M J Hilz

Universitätsklinikum Erlangen, Erlangen, Bavaria, Germany

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Publications (226)614.17 Total impact

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    Stroke 12/2014; 46(1). DOI:10.1161/STROKEAHA.114.006283 · 6.02 Impact Factor
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    ABSTRACT: ObjectiveA study was undertaken to determine associations between ischemic stroke sites and poststroke hyperglycemia (PSH).Methods Nondiabetic patients with first ever ischemic stroke confirmed by imaging were prospectively included. Blood glucose level (BGL), National Institute of Health Stroke Scale (NIHSS) score, and clinical parameters were assessed on admission. BGL was dichotomized for elevated versus normal levels using a cutoff value of >7.0 mmol/l. Clinical parameters were correlated with BGL and were compared between patient groups with elevated versus normal glucose values. A voxel-based lesion symptom mapping (VLSM) analysis adjusted for confounding variables was performed correlating sites of ischemic lesions with PSH.ResultsOf 1,281 stroke patients screened, 229 (mean age = 66.3 ± 15.9 years) met the inclusion criteria. Patients with elevated BGL were older, had higher NIHSS scores, and had larger infarcts compared to those without elevated glucose levels. Spearman rank analysis showed correlations between BGL and age, infarct size, heart rate (HR), and NIHSS scores (p ≤ 0.05). The VLSM analysis adjusted for these confounding factors demonstrated associations between PSH and damaged voxels in right hemispheric insular and opercular areas.InterpretationThe data indicate that damage in the right insulo-opercular areas contributes to PSH. The association between sympathetically mediated increase of HR and BGL suggests disinhibition of sympathetic outflow as a possible mechanism for PSH. Ann Neurol 2015;77:262-268.
    Annals of Neurology 12/2014; 77(2). DOI:10.1002/ana.24322 · 11.91 Impact Factor
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    ABSTRACT: Background Autonomic arousal-responses to emotional stimuli change with age. Age-dependent autonomic responses to music-onset are undetermined. Objective To determine whether cardiovascular-autonomic responses to “relaxing” or “aggressive” music differ between young and older healthy listeners. Methods In ten young (22.8 ± 1.7 years) and 10 older volunteers (61.7 ± 7.7 years), we monitored respiration (RESP), RR-intervals (RRI), systolic- and diastolic-blood-pressures (BPsys, BPdia) during silence and 180 second presentations of two “relaxing” and two “aggressive” classical-music excerpts. Between both groups, we compared RESP, RRIs, BPs, spectral-powers of mainly sympathetic low- (LF: 0.04-0.15Hz) and parasympathetic high-frequency (HF: 0.15-0.5Hz) RRI-oscillations, RRI-LF/HF-ratios, RRI-total-powers (TP-RRI), and BP-LF-powers during 30 seconds silence, 30 seconds music-onset, and the remaining 150 seconds of music presentation (analysis-of-variance and post-hoc analysis; significance: p < 0.05). Results During silence, both groups had similar RRIs, LF/HF-ratios and LF-BPs; RESP, LF-RRI, HF-RRI, TP-RRI were lower, but BPs were higher in older than younger participants. During music-onset, “relaxing” music decreased RRIs in older and increased BPsys in younger participants, while “aggressive” music decreased RRIs and increased BPsys, LF-RRI, LF/HF-ratios, TP-RRI in older, but increased BPsys, RESP and decreased HF-RRI and TP-RRI in younger participants. Signals did not differ between groups during the last 150 seconds of music presentation. Conclusions During silence, autonomic modulation was lower - but showed sympathetic predominance - in older than younger persons. Responses to music-onset, particularly “aggressive” music, reflect more of an arousal- than an emotional-response to music valence, with age-specific shifts of sympathetic-parasympathetic balance mediated by parasympathetic withdrawal in younger and by sympathetic activation in older participants.
    Autonomic neuroscience: basic & clinical 07/2014; 183. DOI:10.1016/j.autneu.2014.02.004 · 1.82 Impact Factor
  • Autonomic Neuroscience 08/2013; 177(1):57. DOI:10.1016/j.autneu.2013.05.122 · 1.37 Impact Factor
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    ABSTRACT: Background: Platelet counts (PCs) <100,000/µl are considered as a contraindication for intravenous thrombolysis (IVT). While US guidelines recommend IVT initiation before the availability of clotting tests, the guidelines of the European Stroke Organization give no such practical advice. We aimed to assess the incidence of thrombocytopenia in IVT patients, outcome after thrombolysis in affected patients and the time gained by initiating treatment prior to availability of PC results. Methods: All patients with thrombocytopenia were identified in our prospectively acquired thrombolysis database. Baseline demographic data, intracerebral hemorrhage rates as well as functional outcome were assessed. The median time between initiation of thrombolysis and availability of PCs was calculated. Results: Of 625 IVT patients, 3 (0.5%) had thrombocytopenia at stroke onset. None of them developed intracerebral hemorrhage (ICH) or died during the follow-up. Waiting for PCs would have delayed treatment in 72.4% of the patients, with a median hypothetical delay of 22 min (interquartile range: 11-41 min). Conclusions: To date, there are no sufficient data to evaluate the ICH risk in thrombocytopenic patients. However, thrombocytopenia is rare in IVT patients. Thus, generally waiting for PC results prior to initiation of IVT is not warranted. Avoiding this significant delay yields shorter door-to-needle times and potentially more effective treatment. Copyright © 2013 S. Karger AG, Basel.
    European Neurology 03/2013; 69(5):317-320. DOI:10.1159/000345702 · 1.36 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: Pharmacological blockade showed sympathetic origin of 0.03 to 0.15 Hz blood pressure (BP) oscillations and parasympathetic origin of 0.15 to 0.5 Hz RR-interval (RRI) oscillations, but has not been used to determine origin of cerebral blood flow velocity (CBFV) oscillations at these frequencies. This study evaluated by pharmacological blockade whether 0.1 Hz CBFV oscillations are related to sympathetic and 0.2 Hz CBFV oscillations to parasympathetic modulation. METHODS: In 11 volunteers (24.6±2.3 years), we monitored RRIs, BP, and proximal middle cerebral artery CBFV, at rest, during 180 s sympathetic BP activation by 0.1 Hz sinusoidal neck suction (NS), and during 180 s parasympathetic RRI activation by 0.2 Hz NS. We repeated recordings after 25 mg carvedilol, and after 0.04 mg/kg atropine. Autoregressive analysis quantified RRI-, BP-, and CBFV-spectral powers at 0.1 Hz and 0.2 Hz. We compared parameters at rest, during 0.1 Hz, or 0.2 Hz NS, with and without carvedilol or atropine (analysis of variance, post hoc testing; significance, P<0.05). RESULTS: Carvedilol significantly increased RRIs and lowered BP, CBFV, and 0.1 Hz RRI-, BP-, and CBFV-powers at baseline (P=0.041 for CBFV-powers), and during 0.1 Hz NS-induced sympathetic activation (P<0.05). At baseline and during 0.2 Hz NS-induced parasympathetic activation, atropine lowered RRIs and 0.2 Hz RRI-powers, but did not change BP, CBFV, and 0.2 Hz BP- and CBFV-powers. CONCLUSIONS: Attenuation of both 0.1 Hz CBFV and BP oscillations after carvedilol indicates a direct relation between 0.1 Hz CBFV oscillations and sympathetic modulation. Absent effects of atropine on BP, CBFV, and 0.2 Hz BP and CBFV oscillations suggest that there is no direct parasympathetic influence on 0.2 Hz BP and CBFV modulation.
    Stroke 02/2013; 44(4). DOI:10.1161/STROKEAHA.111.680256 · 6.02 Impact Factor
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    ABSTRACT: Fabry's disease is an X-chromosome linked lysosomal storage disorder with alpha-galactosidase A deficiency and subsequent multiple organ involvement. An early and common symptom also in later stages of the disease is pain. This pain depends on various precipitating factors and can severely compromise the quality of life. So-called Fabry crises can lead to the necessity for intensive care treatment. The pain can be classified as predominantly neuropathic and is difficult to treat. In addition, medication has to be adjusted to concomitant cardiac and renal involvement in Fabry's disease. This review gives guidance for pain therapy in Fabry's disease based on the available evidence and on experience.
    Der Internist 01/2013; 54(1-1):121-30. DOI:10.1007/s00108-012-3204-5 · 0.27 Impact Factor
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    ABSTRACT: Fabry's disease is an X-chromosome linked lysosomal storage disorder with α-galactosidase A deficiency and subsequent multiple organ involvement. An early and common symptom also in later stages of the disease is pain. This pain depends on various precipitating factors and can severely compromise the quality of life. So-called Fabry crises can lead to the necessity for intensive care treatment. The pain can be classified as predominantly neuropathic and is difficult to treat. In addition, medication has to be adjusted to concomitant cardiac and renal involvement in Fabry's disease. This review gives guidance for pain therapy in Fabry's disease based on the available evidence and on experience.
    Der Internist 12/2012; · 0.27 Impact Factor
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    ABSTRACT: Localized head and neck cooling might be suited to induce therapeutic hypothermia in acute brain injury such as stroke. Safety issues of head and neck cooling are undetermined and may include cardiovascular autonomic side effects that were identified in this study. Ten healthy men (age 35±13 years) underwent 120 minutes of combined head and neck cooling (Sovika, HVM Medical). Before and after onset of cooling, after 60 and 120 minutes, we determined rectal, tympanic, and forehead skin temperatures, RR intervals, systolic and diastolic blood pressures (BP), laser-Doppler skin blood flow at the index finger and cheek, and spectral powers of mainly sympathetic low-frequency (0.04-0.15 Hz) and parasympathetic high-frequency (0.15-0.5 Hz) RR interval oscillations and sympathetic low-frequency oscillations of BP. We compared values before and during cooling using analysis of variance with post hoc analysis; (significance, P<0.05). Forehead skin temperature dropped by 5.5±2.2°C with cooling onset and by 12.4±3.2°C after 20 minutes. Tympanic temperature decreased by 4.7±0.7°C within 40 minutes, and rectal temperature by only 0.3±0.3°C after 120 minutes. Systolic and diastolic BP increased immediately on cooling onset and rose by 15.3±20.8 mm Hg and 16.5±13.4 mm Hg (P=0.004) after 120 minutes, whereas skin blood flow fell significantly during cooling. RR intervals and parasympathetic RR interval high-frequency powers increased with cooling onset and were significantly higher after 60 and 120 minutes than they were before cooling. Head and neck cooling prominently reduced tympanic temperature and thus might also induce intracerebral hypothermia; however, it did not significantly lower body core temperature. Profound skin temperature decrease induced sympathetically mediated peripheral vasoconstriction and prominent BP increases that are not offset by simultaneous parasympathetic heart rate slowing. Prominent peripheral vasoconstriction and BP increase must be considered as possibly harmful during head and neck cooling.
    Stroke 05/2012; 43(8):2142-8. DOI:10.1161/STROKEAHA.112.652248 · 6.02 Impact Factor
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    ABSTRACT: Isolated vasospasms of the extracranial internal carotid artery (ICA) are rare causes of cerebral ischemia.(1,2) Pathophysiology of ICA vasospasms is not yet understood and may be associated with altered autonomic ICA innervation.
    Neurology 05/2012; 78(23):1892-4. DOI:10.1212/WNL.0b013e318258f7ab · 8.30 Impact Factor
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    ABSTRACT: In patients with familial dysautonomia (FD), prominent orthostatic hypotension (OH) endangers cerebral perfusion. Supine repositioning or abdominal compression improves systolic and diastolic blood pressure (BPsys and BPdia). To determine whether OH recovers faster with combined supine repositioning and abdominal compression than with supine repositioning alone. In 9 patients with FD (17.8 ± 3.9 years) and 10 healthy controls (18.8 ± 5 years), we assessed 2-min averages of BPsys, BPdia, and heart rate (HR) during supine rest, standing, supine repositioning, another supine rest, second standing, and supine repositioning with abdominal compression by leg elevation and flexion. We determined BPsys- and BPdia-recovery-times as intervals from return to supine until BP reached values equivalent to each participant's 2-min average at supine rest minus two standard deviations. Differences in signal values and BP-recovery-times between groups and positions were assessed by ANOVA and post hoc testing (significance: P < 0.05). Patients with FD had pronounced OH that improved with supine repositioning. However, BP only reached supine rest values with additional abdominal compression. In controls, BP was stable during positional changes. Without abdominal compression, BP-recovery-times were longer in patients with FD than those in controls, but similar to control values with compression (BPsys: 83.7 ± 64.1 vs 36.6 ± 49.5 s; P = 0.013; BPdia: 84.6 ± 65.2 vs 35.3 ± 48.9 s; P = 0.009). Combining supine repositioning with abdominal compression significantly accelerates recovery from OH and thus lowers the risk of hypotension-induced cerebral hypoperfusion.
    Acta Neurologica Scandinavica 05/2012; 126(3):162-70. DOI:10.1111/j.1600-0404.2012.01670.x · 2.44 Impact Factor
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    ABSTRACT: Epileptische Aktivität hat eine modulierende Wirkung auf das autonome Nervensystem. Es gibt Hinweise, dass der Einfluss der Großhirnhemisphären auf das kardiovaskuläre System lateralisiert ist. Die bisherigen Untersuchungen kamen jedoch zu widersprüchlichen Ergebnissen. In der vorliegenden Studie wurden komplex-partielle Anfälle von Patienten mit Temporallappenepilepsie im Rahmen eines prächirurgischen EEG-Monitorings mittels invasiver EEG-Ableitungen aufgezeichnet und die Herzfrequenz präiktual und iktual analysiert. Die invasive Ableitung erlaubte dabei eine eindeutige Fokuslokalisation. Untersucht wurden 27 Patienten mit Temporallappenepilepsie (16 rechts, 11 links temporal). Beide Gruppen zeigten einen signifikanten Anstieg der Herzfrequenz im Anfall. Präiktual stieg die Herzfrequenz in der Gruppe der Patienten mit Fokus im Bereich des rechten Temporallappens signifikant an, in der Gruppe mit Fokus im linken Temporallappen zeigten sich keine bedeutsamen Veränderungen. Unsere Ergebnisse bestätigen die Hypothese einer Hirnasymmetrie mit Überwiegen der Steuerung sympathischer Innervation durch die rechte Hemisphäre. Epileptic activity can modulate reactions of the autonomic nervous system. Although there is some evidence of a differential left/right hemispheric influence on the cardiovascular system, diverse investigations have shown controversial results. In our study, complex partial seizures of patients with temporal lobe epilepsy were recorded using subdural electrodes, thus providing reliable information on the focus side. We analyzed the preictal and ictal heart rates of 27 patients, 16 revealing right and 11 revealing left temporal foci. During the seizures, both groups showed a significant increase in heart rate. Preictal tachycardia was only significant in the right focus group, whereas no significant change in heart rates could be detected in the left focus group. Our results confirm a right hemispheric lateralization of sympathetic cardiac control.
    Der Nervenarzt 04/2012; 71(6):477-480. DOI:10.1007/s001150050610 · 0.86 Impact Factor
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    ABSTRACT: In untreated Fabry patients without overt autonomic dysfunction and normal baroreflex sensitivity (BRS) at rest, BRS is impaired during orthostatic, sympathetic challenge but normalizes after enzyme-replacement therapy (ERT) (Hilz et al., J Hypertens 2010; 28:1438-1448). This study evaluated BRS during parasympathetic challenge with six cycles per minute metronomic deep breathing (MDB) in Fabry patients before and after ERT. In 22 Fabry patients (28 ± 8 years), we monitored RR-intervals (RRIs), SBP, and respiratory frequency during spontaneous breathing (spont_breath) and MDB, before and after 18 (11 patients) or 23 months (11 patients) of biweekly ERT (1.0 mg/kg agalsidase beta). We determined spectral powers of mainly sympathetic low-frequency (0.04-0.15 Hz) RRI fluctuations, parasympathetic high-frequency (0.15-0.5 Hz) RRI fluctuations, sympathetically mediated low-frequency powers of SBP and high-frequency powers of SBP. We calculated BRS (ms/mmHg) during spont_breath and MDB as low-frequency-high-frequency alpha index (coherence >0.5). We compared parameters during spont_breath and MDB within and between patients before and after ERT and 15 age-matched (27 ± 5 years) healthy men (RANOVA and posthoc analysis; significance: P < 0.05). During spont_breath and MDB, parameters were similar between groups. Within the three groups, RRIs were lower, whereas RRI low-frequency powers and SBP low-frequency powers were higher during MDB than during spont_breath. BRS was similar during MBD and spont_breath in untreated patients (P > 0.05), but increased significantly with MDB in patients after ERT (P = 0.048) and in controls (P = 0.035). In untreated Fabry patients, MDB uncovers impaired BRS. After 18 or 23 months of ERT, MDB-induced BRS increase is similar in Fabry patients and controls, demonstrating that ERT not only restores sympathetic but also parasympathetic baroreflex activation.
    Journal of Hypertension 12/2011; 29(12):2387-94. DOI:10.1097/HJH.0b013e32834c31db · 4.22 Impact Factor
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    ABSTRACT: Fabry disease (FD) is an X-linked lysosomal storage disorder which may lead to impaired peripheral nerve function, mostly affecting small nerve fibers, and to neuropathic pain. Characteristics of the neuropathy associated with FD and the covariates for its development and temporal course have not been described in a large cohort. We studied small fiber function and morphology in 120 Fabry patients at baseline and in subgroups of these until 4-year follow-up. Baseline neurological (89/120) and electrophysiological (106/120) examination was mostly normal. Quantitative sensory testing revealed impaired cold detection thresholds in 84% of men and 39% of women. Lower leg intraepidermal nerve fiber density (IENFD) was reduced to 46% in Fabry patients compared to controls and to 12.5% in men with impaired renal function. Patients with abnormal IENFD more often had pain. Group means for IENFD did not improve under enzyme replacement therapy (ERT), but IENFD in the back increased under ERT in 4/15 patients with good renal function and clinical improvement. Cutaneous cytokine gene expression did not differ from controls. We conclude that ERT may improve proximal skin innervation in patients with good renal function, but does not protect small fiber function in men with impaired renal function.
    Journal of the Peripheral Nervous System 12/2011; 16(4):304-14. DOI:10.1111/j.1529-8027.2011.00365.x · 2.57 Impact Factor
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    ABSTRACT: Experimental evidence indicates that iron plays a key role in edema formation after intracerebral hemorrhage (ICH). We investigated the relationship between ICH radiopacity on CT as a marker of hematoma iron content and perihemorrhagic edema (PHE) after ICH. We retrospectively investigated patients with spontaneous lobar and ganglionic supratentorial ICH who received follow-up CT scans during the first 7days after symptom onset (d1, d2-4, d5-7). Measurements of ICH and edema volumes were taken using a semiautomatic threshold-based volumetric algorithm. Radiopacity of the blood clot was determined using the mean Hounsfield unit (HU) count of the ICH. A total of 117 patients aged 71.92±11.55years with spontaneous ICH (34.63±32.44ml) were included in the analysis. Mean ICH radiopacity was 59.7±3.4HU. We found significantly larger relative PHE at d2-4 (1.7±0.9 vs. 1.3±0.8; P=0.032) and d5-7 (2.0±1.3 vs. 1.3±0.9; P=0.007) and larger peak relative PHE (2.3±1.6 vs. 1.6±1.1; P=0.006) in patients with ICH radiopacity >60HU (n=59), as compared to patients with ICH radiopacity <60HU (n=58). Higher ICH radiopacity, reflecting higher in vivo hematoma iron content, is associated with more PHE after ICH.
    European Journal of Neurology 09/2011; 19(3):525-8. DOI:10.1111/j.1468-1331.2011.03526.x · 3.85 Impact Factor
  • Autonomic Neuroscience 09/2011; 163(1):119-119. DOI:10.1016/j.autneu.2011.05.218 · 1.37 Impact Factor
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    ABSTRACT: Data concerning the long-term prognosis after stroke in low-income and middle-income countries are limited. We aimed to establish survival and dependency at 5 years after a first-ever-in-a-lifetime stroke in Grodno, Belarus. All residents of Grodno with a suspected acute stroke were registered prospectively and assessed over a period of 12 months in 2001. Patients were followed-up prospectively at 3 and 12 months, and then annually up to 5 years after the index event. There were 671 cases of first-ever-in-a-lifetime stroke, and follow-up data after 5 years were available for 653 of these patients (97.3%); 18 people (2.7%) were lost to follow-up. One hundred ninety patients (29.1%) died during the first 28 days of stroke. The case fatality rate at 3 months was 32.2% (210/653), at 12 months it was 37.4% (244/653), and at 5 years it was 58.8% (384/653). Of the 269 survivors at 5 years, 130 (48.3%) were independent (modified Rankin score, 0-2), and 139 (51.7%) were disabled (modified Rankin score, ≥3). At 5 years, the cumulative risk of death or disability after first-ever-in-a-lifetime stroke was 80.1% (523/653). Stroke in Belarus is associated with a very high risk of death or dependency at 5 years.
    Stroke 08/2011; 42(11):3274-6. DOI:10.1161/STROKEAHA.111.625400 · 6.02 Impact Factor
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    ABSTRACT: Stroke is frequently associated with autonomic dysfunction, which causes secondary cardiovascular complications. Early diagnosis of autonomic imbalance prevents complications, but it is only available at specialized centers. Widely available surrogate markers are needed. This study tested whether stroke severity, as assessed by National Institutes of Health Stroke Scale (NIHSS) scores, correlates with autonomic dysfunction and thus predicts risk of autonomic complications. In 50 ischemic stroke patients, we assessed NIHSS scores and parameters of autonomic cardiovascular modulation within 24 hours after stroke onset and compared data with that of 32 healthy controls. We correlated NIHSS scores with parameters of total autonomic modulation (total powers of R-R interval [RRI] modulation; RRI standard deviation [RRI-SD], RRI coefficient of variation), parasympathetic modulation (square root of the mean squared differences of successive RRIs, RRI-high-frequency-powers), sympathetic modulation (normalized RRI-low-frequency-powers, blood pressure-low-frequency-powers), the index of sympatho-vagal balance (RRI-LF/HF-ratios), and baroreflex sensitivity. Patients had significantly higher blood pressure and respiration, but lower RRIs, RRI-SDs, RRI coefficient of variation, square root of the mean squared differences of successive RRIs, RRI-low-frequency-powers, RRI-high-frequency-powers, RRI-total powers, and baroreflex sensitivity than did controls. NIHSS scores correlated significantly with normalized RRI-low-frequency-powers and RRI-LF/HF-ratios, and indirectly with RRIs, RRI-SDs, square root of the mean squared differences of successive RRIs, RRI-high-frequency-powers, normalized RRI-high-frequency-powers, RRI-total-powers, and baroreflex sensitivity. Spearman-Rho values ranged from 0.29 to 0.47. Increasing stroke severity was associated with progressive loss of overall autonomic modulation, decline in parasympathetic tone, and baroreflex sensitivity, as well as progressive shift toward sympathetic dominance. All autonomic changes put patients with more severe stroke at increasing risk of cardiovascular complications and poor outcome. NIHSS scores are suited to predict risk of autonomic dysregulation and can be used as premonitory signs of autonomic failure.
    Stroke 06/2011; 42(6):1528-33. DOI:10.1161/STROKEAHA.110.607721 · 6.02 Impact Factor
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    ABSTRACT: Fabry disease is an inherited metabolic disorder characterized by progressive lysosomal accumulation of lipids in a variety of cell types, including neural cells. Small, unmyelinated nerve fibers are particularly affected and small fiber peripheral neuropathy often clinically manifests at young age. Peripheral pain can be chronic and/or occur as provoked attacks of excruciating pain. Manifestations of dysfunction of small autonomic fibers may include, among others, impaired sweating, gastrointestinal dysmotility, and abnormal pain perception. Patients with Fabry disease often remain undiagnosed until severe complications involving the kidney, heart, peripheral nerves and/or brain have arisen. An international expert panel convened with the goal to provide guidance to clinicians who may encounter unrecognized patients with Fabry disease on how to diagnose these patients early using simple diagnostic tests. A further aim was to offer recommendations to control neuropathic pain. We describe the neuropathy in Fabry disease, focusing on peripheral small fiber dysfunction - the hallmark of early neurologic involvement in this disorder. The clinical course of peripheral pain is summarized, and the importance of medical history-taking, including family history, is highlighted. A thorough physical examination (e.g., angiokeratoma, corneal opacities) and simple non-invasive sensory perception tests could provide clues to the diagnosis of Fabry disease. Reported early clinical benefits of enzyme replacement therapy include reduction of neuropathic pain, and adequate management of residual pain to a tolerable and functional level can substantially improve the quality of life for patients. Our recommendations can assist in diagnosing Fabry small fiber neuropathy early, and offer clinicians guidance in controlling peripheral pain. This is particularly important since management of pain in young patients with Fabry disease appears to be inadequate.
    BMC Neurology 05/2011; 11:61. DOI:10.1186/1471-2377-11-61 · 2.49 Impact Factor
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    ABSTRACT: Fabry disease is an inherited disorder of lipid metabolism caused by deficient activity of the lysosomal enzyme α-galactosidase A. Burning peripheral pain with triggered crises of excruciating pain and gastrointestinal dysmotility point to Fabry small fiber neuropathy; angiokeratoma, corneal deposits, and hypohidrosis are other common early manifestations. Progressive dysfunction of the kidneys, heart, and/or brain develops in adulthood. Diagnosis is often delayed which is of great concern, as therapeutic outcomes with enzyme replacement therapy are generally more favorable in early stages of Fabry disease. Results of a survey among 360 rheumatologists and pediatricians clinically managing patients with rheumatologic conditions demonstrate that Fabry manifestations are generally poorly recognized and that awareness of appropriate diagnostic tests is low. To raise awareness about the musculoskeletal aspects of Fabry disease among rheumatologists, the International Musculoskeletal Working Group on Lysosomal Storage Disorders has reviewed the current knowledge. We propose a diagnostic algorithm with burning pain in hands and feet and triggered attacks of excruciating pain as keystones. Evidence of autonomic nerve dysfunction and simple temperature sensitivity testing can provide important diagnostic clues. Multi-systemic involvement should be explored by taking a detailed medical history, including family history, and performing a thorough physical examination and appropriate laboratory workup. Confirmatory tests include the α-Gal A enzyme activity assay (males) and genetic testing (females). We propose that medical specialists use our diagnostic algorithm when evaluating individuals with peripheral neuropathic pain.
    Clinical Rheumatology 04/2011; 30(4):467-75. DOI:10.1007/s10067-010-1445-z · 1.77 Impact Factor

Publication Stats

4k Citations
614.17 Total Impact Points


  • 1988–2014
    • Universitätsklinikum Erlangen
      • Department of Neurology
      Erlangen, Bavaria, Germany
  • 1989–2013
    • Friedrich-Alexander Universität Erlangen-Nürnberg
      • Department of Neurology
      Erlangen, Bavaria, Germany
  • 2009–2012
    • NYU Langone Medical Center
      • • Department of Medicine
      • • Department of Psychiatry
      New York, New York, United States
    • Tbilisi State Medical University
      Tbilsi, T'bilisi, Georgia
  • 1994–2009
    • CUNY Graduate Center
      New York, New York, United States
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 2003
    • Jagiellonian University
      Cracovia, Lesser Poland Voivodeship, Poland