Background: Magnetic resonance imaging (MRI) studies in primary progressive multiple sclerosis (PPMS) have shown a reduced frequency of enhancement with the contrast agent gadolinium-DTPA (Gd-DTPA), in comparison with...Background: Magnetic resonance imaging (MRI) studies in primary progressive multiple sclerosis (PPMS) have shown a reduced frequency of enhancement with the contrast agent gadolinium-DTPA (Gd-DTPA), in comparison with relapsing-remitting multiple sclerosis (RRMS), and it has been suggested that there may be a less important role for inflammation in its pathogenesis. However, the earliest clinical stages of PPMS have not been studied and thus it has not been possible to exclude the existence of an early inflammatory phase. Abstract:Objective: To study the presence, characteristics, and implications of inflammation in early PPMS. Methods: 45 patients with a mean disease duration of 3.3 years had triple dose Gd enhanced MRI, expanded disability status scale (EDSS), and multiple sclerosis functional composite (MSFC) assessments at baseline. Repeat MRI was done at 1 and 2 months in 24 patients, and at 6 months in 38. Results: Enhancing brain lesions were present in 42%of patients at baseline but enhancing cord lesions were uncommon (7%); 85%of enhancing lesions enhanced for one month or less. Patients with enhancing lesions had greater disability (EDSS, p = 0.027; MSFC, p = 0.026) and more MRI abnormalities (greater T2 load, p = 0.008; greater T1 hypointensity load, p = 0.001; and reduced partial brain volume, p = 0.012) than those without enhancement. Enhancement at 6 months was seen in 32%of patients and was restricted to a subset of patients who enhanced at baseline. Conclusions: Enhancement is present in some cases of early PPMS and is associated with greater disease impact in terms of both clinical and MRI measures.展开更多
Fabry’s disease is an X-linked lysosomal storage disorder. α-Galactosidase deficiency leads to accumulation of globotriaosylceramide mainly in endothelial and smooth muscle cells. Cerebrovascular symptoms with predo...Fabry’s disease is an X-linked lysosomal storage disorder. α-Galactosidase deficiency leads to accumulation of globotriaosylceramide mainly in endothelial and smooth muscle cells. Cerebrovascular symptoms with predominant affection of the vertebrobasilar circulation are one of the major sources of morbidity in Fabry’s disease. We present a Hungarian family with Fabry’s disease caused by a new mutation in the α-galactosidase A gene (GLA), and describe a variant expression of the disease. Megadolichoba- silar anomaly was diagnosed in two male patients in the family who died of thrombosis. In another female patient who had suffered from disturbance of the vertebrobasilar circulation, a strongly dilated basilar artery without thrombosis was found at autopsy. Another three family members had basilar strokes and large and elongated basilar arteries on MRI. Genetic analysis disclosed a c.47T→C missense mutation resulting in L16P in the amino acid sequence of the α-galactosidase protein. This report suggests that megadolichobasilar anomaly is potentially life-threaten- ing, and that L16P is a disease-causing mutation in patients with Fabry’s disease. Early enzyme replacement therapy may prevent the development of these irreversible cerebrovascular complications.展开更多
The authors sought to identify clinical and MRI predictors of outcome in primary progressive multiple sclerosis (PPMS). Clinical and MRI assessments were performed at baseline and 2 and 5 years (clinical only). At bas...The authors sought to identify clinical and MRI predictors of outcome in primary progressive multiple sclerosis (PPMS). Clinical and MRI assessments were performed at baseline and 2 and 5 years (clinical only). At baseline, disease duration, expanded disability status scale (EDSS) and brain volume predicted outcome. Adding short-term change variables, baseline EDSS, changes in T2.lesion load and cord area, and number of new lesions were predictive. Clinical and MRI variables predict long-term outcome in PPMS.展开更多
文摘Background: Magnetic resonance imaging (MRI) studies in primary progressive multiple sclerosis (PPMS) have shown a reduced frequency of enhancement with the contrast agent gadolinium-DTPA (Gd-DTPA), in comparison with relapsing-remitting multiple sclerosis (RRMS), and it has been suggested that there may be a less important role for inflammation in its pathogenesis. However, the earliest clinical stages of PPMS have not been studied and thus it has not been possible to exclude the existence of an early inflammatory phase. Abstract:Objective: To study the presence, characteristics, and implications of inflammation in early PPMS. Methods: 45 patients with a mean disease duration of 3.3 years had triple dose Gd enhanced MRI, expanded disability status scale (EDSS), and multiple sclerosis functional composite (MSFC) assessments at baseline. Repeat MRI was done at 1 and 2 months in 24 patients, and at 6 months in 38. Results: Enhancing brain lesions were present in 42%of patients at baseline but enhancing cord lesions were uncommon (7%); 85%of enhancing lesions enhanced for one month or less. Patients with enhancing lesions had greater disability (EDSS, p = 0.027; MSFC, p = 0.026) and more MRI abnormalities (greater T2 load, p = 0.008; greater T1 hypointensity load, p = 0.001; and reduced partial brain volume, p = 0.012) than those without enhancement. Enhancement at 6 months was seen in 32%of patients and was restricted to a subset of patients who enhanced at baseline. Conclusions: Enhancement is present in some cases of early PPMS and is associated with greater disease impact in terms of both clinical and MRI measures.
文摘Fabry’s disease is an X-linked lysosomal storage disorder. α-Galactosidase deficiency leads to accumulation of globotriaosylceramide mainly in endothelial and smooth muscle cells. Cerebrovascular symptoms with predominant affection of the vertebrobasilar circulation are one of the major sources of morbidity in Fabry’s disease. We present a Hungarian family with Fabry’s disease caused by a new mutation in the α-galactosidase A gene (GLA), and describe a variant expression of the disease. Megadolichoba- silar anomaly was diagnosed in two male patients in the family who died of thrombosis. In another female patient who had suffered from disturbance of the vertebrobasilar circulation, a strongly dilated basilar artery without thrombosis was found at autopsy. Another three family members had basilar strokes and large and elongated basilar arteries on MRI. Genetic analysis disclosed a c.47T→C missense mutation resulting in L16P in the amino acid sequence of the α-galactosidase protein. This report suggests that megadolichobasilar anomaly is potentially life-threaten- ing, and that L16P is a disease-causing mutation in patients with Fabry’s disease. Early enzyme replacement therapy may prevent the development of these irreversible cerebrovascular complications.
文摘The authors sought to identify clinical and MRI predictors of outcome in primary progressive multiple sclerosis (PPMS). Clinical and MRI assessments were performed at baseline and 2 and 5 years (clinical only). At baseline, disease duration, expanded disability status scale (EDSS) and brain volume predicted outcome. Adding short-term change variables, baseline EDSS, changes in T2.lesion load and cord area, and number of new lesions were predictive. Clinical and MRI variables predict long-term outcome in PPMS.
