Thrombolysis has been shown to improve the 3-month outcome of patients with ischemic stroke, but knowledge of the long-term effect of thrombolysis is limited.
The present study compares the long-term ...outcome of stroke patients who were treated with intra-arterial thrombolysis (IAT) using urokinase with the outcome of patients treated with aspirin. The modified Rankin Scale (mRS) was used to assess the outcome; 173 patients treated with IAT and 261 patients treated with aspirin from the Bernese Stroke Data Bank were eligible for the study. A matching algorithm taking into account patient age and stroke severity on admission (as measured by the National Institute of Health Stroke Scale NIHSS) was used to assemble an IAT and an aspirin group.
One hundred and forty-four patients treated with IAT and 147 patients treated with aspirin could be matched and included in the comparative analysis. The median NIHSS score was 14 in each group. At 2 years, 56% of the patients treated with IAT and 42% of the patients treated with aspirin achieved functional independence (mRS, 0 to 2; P=0.037). Clinical outcome was excellent (mRS, 0 to 1) in 40% of the IAT and in 24% of the aspirin patients (P=0.008). Mortality was 23% and 24%, respectively.
The present study provides evidence for a sustained effect of IAT when assessed 2 years after the stroke.
We aimed to assess quality of life (QOL) and its predictors in stroke survivors after local intra-arterial thrombolysis (IAT) as well as to measure QOL according to the site of pretreatment vessel ...occlusion.
From January 2000 to April 2004, 175 consecutive patients underwent IAT for acute ischemic stroke. Clinical and radiological data were collected prospectively. We contacted 135 stroke survivors after a mean of 923 (+/-431) days, 132 responded. QOL, assessed with EuroQol (EQ-5D), and functional abilities, measured with the modified Rankin Scale (mRS) and the Barthel Index, were compared, and predictors of QOL were analyzed.
Measured with EQ-5D, 56% of the patients reported a good QOL (EQ-5D Index >or=70). Low mRS and high Barthel Index scores at follow-up were associated with better overall QOL (Kendall's tau >0.5). Nevertheless, 25% of the functionally independent patients (mRS 0-2) indicated a markedly impaired QOL (EQ-5D Index <70) and 10% of disabled patients indicated good QOL. QOL was significantly lower in patients with occlusion of the internal carotid artery compared to patients with occlusion of the basilar artery or the M1, M2 or M3/4 segment of the middle cerebral artery (EQ-5D Index: p = 0.005). A high National Institute of Health Stroke Scale score on admission and occlusion of the internal carotid artery were independent predictors of impaired QOL (p < 0.05).
More than half of the stroke survivors treated with IAT reported a good QOL, mostly survivors with mild disabilities. QOL assessment gives information that is not provided by traditional outcome scores. Our results support guidelines to measure QOL in stroke research.
Abstract 1181
Poster Board I-203
MNGIE is an autosomal recessive disorder of nucleotide metabolism due to TYMP gene mutations that cause loss of activity of thymidine phosphorylase (TP). As a result, ...thymidine (Thd) and deoxyuridine (dUrd) plasma and tissue levels increase and cause nucleotide pool imbalances. This leads to instability of mitochondrial DNA with loss of mitochondrial respiratory chain functions. Clinical consequences manifest as a multisystemic disease with severe gastrointestinal dysmotility, most severe cachexia (BMI 10-17 kg/m2 in our patients), ptosis and/or ophthalmoparesis, peripheral neuropathy and leukencephalopathy. While TP is not expressed in all tissues, cellular and plasma Thd and dUrd levels appear to be in equilibrium among all body compartments. Mononuclear white blood cells and platelets are rich in TP activity and can transiently restore TP activity upon transfusions. Therefore allogeneic HSCT was tested as a permanent replacement therapy by several teams. A coorperative group under the auspices of the WBMT collected the global experiences. So far, 10 patients underwent an attempt for HSCT between 2005-2009. One patient stopped conditioning due to toxicity and did not proceed to transplantation. Nine patients had 12 allogeneic HSCT. They were 6 males and 3 females with a median age of 28y (range 10-41y) at transplantation. All were symptomatic at time of HSCT (5 on parenteral nutrition). A variety of different conditioning regimens and GvHD prevention strategies were used. Fludarabine was included in all conditioning regimens, combined with busulfan or cyclosphoshamide, melphalan, thiotepa or TBI. T cell depletion (TCD) with ATG, alemtuzumab or in vitro TCD was performed in 10 HSCT. GvHD prevention with sirolimus or calcineurin inhibitors was used in combination with mycophenolate mofetil or methotrexate. Graft source for first transplants was peripheral blood stem cells (PBSC) in 4, bone marrow (BM) in 3 and cord blood in 2. PBSC and BM donors were HLA-identical siblings in 2, phenotypic identical parent in 1 and unrelated donors in 4 (3 with 10/10 HLA-match, 1 with 9/10-match). Engraftment was problematic. Three primary graft failures and two late graft failures were observed. A second HSCT was performed in three patients, all engrafted but two died due to TRM. The two patients without a second HSCT died from their disease. Four patients developed acute GvHD grade I-IV.
To date, five patients are alive 8-48 months posttransplant, three after related PBSC-HSCT, one after unrelated BM-HSCT (10/10-HLA identical), one after two HSCTs with BM and PBSC respectively from the same unrelated 10/10-HLA identical donor. In all of these patients metabolism normalized as measured by normal Thd and dUrd levels. All surviving patients are off parenteral nutrition without further weight loss or increase in body weight. Gastrointestinal symptoms improved and in the two patients with the longest follow up a slight improvement of neurological symptoms can be observed now. Further time is needed to determine whether other disturbed organ functions will be reversible.
Allogeneic HSCT can restore full metabolic function and halt and restore clinical signs and symptoms in this otherwise unrelenting progressive disease. Engraftment was identified as a key obstacle. Still, the optimal transplant regimen needs to be defined to improve patients' outcome. A common consensus transplant protocol and disease specific pre- and posttransplant evaluation protocol was developed with participation of all involved teams.
Gratwohl:Amgen: Research Funding; Roche: Research Funding; Novartis: Research Funding; BMS: Research Funding; Pfizer: Research Funding. Hirano:Athena Diagnostics: Speakers Bureau; Pfizer: Research Funding.
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