Presence Of Small Fiber Neuropathy Research Articles

AB0494 COMPARISON OF CUTANEOUS SILENT PERIOD PARAMETERS IN PATIENTS WITH PRIMARY SJÖGREN’S SYNDROME WITH THE HEALTHY POPULATION

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 examinations, causes the peripheral nervous system involvement to be underestimated in the course of the disease and causes pain-related symptoms in patients that cannot be explained by routine examinations (2). Various methods can be used in the detection of SFN, and cutaneous silent period (CSP) measurement is gaining popularity recently due to its non-invasiveness and practical application (3).ObjectivesEvaluating SFN involvement in patients with pSS using CSP and evaluating its relationship with clinical parameters.MethodsPatients with a diagnosis of pSS followed in the rheumatology outpatient clinic 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 in the upper extremity of all participants. 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. Comparison of CSP parameters between patients with pSS and healthy volunteers was determined as the primary outcome measure. The secondary outcome measure was the relationship between CSP parameters and ESSPRI, HADS, SF-36, LANSS and CSI scores.ResultsA total of 36 patients and 36 healthy controls were included in the final analyses. There was no significant difference between the two groups in terms of demographic data. The mean CSP latency was significantly longer in patients with a mean of 78.18 (±7.51) when compared to controls with a mean of 67.91 (±6.41) (95% CI: 6.98- 13.55, p<0.001). Mean CSP duration was also significantly shorter in patients with a mean of 33.40 (±6.93) (95% CI: 9.57 -15.31, p<0.001). There were no significant differences in CSP parameters (latency and duration, respectively) according to patients’ neuropathic pain or central sensitization profile (p>0.05 for all analyses). There were significant correlations of CSP parameters with ESSPRI dryness (r=0.469, p=0.004; r=-0.553, p<0.001), fatigue (r=0.42, p=0.011; r=-0.505, p=0.002), pain (r=0.428, p=0.009; r=-0.57, p<0.001) subscores and mean ESSPRI score (r=0.631, p<0.001; r=-0.749, p<0.001). Significant correlations were not found between CSP parameters and SF-36 scores, other than CSP duration and “pain” subscore (r=-0.395, p=0.017). When the other correlations were investigated there were no significant correlations other than CSP duration and the HADS anxiety score (r=-0.201, p=0.02).ConclusionAs an indicator of CSP measurement, SFN is more common in patients with pSS than in the healthy population. The association with important clinical symptoms of the disease course such as dryness, fatigue, pain and anxiety highlights the importance of detecting small fiber neuropathy.

IDF21-0399 Association between Diabetic Peripheral Neuropathy and Vitamin D Deficiency in Georgian Patients with T2D by Sudoscan

Background: Diabetic peripheral neuropathy (DPN) is one of the major chronic complications of diabetes and leading high-risk factor of foot ulcers/amputations. Its early detection/management is therefore of primary importance. About 60-70% of diabetic patients will eventually develop DPN. The cause of diabetic neuropathy is multifactorial, including poor diabetes control, diabetes duration, metabolic/vascular factors, etc. Vitamin D (VitD) deficiency is a common global public health problem. VitD deficiency contributes significantly to pathogenesis of both types of diabetes by impairing insulin secretion and increasing insulin resistance. Aim: Our aim was to assess correlation between serum levels of 25(OH) VitD and DPN in Georgian patients with type 2 diabetes mellitus (T2DM). Method: Patients supervised and treated at our Center were selected; 80 T2DM patients (35 males and 45 females) with previously diagnosed DPN and VitD deficiency were enrolled in this study and comprised the Study Group/SG; their mean age was 45±5 yrs and diabetes duration varied from 5 to 10 yrs. Age and diabetes duration match 50 patients (22 males and 33 females ), without previously diagnosed DPN and normal VitD level were used as controls (CG). HbA1c in SG was 8.3±1.5% and in CG – 7.4±1.4%. Neurological tests and examinations with Sudoscan (a non–invasive method for the assessment of the small fiber function, Impeto Medical, France) were performed in all the patients. In the SG results of all neurological tests (monofilament test, tip-term/temperature test, vibration test) were positive, Sudoscan examination revealed presence of small fiber neuropathy in these patients. In CG patients all neurological tests were performed and all, except Sudoscan, were negative; while Sudoscan revealed presence of small fiber neuropathy in this group as well. Vitamin D was measured in both groups. Results: Comparison of the data obtained for the SG and CG showed that VitD concentration was significantly lower in T2DM patients with DPN (both large and small fiber), than in patients with only small fiber DPN and normal VitD levels. In 76 out of 80 SG patients the levels of 25(OH) VitD were low (<20 ng/ml); while in 44 out of 50 patients in the CG they were within the normal range (30-50 ng/ml). Discussion: This study showed that VitD deficiency is present in Georgian patients with DPN; it may play significant role in development of DPN; normalization and control of VitD level may prevent progression of the peripheral nerve damage. Thus, it is relevant to regularly check VitD levels and maintain them within the normal range. Observations will continue.

Prevalence and Risk Factors of Peripheral Neuropathy in Parkinson's Disease.

A lesser studied aspect of Parkinson's disease (PD) is its associated peripheral sensory-motor neuropathy. Peripheral neuropathy is an intriguing aspect of PD, a problem not given sufficient attention and which if tackled properly could make a difference to the multifaceted sufferings of the PD patient. Studies regarding the prevalence of peripheral neuropathy and its risk factors in patients with PD are scarce from the Indian subcontinent. This prospective observational study was conducted in a tertiary care teaching hospital in South India. Patients diagnosed with idiopathic Parkinson's disease (IPD) were screened and enrolled. All the patients underwent detailed evaluation of symptoms, signs, and electrophysiology (Nerve conduction study, Sympathetic skin response), stimulated skin wrinkling with Eutectic Mixture of Local Anesthetics. Patients found to have large/small fiber neuropathy underwent additional tests to exclude other causes of neuropathy. A total of 154 patients with IPD were enrolled in the study (mean age: 61.96 ± 9.15 years, mean duration of disease was 4.08 ± 3.16 years). The mean Hoehn and Yahr (H and Y) score was 2.3 ± 0.825 and the mean Unified Parkinsons Disease Rating Scale (UPDRS)-3 score in the ON state was 23.07 ± 11.14. The mean cumulative levodopa dose was 482.68 ± 651.76 (median: 292; range: 4728.57) grams. Peripheral neuropathy was found in 49 patients (31.8%), large fiber in 28 (18.2%) and small fiber in 47 (30.5%); an overlap of large and small fiber neuropathy was seen in 26 patients (16.9%). Around 34% of patients had serum homocysteine levels >20 mg/dl. In univariate analysis, duration of disease, levodopa cumulative dose, serum homocysteine level, H and Y score, UPDRS-3 ON score, Toronto Clinical Neuropathy Score (P < 0.001 for all), age at presentation, and rigidity predominant presentation (P = 0.02 for both) were associated with large fiber neuropathy. All of these variables were also associated with the presence of small fiber neuropathy (P = 0.004 for age at presentation and P < 0.001 for rest), except the type of PD presentation. However, in multivariate logistic regression analysis, only duration of disease, levodopa cumulative dose, and H and Y score were associated with the presence of large and small fiber neuropathy. In our cohort, majority of the patients were in early-stage PD and around one-fifth and one-third of patients suffer from large and small fiber polyneuropathy, respectively. Large and small fiber neuropathy in PD is mainly associated with duration of disease, levodopa cumulative dose, and H and Y score.

Gulf war illness, post-HPV vaccination syndrome, and Macrophagic Myofasciitis. Similar disabling conditions possibly linked to vaccine-induced autoimmune dysautonomia.

1) To systematically review all original articles investigating the association of vaccines with gulf war illness, 2) To discuss gulf war illness, Macrophagic Myofasciitis, and post-HPV vaccination syndrome clinical similarities, 3) To discuss emergent pathogenetic mechanisms proposed for post-HPV vaccination syndrome that may be also relevant to gulf war illness and Macrophagic Myofasciitis. All original epidemiological studies (n = 11) found a positive association between vaccination and gulf war illness development. Chronic fatigue, widespread pain and cognitive impairment characterize the three syndromes under discussion. Anti-adrenergic receptor antibodies, dysautonomia and small fiber neuropathy have been recently described in patients with post-HPV vaccination syndrome. post-HPV vaccination syndrome, Macrophagic Myofasciitis, and gulf war illness analogy suggests that some vaccines or multiple vaccinations in a very short period of time may induce, in susceptible individuals, chronic pain, fatigue and dyscognition. Vaccine-induced autoimmune dysautonomia is hypothesized as the common pathogenetic mechanism for this symptom cluster. Further research on the presence of small fiber neuropathy, adrenergic receptor antibodies, and abnormal autonomic function tests in the three syndromes under discussion may help to elucidate this hypothesis.

C-Fiber Loss as a Possible Cause of Neuropathic Pain in Schwannomatosis.

Schwannomatosis is the third form of neurofibromatosis and characterized by the occurrence of multiple schwannomas. The most prominent symptom is chronic pain. We aimed to test whether pain in schwannomatosis might be caused by small-fiber neuropathy. Twenty patients with schwannomatosis underwent neurological examination and nerve conduction studies. Levels of pain perception as well as anxiety and depression were assessed by established questionnaires. Quantitative sensory testing (QST) and laser-evoked potentials (LEP) were performed on patients and controls. Whole-body magnetic resonance imaging (wbMRI) and magnetic resonance neurography (MRN) were performed to quantify tumors and fascicular nerve lesions; skin biopsies were performed to determine intra-epidermal nerve fiber density (IENFD). All patients suffered from chronic pain without further neurological deficits. The questionnaires indicated neuropathic symptoms with significant impact on quality of life. Peripheral nerve tumors were detected in all patients by wbMRI. MRN showed additional multiple fascicular nerve lesions in 16/18 patients. LEP showed significant faster latencies compared to normal controls. Finally, IENFD was significantly reduced in 13/14 patients. Our study therefore indicates the presence of small-fiber neuropathy, predominantly of unmyelinated C-fibers. Fascicular nerve lesions are characteristic disease features that are associated with faster LEP latencies and decreased IENFD. Together these methods may facilitate differential diagnosis of schwannomatosis.

Fibromyalgia and small fiber neuropathy: the plot thickens!

Several groups of investigators have described the presence of small fiber neuropathy in fibromyalgia patients. This writing discusses how this new finding could renovate fibromyalgia concept, diagnosis, and treatment. Predominant rheumatology thinking proposes fibromyalgia as a "centralized pain syndrome." An alternative hypothesis views fibromyalgia as a stress-related dysautonomia with neuropathic pain features. Dorsal root ganglia may be the key autonomic-nociceptive short-circuit sites. The recent recognition of small fiber neuropathy in a large subgroup of fibromyalgia patients reinforces the dysautonomia-neuropathic hypothesis and validates fibromyalgia pain. These new findings support fibromyalgia as a primarily neurological entity, nevertheless, rheumatologist will likely remain the best equipped specialist to diagnose fibromyalgia and differentiate it from other multi-symptomatic rheumatic syndromes. Skin biopsy and corneal confocal microscopy will probably become useful fibromyalgia diagnostic tests. Dorsal root ganglia sodium channel blockers are potential fibromyalgia analgesic medications. Subgroups of young girls with "autoimmune neuropathic fibromyalgia" may respond to immunoglobulin therapy. Multimodal intervention directed to regain autonomic nervous system resilience will likely remain the cornerstone for fibromyalgia therapy.

High Level of Gingival Inflammation in Subjects with Type 1 Diabetes Despite Regular Dental Visits and Limited Microvascular Complications

The aim of the study was to evaluate small fiber neuropathy and periodontal health conditions on a cohort of patients with type 1 diabetes. The study participants were 18 females and 23 males with a mean age of 37.9 years (age range: 18-83 years). First, a routine medical examination was conducted at the Diabetology Clinics of the Geneva Universtity Hospital. Electrochemical skin conductance (ESC) was measured by Sudoscan, a noninvasive tool for detecting diabetic small fiber neuropathy. Participants were further examined for presence of periodontal disease by means of Plaque and Gingival indices (PI and GI respectively), probing depth (PD) and bleeding on probing. Self-reported attitudes and behavior regarding dental care was also collected during the visit. The mean duration of affliction with diabetes was 14.6 ±11.9 years, with a mean glycosylated heamoglobin (HbA1c) of 7.96±1.68%. The Sudoscan measurements showed an average ESC value between right and left sides for the hands of 68.2±13.4 microSiemenns (µS) and for the feet an ESC value of 79±6.9 µS. Seven percent of the subjects presented moderate dysfunction (ESC values 60-40 µS) whereas only one subject presented severe dysnfunction (&amp;lt; 40 µS). The periodontal examination revealed that all patients (except from 2) had signs of gingivitis, defined as presence of at least 2 sites with a GI&amp;gt;1. Gingival inflammation and bleeding on probing was present in 66% of the participants in more than 20% of sites independently of the presence of small fiber neuropathy. Periodontitis was observed in 15% of the subjets with a mean of 13 sites with PD&amp;gt;4mm and bleeding on probing. The majority of subjects (70%) reported having regular dental visits at least once per year. In the present cohort of patients with type 1 diabetes the main finding was the occurrence of pronounced gingival inflammation in the majority of subjects independently of small fiber neuropathy and despite regular dental visits. Disclosure M. Roy: None. G. Gastaldi: Speaker's Bureau; Self; Abbott, Eli Lilly and Company, Novo Nordisk A/S, Medtronic, Dexcom, Inc., Sanofi, Roche Diabetes Care Health and Digital Solutions, Boehringer Ingelheim GmbH. A. Mombeli: None. C. Giannopoulou: None.

Dermal sheet preparations in the evaluation of dermal innervation in Parkinson’s disease and multiple system atrophy

Evaluation of dermal nerve fibers in conventional vertical sections is difficult because of the small number of fibers available for examination. In this study, we evaluated dermal sheet mounts for fibers in which the majority of fibers can be visualized. We compared the dermal small fiber density in six Parkinson's disease (PD) and six multiple system atrophy (MSA) patients using dermal sheet preparations (DSP). DSP are based on epidermal-dermal separations and immunostaining of the entire dermis by the nerve growth factor receptor p75 antibody that stains both autonomic and sensory fibers. The small fiber density was reduced in PD compared with MSA (p < 0.0001), suggesting the presence of small fiber neuropathy in PD. DSP offer a unique method of evaluation of dermal nerve fibers. This method can be used to evaluate small nerve fibers in many neurological disorders such as MSA and PD.