Early cardiac sympathetic denervation in hereditary transthyretin amyloidosis: 123I-metaiodobenzylguanidine findings and correlation with skin biopsy

Background: Small fiber neuropathy (SFN) leads to sensory and autonomic dysfunction by affecting small-diameter myelinated A-delta and unmyelinated C fibers, with vitamin B12 deficiency identified as one of its causes. Objectives: To achieve early diagnosis of SFN in patients with vitamin B12 deficiency and to illustrate the impact of vitamin B12 replacement therapy using noninvasive electrophysiological tests. Materials and Methods: Patients aged 18 to 65 with vitamin B12 deficiency experiencing neuropathic pain or autonomic symptoms were included. A control group consisted of asymptomatic, healthy volunteers with normal B12 levels. Neurological examinations, cutaneous silent period (CSP), sympathetic skin response (SSR), and cardiovascular autonomic tests (R-R interval variability during the Valsalva maneuver [RRIV-VM] and standing [RRIV-S]) were performed at admission and six months later. Patients received 1000 mcg cyanocobalamin intramuscularly daily for one week, weekly for one month, and monthly for three months. Results: The final analyses included 25 patients and 25 controls. At admission, patients had significantly longer CSP and SSR latencies compared to controls (P = 0.047, P < 0.001) and shortened CSP durations (P = 0.043). The SSR amplitude was lower in patients but not significantly (P = 0.823). Post-treatment, CSP latency, CSP duration, and SSR latency significantly improved (P < 0.001, P = 0.002, P < 0.001). Positive symptoms and autonomic symptoms improved significantly after treatment (P = 0.039, P = 0.016). The number of patients with neuropathic pain significantly decreased (P = 0.008). Conclusion: CSP latency, CSP duration, and SSR latency are effective, non-invasive, and cost-effective screening tests for diagnosing SFN in individuals with B12 deficiency. These tests are also valuable for monitoring the progression of SFN following vitamin B12 replacement therapy. The study supports the use of these noninvasive electrophysiological tests to enhance early diagnosis and treatment efficacy in SFN associated with vitamin B12 deficiency.

IntroductionEvaluating small nerve fibers in patients with systemic lupus erythematosus (SLE) using cutaneous silent period (CSP) and skin biopsy and assesssing the relationship between clinical signs, autoantibodies and neuropathic pain score.Objective – methodsFifty one SLE patients and 46 healthy volunteers were included in this study. Nerve conduction studies and CSP were performed both on upper and lower limbs in subjects. Skin biopsy was performed and the number of epidermal nerve density and IL-6 staining were evaluated.ResultsIn SLE patients, CSP latencies were significantly prolonged both in lower and upper limbs and lower and upper extremity CSP durations were significantly shorter when compared to controls (p < 0.001). The number of epidermal nerve was significantly lower in SLE patients when compared to healthy controls (p < 0.001).ConclusionWe detected marked small nerve fiber damage in both lower and upper limbs in SLE patients using CSP. Decreased epidermal nerve density also supports this finding.

The cutaneous silent period in diabetes mellitus

P627: Is precautionary neurophysiological monitoring useful for beta-thalassemia patients?

Cutaneous silent period changes in Type 2 diabetes mellitus patients with small fiber neuropathy

Background. Established electrophysiological methods have limited clinical utility in the diagnosis of small fiber neuropathy. The cutaneous silent period (CSP) may be useful as a method for the evaluation of smaller and unmyelinated fiber dysfunctions. Hyperlipidemia is a very rare cause of small fiber neuropathy. In this study, hyperlipidemia and small fiber neuropathy in symptomatic patients with normal nerve conduction studies were evaluated with autonomic tests and cutaneous silent periods. Methods. Twenty-five patients with clinically suspected small fiber neuropathy and 23 healthy volunteers were included. CSP latency and duration, as well as CSP latency difference of the upper and lower extremities, were examined. Two tests were used to assess the autonomic nervous system, namely, the R-R interval variation test in basal and profound breath conditions and the sympathetic skin response. Results. Twenty-five patients with clinically suspected small fiber neuropathy and normal nerve conduction studies were compared with 23 controls. In the upper extremities, patients had prolonged CSP latencies (P = 0.034) and shortened CSP durations (P = 0.039), whereas in the lower extremities, patients had shortened CSP durations (P = 0.001). The expiration-to-inspiration ratios were also reduced in patients groups. There was no significant difference between sympathetic skin response latencies and amplitude of the case and control groups. Conclusion. Our findings indicate that CSP may become a useful technique for the assessment of small fiber neuropathy in hyperlipidemic patients.

Background and Objectives:Small fiber neuropathy cannot be detected using conventional nerve conduction studies. The use of the cutaneous silent period (CSP) could represent an effective non-invasive test in evaluating the small nerve fibers. The current work aimed to evaluate the CSP among healthy individuals across different decades and assess the effect of gender on CSP values.Methods:71 healthy volunteers with an age range of 20-60 years were included in this study. Several CSP parameters were measured, including CSP latencies and duration of the median, ulnar, and sural nerves.Results:We obtained the mean CSP parameters for the mentioned upper and lower limb nerves across different decades. Age had a significant impact on CSP latencies. Males showed longer latencies than females. No significant inter-side CSP difference was noted.Conclusion:The CSP test is a non-invasive tolerable test and could serve as an important addition to routine electrophysiological examination. The age and gender significantly impact the CSP latency. The establishment of normative data and an understanding of the effects of age and gender is essential for proper employment.

This study was undertaken to assess skin biopsy as a marker of disease onset and severity in hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN), a treatable disease. In this single center retrospective study, skin Congo red staining and intraepidermal nerve fiber density (IENFD) were evaluated in symptomatic ATTRv-PN patients and asymptomatic TTR gene mutation carriers between 2012 and 2019. Non-ATTRv subjects with suspected small fiber neuropathy who underwent skin biopsy during the same timespan were used as controls. One hundred eighty-three symptomatic ATTRv-PN patients, 36 asymptomatic carriers, and 537 non-ATTRv patients were included. Skin biopsy demonstrated amyloid depositions in 80% of the 183 symptomatic cases. Skin amyloid deposits were found in 75% of early stage ATTRv-PN patients, and in 14% of asymptomatic carriers. All 183 symptomatic and 34 of 36 asymptomatic patients displayed decreased ankle IENFD with a proximal-distal gradient distribution, and reduced IEFND correlated with disease severity and duration. Our study demonstrates skin amyloid deposits are a marker of ATTRv-PN disease onset, and decreased IENFD a marker of disease progression. These results are of major importance for the early identification of ATTRv-PN patients in need of disease-modifying treatments.

We assessed the cutaneous silent period (CSP) in 24 patients with Fabry disease with small-fiber sensory neuropathy and 12 normal subjects to test the hypothesis that small-diameter afferents are responsible for producing the CSP. Sensory nerve conduction studies and quantitative sensory testing for cold and vibration detection thresholds were also measured. Overall, Fabry patients had impaired thermal, but not vibration, detection thresholds, with greatest impairment in the feet. In the upper extremity, CSP latencies, duration, and suppression of electromyographic activity (EMG) did not differ. In the lower extremity, patients had reduced suppression of EMG during the CSP compared to normal controls. CSP durations exhibited a bimodal distribution in patients, including a subset of seven patients with durations shorter than all controls. This subset had profound loss of thermal sensation in the feet, but this was also true of some patients who had normal CSPs. Patients with shortened CSPs had modestly elevated vibration thresholds and reduced sensory potentials in comparison to patients with normal CSPs. Reduced CSPs in Fabry patients are associated with, but not entirely explained by, the severity of small-fiber neuropathy as measured by quantitative sensory testing. The possibility that large-diameter fibers provide a minor contribution to producing the CSP should be considered.

Utility of the cutaneous silent period in patients with diabetes mellitus

Small fiber neuropathy (SFN) is one of the main neurological manifestations in primary Sjögren's Syndrome (pSS). For the detection of SFN, cutaneous silent period (CSP) measurement is gaining popularity recently due to its non-invasiveness and practical application. Evaluating SFN involvement in patients with pSS using CSP and evaluating its relationship with clinical parameters. Patients with a diagnosis of pSS and healthy volunteers demographically homogeneous with the patient group were included in the study. The CSP responses were recorded over the abductor pollicis brevis muscle. The latency and duration values of the responses were obtained. In patient group, EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), Hospital Anxiety and Depression Scale (HADS), Short Form-36 (SF-36) questionnaire, Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) and Central Sensitization Inventory (CSI) were applied for the evaluation of symptom severity, mood, quality of life, presence of neuropathic pain and central sensitization, respectively. The mean CSP latency was significantly longer in patient group compared to control group (p < 0.001). Mean CSP duration was also significantly shorter in patient group (p < 0.001). There were no significant differences in CSP parameters according to patients' neuropathic pain or central sensitization profile. There were significant correlations of CSP parameters (latency and duration, respectively) with ESSPRI dryness (ρ = 0.469, p = 0.004; ρ = -0.553, p < 0.001), fatigue (ρ = 0.42, p = 0.011; ρ = -0.505, p = 0.002), pain (ρ = 0.428, p = 0.009; ρ = -0.57, p < 0.001) subscores and mean ESSPRI score (ρ = 0.631, p < 0.001; ρ = -0.749, p < 0.001). When SF-36 subscores and CSP parameters were investigated, a significant correlation was found only between "bodily pain" subscore and CSP duration (ρ = -0.395, p = 0.017). In HADS, LANSS and CSI evaluations, a significant correlation was found only between HADS anxiety score and the CSP duration (ρ = 0.364, p = 0.02). As indicated by CSP measurement, SFN is more prominent in patients with pSS than in the healthy population. It is important to investigate the presence of SFN because of its correlation with the leading symptoms in the clinical spectrum of pSS.

BackgroundNeurological involvement has a great importance in the clinical spectrum of primary Sjögren’s syndrome (pSS) (1). The presence of small fiber neuropathy (SFN), which cannot be detected in routine electrophysiological...

Objective: The aim of this study was to investigate cutaneous-silent-period (CSP) parameters in patients with type 2 diabetes mellitus (DM) and examine the effects of Alpha-lipoic acid (ALA) treatment on CSP which, to our knowledge, have not been investigated till date in the literature. Background Small myelinated (A-d) and unmyelinated (C) somatic sensory fibers are initially affected and may be the earliest exhibited sign of neuropathy in glucose dysmetabolism. Cutaneous silent period (CSP) is an inhibitory spinal reflex and its afferents consist of A-d nerve fibers. Design/Methods: A total of 17 patients with DM and 25 healthy volunteers were studied. CSP latency and duration in the upper and lower extremities were examined in the two groups. In DM patients, the variables were examined before and after ALA treatment. Results: Upper-extremity CSP latency {79,50 (59,50-89,50) ms} was longer in patients, compared with controls {73,75 (56,00-85,25) ms} (p=0,007). Lower-extremity CSP latency was longer {112,75 (78,25-152,75) ms} in patients, compared with controls {96,25 (80,00-113,00) ms} (p Conclusions: The results suggest that ALA treatment may improve small-fibre neuropathy (SFN) in DM patients. CSP may be used as a measure of ALA treatment effectiveness. Disclosure: Dr. Yucel has nothing to disclose. Dr. Oz has nothing to disclose. Dr. Akgun has nothing to disclose. Dr. Taslipinar has nothing to disclose. Dr. Erdogan has nothing to disclose. Dr. Yasar has nothing to disclose. Dr. Ulas has nothing to disclose. Dr. Odabasi has nothing to disclose.

ObjectivesPatients with Parkinson's disease (PD) highly complain of pain, probably due to the lowered pain threshold caused by dopamine deficiency. Nonetheless, only a few studies have investigated the effects of anti-PD medications on “pain inhibits pain” ability. This study aimed to evaluate conditioned pain modulation (CPM) using the cutaneous silent period (CSP) and the numerical rating scale (NRS) and to investigate the effect of anti-PD medications on CPM.Materials and methodsThe CSP was recorded in 40 patients with PD under drug-on and drug-off conditions. Changes in the CSP elicited by electrical test stimulation and in the NRS when the patients experienced pain with cold pressure as a conditioned stimulus were assessed. A shortened CSP duration or reduced CSP score due to cold pressure were interpreted as objective CPM responses.ResultsThe CSP latency was analyzed in 22 patients when the electromyographic contamination in the CSP waveform was low. The CSP duration shortening during cold pressure was significantly greater under the drug-on condition than under the drug-off condition. The change in CSP duration exhibited a significant correlation with the change in the NRS scores. CSP score analysis was performed on 18 patients in whom latency analysis was difficult owing to electromyographic contamination. In the drug-on state, conditioned cold-pressure pain significantly decreased the CSP score.ConclusionsDynamic changes in the CSP caused by cold pressure in patients with PD suggest that anti-PD medications may enhance CPM ability.

To explore the relationship between clinical features, electrophysiology and intraepidermal nerve fiber density (IENFD) in peripheral neuropathy with small fibers involvement and determine the diagnostic value of 13-item small-fiber neuropathy and symptoms inventory questionnaire (SFN-SIQ) and neuropathy symptom score [lower limb] (NSS [LL]) in small fiber neuropathy (SFN). A total of 34 consecutive patients with peripheral neuropathy with symptoms of small fibers were enrolled and divided into two groups of small fiber injury and small and large fiber injury.SFN-SIQ, NSS [LL] and neuropathy disability score [lower limb] (NDS [LL]) were administered.Nerve conduction studies and skin biopsy were conducted in unilateral lower limb. The relationship between IENFD and these scales was assessed by partial correlation.Receiver operating characteristic analysis was applied for evaluating the diagnostic value of SFN-SIQ and NSS [LL] in small fiber injury. Independent sample t test was used to compare various parameters of two groups. And similar statistical method was used for IENFD abnormal and normal groups to detect the clinicoelectrophysiological differences. According to the international normative reference of IENFD, 13 patients could be diagnosed with peripheral neuropathy with small fibers involvement. IENFD was moderately correlated with SFN-SIQ (r = 0.437, P = 0.012) and marginally correlated with NSS [LL] (r = 0.334, P = 0.062). The diagnostic value of SFN-SIQ and NSS [LL] was moderate for small fiber injury (Az = 0.753, P = 0.012 for SFN-SIQ, Az = 0.712, P = 0.040 for NSS [LL]) and the best diagnostic indicator of each scale was 6. The value of NDS [LL] was apparently elevated in small and large fiber injury group versus small fiber injury group (t = -5.605, P < 0.001). The IENFD abnormal group had a higher NSS [LL] value than that of the IENFD normal group (t = -2.047, P = 0.049). No differences of electrophysiological parameters existed between IENFD abnormal and normal groups. Chinese normative reference of IENFD should be formulated for the diagnosis of small fiber neuropathy. SFN-SIQ and NSS [LL] may screen for small fiber neuropathy and both are convenient during patient follow-ups.Large sample studies are warranted to further evaluate the clinical values of SFN-SIQ and NSS [LL].