INTRODUCTIONHereditary transthyretin amyloidosis polyneuropathy (ATTRv-PN) presymptomatic carriers often show preclinical abnormalities at small fiber-related diagnostic tests. However, no validated ...biomarker is currently available to use for presymptomatic carriers' follow-up, thus helping therapeutic decision making. Our study aimed at assessing nerve conduction study (NCS), quantitative sensory testing (QST), and skin biopsy parameters in a large cohort of late-onset ATTRv presymptomatic carriers and to evaluate whether they correlated with predicted age of disease onset (PADO). METHODSLate-onset ATTRv presymptomatic carriers were consecutively enrolled and underwent NCS, QST, and skin biopsy with intraepidermal nerve fiber density (IENFD) evaluation from a distal and a proximal site. Douleur Neuropathique-4 (DN4) and Small Fiber Neuropathy-Symptoms Inventory (SFN-SIQ) were used to assess painful and small fiber neuropathy-related symptoms. PADO and time-to-PADO (delta-PADO) were estimated for each carrier, and correlations with diagnostic test measures were analyzed. RESULTSForty presymptomatic ATTRv subjects were enrolled. Twenty carriers (50%) had distal IENFD reduction, with a non-length-dependent distribution in 73% of cases. Eleven subjects (27.5%) had cold and/or warm detection threshold (CDT and/or WDT) abnormalities at QST. Delta-PADO positively correlated with sural sensory nerve action potential (SNAP) amplitude (r = .416, p = .004), and z-values of QST parameters like CDT (r = .314, p = .028), WDT (r = -.294, p = .034), and mechanical detection threshold (MDT; r = -.382, p = .012). Simple linear regression models showed a linear relation between delta-PADO and sural SAP, CDT, and MDT. CONCLUSIONSOur findings confirm that IENFD reduction and QST abnormalities may occur early in ATTRv presymptomatic carriers, often with a non-length-dependent pattern. However, only sural SAP amplitude and QST parameters correlated with delta-PADO, suggesting that serial combined QST and NCS evaluation could be useful in ATTRv presymptomatic carriers' follow-up.
Patients with myotonic dystrophy frequently complain of hypersomnolence, a symptom which seriously restricts their social life. The pathogenesis of this symptom is a matter of debate: it has been ...attributed to both alveolar hypoventilation and pathological changes in the brainstem. As selegiline has been shown to reduce the number of sleep attacks in narcolepsy, we tested whether hypersomnolence in myotonic dystrophy would respond to the same treatment. Ten patients with myotonic dystrophy received selegiline/placebo (20 mg daily) in a double-blind crossover trial. We monitored daytime sleepiness by means of a multiple sleep latency test. Treatment appeared to be well tolerated but did not alter hypersomnolence in myotonic dystrophy. Further studies to assess the effect of higher doses of selegiline are warranted.
A case of reversible encephalopathy during treatment with Amphotericin-B (AMB) is described. The comparison of the clinical course of AMB encephalopathy with total dose of AMB, cranial radiotherapy ...and MRI data available in previously reported cases, shows that this complication is characterized by a progressive, dose-dependent course, possibly influenced by cranial irradiation.
We performed signal-averaged electrocardiography and 24-h ambulatory electrocardiographic monitoring in 53 patients with myotonic dystrophy to determine the incidence and clinical significance of ...ventricular late potentials. Patients were followed up for a mean period of 31 ± 17 months (range 11–68 months). At entry, none of the patients had bundle branch block on 12-lead electrocardiogram and none had wall motion abnormalities on routine echocardiogram. Also, no patient had history of syncope or clinical evidence of ischemic heart disease or a documented sustained ventricular tachycardia. A group of 47 healthy subjects matched for age and sex also underwent signal-averaged electrocardiography for comparison with the patient group. Late potentials were diagnosed in the presence of at least two of the following measures: duration of the filtered QRS > 114 ms, root-mean-square voltage of the terminal 40 ms of the filtered QRS < 20 μV, and duration of the low-amplitude (< 40 μV) signals of terminal filtered QRS > 38 ms. Late potentials were more frequent in patients than in controls: 18 of the 53 patients (34%) showed late potentials compared with four of the 47 controls (8.5%) (
P < 0.01). In 45 patients (85%) no ventricular ectopy (40 cases) or infrequent premature ventricular complexes (five cases) were detected on Holter monitoring. Complex ventricular arrhythmias were traced in the remaining eight patients. These were six of the 18 patients with, and two of the 45 patients without late potentials (33% vs. 6%, respectively;
P < 0.01). Only two of the eight patients with complex ventricular arrhythmias were documented to have repeated three-beat runs of ventricular tachycardia; both patients also had late potentials. During the period of observation there were no sudden deaths. Two patients required permanent pacemakers for appearance of serious conduction defects and recurrent syncope. Therefore, ventricular late potentials are a frequent finding in patients with myotonic dystrophy. In our series they were sensitive in predicting complex ventricular arrhythmias being present in 75% of cases and correctly identifying the patients with ventricular tachycardia. However, specificity and positive predictive value were unacceptable due to the high false-positive rate. Also, the absence of cardiac catastrophic events during follow-up calls in question the prognostic value of ventricular late potentials in myotonic dystrophy.
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