant. The calorigenic reaction to cold water immersion was demonstrable for all groups but more efficient in subjects receiving either balanced or HC diets, suggesting that HP and HL diets reduce cold adaptation.

[Anticoagulants: when, which, how, how much, until when: these are still the questions. I]. / Anticoagulantes: cuándo, cuál, cómo, cuánto, hasta cuándo; ésta sigue siendo la cuestión. I.

OBJECTIVE: To analyze the available data in the literature so as to suggest a scheme for use when anticoagulating patients with ischemic vascular disease. DEVELOPMENT: We analyzed the most relevant publications on the use of anticoagulation in cerebrovascular disease, published since 1940. Studies and meta-analysis of anticoagulation--oral, intravenous using heparin and subcutaneous using low molecular weight heparin--in acute and recurrent stroke. This data on anticoagulation was then applied to different aspects of cerebrovascular disease such as disease of the great intracranial and extracranial vessels (dissection, occlusion and intraluminal thrombus), the penetrating vessels, venous system, hypercoagulation states and particular therapeutic uses such as anticoagulation in cerebral hemorrhage, and the use of thrombolytic agents. CONCLUSIONS: Anticoagulants are frequently used in cerebrovascular disease in spite of the lack of studies giving first level support of its efficacy (randomized studies with low false positive and false negative errors) and the fact that some studies have failed to confirm the efficacy of this treatment. With the analysis presented, we have tried to show that the failure to define the role of anticoagulants is mainly due to limitations in design of the methods used in the studies carried out. The basic shortcoming has been the search for one single treatment which could be effective for the entire spectrum of cerebrovascular disease.

[Anticoagulants: when, which, how much, until when: these are still the questions.II]. / Anticoagulantes: cuándo, cuál, cómo, cuánto, hasta cuándo; ésta sigue siendo la cuestión. II.

OBJECTIVE: To analyze the different presentations of ischemic cerebrovascular disease and develop algorithms for treatment in those different possible settings. DEVELOPMENT: We present an analysis of the publications in which the clinical, diagnostic and therapeutic features of aorto-emboli and cardio-emboli (patent foramen ovale, septal aneurysm, bacterial endocaritis, etc.) have been defined. We suggest an algorithm with general parameters for the use of anticoagulants in cerebrovascular disease. Subsequently we specifically consider the decision as to the moment to start anticoagulation, selection of the type of anticoagulant, dosage, route of administration and duration of the treatment. Because of the implications for treatment, we assess the therapeutic options when haemorrhagic infarcts occur. CONCLUSIONS: Based on studies in the literature showing benefit in individualized cerebrovascular disorders, and the anecdotic experiences of Drs. Miller Fisher, Caplan, Pessin and the writer, over the past 40 years using anticoagulants in the different clinical settings described, some parameters for treatment are proposed. We emphasize that whilst patients with different types of cerebrovascular disease are all grouped together under the unifying term 'stroke', the various treatments evaluated will probably be shown to be inefficient or deleterious. The line of treatment suggested in this review is based on the definition of the different cerebrovascular scenarios according to their aetiology and mechanisms, so as to obtain the most suitable treatment in each case.

[Thrombolytic therapy of cerebrovascular disorders]. / Terapia trombolítica en la enfermedad cerebrovascular.

OBJECTIVE: To analyze the available scientific evidence regarding treatment with thrombolytic agents in patients with cerebrovascular disease and present this in the context of daily practice. DEVELOPMENT: Publication of the NINDS study of treatment with t-PA for acute cerebral ischemia led to approval of this treatment for cerebrovascular disease. However, this therapy is associated with a significant frequency of hemorrhagic complications. We analyzed the most relevant studies on the use of thrombolytic drugs. The results of their intravenous and intra-arterial administration were compared with regard to the frequency of recanalization and hemorrhagic complications. We evaluated the results of physician's surveys on the use of t-PA since publication of the NINDS study. These results are interpreted in the context of the potentially generalized use of this treatment. CONCLUSIONS: Although in the NINDS study, administration of i.v. t-PA within three hours of an arterial occlusion resulted in a lower frequency of disability at three months, these results cannot be extrapolated to all medical settings. Until there is a more precise definition of the type of thrombolytic agent, dosage, route of administration, therapeutic window and concomitant use of other drugs, thrombolytic agents should preferably be used in centres specialized in the treatment of cerebrovascular disorders.

[Diagnosis and treatment of symptomatic and asymptomatic carotid disease]. / Diagnóstico y tratamiento de la enfermedad carotídea sintomática y asintomática.

OBJECTIVE: Provide a management strategy for the evaluation and treatment of extracranial internal carotid artery disease. BACKGROUND: Despite 50 years that have elapsed since the first carotid artery endarterectomy, surgical indications in symptomatic and asymptomatic carotid artery disease remain controversial. DESIGN: The most important studies on the treatment of symptomatic and asymptomatic internal carotid artery disease were reviewed. Special scenarios were analyzed including: intraluminal thrombus, carotid artery occlusion, dissection, ulceration, fibromuscular dysplasia, re-stenosis post endarterectomy and carotid artery disease coexisting with coronary artery disease. The current status of carotid angioplasty was discussed briefly. CONCLUSIONS: A patient-individualized approach based on the aforementioned studies and personal experience is provided. Endarterectomy is recommended in greater than 70% ICA symptomatic stenosis, in certain patients with 50 to 69% symptomatic stenosis, and exceptionally in asymptomatic patients, patients with associated coronary artery disease, ulceration, intraluminal thrombus and other less frequent scenarios.

[Dementia: clinic and diagnosis]. / Demencia: clínica y diagnóstico.

Decline of the cognitive functions necessary for activities of daily living results in a spectrum ranging from benign forgetfulness and minimal cognitive impairment to dementia. The latter is characterized by personality and behavioral changes. Alzheimer's disease is the most frequent cause of dementia affecting almost one of two people older than 80 years. Lewy body and cerebrovascular disease are also frequent causes of cognitive decline. Recent studies have revealed genetic aspects of Alzheimer's disease and the role of certain enzymes in the pathophysiology of fibrillary amyloid deposition. The aim in cognitive disease is an early diagnosis to initiate therapy and adapting measures in the patient's daily routines. The diagnosis is basically clinical with neuroimaging and neuropsychological tests' support. The EEG, SPECT, LP and other studies are only useful in a few specific scenarios. At present, a few promising therapies are being evaluated. Family support is of vital importance.