Assessing small fiber neuropathy and subtle cardiac involvement in Fabry disease

Abstract Fabry disease (FD) is an X-linked lysosomal storage disorder characterized by reduced or absent activity of the enzyme α-galactosidase A. Due to systemic accumulation of glycolipids, FD phenotype is diverse, and diagnosis may be challenging. Clinical manifestations include small fiber neuropathy, renal dysfunction, cardiac involvement, cerebrovascular disease, among others. In the present study, we describe biopsy proven small fiber neuropathy and subclinical cardiac involvement in two cousins diagnosed with FD secondary to a recently described pathogenic variant, highlighting the importance of diagnostic tools to document organ damage and allow early treatment.

Role of skin punch biopsy in diagnosis of small fiber neuropathy-A review for the neuropathologist

Over the last three decades, skin punch biopsy has become the gold standard for diagnosis of small fiber neuropathies, including autonomic neuropathies commonly seen in diabetics, patients with HIV, and children with hereditary sensory autonomic neuropathies and toxin-induced neuropathy. Clinical, biochemical, electrophysiological tests are inconclusive, making it difficult to diagnose and initiate treatment. A skin punch biopsy is easy to perform in the outpatient clinic, is highly sensitive, and provides an objective diagnosis. Importantly, it helps avoid performing invasive nerve biopsy in patients with small fiber neuropathy, thereby preventing complications such as non-healing of the biopsy site, which is common in these patients. Secondly, the greatest advantage of skin punch biopsies is that they can be repeated any number of times, unlike a nerve biopsy, and are useful to evaluate disease progression and therapeutic response. More recently, its use has been expanded to the diagnosis of large fiber neuropathies, inherited demyelinating neuropathies, etc., obviating the need for a nerve biopsy. The European Federation of Neurological Societies has published guidelines for evaluation to ensure uniformity with regard to the site of biopsy, processing, and quantification. The evaluation of the skin biopsy involves morphometric assessment of the intraepidermal nerve fiber density using PGP 9.5 immunostained sections by bright-field microscopy. This review focuses on the practical aspects of skin punch biopsy and its utility for the practicing pathologist.

Investigation of nerve fibers in the skin by biopsy: technical aspects, indications, and contribution to diagnosis of small-fiber neuropathy

ABSTRACT Skin biopsy with investigation of small-diameter nerve fibers in human epidermis and dermis has been proven to be a useful method for confirming small-fiber neuropathy. In medical practice, small-fiber neuropathy is increasingly recognized as a leading cause of neuropathic pain. It is a prevalent complaint in medical offices, brought by patients often as a "painful burning sensation". The prevalence of neuropathic pain is high in small-fiber neuropathies of different etiologies, especially in the elderly; 7% of population in this age group present peripheral neuropathy. Pain and paresthesia are symptoms which might cause disability and impair quality of life of patients. The early detection of small-fiber neuropathy can contribute to reducing unhealthy lifestyles, associated to higher incidence of the disease.

Clinical analysis of skeletal muscle and small fiber involvement associated with anti-contactin-associated protein-like 2 antibodies positive Morvan syndrome / 中华神经科杂志

Objective:To analyze the clinical data of a patient with anti-contactin- associated protein-like 2 (CASPR2) antibodies-related Morvan syndrome (MoS) and the related literature, and summarize the clinical characteristics of MoS patients.Methods:Clinical data of a CASPR2 antibodies-related MoS patient who was admitted in the Department of Neurology, the First Medical Center of Chinese People′s Liberation Army General Hospital in June 2021 were collected. CASPR2 IgG was detected by cell-based assay. Positron emission tomography/computed tomography (PET/CT), skin sympathetic response (SSR) and other examinations were performed. Clinical profiles of MoS patients were summarized by database retrieval.Results:The patient was a 55-year-old man presenting with peripheral nerve hyperexcitability, autonomic dysfunctions, neuropsychiatric symptoms and pain. Physical examination showed cognitive impairment, muscle quivering and absent deep-tendon reflexes. There was no family history of MoS and poisons exposure in this patient. Auxiliary examination showed serum creatine kinase was elevated (570 U/L) and antinuclear antibodies were positive (granular-type 1∶320). Other rheumatic and immunological antibodies, erythrocyte sedimentation rate, autoantibody profile, tumor marker, thyroid function, etc, were normal. Cerebrospinal fluid (CSF) protein and immunoglobulin were slightly higher. CASPR2 antibodies were positive in both serum and CSF (serum: 1∶100, CSF: 1∶10). Needle electromyography showed myokymic discharges, motor and sensory nerve conduction velocities were normal. SSR showed no waveform was elicited from both hands and feet. Cranial magnetic resonance imaging suggested scattered ischemic changes in the brain. PET/CT showed local metabolism increased slightly in soft tissues of bilateral shoulder and back, right lumbar and back muscles and bilateral gluteus medius. A total number of 232 cases of MoS patients were found in literature reports, most of which were male. The most common clinical manifestations were sleep disorders, and cognitive deficits accounted for 32.3%. Among them, skeletal muscle involvement was found in only 1 case by PET, and 4 patients had SSR abnormalities. Most of the patients had favorable neurological outcomes after the immunotherapy.Conclusions:MoS, as an autoimmune syndrome, may present with high uptake of skeletal muscle in PET/CT examination. Skeletal muscle involvement is a rare clinical manifestation of this disease. SSR as an electrophysiological test to evaluate autonomic neuropathy, its clinical value should be further strengthened.

Caracterización neurofisiológica de la función de fibra pequeña en mujeres heterocigotas con enfermedad de Fabry / Neurophysiologic characterization of small fiber function in heterozigous women with Fabry disease

RESUMEN INTRODUCCIÓN: La enfermedad de Fabry (EF) es una enfermedad genética, causada por el déficit de la enzima alfa galactosidasa A (α-Gal A), lo que provoca la acumulación de glicoesfingolípidos en los tejidos. Sus manifestaciones clínicas son variables. Estudios en mujeres heterocigotas reportan la existencia de dolor neuropático como manifestación de neuropatía de fibra pequeña. OBJETIVO: Determinar la presencia de neuropatía de fibra pequeña en mujeres heterocigotas para la EF, mediante la prueba cuantitativa sensorial. MATERIALES Y MÉTODOS: Se evaluaron 33 mujeres heterocigotas para EF y 33 mujeres sanas, con características demográficas similares. A todas se les aplicó la prueba cuantitativa sensorial (Quantitative Sensory Testing por medio de la detección de umbrales de frío (Colà Detection Threshold), calor (Warm Detection Threshold), dolor inducido por calor (Heat-pain Detection Thresholds) y vibración (Vibratory Detection Threshold) en los miembros superior e inferior, utilizando un sistema asistido por computador versión IV (CASE IV, WR Medical Electronics Co., Stillwater, MN). Adicionalmente, al grupo de mujeres heterocigotas para EF, se le evaluó la percepción subjetiva de dolor neuropàtico mediante el cuestionario de síntomas sensitivos neuropáticos positivos (Positive Neuropathic Sensory Symptom). Los resultados de la prueba cuantitativa sensorial se compararon entre los grupos. También se estableció la correlación entre la prueba cuantitativa sensorial y los resultados del cuestionario de síntomas sensitivos neuropáticos positivos. RESULTADOS: Se encontró una diferencia estadísticamente significativa en las pruebas de vibración (p = 0,008), calor (p = 0,017) y dolor inducido por calor (p = 0,04) en el miembro inferior en las mujeres heterocigotas para EF, comparado con el grupo control. Se encontró una correlación inversa estadísticamente significativa entre la intensidad del dolor quemante y el dolor inducido por calor en el miembro inferior (p = 0,018, r = -0,48) y entre la intensidad del dolor al ser rozado o tocado y el dolor inducido por calor en el miembro inferior (p = 0,006, r = -0,49). CONCLUSIÓN: En las mujeres heterocigotas para EF, las pruebas objetivas para establecer la presencia de neuropatía de fibra pequeña son anormales en miembros inferiores y se correlacionan con los síntomas sensitivos.

SUMMARY INTRODUCTION: Fabry disease is a genetic condition caused by alpha-galactosidase A deficiency triggering glycosphingolipid accumulation in tissues. Clinical manifestations are variable. Studies in heterozigous females report the existence of neuropathic pain as manifestation of small fiber neuropathy. OBJECTIVE: To determine presence of small fiber neuropathy in heterozigous females with Fabry disease through Quantitative Sensory Testing (QST). MATERIALS AND METHODS: 33 heterozigous females with fabry disease and 33 healthy females with similar demographic characteristics were evaluated. QST was performed to every female evaluating Cold detection Threshold (CDT), Warm Detection Threshold (WDT), Heat-pain Detection Threshold (HPDT) and Vibratory Detection Threshold (VDT) in upper and lower limbs through Computer Assisted Sensory Examination software (CASE IV, WR Medical Electronics Co., Stillwater, MN). Subjective perception of neuropathic pain was measured through Positive Neuropathic Sensory Symptom questionnaire (P-NSS) in heterozigous females with Fabry disease. QST results were compared between groups. Correlations between QST and P-NSS were established. RESULTS: Statistically significant differences were observed in VDT (p= 0,008), WDT (p= 0,017) and HPDT (p= 0,04) in lower limbs of heterozigous females with Fabry disease compared with control group. Negative correlation was found among burning pain intensity and HPDT at lower limbs (p= 0,018, r= -0,48) and among pain intensity to light touch and HPDT in lower limbs (p= 0,006, r=-0,49). CONCLUSIONS: Objective tests to establish presence of small fiber neuropathy in heterozigous females with Fabry disease are abnormal at lower limbs and correlate with sensory symptoms.

Suffering among patients with cancer undergoing neurotoxic chemotherapy: a phenomenological approach / Sufrimiento de pacientes con cáncer en quimioterapia neurotóxica: un abordaje fenomenológico / Sofrimento de pacientes com câncer em quimioterapia neurotóxica: uma abordagem fenomenológica

ABSTRACT Objective: reveal experiences of cancer patients undergoing neurotoxic chemotherapy. Method: phenomenology-based, qualitative study, carried out with nine adult patients in antineoplastic neurotoxic treatment, interviewed in June and July 2018. The testimonies were analyzed using an empirical comprehensive model. Results: the following categories were delineated: nerves on edge: perception of limitations caused by neuropathic pain induced by chemotherapy; chemotherapy drains me of energy; the suffering of starting again; the suffering of enduring it; alone in a desert, I heard the cry of my silence; chemotherapy: an infusion of hope; and there is no suffering on earth that heaven cannot heal. Conclusion: the study presented various meanings of suffering that emerge from experiences with neurotoxic treatment and found that many dimensions of suffering interpenetrate, making it impossible to disassociate them.

RESUMEN Objetivo: revelar experiencias de pacientes con cáncer que se sometieron a terapia con quimioterápicos neurotóxicos. Método: Estudio cualitativo fundamentado en la fenomenología, realizado con nueve pacientes adultos tratados con antineoplásicos neurotóxicos, entrevistados entre junio y julio de 2018. Los testimonios fueron analizados según el modelo empírico-comprensivo. Resultados: se determinaron las categorías: Con los nervios a flor de piel -percepción de limitaciones provocadas por el dolor neuropático inducido por la quimioterapia-, La quimioterapia que acaba con mi energía; El sufrimiento de recomenzar; El sufrimiento de soportar; Solo, en un desierto, oí el grito de mi silencio; Quimioterapia -una infusión de esperanza-; y No hay sufrimiento en la tierra que el cielo no pueda curar. Conclusión: el estudio presentó varios significados de sufrimiento que surgen de la experiencia con el tratamiento neurotóxico, manifestando que muchas de las dimensiones del sufrimiento se entrecruzan, siendo imposible disociarlas.

RESUMO Objetivo: desvelar experiências de pacientes com câncer que se submeteram à terapia com quimioterápicos neurotóxicos. Método: estudo qualitativo, fundamentado na fenomenologia, realizado com nove pacientes adultos em tratamento com antineoplásicos neurotóxicos, entrevistados em junho e julho de 2018. Os depoimentos foram analisados segundo o modelo empírico-compreensivo. Resultados: foram reveladas as categorias: com os nervos à flor da pele - percepção das limitações provocadas pela dor neuropática induzida pela quimioterapia; a quimioterapia que acaba com a minha energia; o sofrimento de recomeçar; o sofrimento de suportar; sozinho, em um deserto, ouvi o grito do meu silêncio; quimioterapia - uma infusão de esperança; e, não há sofrimentos na terra que o céu não possa curar. Conclusão: o estudo apresentou vários significados de sofrimento que emergem da experiência com o tratamento neurotóxico, relatando que muitas das dimensões do sofrimento interpenetram-se, sendo impossível dissociá-las.

Prueba diagnóstica de disfunción sudomotora en la detección precoz de la neuropatía diabética / Sudomotor dysfunction diagnostic test for early detection of diabetic neuropathy

Background: Sudomotor dysfunction may appear in early stages of diabetic neuropathy. Aim: To evaluate the diagnostic capacity of the Neuropad test, based on the detection of sudomotor dysfunction, as an early indicator of diabetic neuropathy. Material and Methods: In Forty-two type 2 diabetic patients, the Neuropad test was compared with the 10 g monofilament test (proposed in the technical orientation of diabetic foot of the Ministry of Health of Chile), deep and thermal sensitivity. Results: The surface sensitivity assessed with a brush had a sensitivity and specificity of 18.8 and 100% respectively when compared with the 10 g monofilament. When compared with the Neuropad, the figures were 9 and 100%, respectively. Pain perception sensitivity and specificity were 13 and 100% respectively when compared with the 10 g monofilament. The figures were 6 and 100%, when compared with the Neuropad. Thermal discrimination had a sensitivity and specificity of 88 and 33% respectively when compared with the 10 g monofilament. The figures were 75 and 25% respectively when compared with the Neuropad. The deep sensitivity evaluated with a 128 Hz tuning fork had a sensitivity and specificity of 31 and 100% respectively when compared with the 10 g monofilament. The figures were 16 and 31% respectively when compared with the Neuropad. The Neuropad had a sensitivity and specificity of 94 and 29% respectively were compared with the 10 g monofilament. Conclusions: Neuropad had a good diagnostic yield for the early detection of sudomotor dysfunction.

Small fiber neuropathy and related factors in patients with systemic lupus erythematosus; the results of cutaneous silent period and skin biopsy

Abstract Introduction Evaluating 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 - methods Fifty 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. Results In 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). Conclusion We 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.(AU)

Dolor neuropático, pensemos en Enfermedad de Fabry

RESUMEN El dolor es la razón más común de consulta y de búsqueda de atención médica, y el que presenta una mayor dificultad al recibir un paciente es el dolor neuropático. Una de las neuropatías de fibras finas por excelencia es la enfermedad de Fabry, un desorden poco conocido. El objetivo de esta revisión fue cotejar la bibliografía disponible para determinar los puntos clave en el manejo de esta enfermedad, usando herramientas de búsqueda como Up To Date, Pubmed y Google Scholar. Luego de la revisión de más de 30 artículos científicos se pudo concluir que el característico dolor y la hiposensibilidad térmica se deben al acúmulo de glicolípidos que producen una neuropatía de fibras finas. Esto se asocia a un cuadro de dolores quemantes en manos y pies que puede presentar gran dificultad al momento del diagnóstico y tratamiento. De este modo, sospechar el diagnóstico conlleva una serie de pasos desde la historia clínica y examen físico, que son de gran importancia, hasta la determinación bioquímica porcentual de la ausencia de actividad de la alfa-galactosidasa A hasta los exámenes neurológicos e histológicos. Se llegó a la conclusión de que las características clínicas de esta enfermedad pueden ser típicas en la mayoría de los pacientes, sin embargo se debería conocer la fisiopatología subyacente al problema y diferenciar el manejo de un dolor crónico con el de las crisis de dolor. Esto es imperioso debido a la importancia de instaurar la terapia especifica lo antes posible.

ABSTRACT Pain is the most common reason for consulting and seeking medical attention, and the one that presents the greatest difficulty in receiving a patient is neuropathic pain. One of the neuropathies of small fibers par excellence is Fabry Disease, a little known disorder. The objective of this review was to collate the available bibliography to determine the key points in the management of this disease, using search tools such as Up To Date, Pubmed and Google Scholar. After reviewing more than 30 scientific articles, it was concluded that the characteristic pain and thermal hyposensitivity are due to the accumulation of glycolipids that produce a neuropathy of small fibers. This is associated with a picture of burning pains in the hands and feet that can present great difficulty at the time of diagnosis and treatment. Thus, suspecting the diagnosis involves a series of steps from the clinical history and physical examination, which are of great importance, to the percentage biochemical determination of the absence of activity of alpha-galactosidase A until neurological and histological examinations. It was concluded that the clinical characteristics of this disease may be typical in most patients, however, the pathophysiology underlying the problem should be known and the management of chronic pain should be differentiated from that of pain crises. This is imperative because of the importance of establishing the specific therapy as soon as possible.

Nosocomial treatment-induced neuropathy of diabetes: An important cause of painful and autonomic neuropathy in hospitalized diabetes mellitus patients

@#Treatment-induced neuropathy of diabetes (TIND) is an acute painful autonomic small-fiber neuropathy that develops following an abrupt improvement in glycaemia control. Recent reports suggest TIND is a significant problem in tertiary neuropathy clinics. TIND in hospitalized patients with poor initial glycaemia control, that we refer to as nosocomial TIND, has not been well-studied. We describe the demographic, clinical features and indices of glycaemia control in 5 consecutive nosocomial TIND patients. TIND was defined using recently published criteria. Pre-meal capillary blood glucose recordings performed during the period of HbA1c decline was used to calculate glycaemic variability. All the nosocomial TIND patients were hospitalized for prolonged periods for serious medical conditions that warranted good glycaemia control, namely severe sepsis, diabetic ketoacidosis, stroke, heart failure and traumatic head injury. They had raised, double-digit, HbA1c levels at admission that subsequently dropped precipitously with tight in-patient glycaemia control protocols. These patients had multiple, largely asymptomatic, hypoglycaemic episodes. Glycaemic variability also appeared to be high in this cohort. TIND may be a significant cause of morbidity in hospitalized diabetic patients with poor glycaemia control. Not all patients developed both autonomic and painful neuropathies, raising the possibility of forme-fruste TIND

‘Sirim’ (Cold) Pain as a Common Symptom in Korean Patients with Clinically Suspected Small-Fiber Neuropathy

BACKGROUND AND PURPOSE: Diagnosing small-fiber neuropathy (SFN) is challenging because there is no gold-standard test and few diagnostic tests. This study investigated the clinical symptom profile and its associations with the results of quantitative sensory testing (QST) and the quantitative sudomotor axon reflex test (QSART) as well as the quality of life (QOL) in patients with clinically suspected SFN. METHODS: This study involved 63 patients with clinically suspected length-dependent SFN. Assessments were performed using QST, QSART, SFN Symptoms Inventory Questionnaire, Neuropathic Pain Symptom Inventory, ‘Sirim’ frequency and ‘Sirim’ (cold) pain severity, and 36-item Short-Form Health Survey. Multiple logistic and linear regression analyses were performed to predict risk factors for QST or QSART abnormalities and QOL, respectively. RESULTS: ‘Sirim’ and ‘Sirim’ pain was the most-common (84%) and the most-severe complaint (mean score of 6.3 on a numerical rating scale ranging from 0 to 10) in patients with clinically suspected SFN. The findings of QST [cold detection threshold (CDT)] and QSART were abnormal in 71% (n=45/57) and 62% (n=39/56) of the patients, respectively. An abnormal CDT was correlated with more-severe stabbing pain (odds ratio=2.23, 95% CI=1.02–4.87, p=0.045). Restless-leg symptoms (β=−7.077) and pressure-evoked pain (β=−5.034) were independent predictors of the physical aspects of QOL. CONCLUSIONS: ‘Sirim’ pain, similar to cold pain, should be considered a major neuropathic pain in SFN. Among pain characteristics, stabbing pain of a spontaneous paroxysmal nature may be more pronounced in the setting of dysfunctional Aδ fibers with functional autonomic C fibers.

Compromiso neuropático y autonómico en Enfermedad de Fabry: presentación de casos clínicos / Neuropathy and Fabry's disease: report of five cases

Fabry's disease is an X-linked multisistemic lisosomal storage disorder caused by deficiency or absence in α-Galatosidase A. Symptoms develop early in childhood with small fiber neuropathy, autonomic disorders and skin lesions (angiokeratomas). More severe in males, patients develop over years heart disease (hypertrophic cardiomyopathy, bradycardia), proteinuria, renal failure, transient ischemic attacks and stroke, associated with decreased life expectancy. We report five patients with Fabry's disease aged between 21 to 56 years and with family history. Neuropathic symptoms are described and neurophysiological testing findings of nerve conduction studies, quantitative sensory testing, autonomic testing and sympathetic skin response are presented.

Definition and diagnosis of small fiber neuropathy: consensus from the Peripheral Neuropathy Scientific Department of the Brazilian Academy of Neurology / Definição e diagnóstico de neuropatia de fibras finas: consenso do Departamento Científico de Neuropatias Periféricas da Academia Brasileira de Neurologia

ABSTRACT The aim of this study was to describe the results of a Brazilian Consensus on Small Fiber Neuropathy (SFN). Fifteen neurologists (members of the Brazilian Academy of Neurology) reviewed a preliminary draft. Eleven panelists got together in the city of Fortaleza to discuss and finish the text for the manuscript submission. Small fiber neuropathy can be defined as a subtype of neuropathy characterized by selective involvement of unmyelinated or thinly myelinated sensory fibers. Its clinical picture includes both negative and positive manifestations: sensory (pain/dysesthesias/pruritus) or combined sensory and autonomic complaints, associated with an almost entirely normal neurological examination. Standard electromyography is normal. A growing list of medical conditions is associated with SFN. The classification of SFN may also serve as a useful terminology to uncover minor discrepancies in the normal values from different neurophysiology laboratories. Several techniques may disclose sensory and/or autonomic impairment. Further studies are necessary to refine these techniques and develop specific therapies.

RESUMO O objetivo deste estudo é descrever os resultados de um Consenso Brasileiro sobre Neuropatia de Fibras Finas (NFF). Quinze neurologistas (membros da Academia Brasileira de Neurologia) revisaram uma versão preliminar do artigo. Onze panelistas se reuniram na cidade de Fortaleza para discutir e terminar o texto para a submissão do manuscrito. NFF pode ser definida como um subtipo de neuropatia caracterizada pelo envolvimento seletivo de fibras sensitivas amielínicas ou pouco mielinizadas. Seu quadro clínico inclui manifestações negativas e positivas: sensitivas (dor/disestesias/prurido) ou queixas sensitivas e autonômicas combinadas, associadas a exame neurológico quase totalmente normal. A eletromiografia convencional é normal. Uma lista crescente de condições médicas causa NFF. NFF também pode servir como uma terminologia útil para referenciar pequenas discrepâncias nos valores normais de diferentes laboratórios de neurofisiologia. Diferentes técnicas podem evidenciar anormalidades sensitivas e/ou autonômicas. São necessários mais estudos para refiná-las e para o desenvolvimento de terapias específicas.

The Availability of Quantitative Assessment of Pain Perception in Patients With Diabetic Polyneuropathy

OBJECTIVE: To evaluate the usefulness of the quantitative assessment of pain perception (QAPP) in diabetic polyneuropathy (DPN) patients. METHODS: Thirty-two subjects with DPN were enrolled in this study. The subjects’ pain perception was assessed quantitatively. Current perception threshold (CPT) and pain equivalent current (PEC) were recorded. All patients were tested with a nerve conduction study (NCS) for evaluation of DPN and pain-related evoked potential (PREP) for evaluation of small fiber neuropathy (SFN) on bilateral upper and lower limbs. All patients were asked to participate in tests such as visual analogue scale (VAS) and SF-36 Health Survey Version 2 to evaluate their subjective pain and quality of life, respectively. RESULTS: The PEC of QAPP showed significant correlations with VAS (p=0.002) and physical function surveyed with SF-36 Health Survey Version 2 (p=0.035). The results of QAPP had no correlation with NCS, but there was a significant relationship between the CPT of QAPP and PREP (p=0.003). CONCLUSION: The QAPP may be useful not only in providing objective evaluations of subjective pain in patients with DPN but also in the assessment of diabetic SFN.

Small Fiber Neuropathy and Postural Orthostatic Tachycardia Syndrome after Human Papillomavirus Vaccination

We describe a 44-year-old woman with paresthesia, fatigue, and palpitation, 10 days after human papillomavirus (HPV) vaccination. The quantitative sensory test showed abnormal detection threshold in her foot. Tilt test result indicated postural orthostatic tachycardia syndrome. Symptoms were improved after immunomodulating therapy, pain control drug, and oral beta blocker medication. This is first case report for small fiber neuropathy and autonomic dysfunction after HPV vaccination in Korea.

Rapid, Objective and Non-invasive Diagnosis of Sudomotor Dysfunction in Patients With Lower Extremity Dysesthesia: A Cross-Sectional Study

OBJECTIVE: To determine whether patients with lumbosacral (LS) radiculopathy and peripheral polyneuropathy (PPNP) exhibit sudomotor abnormalities and whether SUDOSCAN (Impeto Medical, Paris, France) can complement nerve conduction study (NCS) and electromyography (EMG). METHODS: Outpatients with lower extremity dysesthesia underwent electrophysiologic studies and SUDOSCAN. They were classified as normal (group A), LS radiculopathy (group B), or PPNP (group C). Pain severity was measured by the Michigan Neuropathy Screening Instrument (MNSI) and visual analogue scale (VAS). Demographic features, electrochemical skin conductance (ESC) values on hands and feet, and SUDOSCAN-risk scores were analyzed. RESULTS: There were no statistical differences in MNSI and VAS among the three groups. Feet-ESC and hands-ESC values in group C were lower than group A and B. SUDOSCAN-risk score in group B and C was higher than group A. With a cut-off at 48 microSiemens of feet-ESC, PPNP was detected with 57.1% sensitivity and 94.2% specificity (area under the curve [AUC]=0.780; 95% confidence interval [CI], 0646–0.915). With a SUDOSCAN-risk score cut-off at 29%, NCS and EMG abnormalities related to LS radiculopathy and PPNP were detected with 64.1% sensitivity and 84.2% specificity (AUC=0.750; 95% CI, 0.674–0.886). CONCLUSION: SUDOSCAN can discriminate outpatients with abnormal electrophysiological findings and sudomotor dysfunction. This technology may be a complementary tool to NCS and EMG in outpatients with lower extremity dysesthesia.

Small Fiber Neuropathy in Fabry Disease: a Review of Pathophysiology and Treatment

Abstract Fabry disease is an inherited metabolic disorder characterized by progressive lysosomal accumulation of glycolipids 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 a young age. Neuropathic pain and pain attacks are often the presenting symptoms of the disease and start at an average age of 9 years in male patients and 16 years in female patients, but currently a systematic literature review in early childhood showed the presence of these symptoms before the age of 5 years. Clinical studies have shown that enzyme replacement therapy may improve the overall pain scores and pain intensity in patients; improvements in pain outcomes have been sustained during the long-term follow-up, allowing many patients to reduce their use of pain medication. Some indirect evidence from dose-switching studies suggests that enzyme replacement therapy dose may be of relevance to pain outcomes. Considering that damage to small nerve fibers occurs early, prompt treatment is important in order to limit damage to the peripheral nervous system. In this article a comprehensive overview of the existing literature on small nerve fiber pathophysiology and the relationship with neuropathic pain and treatment response in children and adults with Fabry disease is presented.

A Case-Control study of the prevalence of neurological diseases in inflammatory bowel disease (IBD) / Um estudo de caso-controle da prevalência de doenças neurológicas na doença inflamatória intestinal (DII)

Neurological diseases are common in inflammatory bowel disease (IBD) patients, but their exact prevalence is unknown. Method We prospectively evaluated the presence of neurological disorders in 121 patients with IBD [51 with Crohn's disease (CD) and 70 with ulcerative colitis (UC)] and 50 controls (gastritis and dyspepsia) over 3 years. Results Our standard neurological evaluation (that included electrodiagnostic testing) revealed that CD patients were 7.4 times more likely to develop large-fiber neuropathy than controls (p = 0.045), 7.1 times more likely to develop any type of neuromuscular condition (p = 0.001) and 5.1 times more likely to develop autonomic complaints (p = 0.027). UC patients were 5 times more likely to develop large-fiber neuropathy (p = 0.027) and 3.1 times more likely to develop any type of neuromuscular condition (p = 0.015). Conclusion In summary, this is the first study to prospectively establish that both CD and UC patients are more prone to neuromuscular diseases than patients with gastritis and dyspepsia. .

Doenças neurológicas são comuns em pacientes com doença inflamatória intestinal (DII), mas sua prevalência exata é desconhecida. Métodos Nós estudamos prospectivamente a presença de distúrbios neurológicos em 121 pacientes com DII [51 com doença de Crohn (DC) e 70 com colite ulcerativa (RCU)] e 50 controles (gastrite e dispepsia) ao longo de 3 anos. Resultados A avaliação neurológica padronizada (que incluiu testes eletrodiagnósticos) demonstrou que pacientes com DC foram 7,4 vezes mais propensos a desenvolver neuropatias de fibras grossas do que os controles (p = 0,045), 7,1 vezes mais propensos a desenvolver qualquer tipo de condição neuromuscular (p = 0,001) e 5,1 vezes mais propensos a desenvolver queixas autonômicas (p = 0,027). Pacientes com RCU foram 5 vezes mais propensos de desenvolver neuropatia de fibras grossas (p = 0,027) e 3,1 vezes mais propensos a desenvolver qualquer tipo de condição neuromuscular (p = 0,015). Conclusão Em resumo, este é o primeiro estudo prospectivo a estabelecer que os pacientes tanto com DC quanto de RCU são mais propensos a doenças neuromusculares do que os pacientes com gastrite e dispepsia. .

Skin Biopsy: Emerging Method for Small Nerve Fiber Evaluation / 대한임상신경생리학회지

Skin biopsy with investigation of small nerve fiber in human epidermis and dermis has been proven to be a useful method for demonstration of small fiber neuropathy. Quantification of intraepidermal nerve fiber density using anti-Protein Gene Product 9.5 (PGP 9.5) antibody is standardized method to diagnose the small fiber neuropathy. Skin biopsy method also makes it possible to differentiate the type of nerve fibers by using different antibodies. Quantification of dermal structures with different type of nerve fibers could be used to invest pathophysiologic mechanism of diseased state.

Small fiber dysfunction in patients with Wilson's disease / Disfunção de fibras finas em pacientes com doença de Wilson

Objective: Patients with Wilson’s disease (WD) may develop a wide variety of neuropsychiatric symptoms, but there are few reports of autonomic dysfunction. Here, we described evidence of small fiber and/or autonomic dysfunction in 4 patients with WD and levodopa-responsive parkinsonism. Method: We reviewed the charts of 4 patients with WD who underwent evaluation for the presence of neuromuscular dysfunction and water-induced skin wrinkling test (SWT). Results: Two men and 2 women (33±3.5 years) with WD were evaluated. They all had parkinsonism at some point during their disease course. Parkinsonism on patient 4 almost completely subsided with treatment of WD. Two patients had significant sensory and 2 significant autonomic complaints, including syncopal spells. NCS/EMG was normal in all but SWT was abnormal in half of them (mean 4-digit wrinkling of 0.25 and 1). Discussion: A subset of patients with WD exhibit evidence of abnormal skin wrinkling test (small fiber neuropathy). .

Objetivo: Pacientes com doença de Wilson (DW) podem desenvolver uma ampla variedade de sintomas neuropsiquiátricos, mas existem poucos relatos de disfunção autonômica. Aqui, nós descrevemos evidência de disfunção de fibras finas/autonômica em 4 pacientes com DW e parkinsonismo responsivo à levodopa. Método: Nós revisamos os prontuários de 4 pacientes com DW que foram submetidos a avaliação neuromuscular e ao teste de quantificação do enrugamento cutâneo (TEC). Resultados: Dois homens e 2 mulheres (33±3,5 anos) com DW foram avaliados. Todos apresentaram parkinsonismo durante o curso de sua doença. Parkinsonismo no paciente 4 quase completamente desapareceu com tratamento da DW. Dois pacientes apresentaram queixas sensitivas e 2 apresentaram queixas autonômicas significativas incluindo episódios de síncope. Eletroneuromiografia foi normal em todos e TEC foi anormal em metade deles (score do TEC nos 4 dedos de 0,25 e 1). Discussão: Um subgrupo de pacientes com DW apresenta evidência de TEC anormal (neuropatia de fibras finas). .