6. Ortiz A, Oliveira JP, Wanner C, et al.Recommendations and guidelines for the diagnosis and treatment of Fabry nephropathy inadults. Nat Clin Pract Nephrol. 2008;4:327–336.

7. Remuzzi G, Benigni A, Remuzzi A. Mechanisms of progression and regression of renal lesions of chronic nephropathies anddiabetes. J Clin Invest. 2006;116:288–296.

Stroke: Prevention and ManagementDr. Pippa Tyrrell

University of Manchester and Salford Royal Foundation Hospitals Trust, Manchester, United Kingdom

Stroke is the third most common cause of death and the most common cause of adult neurologic disability in theWestern world. It can have devastating effects on patients and their families. It is increasingly recognized as apotentially preventable and treatable disease, and over the past decade there have been very significant changes inservice provision and treatment, with improvement in outcomes.

Primary prevention of stroke does not differ from the prevention of vascular disease in general. Encouragementof a healthy lifestyle (avoidance of smoking, increased exercise, and a healthy diet), together with blood pressuremanagement, detection, management of diabetes and dyslipidemia, and detection and management of atrial fibril-lation, are the cornerstones of stroke prevention, both primary and secondary. Immediate recognition and man-agement of transient ischemic attack (TIA), including early detection of symptomatic carotid stenosis and appro-priate intervention (eg, carotid endarterectomy), reduces subsequent stroke risk. In the United Kingdom, daily TIAclinics have improved the speed with which patients are assessed and treated.

When a stroke occurs, very rapid treatment is likely to improve outcome significantly. Around 10% to 15% ofstrokes are due to primary intracerebral hemorrhage, while most are secondary to ischemia. Secondary excitotoxicand inflammatory processes rapidly damage tissue, so that the early treatment is essential (“time is brain”).Thrombolysis with tissue plasminogen activator given within 4.5 hours of symptom onset (following computedtomography to rule out hemorrhage) reduces subsequent disability. There is currently no available neuroprotectivetreatment, but early admission to a stroke unit and early aspirin administration reduce the risks for death anddependency. There is some evidence of benefit of hemicraniectomy for people with “malignant middle cerebralartery infarction” and of intra-arterial interventions including thrombectomy for selected patients. Treatment ofintracerebral hemorrhage is unsatisfactory, with a high mortality rate. There is equipoise about the benefit ofsurgery in these patients, and apart from rapid reversal of anticoagulation, treatment is generally supportive.

Many patients are left with significant disability following a stroke, and early mobilization and appropriatepositioning, together with early therapy interventions, can improve outcome. Patients benefit from early supporteddischarge programs and need continued support, particularly psychological and social support—sometimes life-long. There is good evidence that care in a stroke unit and follow-up by an experienced multidisciplinary team canhave a significant effect on whether a patient is able to return to a normal life following a stroke. Secondaryprevention of further stroke is a vital part of poststroke management.

Neuropathic PainProf. Claudia Sommer

Department of Neurology, University of Würzburg, Würzburg, Germany

Neuropathic pain is very often the earliest symptom of Fabry disease. Episodes of severe burning pain may occurfrom early childhood, typically in the feet and hands. These episodes are usually triggered by febrile infections, heator cold exposure, physical exertion, or emotional stress and are known as “Fabry crises.” Often, the pain experi-enced by these children is misinterpreted as a symptom of infection rather than being recognized as a manifestationof Fabry disease. About 75% of adults with Fabry disease experience pain. Pain increases with physical exertionand thus contributes to problems in the workplace in many patients. Some patients can differentiate between Fabrycrises and a different type of neuropathic pain that is persistent and tends to resemble the classic, polyneuropathy-associated, distal, symmetric, burning pain with tingling paresthesias. These symptoms are caused by small fiber

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neuropathy, a type of polyneuropathy that affects mainly the C fibers and A� fibers. Small fiber neuropathy leadsto reduced skin innervation, which is more pronounced in the extremities than on the trunk. The exact mechanismunderlying the different types of neuropathic pain in Fabry disease is unknown. One presumed cause is damage tonociceptors from globotriaosylceramide deposits in the spinal ganglia and supplying blood vessels.

There are several national and international guidelines on the treatment of neuropathic pain, such as that by theEuropean Federation of Neurological Societies. For painful peripheral neuropathies in general, and more specifi-cally for diabetic neuropathy, a number of drugs are recommended, among them duloxetine, pregabalin, gabap-entin, venlafaxine, tricyclic antidepressants, tramadol, and oxycodone. For neuropathic pain in Fabry disease, thereis moderate evidence from small trials that drugs affecting the sodium channels (ie, phenytoin and carbamazepine)may be efficient. There is also moderate evidence for an effect of gabapentin. In severe pain crises, morphine orintravenous lidocaine may help. Care has to be taken to monitor for the potential side effects of these drugs.Enzyme-replacement treatment (ERT) may reduce the attack frequency and intensity of pain. However, pain israrely abolished under ERT, so additional symptomatic treatment may be necessary.

Overall, the detection and correct interpretation of neuropathic pain are essential because they may provide aninitial clue as to the presence of Fabry disease; because an early diagnosis can help to avoid life expectancy–limitingorgan involvement later on; and because the correct diagnosis of neuropathic pain is essential for the initiation ofadequate symptomatic therapy and, hence, improvement in quality of life.

Children With Fabry DiseaseDr. Uma Ramaswami, FRCPCH

Pediatric Metabolic Unit, Addenbrooke’s Hospital, Cambridge, United Kingdom

Anderson Fabry disease (Fabry disease), OMIMM 301500, is an X-linked lysosomal storage disorder and is causedby mutations in the GLA gene, which encodes the lysosomal enzyme �-galactosidase A. Functionally relevantenzyme deficiency results in the progressive accumulation of ceramide trihexoside (CTH; also known as globotri-aosylceramide [Gb-3 or GL-3]) within the lysosomes and causes slowly progressive multiorgan disease. Obligateheterozygote females often have clinical manifestations, although symptom onset and severity are more variablethan in men with Fabry disease.

Children experience an early onset of clinical manifestations, with a median age at onset of symptoms of 6 yearsin boys and 9 years in girls. Gastrointestinal symptoms, neuropathic pain, and lethargy are the most common earlysymptoms, with impaired quality of life causing early disease burden. Early progression of disease can be monitoredby careful ophthalmologic evaluation, with retinal vessel tortuosity correlating with disease severity.

Over the past decade, there have been encouraging pediatric data on the safety and early efficacy of enzyme-replacement therapy (ERT). In the United Kingdom, at-home therapy has revolutionized the way we managechildren on ERT and hence improved compliance with treatment.

The goals of early treatment with ERT in childhood are to reduce early disease burden; to improve the qualityof life of these young patients; and to ultimately delay and/or prevent the progression of adult-onset, life-threateningcomplications such as end-stage renal disease, stroke, and cardiomyopathy. However, it is vitally important thatthese children are provided with comprehensive and holistic care. This presentation will address the use of anal-gesics for neuropathic pain; angiotensin-converting enzyme inhibitors for proteinuria in childhood; the convenienceof intravascular devices, such as portable catheters; and community-related and other practical management issuesin children with Fabry disease.

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