Waiting for platelet counts causes unsubstantiated delay of thrombolysis therapy.

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.

Combined counter-maneuvers accelerate recovery from orthostatic hypotension in familial dysautonomia.

BACKGROUND: 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). OBJECTIVE: To determine whether OH recovers faster with combined supine repositioning and abdominal compression than with supine repositioning alone. METHODS: 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). RESULTS: 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). CONCLUSION: Combining supine repositioning with abdominal compression significantly accelerates recovery from OH and thus lowers the risk of hypotension-induced cerebral hypoperfusion.

Radiopacity of intracerebral hemorrhage correlates with perihemorrhagic edema.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Higher ICH radiopacity, reflecting higher in vivo hematoma iron content, is associated with more PHE after ICH.

Neurological complications in Fabry disease.

In Fabry disease, deficiency of α-galactosidase A results in the accumulation of glycosphingolipids in body fluids and tissues including corneas, blood vessels, kidneys and also structures of the central and peripheral nervous system. Many patients show cardiovascular and cerebrovascular dysfunction. Cerebrovascular dysfunction is particularly associated with a high risk of strokes and of mortality even at a young age. The prevalence and severity of cerebrovascular complications increase with patients'age. Clinical data as well as histologic and neurophysiologic studies showed predominantly small fiber dysfunction in patients with Fabry disease. We recently performed quantitative sensory testing in patients with Fabry disease and found reduced cold and heat-pain detection thresholds, while nerve conduction velocities were only mildly reduced. From our findings, we concluded that small fiber dysfunction is more prominent than large fiber dysfunction in Fabry patients. Clinically, small fiber dysfunction contributes to recurrent episodes of burning and lancinating pain and paresthesias in the distal extremities. Such episodes can be typically triggered by changes of the environmental temperature, particularly by warming. Moreover, dysfunction of small thinly-myelinated and unmyelianated nerve fibers accounts for altered sympathetic and parasympathetic modulation. Sympathetic dysfunction explains the hypohidrosis and a subsequent poor exercise and heat tolerance. Enzyme replacement therapy (ERT) with recombinant human α-galactosidase A is available. We could demonstrate improvement of small fiber neuropathy and neuropathic pain after 18-23 months of ERT, which probably resulted from glycosphingolipid clearing from perineurial cells, axons and Schwann cells or from blood vessels supplying the nerves.

Relation between ictal asystole and cardiac sympathetic dysfunction shown by MIBG-SPECT.

OBJECTIVE: Tachyarrhythmias are common during epileptic seizures while bradyarrhythmias or asystoles are less frequent. Ictal asystole might be related to epilepsy-induced cardiac sympathetic denervation. METHODS: To evaluate cardiac post-ganglionic denervation in epilepsy patients with ictal asystoles we assessed I123-meta-iodobenzylguanidine (MIBG) as a marker of post-ganglionic cardiac norepinephrine-uptake, using single photon emission computed tomography (MIBG-SPECT). RESULTS: In five of 844 patients with presurgical video-electroencephalography-monitoring, we recorded ictal asystoles during nine of 37 seizures. Asystole patients underwent cardiologic examination (Holter-electrocardiogram, echocardiogram) and cardiac MIBG-SPECT. We compared cardiac MIBG uptake in the asystole patients to the uptake in 18 temporal lobe epilepsy (TLE) patients without bradyarrhythmias and in 14 controls without cardiac or neurological disease. As the cardiological examinations were unremarkable in all subjects, the heart/mediastinum-MIBG-uptake ratios (H/M-ratios) differed significantly between the three groups (P = 0.004). H/M-ratios were lower in asystole TLE patients (mean +/- SD: 1.58 +/- 0.3) than in patients without asystole (1.81 +/- 0.18; P = 0.037) or controls (1.96 +/- 0.16). CONCLUSIONS: Pronounced reduction in cardiac MIBG uptake of asystole patients indicates post-ganglionic cardiac catecholamine disturbance. Impaired sympathetic cardiac innervation limits adjustment and heart rate modulation, and may increase the risk of asystole and ultimately sudden unexpected death in epilepsy (SUDEP).

Advanced electrocardiographic predictors of mortality in familial dysautonomia.

OBJECTIVE: To identify electrocardiographic predictors of mortality in patients with familial dysautonomia (FD). METHODS: Ten-minute resting high-fidelity 12-lead electrocardiograms (ECGs) were obtained from 14 FD patients and 14 age/gender-matched healthy subjects. Multiple conventional and advanced ECG parameters were studied for their ability to predict mortality over a subsequent 4.5-year period, including representative parameters of heart rate variability (HRV), QT variability (QTV), T-wave complexity, signal averaged ECG, and 3-dimensional ECG. RESULTS: Four of the 14 FD patients died during the follow-up period, three with concomitant pulmonary disorder. Of the ECG parameters studied, increased non-HRV-correlated QTV and decreased HRV were the most predictive of death. Compared to controls as a group, FD patients also had significantly increased ECG voltages, JTc intervals and waveform complexity, suggestive of structural heart disease. CONCLUSION: Increased QTV and decreased HRV are markers for increased risk of death in FD patients. When present, both markers may reflect concurrent pathological processes, especially hypoxia due to pulmonary disorders and sleep apnea.

A simple deep breathing test reveals altered cerebral autoregulation in type 2 diabetic patients.

AIMS/HYPOTHESIS: Patients with diabetes mellitus have an increased risk of stroke and other cerebrovascular complications. The purpose of this study was to evaluate the autoregulation of cerebral blood flow in diabetic patients using a simple method that could easily be applied to the clinical routine screening of diabetic patients. METHODS: We studied ten patients with type 2 diabetes mellitus and 11 healthy volunteer control participants. Continuous and non-invasive measurements of blood pressure and cerebral blood flow velocity were performed during deep breathing at 0.1 Hz (six breaths per minute). Cerebral autoregulation was assessed from the phase shift angle between breathing-induced 0.1 Hz oscillations in mean blood pressure and cerebral blood flow velocity. RESULTS: The controls and patients all showed positive phase shift angles between breathing-induced 0.1 Hz blood pressure and cerebral blood flow velocity oscillations. However, the phase shift angle was significantly reduced (p < 0.05) in the patients (48 +/- 9 degrees ) compared with the controls (80 +/- 12 degrees ). The gain between 0.1 Hz oscillations in blood pressure and cerebral blood flow velocity did not differ significantly between the patients and controls. CONCLUSIONS/INTERPRETATION: The reduced phase shift angle between oscillations in mean blood pressure and cerebral blood flow velocity during deep breathing suggests altered cerebral autoregulation in patients with diabetes and might contribute to an increased risk of cerebrovascular disorders.

In vivo detection of hepatitis C virus (HCV) RNA in the brain in a case of encephalitis: evidence for HCV neuroinvasion.

We report here a 27-year-old woman who presented with encephalitis of unknown origin. Magnetic resonance imaging (MRI) of the brain revealed leukoencephalopathy, cerebrospinal fluid showed signs of inflammation. Serum and brain biopsy tissue was tested positive for hepatitis C virus (HCV). Neuropathological investigation supported the hypothesis of viral encephalitis. C3, C4 and cryoglobulins as well as cerebral MR-angiography were normal. Neurological complications of HCV infection other than hepatic encephalopathy are generally attributed to parainfectious phenomena. This is the first case of HCV-RNA detection in vivo in human brain in literature and it raises the possibility that HCV is able to induce encephalitis caused by neurotrophism. This is supported by the fact that there is a growing body of literature on HCV-induced cerebral dysfunction and laboratory findings indicating HCV neuroinvasion.

Effects of vagus nerve stimulation on cardiovascular regulation in patients with epilepsy.

OBJECTIVE: To evaluate the impact of vagus nerve stimulation (VNS) on heart rate and blood pressure (BP) modulation in epilepsy patients. MATERIAL AND METHODS: Twenty-one epilepsy patients with VNS were tested during on (60 s) and off (5 min) phases. We monitored BP, RR intervals (RRI) and respiration. Spectral analysis was performed in low- (LF: 0.04-0.15 Hz) and high-frequency bands (HF: 0.15-0.5 Hz). For coherences above 0.5, we calculated the LF transfer function between systolic BP and RRI, and the HF transfer function gain and phase between RRI and respiration. Differences between the on and off phases were evaluated using Wilcoxon test. RESULTS: VNS did not change RRI and BP values. The LF power of BP and the LF and HF power of RRI increased significantly. There was a slight change in the RRI/BP LF gain and the RRI/respiration HF gain (ns). The HF phase between RRI and respiration decreased significantly. CONCLUSIONS: Our findings show that VNS influences both sympathetic and parasympathetic cardiovascular modulation. However, our results also show that VNS does not negatively influence autonomic cardiovascular regulation.

Cardiovascular autonomic function in poststroke patients.

BACKGROUND: Autonomic dysregulation is frequent in acute ischemic stroke. Several studies concluded that imbalance between sympathetic and parasympathetic cardiovascular function predisposes to malignant cardiac arrhythmia. However, there are few data on cardiovascular autonomic function in post-acute stroke patients. OBJECTIVE: To study cardiovascular autonomic function 18 to 43 months after lacunar stroke. PATIENTS AND METHODS: We continuously monitored R-R intervals (RR(int)), mean blood pressure (BP(mean)), and respiration in 15 patients (8 women, aged 43 to 73 years) after right-sided stroke, in 13 patients (7 women, aged 50 to 75 years) after left-sided stroke, and in 21 age- and sex-matched controls at rest. We used autoregressive spectral analysis to assess sympathetic and parasympathetic modulation as powers of RR(int) and BP(mean) oscillations in the low-frequency (LF: 0.04 to 0.15 Hz) and high-frequency bands (HF: 0.15 to 0.5 Hz). RESULTS: Mean values of RR(int), BP(mean), and respiratory frequency did not differ between patients after right- or left-sided stroke and controls (p > 0.05). Patients after right-sided stroke showed a trend toward elevated LF power of RR(int) as compared with patients after left-sided stroke and controls (p < 0.10). HF powers of RR(int) were reduced in patients after right- and left-sided stroke as compared with controls (p < 0.05). LF/HF ratio of RR(int) was elevated in patients after right-sided stroke as compared with patients after left-sided stroke and controls (p < 0.05). CONCLUSION: Irrespective of the side of the ischemia, post-acute stroke patients showed a parasympathetic cardiac deficit. Additionally, sympathetic cardiovascular modulation was increased in patients after right-sided stroke. Post-acute stroke patients might be at an increased risk for cardiac arrhythmia after unopposed sympathetic stimulation.

Acute onset of fatal vegetative symptoms: unusual presentation of adult Alexander disease.

Since genetic analysis of the GFAP gene for the diagnosis of adult Alexander disease (AD) has been established in 2001, several cases of both sporadic and familial cases of AD have been described. Except for one patient, all subjects revealed glial fibrillary acidic protein (GFAP) mutations, and clinical progression of symptoms, mainly bulbar and pseudobulbar, were moderate. Here we report on a patient with acute onset of vegetative symptoms, rapid progression, and death within 2 months. Although histology and final magnetic resonance imaging (MRI) were characteristic of AD, sequencing of the encoding GFAP gene revealed no mutation. We believe that this case report expands the so far known clinical spectrum and MRI dynamics of adult AD, and suggest that analysis of the coding part of GFAP may be inconclusive in rare cases. In such patients, only histology may lead to definitive diagnosis.

Deep brain stimulation improves orthostatic regulation of patients with Parkinson disease.

OBJECTIVE: To evaluate whether subthalamic nucleus (STN) stimulation has an effect on the orthostatic regulation of patients with Parkinson disease (PD), we studied cardiovascular regulation during on and off phases of STN stimulation. METHODS: We examined 14 patients with PD (mean age 58.1 +/- 5.8 years, 4 women, 10 men) with bilateral STN stimulators. Patients underwent 3 minutes of head-up tilt (HUT) testing during STN stimulation and after 90 minutes interruption of stimulation. We monitored arterial blood pressure (BP), RR intervals (RRI), respiration, and skin blood flow (SBF). Baroreflex sensitivity (BRS) was assessed as the square root of the ratio of low-frequency power of RRI to the low-frequency power of systolic BP for coherences above 0.5. RESULTS: During the on phase of the STN stimulation, HUT induced no BP decrease, a significant tachycardia, and a significant decrease of SBF. During the off phase of stimulation, HUT resulted in significant decreases in BPsys and RRI and only a slight SBF decrease. HUT induced no change of BRS during stimulation, but lowered BRS when the stimulator was off (p < 0.05). CONCLUSIONS: STN stimulation of patients with PD increases peripheral vasoconstriction and BRS and stabilizes BP, thereby improving postural hypotension in patients with PD. The results indicate that STN stimulation not only alleviates motor deficits but also influences autonomic regulation in patients with PD.

Altered cerebral regulation in type 2 diabetic patients with cardiac autonomic neuropathy.

AIMS/HYPOTHESIS: Assessment of cerebral regulation in diabetic patients is often problematic because of the presence of cardiac autonomic neuropathy. We evaluated the technique of oscillatory neck suction at 0.1 Hz to quantify cerebral regulation in diabetic patients and healthy control subjects. SUBJECTS AND METHODS: In nine type 2 diabetic patients with cardiac autonomic neuropathy and 11 age-matched controls, we measured blood pressure and cerebral blood flow velocity responses to application of 0.1 Hz neck suction. We determined spectral powers and calculated the transfer function gain and phase shift between 0.1 Hz blood pressure and cerebral blood flow velocity oscillations as parameters of cerebral regulation. RESULTS: In the patients and control subjects, neck suction did not significantly influence mean values of the RR interval, blood pressure and cerebral blood flow velocity. The powers of 0.1 Hz blood pressure and cerebral blood flow velocity oscillations increased in the control subjects, but remained stable in the patients. Transfer function gain remained stable in both groups. Phase shift decreased in the patients, but remained stable in control subjects. CONCLUSIONS/INTERPRETATION: The absence of an increase in the power of 0.1 Hz blood pressure and cerebral blood flow velocity oscillations confirmed autonomic neuropathy in the diabetic patients. Gain analysis did not show altered cerebral regulation. The decrease in phase shift in the patients indicates a more passive transmission of neck suction-induced blood pressure fluctuations onto the cerebrovascular circulation, i.e. altered cerebral regulation, in the patients, and is therefore suited to identifying subtle impairment of cerebral regulation in these patients.

Impairment of parasympathetic baroreflex responses in migraine patients.

OBJECTIVES: The aim of this study was to assess baroreflex regulation of the heart rate and blood vessels in migraine patients in comparison with healthy controls. METHODS: In 30 migraine patients who were in a headache-free phase, aged 34 +/- 2 years, and 30 healthy controls, aged 34 +/- 3 years, we applied oscillatory neck suction at 0.1 Hz to assess the sympathetic modulation of the heart and blood vessels and at 0.2 Hz to assess the effect of parasympathetic stimulation on the heart. Breathing was paced at 0.25 Hz. Electrocardiographic RR-intervals, blood pressure and respiration were continuously recorded. Responses to the baroreflex stimulations were assessed as the changes in power of the RR-interval and blood pressure fluctuations at the relevant stimulating frequency from the baseline values. RESULTS: Systolic and diastolic blood pressure responses to the 0.1 Hz neck suction pressure were not significantly different between the patients and controls. The RR-interval oscillatory response to 0.2 Hz neck suction was significantly less (P < 0.05) in the migraine patients (4.45 +/- 0.27 ln ms2) compared with the controls (5.48 +/- 0.36 ln ms2). CONCLUSION: These results suggest that baroreflex-mediated cardiovagal responses are reduced in migraine patients. However, the sympathetic-mediated baroreflex control of the blood vessels is intact in the migraine patients. The autonomic nervous system may have a role in the pathophysiology of migraine.

Enhanced external counterpulsation does not compromise cerebral autoregulation.

OBJECTIVES: Enhanced external counterpulsation (EECP) rhythmically augments blood pressure (BP) by diastolic lower-body compression. Recently, we showed decreased mean cerebral blood flow velocity (CBFVmean) in young healthy persons during EECP, but unchanged CBFVmean in atherosclerotic patients. In this study, we assessed EECP effects on dynamic cerebral autoregulation (CA). MATERIAL & METHODS: In 23 healthy persons and 15 atherosclerotic patients we monitored heart rate (HR), mean BP (BPmean) and CBFVmean before and during 5 min EECP. We analyzed spectral powers of HR, BPmean and CBFVmean in the low (LF: 0.04-0.15 Hz) and high (HF: 0.15-0.5 Hz) frequency ranges to determine CA from the LF-transfer function gain and phase shift between BPmean and CBFVmean oscillations. RESULTS: EECP increased HR and BPmean, while transfer function gain and phase shift remained stable. CONCLUSIONS: Stable gain and phase values suggest that EECP does not compromise CA and, therefore, does not seem to bear cerebrovascular risks.

Sympathetic and parasympathetic baroreflex dysfunction in familial dysautonomia.

OBJECTIVE: To assess the possible abnormalities in the baroreflex modulation of both the heart and the arterial vasculature, in order to better evaluate the role of baroreflex abnormalities in the generation of the cardiovascular symptoms and complications affecting the familial dysautonomia (FD) patient. METHODS: Twenty-one FD patients and 22 controls underwent 3 minutes of passive head-up tilt (HUT) and baroreceptor stimulation by means of sinusoidal neck suction (NS; 0 to -30 mm Hg; 0.1 Hz [LF] and 0.2 Hz [HF]). Respiration was maintained constant during NS at 15 breaths/minute. The authors monitored RR-intervals (RRI), blood pressure (BP) (Colin), and respiration. NS induced changes of RRI and BP were determined by spectral analysis. RESULTS: HUT showed orthostatic hypotension without compensatory tachycardia in FD patients but not in controls. LF-NS increased LF power of RRI and BP and HF-NS increased HF power of RRI in controls, but not in FD patients. CONCLUSIONS: Familial dysautonomia patients have a widespread baroreflex abnormality, involving both the efferent sympathetic arm on the resistance vessels, and the sympathetic and parasympathetic efferent arms on the heart. Therefore, the abnormalities in the control of blood pressure-i.e., supine hypertension, orthostatic hypotension, blood pressure lability-and heart rate-i.e., bradyarrhythmias-are likely due to baroreflex abnormalities.

Enhanced external counterpulsation improves skin oxygenation and perfusion.

BACKGROUND: Enhanced external counterpulsation (EECP) augments diastolic and reduces systolic blood pressures. Enhanced external counterpulsation has been shown to improve blood flow in various organ systems. Beneficial effects on skin perfusion might allow EECP to be used in patients with skin malperfusion problems. This study was performed to assess acute effects of EECP on superficial skin blood flow, transdermal oxygen and carbon dioxide pressures. MATERIALS AND METHODS: We monitored heart rate, blood pressure, transdermal blood flow as well as oxygen and carbon dioxide pressures in 23 young, healthy persons (28 +/- 4 years) and 15 older patients (64 +/- 7 years) with coronary artery disease before, during and 3 min after 5 min EECP. Friedman test was used to compare the results of 90-s epochs before, during and after EECP. Significance was set at P < 0.05. RESULTS: Enhanced external counterpulsation increased heart rate and mean blood pressure. During EECP, transdermal oxygen pressure and concentration of moving blood cells increased while transdermal carbon dioxide pressure and velocity of moving blood cells decreased significantly in both groups. After EECP, transdermal carbon dioxide pressure was still reduced while the other parameters returned to baseline values. CONCLUSIONS: Improved skin oxygenation and carbon dioxide clearance during EECP seem to result from the increased concentration and reduced flow velocity, i.e. prolonged contact time, of erythrocytes. The increased concentration of moving blood cells and the decreased velocity of moving blood cells at both tested skin sites indicate peripheral vasodilatation.

Enzyme replacement therapy improves function of C-, Adelta-, and Abeta-nerve fibers in Fabry neuropathy.

BACKGROUND: Peripheral neuropathy in Fabry disease predominantly involves small nerve fibers. Recently, enzyme replacement therapy (ERT) with recombinant human alpha-galactosidase A has become available. OBJECTIVE: To evaluate whether ERT improves Fabry neuropathy. METHODS: In 22 Fabry patients (age 27.9 +/- 8.0 years) undergoing ERT with recombinant human alpha-galactosidase A (agalsidase beta) for 18 (n = 11) or 23 (n = 11) months and in 25 control subjects (age 29.0 +/- 10.4 years), the authors performed quantitative sensory testing using the 4, 2, and 1 stepping algorithm (CASE IV). Detection thresholds of vibration (VDT) on the first toe were assessed; cold detection thresholds (CDT), heat-pain onset (HP 0.5), and intermediate heat-pain (HP 5.0) assessments were made on the dorsum of the feet. Patient values above mean + 2.5 SD of control values were considered abnormal. RESULTS: Before ERT, VDT, CDT, HP 0.5, and HP 5.0 were higher in patients than control subjects (p < 0.05). Following ERT, patients developed lower thresholds than prior to ERT for VDT (15.5 +/- 3.5 vs 14.3 +/- 4.1; p < 0.05), HP 0.5 (22.3 +/- 6.7 vs 19.4 +/- 1.3; p < 0.01), and HP 5.0 (27.3 +/- 5.6 vs 22.5 +/- 2.3; p < 0.01). Moreover, fewer patients had abnormal results of VDT (2 vs 4), CDT (7 vs 12), HP 0.5 (0 vs 9), and HP 5.0 (4 vs 20) after than before ERT. CONCLUSIONS: ERT therapy with agalsidase beta significantly improves function of C-, Adelta-, and Abeta-nerve fibers and intradermal vibration receptors in Fabry neuropathy. Lack of recovery in some patients with abnormal cold or heat-pain perception suggests the need for early ERT, prior to irreversible nerve fiber loss.