[Thrombolytic treatment of acute cerebral infarction]. / Trombolysebehandling af akut cerebralt infarkt.

INTRODUCTION: Thrombolytic therapy of acute ischaemic stroke within three hours of the onset of symptoms is approved by health authorities in the USA and Canada, but not in Europe. METHODS: We report seven patients treated with recombinant tissue plasminogen activator (rtPA) within three hours of the onset of stroke according to an open protocol following internationally accepted guidelines. RESULTS: Three patients with initial severe neurological deficits made an almost complete recovery within the first 24 hours after treatment. Two patients had a partial remission, and two patients had no benefit. There were no bleeding complications. DISCUSSION: The present results are in accordance with the Cochrane Library's analysis of published data regarding thrombolytic therapy.

Ultrasonic echolucent carotid plaques predict future strokes.

BACKGROUND: We tested prospectively the hypothesis that stroke development can be predicted by echolucency of carotid atherosclerotic plaques in previously symptomatic and asymptomatic patients. METHODS AND RESULTS: We followed incidence of ipsilateral ischemic strokes for 4.4 years in 111 asymptomatic and 135 symptomatic patients with >/=50% relevant carotid artery stenosis. At inclusion, echogenicity of carotid plaques and degree of stenosis were evaluated with high-resolution B-mode ultrasound with computer-assisted image processing and Doppler ultrasound, respectively. We observed 44 ipsilateral ischemic strokes. In symptomatic patients, relative risk of ipsilateral ischemic stroke for echolucent versus echorich plaques was 3.1 (95% CI, 1.3 to 7.3), whereas for 80% to 99% versus 50% to 79% stenosis, the relative risk was 1.4 (95% CI, 0.7 to 3.0). Relative to symptomatic patients with echorich 50% to 79% stenotic plaques, those with echorich 80% to 99% stenotic plaques, echolucent 50% to 79% stenotic plaques, and echolucent 80% to 99% stenotic plaques had relative risks of ipsilateral ischemic strokes of 3.1 (95%CI, 0.7 to 14), 4.2 (95% CI, 1.2 to 15), and 7.9 (95% CI, 2.1 to 30), equivalent to absolute risk increases of 11%, 18%, and 28%. This was not observed in previously asymptomatic patients. CONCLUSIONS: Echolucent plaques causing >/=50% diameter stenosis by Doppler ultrasound are associated with risk of future stroke in symptomatic but not asymptomatic individuals. This suggests that measurement of echolucency, together with degree of stenosis, may improve selection of patients for carotid endarterectomy.

Immunoglobulin treatment versus plasma exchange in patients with chronic moderate to severe myasthenia gravis.

The purpose of this study was to compare the efficacy of high-dose intravenous immunoglobulin (IVIG) treatment with plasma exchange in patients suffering from moderate to severe myasthenia gravis (MG) in a stable phase. There are no controlled studies comparing IVIG with plasma exchange in patients who despite immunosuppressive treatment have persistent incapacitating MG symptoms. This was a controlled crossover study. Twelve patients with generalized moderate to severe MG on immunosuppressive treatment for at least 12 months were included. The patients were evaluated clinically using a quantified MG clinical score (QMGS) before and at follow-up visits after each treatment. One week after the treatments, the patients who received plasma exchange treatment showed a significant improvement in QMGS compared to baseline but although some improvement was seen after IVIG this did not reach statistical significance. Four weeks after both plasma exchange and IVIG treatments, there was a significant improvement in QMGS compared to baseline. One week and 4 weeks after treatment, no significant difference between the 2 treatments was found. Both treatments have a clinically significant effect 4 weeks out in patients with chronic MG, but the improvement has a more rapid onset after plasma exchange than after IVIG.

[Ischemic cerebral apoplexy in children]. / Iskaemisk apoplexia cerebri hos børn.

During two years we identified eight children aged 1.5-10 years with cerebral ischaemic stroke. Prior to the stroke seven of eight children were in full health. Predisposing factors were endocarditis and trauma. Four children had prodomal symptoms prior to the infarction. All had acute hemiparesis on admission. Three of the children had fever, and five had varicellazoster infection three to 18 months prior to the stroke. Three children had convulsions. Seven of eight children had stenoses or occlusions of the middle cerebral or the basilar artery. Five children have persistent deficits and none have died. The children did not have coagulopathies, hypertension or arteriosclerosis. Echocardiography did not show patent foramen ovale. Early clinical and neuroradiological investigations are of importance in reaching the appropriate diagnosis.

LDL receptor mutations and ApoB mutations are not risk factors for ischemic cerebrovascular disease of the young, but lipids and lipoproteins are.

BACKGROUND: The genetic background for ischemic cerebrovascular disease of the young and the role of lipids and lipoproteins as risk factors are not clear. METHODS: We determined five LDL receptor mutations (Trp23Stop, Trp66Gly, Trp556Ser, 313+1G --> A, 1846-1G --> A) and three apolipoprotein B mutations (Arg3500Gln, Arg3500Trp, Arg3531Cys), and other risk factors for ischemic cerebrovascular disease in 80 patients (36 women, 44 men) with onset of disease before the age of 50 years compared with 3366 individuals from a general population sample within the same age range. RESULTS: None of the patients were carriers of mutations in the LDL receptor (Trp23Stop, Trp66Gly, Trp556Ser, 313+1G --> A, 1846 - 1G --> A) or the apolipoprotein B gene (Arg3500Gln, Arg3500Trp, Arg3531Cys) associated with hypercholesterolemia. However, on univariate analysis as well as on logistic regression analysis allowing for age and gender, plasma cholesterol (OR 1.4; P < 0.0005), HDL-cholesterol (OR 0.4; P < 0.005), diabetes (OR 5.8; P < 0.0001), and hypertension (OR 3.9; P < 0.001) were significant predictors of ischemic cerebrovascular disease. CONCLUSIONS: The five most common LDL receptor mutations in Danish patients with familial hypercholesterolemia and three mutations in the apolipoprotein B gene did not predispose to ischemic cerebrovascular disease of the young. However, cholesterol and HDL-cholesterol are important risk factors for ischemic cerebrovascular disease of the young in the present study. The elevation in cholesterol could in some patients be due to rare LDL receptor mutations not tested for, and could in other patients be multifactorial in origin.

Neurological abnormalities in schizophrenic patients: a prospective follow-up study 5 years after first admission.

OBJECTIVE: The aim of this study was to examine the temporal stability of neurological abnormalities in first-episode schizophrenic patients, and to clarify the relationships between such abnormalities and psychopathology. METHOD: A total of 18 schizophrenic patients, 11 non-schizophrenic patients and 10 healthy volunteers were examined neurologically at first admission and 5 years later. RESULTS: A significant increase in the number of neurological abnormalities was seen in schizophrenic patients with genetic predisposition and in patients with a non-remitting course of disease. Birth complications had an impact on the occurrence of neurological abnormalities at first admission. CONCLUSION: The association between a deteriorating course of disease and neurological impairment supports the theory that any possible impairment of the brain in schizophrenia is aggravated during the first 5 years of disease.

Autoimmunity and extranodal lymphocytic infiltrates in lymphoproliferative disorders.

OBJECTIVE: To examine the relationship between autoimmunity and extranodal lymphocytic infiltrates in different lymphoproliferative disorders with immunoglobulin alterations. SUBJECTS AND DESIGN: A clinical review combined with a retrospective cohort study of 380 patients, 28 with monoclonal gammopathy of undetermined significance, three with common variable immunodeficiency, 147 with chronic lymphocytic leukaemia, 57 with Waldenström's macroglobulinaemia and 145 with non-Hodgkin's malignant lymphoma. SETTING: A university hospital and The State Serum Institute in Copenhagen. INTERVENTION: Clinical examination of each patient with special attention to chronic inflammatory and autoimmune manifestations. Biopsies were taken from non-infectious infiltrates, some of which were additionally tested with PCR analysis for gene rearrangements. Serological screening with a test battery for various autoantibodies was used in combination with techniques for the detection of M-components and monoclonal B-cell proliferation. MAIN OUTCOME MEASURES: Clinical and/or serological autoimmune manifestations, M-component and other immunoglobulin alterations, and inflammatory tissue changes were studied in patients with chronic inflammatory, polyclonal or oligoclonal pseudolymphomas and in monoclonal, malignant extranodal lymphomas. RESULTS: In 380 consecutive patients, 49 (12.9%) had extranodal manifestations, of whom 47 also had autoimmune manifestations. Nearly half of the 47 patients had more than one autoimmune manifestation. There was a strong correlation between clinical signs and corresponding autoantibodies such as anti-SSA and -SSB antibodies in Sjögren's syndrome (10 cases), antithyroid peroxidase antibodies in thyroiditis and Graves' disease (10 cases), and parietal cell antibodies in gastric ulcers with maltoma (12 cases). Clinical and serological signs of autoimmunity correlated strongly with female sex (34, 72% women; and 13, 28% men) and with immunoglobulin alterations. CONCLUSIONS: To our knowledge this is the first systematic review of B-lymphoproliferative and autoimmune disorders indicating that pseudolymphoma and malignant lymphomas, including maltomas, may develop in the context of a permanent autoantigenic drive.

Combined bilateral submandibular and sublingual swelling, macroglossus, and carpal tunnel syndrome caused by light chain amyloidosis.

Three cases of light chain kappa amyloidosis in multiple myeloma patients are described with remarkable involvement of the tongue and swelling of the sublingual and submandibular regions, and without signs of nephropathy despite Bence Jones kappa proteinuria. All three patients had carpal tunnel syndrome at the beginning of their disease course and only moderate gastrointestinal involvement. Primarily for prognostic reasons, amyloidosis should be suspected in such cases, even in the presence of these highly unusual manifestations, and the diagnosis should be confirmed by unambigously-positive biopsies.

[Is crazy cow disease the cause of the new variant of Creutzfeldt-Jakob syndrome?]. / Forårsager kogalskab den nye variant af Creutzfeldt-Jakobs sygdom?

In 1986, veterinary pathologists discovered spongiform encephalopathy in the brains of two cows in the UK. These two cases turned out to be the beginning of epidemic bovine spongiform encephalopathy (BSE), which culminated in 1992 with more than 3000 cases monthly. In 1996, the British government announced that a distinct variant of CJD (vCJD) had occurred in ten young people in the UK. The cases were notified within the past 1 1/2 years. A link to BSE seemed likely. Transmission studies of the two diseases have demonstrated similar properties such as incubation time, neuropathology and glycoform profile of the pathologically altered prionprotein. In effect, vCJD is very likely to represent human BSE. Epidemiological data suggest that BSE transmission to humans may have occurred only in a limited number of cases. Future studies will have to confirm this. So far, no increase in the incidence of vCJD has been noticed.

[Creutzfeldt-Jakob disease--a human prion disease]. / Mb Creutzfeldt-Jakob--en human prionsygdom.

The human prion diseases, Creutzfeldt-Jakob disease, Gerstmann-Strøaussler-Scheinker syndrome and kuru, are neurodegenerative disorders sharing clinical features of rapidly progressive neurodegenerative dementia and cerebellar symptoms of marked ataxia and tremor, resulting in death within one year after onset. Similar diseases have been described in animals, such as scrapie in sheep and goats, and bovine spongiform encephalopathy in cattle (mad cow disease). The very long incubation period, the lack of a host immune response, and a neurological triad of spongiosis, astrocytosis and amyloid plaque formation have suggested these diseases to have a common aetiology. A highly effective transmissible agent, fundamentally different from viruses, has been identified and the term prion adopted to distinguish it from viruses and viroids. CJD is unique in occurring both in inherited, sporadic and acquired forms.

Bilateral common carotid artery occlusion with minimal neurological deficit: long term follow up in 3 patients.

Three patients, two women and one man, aged 56-70 year (mean 59 years) with modest neurological deficits and bilateral occlusion of the common carotid arteries initially identified by duplex scanning and angiography were followed by repeated clinical and transcranial Doppler examination (TCD) over 6.5 years. Vasomotor reactivity (VMR) was tested by combined examination of TCD and xenon-133 cerebral blood flow (CBF) before and after intravenous administration of 1 g acetazolamide. At follow-up CBF was measured using single photon emission computerised tomography (SPECT). In two patients mean velocities in the middle cerebral artery (MCA) were within the normal range at repetitive examinations with good VMR ranging 30-111%, whereas CBF was reduced in MCA territories ranging 29-36 ml 100 g(-1) min(-1), but increasing 44-69% after acetazolamide, indicating good VMR. These 2 cases had anterograde flow in the ophthalmic artery and siphon. The third patient had very low MCA mean velocities of 21-27 cm sec(-1), increasing 26-33% after acetazolamide. This patient had retrograde flow in the ophthalmic artery and siphon connected with bilateral prolonged episodes of amaurosis fugax and transient ischemic attacks. In all three patients the posterior cerebral arteries were major supplying collaterals having high mean velocities of about 100 cm sec(-1) and high velocities in the basilar arteries of 85 cm sec(-1) as well. During follow up no patient had a new stroke, but all experienced orthostatic dizziness and chronic fatigue.

Multiple autoimmune manifestations in monoclonal gammopathy of undetermined significance and chronic lymphocytic leukemia.

In 18 cases of monoclonal gammopathy of undetermined significance, MGUS (monoclonal gammopathy of undetermined significance), admitted for diagnosed or suspected peripheral neuropathy, 11 patients showed other co-existing autoimmune manifestations. Two had POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-component, and skin symptoms), the others mainly endocrinopathy and polyclonal pseudolymphoma. There were 13 cases of sensorimotor neuropathy, two cases of neuritis, while neuropathy could not be confirmed in three cases. Compared with a retrospective review of autoimmunity in a randomly selected CLL (chronic lymphocytic leukemia) cohort of 115 patients, 13 out of 42 patients with clinical and/or laboratory features of autoimmunity showed co-expression of autoimmune signs, the dominating traits being Coombs positive AIHA (auto-immune hemolytic anemia), platelet autoantibodies, endocrinopathy mainly associated with the thyroid gland, serological and/or rheumatological symptoms, but only one case of sensorimotor neuropathy. Viewed from a current model of acquired autoimmunity it is perhaps not surprising that such autoimmunity is seen predominantly in patients with monoclonal gammopathy. Thus, a high concentration of cross-reacting polyreactive autoantibodies related to the M-component might be present in these patients. Furthermore, quantitative defects of the immunoglobulins including the hypogammaglobulinemia associated with M-components can presumably give rise to a defect of the anti-idiotypic network's regulation of natural autoantibodies and autoimmune manifestations in vivo. Such autoimmune manifestations, which are easily overlooked in CLL may call for additional treatment with immunosuppression and/or intravenous, polyclonal IgG.

Neurological abnormalities in patients with schizophrenia or schizophreniform disorder at first admission to hospital: correlations with computerized tomography and regional cerebral blood flow findings.

Forty-five patients with schizophrenia or schizophreniform disorder admitted to hospital for the first time had a neurological examination, including integrative sensory and complex motor acts, by a trained neurologist. The patients were studied by CT (computerized tomography) and rCBF (regional cerebral blood flow) as well. A control group of 24 healthy volunteers was included. The patients had significantly more neurological abnormalities (NA) than the healthy volunteers. Medication did not explain the discrepancy. The NA were associated with sulcal enlargement and smaller brains as visualized by CT but not with ventricular enlargement. There was no association between the regional flow values and NA.