Continuum (Minneap Minn) 2017 02;23(1, Cerebrovascular Disease):211-237

Purpose Of Review: This article is a practical guide to identifying uncommon causes of stroke and offers guidance for evaluation and management, even when large controlled trials are lacking in these rarer forms of stroke.

Recent Findings: Fabry disease causes early-onset stroke, particularly of the vertebrobasilar system; enzyme replacement therapy should be considered in affected patients. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), often misdiagnosed as multiple sclerosis, causes migraines, early-onset lacunar strokes, and dementia. Read More

Stroke 2017 Jan 29;48(1):30-35. Epub 2016 Nov 29.

From the Department of Neurology, Medical Campus Lake Constance, Klinikum Friedrichshafen, Germany (R.H.); Department of Neurology, University of Ulm, Ulm, Germany (R.H.); Department for Biostatistics and Clinical Epidemiology (U.G.) and Center for Stroke Research (U.G.), Charité-Universitätsmedizin Berlin, Germany; Department of Internal Medicine II, Katharinen Hospital, Unna, Germany (F.W.); Department of Neurology, Austin Health and Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia (V.T.); Department of Neurology, Justus Liebig University Giessen, Germany (C.T.); Department of Neurology (C.E., F.F.) and Clinical Division of Neuroradiology, Vascular and Interventional Radiology, Department of Radiology (C.E.), Medical University of Graz, Austria; Department of Neurology, University of Mannheim, Germany (M.W., M.G.H.); Department of Neurology and Stroke Service, The Adelaide and Meath Hospital, incorporating the National Children's Hospital, Dublin, Ireland (D.J.H.M.); Department of Clinical Neurosciences, Royal Free Campus, UCL Institute of Neurology, London, United Kingdom (D.J.H.M.); Academic Unit of Neurology, School of Medicine, Trinity College Dublin, Ireland (D.J.H.M.); Department of Neurology, Helsinki University Central Hospital, Finland (J.P., T.T.); Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sweden (T.T.); Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden (T.T.); Department of Neurology, University Medicine Greifswald, Ernst Moritz Arndt University of Greifswald, Germany (C.K., B.v.S.); Department of Epidemiology and Biometrics, University of Tübingen, Germany (P.M.); Department of Neurology, New York University School of Medicine (E.K.); Department of Clinical Sciences, Section of Neurology, Lund University, Sweden (B.N.); and Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Germany (A.R.).

Background And Purpose: A patent foramen ovale (PFO) is disproportionately prevalent in patients with cryptogenic stroke. Without alternative explanations, it is frequently considered to be causative. A detailed stratification of these patients may improve the identification of incidental PFO. Read More

PLoS One 2016 11;11(11):e0166290. Epub 2016 Nov 11.

2nd Department of Medicine - Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.

Background: Serum uric acid (UA) elevation is common in patients with cardiovascular, renal and metabolic diseases. However, no study to date has analysed the role of UA in Fabry disease (FD).

Objectives: To evaluate the association between serum UA levels and mortality and morbidity in FD. Read More

J Am Coll Cardiol 2016 Sep;68(10):1037-50

Center for Inherited Cardiovascular Diseases, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Foundation University Hospital Policlinico San Matteo, Pavia, Italy. Electronic address:

Background: Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disease, caused by defects of the alpha-galactosidase A (GLA) gene. AFD can affect the heart, brain, kidney, eye, skin, peripheral nerves, and gastrointestinal tract. Cardiology (hypertrophic cardiomyopathy), neurology (cryptogenic stroke), and nephrology (end-stage renal failure) screening studies suggest the prevalence of GLA variants is 0. Read More

Pediatr Neurol 2016 Nov 29;64:10-20. Epub 2016 Jul 29.

Department of Pediatric Neurology and Metabolic Medicine, Center for Rare Disorders, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany.

Background: Fabry disease, an X-linked disorder of glycosphingolipids, markedly increases the risk of systemic vasculopathy, ischemic stroke, small-fiber peripheral neuropathy, cardiac dysfunction, and chronic kidney disease.

Methods: We performed an extensive PubMed search on the topic of Fabry disease and drew from our cumulative 43 years of experience.

Results: Most of these complications are nonspecific in nature and clinically indistinguishable from similar abnormalities that occur in the context of more common disorders in the general population. Read More

BMC Med Genet 2016 Jul 19;17(1):46. Epub 2016 Jul 19.

Department of Internal Medicine I and Comprehensive Heart Failure Center (CHFC), University Hospital Würzburg, Oberdürrbacher Str. 6, D-97080, Würzburg, Germany.

Background: X-chromosomal inheritance patterns and generally rare occurrence of Fabry disease (FD) account for mono-mutational hemizygous male and heterozygous female patients. Female mutation carriers are usually clinically much less severely affected, which has been explained by a suggested mosaicism in cell phenotype due to random allele shutdown. However, clinical evidence is scarce and potential additional effects in female gene carriers, which might account for specific clinical characteristics such as less severe chronic kidney disease, are yet unknown. Read More

Stroke 2016 Jul 31;47(7):1702-9. Epub 2016 May 31.

From the Department of Cerebrovascular Disease, IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy (A.B., G.B.B., E.A.P., N.T.); Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom (H.S.M.); Department of Bio-Medical Informatics, University of Pavia, Pavia, Italy (S.Q.); Department of Inherited Cardiovascular Disease, Foundation IRCCS Policlinico San Matteo, Pavia, Italy (E.A., M.G.); Neurology Unit, Department of Neuroscience and Sensory Organs, Maggiore Policlinico Hospital Foundation IRCCS Ca' Granda, Milan, Italy (S.L., L.C.); Neurology and Stroke Unit, Department of Urgency (G.M., A.C.), Department of Genetics (C.C., G.G.), and Brain MRI 3T Research Center (P.V.), IRCCS Foundation Casimiro Mondino Neurological Institute, Pavia, Italy; Department of Genetics of Neurodegenerative and Metabolic Diseases, IRCCS Foundation C, Besta Neurological Institute, Milan, Italy (F.T., C.G., S.B.); Department of Medical Genetics, Niguarda Ca' Granda Hospital, Milan, Italy (S.P., L.M.); Department of Genomics for Human Disease Diagnosis and Laboratory of Clinical Molecular Biology, IRCCS San Raffaele hospital, Milan, Italy (P.C., M.F.); University Vita-Salute, Milano, Italy (M.F.); Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Milan, Italy (S.C., D.R., G.P.C.); Neurology Unit, Department of Neuroscience and Sensory Organs, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico Milan, Milan, Italy (S.C., D.R., G.P.C.); Department of Molecular Biology, Scientific Institute IRCCS Eugenio Medea, Bosisio Parini, Lecco, Italy (M.T.B.); Center for amyloidosis, Department of medical Thecnologies, IRCCS Foundation San Matteo Policlinico, Pavia, Italy (L.O., G.M.); Vascular Neurology - Spedali Civili, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy (A. Pezzini, A. Padovani); Stroke Unit, Departmen

Background And Purpose: Lombardia GENS is a multicentre prospective study aimed at diagnosing 5 single-gene disorders associated with stroke (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Fabry disease, MELAS [mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes], hereditary cerebral amyloid angiopathy, and Marfan syndrome) by applying diagnostic algorithms specific for each clinically suspected disease

Methods: We enrolled a consecutive series of patients with ischemic or hemorrhagic stroke or transient ischemic attack admitted in stroke units in the Lombardia region participating in the project. Patients were defined as probable when presenting with stroke or transient ischemic attack of unknown etiopathogenic causes, or in the presence of <3 conventional vascular risk factors or young age at onset, or positive familial history or of specific clinical features. Patients fulfilling diagnostic algorithms specific for each monogenic disease (suspected) were referred for genetic analysis. Read More

Neurology 2016 May 20;86(20):1880-6. Epub 2016 Apr 20.

From the J. Philip Kistler Stroke Research Center, Department of Neurology (N.S.R., L.C., A.S.K., K.M.F.), and the Center for Human Genetic Research, Department of Neurology (N.S.R., D.R.A., V.C., K.B.S.), Massachusetts General Hospital, Boston; Neurogenetics Unit (C.M.L.), School of Medicine of Riberirao Preto, University of São Paulo, Brazil; Division of Medical Genetics (D.P.G.), University of Versailles-St Quentin en Yvelines Paris-Saclay University, France; Fundación para el Estudio de las Enfermedades Neurometabólicas (FESEN) (J.M.P.), Buenos Aires, Argentina; and Departments of Neuroradiology (G.A.H.) and Neurology (C.S., N.Ü.), Fabry Center for Interdisciplinary Therapy (FAZIT) (C.S., N.Ü.), University of Würzburg, Germany.

Objective: Using a semiautomated volumetric MRI assessment method, we aimed to identify determinants of white matter hyperintensity (WMH) burden in patients with Fabry disease (FD).

Methods: Patients with confirmed FD and brain MRI available for this analysis were eligible for this protocol after written consent. Clinical characteristics were abstracted from medical records. Read More

Eur J Intern Med 2016 Jul 12;32:26-30. Epub 2016 Apr 12.

Periodic Fever Research Centre, A. Gemelli Policlinic, Catholic University of the Sacred Heart, Rome, Italy. Electronic address:

Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of alpha-galactosidase A enzyme, which leads to the accumulation of its substrate, the globotriaosylceramide or Gb3, in many organs and tissues. Main clinical manifestations of FD are neuropathic pain, angiokeratomas, proteinuria and renal failure, left ventricular hypertrophy and stroke. Fever is also a possible symptom at the onset of the disease during childhood and adolescence, but it is frequently misdiagnosed, causing a delay in FD diagnosis. Read More

J Med Genet 2016 Jul 18;53(7):495-502. Epub 2016 Mar 18.

Division of Nephrology, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Background: Agalsidase β is a form of enzyme replacement therapy for Fabry disease, a genetic disorder characterised by low α-galactosidase A activity, accumulation of glycosphingolipids and life-threatening cardiovascular, renal and cerebrovascular events. In clinical trials, agalsidase β cleared glycolipid deposits from endothelial cells within 6 months; clearance from other cell types required sustained treatment. We hypothesised that there might be a 'lag time' to clinical benefit after initiating agalsidase β treatment, and analysed the incidence of severe clinical events over time in patients receiving agalsidase β. Read More

J Stroke Cerebrovasc Dis 2016 Jun 14;25(6):1320-5. Epub 2016 Mar 14.

Department of Neurology, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan.

Background And Purpose: Fabry disease (FD) is an X-linked lysosomal storage disorder frequently associated with the central nervous system manifestations. Although white matter hyperintensity (WMH) on MRI has been previously reported, little is known about cerebral microbleeds (CMBs) in patients with FD. Our aim is to investigate the clinical characteristics of CMBs in patients with FD. Read More

Int J Neurosci 2017 Apr 4;127(4):350-355. Epub 2016 Apr 4.

a 1 Department of Neurology, Beijing Tsinghua Changgung Hospital , Beijing , China.

Purpose: Fabry disease is an X-linked lysosomal storage disorder frequently associated with cerebrovascular disease. Data regarding Fabry disease and ischemic stroke has been lacking in China. In this study, we investigated the prevalence of Fabry disease and the distribution of the alpha-galactosidase A (α-GalA) gene - GLA mutations in young stroke patients in the Chinese population and its association with stroke subtypes. Read More

Zhonghua Yi Xue Za Zhi 2015 Jun;95(23):1829-32

Department of Neurology, Peking University First Hospital, Beijing 100034, China; Email:

Objective: To investigate incidence and clinical features of multiple organ involvement in Chinese patients with Fabry disease.

Methods: We collected 151 patients of 31 families with Fabry disease, all of whom were confirmed by classic pathology, decreased α-galactosidase A activity or GLA mutation from the year of 2011 to 2014 in Department of Neurology, Peking University First Hospital. The clinical data included incidence and onset of neuralgia, renal dysfunction, heart disease, hypertension and cerebral stroke. Read More

Joint Bone Spine 2016 Jul 14;83(4):421-6. Epub 2015 Dec 14.

Service de Rhumatologie, Médecine Interne, Site Diaconesses Croix St.-Simon, 125, rue d'Avron, 75020 Paris, France; Centre de Référence Maladies Lysosomales, Site Diaconesses Croix St.-Simon, 125, rue d'Avron, 75020 Paris, France.

Objectives: Fabry disease is a rare X-linked metabolic disorder characterized by a deficiency in the enzyme alpha-galactosidase A. Both males and females can be affected. The main presenting symptom is pain in the extremities, whereas at a more advanced stage, the manifestations include hypertrophic cardiomyopathy, cardiac dysrhythmia, proteinuria, chronic kidney dysfunction, stroke, and hearing loss. Read More

BMC Neurol 2015 Dec 12;15:256. Epub 2015 Dec 12.

Department of Clinical and Experimental Medicine, University of Sassari, Viale S. Pietro, 10, 07100, Sassari, Italy.

Background: The etiologic determinants of stroke in young adults remain a diagnostic challenge in up to one-fourth of cases. Increasing evidences led to consider Fabry's disease (FD) as a possible cause to check up. We aimed at evaluating the prevalence of unrecognized FD in a cohort of patients with juvenile stroke in northern Sardinia. Read More

Intern Med 2015 1;54(23):3069-74. Epub 2015 Dec 1.

Division of Cardiology, Nephrology, Pulmonology, and Neurology, Department of Internal Medicine, Asahikawa Medical University, Japan.

Fabry disease can cause various neurological manifestations. We describe the case of a Japanese woman with Fabry disease who presented with ischemic stroke, aseptic meningitis, and psychiatric symptoms. The patient had a mutation in intron 4 of her α-galactosidase A gene, which was not detected in her family. Read More

J Neurol 2016 Feb 14;263(2):257-62. Epub 2015 Nov 14.

Department of Neurology, New York University School of Medicine, New York, NY, USA.

Mitochondrial diseases, predominantly mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), may occasionally underlie or coincide with ischemic stroke (IS) in young and middle-aged individuals. We searched for undiagnosed patients with MELAS in a target subpopulation of unselected young IS patients enrolled in the Stroke in Young Fabry Patients study (sifap1). Among the 3291 IS patients aged 18-55 years recruited to the sifap1 study at 47 centers across 14 European countries, we identified potential MELAS patients with the following phenotypic features: (a) diagnosed cardiomyopathy or (b) presence of two of the three following findings: migraine, short stature (≤165 cm for males; ≤155 cm for females), and diabetes. Read More

Handb Clin Neurol 2015 ;132:231-48

Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX, USA. Electronic address:

Fabry disease, an X-linked disorder of glycosphingolipids that is caused by mutations of the GLA gene that codes for α-galactosidase A, leads to dysfunction of many cell types and includes a systemic vasculopathy. As a result, patients have a markedly increased risk of developing ischemic stroke, small-fiber peripheral neuropathy, cardiac dysfunction and chronic kidney disease. Virtually all complications of Fabry disease are non-specific in nature and clinically indistinguishable from similar abnormalities that occur in the context of more common disorders in the general population. Read More

PLoS One 2015 25;10(8):e0136352. Epub 2015 Aug 25.

Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.

Background And Purpose: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), caused by mutations in the NOTCH3 gene, is the most common monogenic disorder causing lacunar stroke and cerebral small vessel disease (SVD). Fabry disease (FD) due to mutations in the GLA gene has been suggested as an underdiagnosed cause of stroke, and one feature is SVD. Previous studies reported varying prevalence of CADASIL and FD in stroke, likely due to varying subtypes studied; no studies have looked at a large cohort of younger onset SVD. Read More

J Stroke Cerebrovasc Dis 2015 Nov 19;24(11):2588-95. Epub 2015 Aug 19.

NEUROFARBA Department, University of Florence, v.le Pieraccini 6, 50139 Florence, Italy; Stroke Unit and Neurology, Heart and Vessels Department, Careggi Hospital, l.go Brambilla 3, 50134, Florence, Italy.

Background And Purpose: Cerebrovascular complications are often the first cause of hospitalization in patients with Fabry disease (FD). Screenings for FD among stroke patients have yielded discrepant results, likely as a result of heterogeneous or incomplete assessment. We designed a study to identify FD among adults 60 years of age or younger who were consecutively admitted for acute ischemic stroke or transient ischemic attack (TIA) to a stroke neurology service in Italy. Read More

PLoS One 2015 14;10(8):e0135997. Epub 2015 Aug 14.

Pediatric Neurology and Metabolic Medicine, Center for Rare Disease, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.

Background: Children and patients with cognitive deficits may find it difficult to understand the implication of research. In the European Union (EU), clinical studies outside the EU directives concerning medicinal products or medical devices, i.e. Read More

J Am Soc Nephrol 2016 Mar 16;27(3):952-62. Epub 2015 Jul 16.

Internal Medicine D, Department of Nephrology, Hypertension and Rheumatology, Interdisciplinary Fabry Center Münster,

Because of the shortage of agalsidase-β supply between 2009 and 2012, patients with Fabry disease either were treated with reduced doses or were switched to agalsidase-α. In this observational study, we assessed end organ damage and clinical symptoms with special focus on renal outcome after 2 years of dose-reduction and/or switch to agalsidase-α. A total of 89 adult patients with Fabry disease who had received agalsidase-β (1. Read More

Praxis (Bern 1994) 2015 Jul;104(14):719-29

1 Klinik und Poliklinik für Innere Medizin, Universitätsspital Zürich.

Rev Neurol 2015 Jun;60(12):574-6

Hospital General Universitario de Alicante, Alicante, Espana.

Rev Neurol 2015 Jun;60(12):574

Clinica del Hospital Clinico Lozano Blesa, Zaragoza, Espana.

N Engl J Med 2015 Jul 8;373(3):232-42. Epub 2015 Jun 8.

From the Duke Clinical Research Institute, Duke University School of Medicine, Durham (J.B.G., J.G., M.J.P., E.D.P.) and University of North Carolina School of Medicine, Chapel Hill (J.B.B.) - both in North Carolina; Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom (M.A.B., R.R.H.); Canadian VIGOUR Centre, University of Alberta, Edmonton, AB (P.W.A.) and St. Michael's Hospital, University of Toronto, Toronto (R.J.) - both in Canada; Merck, Kenilworth, NJ (S.S.E., K.D.K., J.K., S.K., P.P.S., S.S.); George Washington University Biostatistics Center, Rockville, MD (J.M.L.); University of Texas Southwestern Medical Center, Dallas (D.K.M.); Munich Diabetes Research Group, Helmholtz Center, Neuherberg, Germany (E.S.); and University of Leuven, Leuven, Belgium (F.V.W.).

Background: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease.

Methods: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. Read More

Stroke 2015 Jul 2;46(7):1975-8. Epub 2015 Jun 2.

From the Department of Neurosciences, Experimental Neurology, KU Leuven, University of Leuven, Leuven, Belgium (V.T.); Department of Neurology, VIB-Vesalius Research Center, University Hospitals Leuven, Leuven, Belgium (V.T.); Center for Stroke Research (U.G.) and Department for Biostatistics and Clinical Epidemiology (U.G.), Charité-University Medical Centre Berlin, Berlin, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Munich, Germany (M.D.); The German Center for Neurodegenerative Diseases (DZNE, Munich), Munich, Germany (M.D.); Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M.D.); Department of Neurology, Medical University of Graz, Graz, Austria (C.E., F.F., R.S.); Albrecht-Kossel-Institute for Neuroregeneration (AKos), Centre for Mental Health Disease (A.-K.G., A.R.) and Institute of Medical Psychology and Medical Sociology Medical Faculty (P.K.), University of Rostock, Rostock, Germany; Department of Neurology, University Medicine Greifswald, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany (C.K., B.v.S.); Department of Neurology, New York University School of Medicine (E.K.); Institut für Klinische Epidemiologie und Angewandte Biometrie (IKEaB), Tübingen, Germany (P.M.); Department of Clinical Sciences Neurology, Lund University, Lund, Sweden (B.N.); Wilhelms University of Muenster, Muenster, Germany (E.B.R.); Stroke Prevention Research Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom (P.M.R.); Department of Neurology, Justus Liebig University Giessen, Giessen, Germany (C.T.); and Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland (T.T.).

Background And Purpose: Family history of stroke is an established risk factor for stroke. We evaluated whether family history of stroke predisposed to certain stroke subtypes and whether it differed by sex in young patients with stroke.

Methods: We used data from the Stroke in Fabry Patients study, a large prospective, hospital-based, screening study for Fabry disease in young patients (aged <55 years) with stroke in whom cardiovascular risk factors and family history of stroke were obtained and detailed stroke subtyping was performed. Read More

Acta Med Croatica 2014 Apr;68(2):223-32

Fabry disease (Anderson-Fabry disease) is one of the most common lysosomal storage diseases (after Gaucher disease) caused by deficient activity of the α-galactosidase A (α-Gal A) enzyme, which leads to progressive accumulation of globotriaosylceramide in various cells, predominantly in endothelium and vascular smooth muscles, with multisystem clinical manifestations. Estimates of the incidence range from one per 40,000 to 60,000 in males, and 1:117,000 in the general population. Pain is usually the first symptom and is present in 60%-80% of affected children, as well as gastrointestinal disturbances, ophthalmologic abnormalities and hearing loss. Read More

Stroke 2015 Jun 21;46(6):1548-53. Epub 2015 Apr 21.

From the Department of Neurology (F.F., C.E., R.S., S.R.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Graz, Austria; Department of Biostatistics and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany (U.G.); Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.-K.G., A.R.); Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany (M.G.H.); Department of Neurology, Klinikum Friedrichshafen, Friedrichshafen, Germany (R.H.); Department of Neurology, Jüdisches Krankenhaus, Berlin, Germany (G.J.J.); Center for Stroke Research Berlin (CSB), Charité Universitätsmedizin, Berlin, Germany (G.J.J.); Justus Liebig University, Giessen, Germany (M.K., C.T.); Department of Neurology, University Medicine Greifswald, Greifswald, Germany (C.K., B.v.S.); Institute for Biostatistics, University of Tübingen, Tübingen, Germany (P.M.); Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland (J.P., T.T.); Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (T.T.); Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden (T.T.); Department of Neurology, University Hospitals Leuven, Leuven, Belgium (V.T.); Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), KU Leuven - University of Leuven, Leuven, Belgium (V.T.); VIB, Vesalius Research Center, Laboratory of Neurobiology, Leuven, Belgium (V.T.); and Department of Clinical Neuroscience, Lund University Hospital, Lund, Sweden (B.N.).

Background And Purpose: Fabry disease (FD) may cause stroke and is reportedly associated with typical brain findings on magnetic resonance imaging (MRI). In a large group of young patients with an acute cerebrovascular event, we wanted to test whether brain MRI findings can serve to suggest the presence of FD.

Methods: The Stroke in Young Fabry Patients (SIFAP 1) study prospectively collected clinical, laboratory, and radiological data of 5023 patients (18-55 years) with an acute cerebrovascular event. Read More

J Cardiovasc Magn Reson 2015 Feb 21;17:22. Epub 2015 Feb 21.

North Shore Heart Research Group, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia.

Background: Sphingolipid deposition in Fabry disease causes left ventricular (LV) hypertrophy, of which the accurate assessment is essential. Cardiovascular magnetic resonance (CMR) has been proposed as the gold standard. However, there is debate in the literature as to whether papillary muscles and trabeculations (P&T) should be included in LV mass (LVM). Read More

Eur Heart J Cardiovasc Imaging 2015 Oct 6;16(10):1129-36. Epub 2015 Mar 6.

Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, 2C2 Walter Mackenzie Health Sciences Centre, Edmonton, Alberta, Canada

Aims: Anderson-Fabry Disease (AFD) is an important cause of cardiomyopathy characterized by concentric left-ventricular hypertrophy (LVH). We evaluated the extent of left-atrial (LA) structural and functional remodelling in this group of patients given that LA remodelling is a marker of adverse outcomes in the presence of LVH.

Methods And Results: Clinical profiles were obtained and cardiac MRI was performed in cohorts of patients with AFD (n = 31), healthy controls (n = 23), and a positive control cohort with known concentric remodelling and LVH (CR/H, n = 21). Read More

Mol Biosyst 2015 Jun;11(6):1543-51

Department of Cardiovascular Medicine, Second University of Naples, Naples, Italy.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal hydrolase α-galactosidase A (α-GalA) that leads to the intra-lysosomal accumulation of globotriaosylceramide (Gb3) in various organ systems. As a consequence, a multisystems disorder develops, culminating in stroke, progressive renal and cardiac dysfunction. Enzyme replacement therapy (ERT) offers a specific treatment for patients affected by FD, though the monitoring of treatment is hindered by a lack of surrogate markers of response. Read More

Neurology 2015 Mar 6;84(10):1009-16. Epub 2015 Feb 6.

From Internal Medicine D, Department of Nephrology, Hypertension and Rheumatology (M.L., M.S., E.B.), Department of Neurology (T.D.), Institute of Sports Medicine, Molecular Genetics of Cardiovascular Disease (B.S., S.-M.B.), Internal Medicine A, Department of Hematology and Oncology (R.M.), Institute of Epidemiology and Social Medicine (H.-W.H.), University Hospital Muenster; and Department of Pediatric and Adolescent Medicine (N.K., M.B.), Villa Metabolica, University Medical Center of the Johannes Gutenberg University, University of Mainz, Germany.

Objectives: Although several reports suggest an increased thromboembolic event rate, especially regarding strokes and TIAs at early age in patients with Fabry disease (FD), the risk for patients with FD to experience these events, the clinical relevance of additional risk factors including the concurrence of factor V Leiden (FVL), and the benefit of enzyme replacement therapy (ERT) regarding these events remain unclear.

Methods: Three hundred four consecutively recruited patients with FD were evaluated for their lifetime occurrence of thromboembolic events such as stroke, TIA, deep vein thrombosis, and pulmonary embolism. The thromboembolic risk was determined in patients with FD and concurrent FVL, and the impact of ERT was assessed. Read More

Cerebrovasc Dis 2015 23;39(2):110-21. Epub 2015 Jan 23.

Department of Neurology, University Medicine, Ernst Moritz Arndt University, Greifswald, Germany.

Background: Patients with carotid artery dissection (CAD) have been reported to have different vascular risk factor profiles and clinical outcomes to those with vertebral artery dissection (VAD). However, there are limited data from recent, large international studies comparing risk factors and clinical features in patients with cervical artery dissection (CeAD) with other TIA or ischemic stroke (IS) patients of similar age and sex.

Methods: We analysed demographic, clinical and risk factor profiles in TIA and IS patients ≤55 years of age with and without CeAD in the large European, multi-centre, Stroke In young FAbry Patients 1 (sifap1) study. Read More

Zhonghua Yi Xue Za Zhi 2014 Dec;94(47):3717-20

Xuanwu Hospital, Capital Medical University, Beijing 100053, China. Email:

Objective: To investigate the prevalence of Fabry disease and GLA gene mutations in young patients with ischemic stroke.

Methods: A total of 269 consecutive hospitalized patients of ischemic stroke, aged between 18-55 years, were recruited. DNA was extracted from peripheral blood. Read More

Rev Neurol 2015 Jan;60(2):93-5

Hospital General Universitario de Alicante, Alicante, Espana.

Cerebrovasc Dis 2014 11;38(6):448-56. Epub 2014 Dec 11.

Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Mainz, Germany.

Background: The central nervous system manifestations in Fabry disease (FD) include progressive white matter lesions (WMLs) and stroke. Due to progressive microvascular involvement, men and women with FD over 35 years of age develop WMLs. Moreover, the prevalence of stroke has been estimated to be 12 times higher in FD compared with the general population. Read More

Stroke 2015 Jan 9;46(1):302-13. Epub 2014 Dec 9.

From the Department of Neurology, New York University School of Medicine (E.K.); Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Mainz, Germany (A.F.); Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany (M.J.H.); Center for Human Genetic Research and Neurology Department (K.S.), Division of Neuroradiology, Department of Radiology (P.C.), Harvard Medical School, Massachusetts General Hospital, Boston; Stroke Unit, Department of Neurosciences, Monash Health and Stroke and Aging Research Group, Department of Medicine, Monash University, Australia (T.G.P.); Department of Neurology, Fundacion Para el Estudio de Enfermedades Neurometabolicas (FESEN), Buenos Aires, Argentina (J.P.); Department of Neuroradiology, University of Salerno, Salerno, Italy (R.M.); and Neurological Unit, Department of Internal Medicine, St Bassiano Hospital, Bassano del Grappa, Italy (A.B.).

J Clin Neurosci 2015 Feb 28;22(2):423-5. Epub 2014 Oct 28.

Department of Internal Medicine, Turku University Hospital, Turku, Finland.

The use of intravenous thrombolytic therapy for acute ischemic stroke is associated with improved outcomes. Fabry disease is an X-linked glycosphingolipid storage disease with vascular endothelial deposits. Affected males with the classic phenotype develop renal, cardiac, and cerebrovascular disease and die prematurely. Read More

BMC Nephrol 2014 Nov 29;15:188. Epub 2014 Nov 29.

Comprehensive Heart Failure Center, University of Würzburg, Oberdürrbacherstr, 6, Würzburg 97080, Germany.

Background: Impairments of health related quality of life (HRQoL) are frequently observed in Fabry disease (FD) and are known to be related to neuropathic pain and cardiovascular events. This study aimed to explore the role of chronic kidney disease (CKD) in a large cohort of patients with FD.

Methods: In 96 patients (53% female; age 40±12 yrs) with genetically proven FD, HRQoL was assessed by the Medical Outcomes Study (SF-36) questionnaire. Read More

Orphanet J Rare Dis 2014 Nov 26;9:178. Epub 2014 Nov 26.

Internal Medicine D, Department of Nephrology, Hypertension and Rheumatology, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149, Muenster, Germany.

Background: Fabry disease (FD) is a multisystemic disorder with typical neurological manifestations such as stroke and small fiber neuropathy (SFN), caused by mutations of the alpha-galactosidase A (GLA) gene. We analyzed 15 patients carrying the GLA haplotype -10C>T [rs2071225], IVS2-81_-77delCAGCC [rs5903184], IVS4-16A>G [rs2071397], and IVS6-22C>T [rs2071228] for potential neurological manifestations.

Methods And Results: Patients were retrospectively analyzed for stroke, transient ischemic attack (TIA), white matter lesions (WML) and SFN with neuropathic pain. Read More

Pediatr Endocrinol Rev 2014 Sep;12 Suppl 1:88-101

Fabry disease (FD) is an X-linked disorder caused by deficiency of the enzyme alpha-galactosidase A, required for the degradation of globotriaosylceramide. Accumulation of substrate occurs in multiple cell types resulting in a multi-system disorder, affecting both males and females. Clinical features include neuropathic pain and angiokeratoma, with subsequent development of proteinuria, renal failure, left ventricular hypertrophy, arrhythmias and stroke. Read More

Arch Clin Neuropsychol 2014 Nov;29(7):642-50

Department of Genetic Medicine, Westmead Hospital and Discipline of Genetic Medicine, Sydney Medical School, Sydney, Australia.

Fabry disease is an X-linked lysosomal storage disorder which can result in renal, cardiac, and cerebrovascular disease. Patients are at increased risk of stroke and neuroimaging studies note cerebrovascular pathology. This study provides a cognitive profile of a cohort of individuals with Fabry disease and investigates the impact of pain, age, renal, cardiac, and cerebrovascular functioning on cognition and psychological functioning. Read More

Gene 2014 Oct 4;549(2):275-9. Epub 2014 Aug 4.

Medical Genetics Institute, Shaare Zedek Medical Center, Affiliated with the Hadassah-Hebrew University School of Medicine, Jerusalem, Israel.

Persons with unexplained early-onset stroke have been targeted for screening surveys for Fabry disease, the most common of the three X-linked lysosomal disorders, because Fabry patients with stroke are more likely to have the life-threatening progressive cardiac and renal manifestations and would therefore most benefit from early diagnosis and intervention with enzyme replacement therapy (ERT). Among 175 Israeli patients with unexplained cryptogenic stroke screened for mutations in the Fabry α galactosidase A (GLA) gene, sequencing identified six with 2-4 GLA intronic variants, one of whose father and three sisters had the same variants. Two variants, c. Read More

Rinsho Shinkeigaku 2014 ;54(5):440-3

Department of Neurology, Ageo Central General Hospital.

A 39-year-old woman developed right hemiparesis in a few days. Magnetic resonance images revealed cerebral infarction in the territory of the left lenticulostriate artery, and MR angiography showed severe stenosis of the middle and anterior cerebral arteries and moderate one of the vertebral arteries. Bilateral and symmetric T1 hyperintensity in the pulvinar (T1-weighted imaging-pulvinar sign; "T1 pulvinar sign") was detected, which is recognized as a key imaging of Fabry disease. Read More

BMC Nephrol 2014 May 6;15:72. Epub 2014 May 6.

31 Harboro Road, Sale, Cheshire M33 5AN, UK.

Fabry disease is a rare, X-linked, lysosomal storage disease caused by mutations in the gene encoding the enzyme alpha-galactosidase A. Complete or partial deficiency in this enzyme leads to intracellular accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in many cell types throughout the body, including the kidney. Progressive accumulation of Gb3 in podocytes, epithelial cells and the tubular cells of the distal tubule and loop of Henle contribute to the renal symptoms of Fabry disease, which manifest as proteinuria and reduced glomerular filtration rate leading to chronic kidney disease and progression to end-stage renal disease. Read More

J Inherit Metab Dis 2014 Nov 15;37(6):969-78. Epub 2014 May 15.

Institute of Health Research, University of Exeter Medical School, Veysey Building, Salmon Pool Lane, Exeter, Devon, UK, EX2 4SG.

Objectives: To determine the effectiveness of enzyme replacement therapy (ERT) for adults and children with Fabry disease.

Design: Cohort study including prospective and retrospective clinical data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Read More

Neurol India 2014 Mar-Apr;62(2):219-21

Department of Neurology, Guglielmo da Saliceto Hospital, Piacenza, Italy.

Acta Clin Croat 2013 Sep;52(3):395-405

Aviva Medical Center, Zagreb, Croatia.

Fabry disease (Anderson-Fabry disease) is one of the most common lysosomal storage diseases (after Gaucher disease) caused by deficient activity of the alpha-galactosidase A (alpha-Gal A) enzyme, which leads to progressive accumulation of globotriaosylceramide in various cells, predominantly in endothelium and vascular smooth muscles, with multisystem clinical manifestations. Estimates of the incidence range from one per 40,000 to 60,000 in males, and 1:117,000 in the general population. Pain is usually the first symptom and is present in 60%-80% of affected children, as well as gastrointestinal disturbances, ophthalmologic abnormalities and hearing loss. Read More

J Am Soc Nephrol 2014 Apr 20;25(4):837-49. Epub 2014 Feb 20.

Department of Medicine, Divisions of Cardiology and Nephrology, Comprehensive Heart Failure Center, Fabry Center for Interdisciplinary Therapy, and.

Because of the shortage of agalsidase-beta in 2009, many patients with Fabry disease were treated with lower doses or were switched to agalsidase-alfa. This observational study assessed end-organ damage and clinical symptoms during dose reduction or switch to agalsidase-alfa. A total of 105 adult patients with Fabry disease who had received agalsidase-beta (1. Read More