Living without pain. Case series of patients with hereditary sensory and autonomic neuropathies in a Canadian tertiary care centre.

Background: Hereditary sensory and autonomic neuropathies (HSANs) are a group of heterogeneous genetic disorders presenting predominantly with sensory and autonomic dysfunction. They are a diverse group of diseases of the peripheral nervous system characterized by profound distal sensory loss and various autonomic and motor disturbances. Objectives: The primary objective of this study was to describe the clinical presentation of children with HSAN to paediatricians. We present clinical features and genetic etiology of patients with HSAN followed in a Canadian tertiary paediatric centre, including suggestions for their monitoring, management, and long-term follow-up. Methods: A retrospective chart review of all patients with HSAN followed from the years 2000 through 2021 was performed. Collected data consisted of patients' demographics, clinical characteristics, imaging, and management. Results: Eight patients were included. The average age at diagnosis was 3.19 ±â€…2.83 years. Insensitivity to pain (100%), dysautonomia (100%), global development delay (87.5%), emesis (62.5%), and self-injury (62.5%) were the most prevalent manifestations of HSAN. The most common co-morbidities were gastroesophageal reflux disease (50%), obstructive sleep apnea (37.5%), attention-deficit hyperactivity disorder (37.5%), and iron deficiency (37.5%). Management was multi-disciplinary, involving neurologists, orthopeds, developmental paediatricians, sleep specialists, and psychiatrists. Conclusion: HSANs are a diverse group of diseases, characterized by profound distal sensory loss, acral mutilations, and variable autonomic disturbances. It is important to recognize the diagnosis in the paediatrician's office in order to set up surveillance and prevent complications.

Description of a patient cohort with Hereditary Sensory Neuropathy type 1 without retinal disease Macular Telangiectasia type 2 - implications for retinal screening in HSN1.

Pathogenic variants in the genes encoding serine palmitoyl transferase (SPTLC1 or SPTLC2) are the most common causes of the rare peripheral nerve disorder Hereditary Sensory Neuropathy Type 1 (HSN1). Macular telangiectasia type 2 (MacTel), a retinal disorder associated with disordered serine-glycine metabolism, has been described in some patients with HSN1. This study aims to further investigate this association in a cohort of people with HSN1. Fourteen patients with a clinically and genetically confirmed diagnosis of HSN1 from the National Hospital for Neurology and Neurosurgery (NHNN, University College London Hospitals NHS Foundation Trust, London, United Kingdom) were recruited to the MacTel Registry, between July 2018 and April 2019. Two additional patients were identified from the dataset of the international clinical registry study (www.lmri.net). Ocular examination included fundus autofluorescence, blue light and infrared reflectance, macular pigment optical density mapping and optical coherence tomography. Twelve patients had a pathogenic variant in the SPTLC1 gene, with p.Cys133Trp in 11 cases (92%) and p.Cys133Tyr in one case (8%). Four patients had a variant in the SPTLC2 gene. None of the patients showed clinical evidence of MacTel. The link between HSN1 and MacTel seems more complex than can solely be explained by the genetic variants. An extension of the spectrum of SPTLC1/2-related disease with phenotypic pleiotropy is proposed. HSN1 patients should be screened for visual symptoms and referred for specialist retinal screening, but the association of the two diseases is likely to be variable and remains unexplained.

Understanding pain perception through genetic painlessness diseases: The role of NGF and proNGF.

Nerve growth factor (NGF), by binding to TrkA and p75NTR receptors, regulates the survival and differentiation of sensory neurons during development and mediates pain transmission and perception during adulthood, by acting at different levels of the nervous system. Key to understanding the role of NGF as a pain mediator is the finding that mutations (namely, R121W, V232fs and R221W) in the NGF gene cause painlessness disease Hereditary Sensory and Autonomic Neuropathy type V (HSAN V). Here we shall review the consequences of these NGF mutations, each of which results in specific clinical signs: R221W determines congenital pain insensitivity with no overt cognitive disabilities, whereas V232fs and R121W also result in intellectual disability, thus showing similarities to HSAN IV, which is caused by mutations in TrkA, rather than to HSAN V. Comparing the cellular, biochemical and clinical findings of these mutations could help in better understanding not only the possible mechanisms underlying HSAN V, but also mechanisms of NGF signalling and roles. These mutations alter the balance between NGF and proNGF in favour of an accumulation of the latter, suggesting a possible role of proNGF as a molecule with an analgesic role. Furthermore, the neurotrophic and pronociceptive functions of NGF are split by the R221W mutation, making NGF variants based on this mutation interesting for designing therapeutic applications for many diseases. This review emphasizes the possibility of using the mutations involved in "painlessness" clinical disorders as an innovative approach to identify new proteins and pathways involved in pain transmission and perception. OUTSTANDING QUESTIONS: Why do homozygous HSAN V die postnatally? What is the cause of this early postnatal lethality? Is the development of a mouse or a human feeling less pain affecting higher cognitive and perceptual functions? What is the consequence of the HSAN V mutation on the development of joints and bones? Are the multiple fractures observed in HSAN V patients due exclusively to the carelessness consequent to not feeling pain, or also to an intrinsic frailty of their bones? Are heterodimers of NGFWT and NGFR221W in the heterozygote state formed? And if so, what are the properties of these heterodimeric proteins? How is the processing of proNGFR221W to NGFR221W affected by the mutation?

Recessive mutations in the neuronal isoforms of DST, encoding dystonin, lead to abnormal actin cytoskeleton organization and HSAN type VI.

Hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders, characterized by a progressive sensory neuropathy often complicated by ulcers and amputations, with variable motor and autonomic involvement. Several pathways have been implicated in the pathogenesis of neuronal degeneration in HSAN, while recent observations point to an emerging role of cytoskeleton organization and function. Here, we report novel biallelic mutations in the DST gene encoding dystonin, a large cytolinker protein of the plakin family, in an adult form of HSAN type VI. Affected individuals harbored the premature termination codon variant p.(Lys4330*) in trans with the p.(Ala203Glu) change affecting a highly conserved residue in an isoform-specific N-terminal region of dystonin. Functional studies showed defects in actin cytoskeleton organization and consequent delayed cell adhesion, spreading and migration, while recombinant p.Ala203Glu dystonin loses the ability to bind actin. Our data aid in the clinical and molecular delineation of HSAN-VI and suggest a central role for cell-motility and cytoskeletal defects in its pathogenesis possibly interfering with the neuronal outgrowth and guidance processes.

The coexistence of a novel WNK1 variant and a copy number variation causes hereditary sensory and autonomic neuropathy type IIA.

BACKGROUND: Hereditary sensory and autonomic neuropathy (HSAN) type II is a group of extremely rare autosomal recessive neurological disorders with heterogeneous clinical and genetic characteristics. METHODS: We performed high-depth next-generation targeted sequencing using a custom-ordered "HSAN" panel, covering WNK1, NTRK1, NGF, SPTLC1 and IKBKAP genes, to identify pathogenic variants of the proband as well as the family members. We also performed whole exome sequencing to further investigate the potential occurrence of additional pathogenic variants in genes that were not covered by the "HSAN" panel. Quantitative real-time PCR was used to identify pathogenic copy number variations (CNVs) and to analyze the mRNA level of WNK1 gene of the family. Western blot analysis was performed to evaluate the WNK1 protein expression level. RESULTS: After sequencing, a novel nonsense variant (c.2747 T > G, p.Leu916Ter) in exon 9 of WNK1 gene was identified in two patients (hemizygous) and their mother (heterozygous). This variant is absent in all public databases as well as in 600 Han Chinese healthy controls. The region of this variant is evolutionary highly conserved. Furthermore, by quantitative real-time PCR using DNA of the pedigree, we revealed a large deletion containing the whole WNK1 gene in two patients. The WNK1 expression levels of the patients were significantly reduced. CONCLUSIONS: Our study firstly revealed that the coexistence of a novel WNK1 nonsense variant and a CNV resulted in HSAN type IIA in a Han Chinese family.

Hereditary Sensory and Autonomic Neuropathies: Adding More to the Classification.

PURPOSE OF REVIEW: Hereditary sensory and autonomic neuropathies (HSANs) are a clinically heterogeneous group of inherited neuropathies featuring prominent sensory and autonomic involvement. Classification of HSAN is based on mode of inheritance, genetic mutation, and phenotype. In this review, we discuss the recent additions to this classification and the important updates on management with a special focus on the recently investigated disease-modifying agents. RECENT FINDINGS: In this past decade, three more HSAN types were added to the classification creating even more diversity in the genotype-phenotype. Clinical trials are underway for disease-modifying and symptomatic therapeutics, targeting mainly HSAN type III. Obtaining genetic testing leads to accurate diagnosis and guides focused management in the setting of such a diverse and continuously growing phenotype. It also increases the wealth of knowledge on HSAN pathophysiologies which paves the way toward development of targeted genetic treatments in the era of precision medicine.

A novel nonsense mutation in WNK1/HSN2 associated with sensory neuropathy and limb destruction in four siblings of a large Iranian pedigree.

BACKGROUND: Hereditary sensory and autonomic neuropathy type 2 (HSAN2) is an autosomal recessive disorder with predominant sensory dysfunction and severe complications such as limb destruction. There are different subtypes of HSAN2, including HSAN2A, which is caused by mutations in WNK1/HSN2 gene. METHODS: An Iranian family with four siblings and autosomal recessive inheritance pattern whom initially diagnosed with HSAN2 underwent whole exome sequencing (WES) followed by segregation analysis. RESULTS: According to the filtering criteria of the WES data, a novel candidate variation, c.3718C > A in WNK1/HSN2 gene that causes p.Tyr1025* was identified. This variation results in a truncated protein with 1025 amino acids instead of the wild-type product with 2645 amino acids. Sanger sequencing revealed that the mutation segregates with disease status in the pedigree. CONCLUSIONS: The identified novel nonsense mutation in WNK1/HSN2 in an Iranian HSAN2 pedigree presents allelic heterogeneity of this gene in different populations. The result of current study expands the spectrum of mutations of the HSN2 gene as the genetic background of HSAN2A as well as further supports the hypothesis that HSN2 is a causative gene for HSAN2A. However, it seems that more research is required to determine the exact effects of this product in the nervous system.

Dexmedetomidine for refractory adrenergic crisis in familial dysautonomia.

OBJECTIVE: Adrenergic crises are a cardinal feature of familial dysautonomia (FD). Traditionally, adrenergic crises have been treated with the sympatholytic agent clonidine or with benzodiazepines, which can cause excessive sedation and respiratory depression. Dexmedetomidine is a centrally-acting α 2-adrenergic agonist with greater selectivity and shorter half-life than clonidine. We evaluated the preliminary effectiveness and safety of intravenous dexmedetomidine in the treatment of refractory adrenergic crisis in patients with FD. METHODS: Retrospective chart review of patients with genetically confirmed FD who received intravenous dexmedetomidine for refractory adrenergic crises. The primary outcome was preliminary effectiveness of dexmedetomidine defined as change in blood pressure (BP) and heart rate (HR) 1 h after the initiation of dexmedetomidine. Secondary outcomes included incidence of adverse events related to dexmedetomidine, hospital and intensive care unit (ICU) length of stay, and hemodynamic parameters 12 h after dexmedetomidine cessation. RESULTS: Nine patients over 14 admissions were included in the final analysis. At 1 h after the initiation of dexmedetomidine, systolic BP decreased from 160 ± 7 to 122 ± 7 mmHg (p = 0.0005), diastolic BP decreased from 103 ± 6 to 65 ± 8 (p = 0.0003), and HR decreased from 112 ± 4 to 100 ± 5 bpm (p = 0.0047). The median total adverse events during dexmedetomidine infusion was 1 per admission. Median hospital length of stay was 9 days [interquartile range (IQR) 3-11 days] and median ICU length of stay was 7 days (IQR 3-11 days). CONCLUSIONS: Intravenous dexmedetomidine is safe in patients with FD and appears to be effective to treat refractory adrenergic crisis. Dexmedetomidine may be considered in FD patients who do not respond to conventional clonidine and benzodiazepine pharmacotherapy.

Intranasal dexmedetomidine for adrenergic crisis in familial dysautonomia.

PURPOSE: To report the use of intranasal dexmedetomidine, an α2-adrenergic agonist for the acute treatment of refractory adrenergic crisis in patients with familial dysautonomia. METHODS: Case series. RESULTS: Three patients with genetically confirmed familial dysautonomia (case 1: 20-year-old male; case 2: 43-year-old male; case 3: 26-year-old female) received intranasal dexmedetomidine 2 mcg/kg, half of the dose in each nostril, for the acute treatment of adrenergic crisis. Within 8-17 min of administering the intranasal dose, the adrenergic crisis symptoms abated, and blood pressure and heart rate returned to pre-crises values. Adrenergic crises eventually resumed, and all three patients required hospitalization for investigation of the cause of the crises. CONCLUSIONS: Intranasal dexmedetomidine is a feasible and safe acute treatment for adrenergic crisis in patients with familial dysautonomia. Further controlled studies are required to confirm the safety and efficacy in this population.

Arthropathy-related pain in a patient with congenital impairment of pain sensation due to hereditary sensory and autonomic neuropathy type II with a rare mutation in the WNK1/HSN2 gene: a case report.

BACKGROUND: Hereditary sensory and autonomic neuropathy (HSAN) type II with WNK1/HSN2 gene mutation is a rare disease characterized by early-onset demyelination sensory loss and skin ulceration. To the best of our knowledge, no cases of an autonomic disorder have been reported clearly in a patient with WNK/HSN2 gene mutation and only one case of a Japanese patient with the WNK/HSN2 gene mutation of HSAN type II was previously reported. CASE PRESENTATION: Here we describe a 54-year-old woman who had an early childhood onset of insensitivity to pain; superficial, vibration, and proprioception sensation disturbances; and several symptoms of autonomic failure (e.g., orthostatic hypotension, fluctuation in body temperature, and lack of urge to defecate). Genetic analyses revealed compound homozygous mutations in the WNK1/HSN2 gene (c.3237_3238insT; p.Asp1080fsX1). The patient demonstrated sensory loss in the "stocking and glove distribution" but could perceive visceral pain, such as menstrual or gastroenteritis pain. She experienced frequent fainting episodes. She had undergone exenteration of the left metatarsal because of metatarsal osteomyelitis at 18 years. Sural nerve biopsy revealed a severe loss of myelinated and unmyelinated nerves. She complained of severe pain in multiple joints, even on having pain impairment. Although non-steroidal anti-inflammatory drugs are generally more effective than acetaminophen for arthritis, in our case, they were ineffective and acetaminophen (2400 mg/day) adequately controlled her pain and improved quality of life. Over 3 months, the numerical rating scale, pain interference scale of the Brief Pain Inventory, and the Pain Catastrophizing Scale decreased from 6/10 to 3/10, from 52/70 to 20/70, and from 22/52 to 3/52 points, respectively. CONCLUSIONS: This is the second reported case of a Japanese patient with WNK/HSN2 gene mutation of HSAN type II and the first reported case of an autonomic disorder in a patient with the WNK/HSN2 gene mutation. Acetaminophen adequately controlled arthropathy related pain in a patient with congenital impairment of pain sensation.

Cardiovascular autonomic neuropathy, erectile dysfunction and lower urinary tract symptoms in men with type 1 diabetes: findings from the DCCT/EDIC.

PURPOSE: We evaluated the association between cardiovascular autonomic neuropathy, and erectile dysfunction and lower urinary tract symptoms in men with type 1 diabetes. MATERIALS AND METHODS: Male type 1 diabetes participants (635) in the DCCT/EDIC were studied. Cardiovascular autonomic neuropathy was assessed by standardized cardiovascular reflex tests including changes in respiratory rate variation with deep breathing, Valsalva maneuver (Valsalva ratio) and changes in supine to standing diastolic blood pressure. Erectile dysfunction was assessed by a proxy item from the International Index of Erectile Function, and lower urinary tract symptoms were assessed with the AUASI (American Urological Association Symptom Index). Multivariable logistic regression models estimated the association between cardiovascular autonomic neuropathy and erectile dysfunction and/or lower urinary tract symptoms, adjusting for time weighted glycemic control, blood pressure, age and other covariates. RESULTS: Men in whom erectile dysfunction and/or lower urinary tract symptoms developed during EDIC had a significantly lower respiratory rate variation and Valsalva ratio at DCCT closeout and EDIC year 16/17 compared to those without erectile dysfunction or lower urinary tract symptoms. In adjusted analysis, participants with cardiovascular autonomic neuropathy had 2.65 greater odds of erectile dysfunction and lower urinary tract symptoms (95% CI 1.47-4.79). CONCLUSIONS: These data suggest that cardiovascular autonomic neuropathy predicts the development of urological complications in men with long-standing type 1 diabetes. Studies evaluating the mechanisms contributing to these interactions are warranted for targeting effective prevention or treatment.

Hereditary sensory and autonomic neuropathy types IV and V in Japan.

Hereditary sensory and autonomic neuropathy (HSAN) is a group of genetic disorders involving varying sensory and autonomic dysfunction. HSAN types IV and V are characterized by congenital generalized loss of pain and thermal sensation. HSAN type IV is additionally accompanied by decreased sweating and intellectual disability. From 2010 to 2013, we (members of the Japanese Research Group on Congenital Insensitivity to Pain) carried out research on HSAN types IV and V. Research by this group included epidemiological data, examination of clinical findings, solutions of disease etiology, investigation of complications and development of their management. Complications were categorized into musculoskeletal complications, oral/dental complications, dermal complications, ocular complications, complications resulting from impaired thermal control, anesthetic considerations, other complications possibly related to autonomic dysfunction, and abnormal mental development and behavior. Treatment and care for patients with HSAN types IV and V require a wide range of knowledge and experience, and a multidisciplinary team approach. Therefore, we produced the "Guideline of Total Management and Care for Congenital Insensitivity to Pain (Ver.1)" in 2012, to provide information for medical specialists based on our knowledge and experience. This guideline includes medical issues, as well as descriptions of social participation and welfare. This review outlines the situation of HSAN types IV and V in Japan, and the recommendations of treatment and care for patients, mostly based on research conducted by the Japanese Research Group.

A Systematic Review of Congenital Insensitivity to Pain, a Rare Disease.

INTRODUCTION: Pain perception, far from being a pathological mechanism, is a crucial protective stimulus to prevent additional injuries. Any disturbance in this complex system poses significant risks to individuals, affecting their quality of life and even their survival. OBJECTIVE: This review aims to explore congenital insensitivity to pain, an extremely rare genetic disorder with an autosomal recessive pattern that results in the inability to perceive pain. We will focus on the well-known subtype, congenital insensitivity to pain with anhidrosis (CIPA). Our research seeks to update existing knowledge through a comprehensive literature review. METHODOLOGY: The review employs a systematic literature review, analyzing various sources and scientific documents, primarily emphasizing CIPA. The review follows the PROSPERO protocol, registered under CRD42023394489. The literature search was performed on the Scopus, PubMed, and Cinahl databases. RESULTS: Our review reveals secondary complications associated with CIPA, such as recurrent bone fractures, temperature insensitivity, self-mutilation, and, occasionally, intellectual disabilities. The limited available information underscores the need for expanding our knowledge. CONCLUSIONS: In summary, CIPA, particularly, presents a significant medical challenge with adverse impacts on quality of life. Early diagnosis, education for families and healthcare professionals, and appropriate nursing care are essential for effective management. This review highlights the necessity of further research and awareness to enhance support for those affected.

A Case of Generalized Xerotic Eczema in a Patient with Congenital Insensitivity to Pain with Anhidrosis.

Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare disease characterized by insensitivity to pain, anhidrosis, and intellectual disability. CIPA is caused by a genetic mutation in the neurotrophic tyrosine receptor kinase 1 (NTRK1) gene on chromosome 1. The anhidrosis leads to cutaneous changes such as skin dryness, lichenification, and impetiginization. Moreover, patients with CIPA may experience repeated trauma and recalcitrant eczema due to excessive scratching of wounds on their skin, because they do not feel any pain. Severe whole-body eczema in a patient with CIPA may be overlooked, leading these patients to be frequently diagnosed with atopic dermatitis and common eczema. Indeed, in patients with treatment-resistant or atypically distributed eczema and underlying anhidrosis, CIPA should be considered as a potential causative disease. Increased awareness of CIPA among dermatologists is necessary to ensure that patients receive an appropriate diagnosis. Herein, we report a rare case of generalized xerotic eczema in a patient with CIPA.

Arthroplasty of a Charcot Knee in a Patient With Congenital Insensitivity to Pain.

Hereditary sensory and autonomic neuropathies (HSANs) include hereditary disorders that cause congenital insensitivity to pain. Moreover, patients diagnosed with such disorders are known to have genetic mutations that alter their deep pain sensation, making them more prone to developing bone and joint complications such as repetitive fractures, joint swelling, and Charcot arthropathy. Neuropathic arthropathy (Charcot joint) is a rare and relatively poorly understood condition; it is suggested to be caused by autonomic dysfunction and repetitive microtrauma and characterized by instability and joint destruction. Diagnosing the idiopathic Charcot joint is challenging and is considered to be a diagnosis of exclusion. In addition, there are limited cases of Charcot knees managed by arthroplasty. Patients with Charcot knees are commonly characterized by profound bone loss, diffuse synovitis, and instability in the knee joint. In this article, we report the case of a 13-year-old patient with known NTRK1 gene mutation who presented with recurrent knee joint swelling episodes and instability without pain. She was diagnosed with Charcot knee joint and underwent right hinged total knee replacement. At one-year follow-up, she continued to have good knee stability and an overall functional gait. Our findings suggest that managing Charcot knee joint with total knee replacement in patients with HSAN may show improvement in terms of stability, swelling, and overall gait.

Pathophysiology of Nociception and Rare Genetic Disorders with Increased Pain Threshold or Pain Insensitivity.

Pain and nociception are different phenomena. Nociception is the result of complex activity in sensory pathways. On the other hand, pain is the effect of interactions between nociceptive processes, and cognition, emotions, as well as the social context of the individual. Alterations in the nociceptive route can have different genesis and affect the entire sensorial process. Genetic problems in nociception, clinically characterized by reduced or absent pain sensitivity, compose an important chapter within pain medicine. This chapter encompasses a wide range of very rare diseases. Several genes have been identified. These genes encode the Nav channels 1.7 and 1.9 (SCN9A, and SCN11A genes, respectively), NGFß and its receptor tyrosine receptor kinase A, as well as the transcription factor PRDM12, and autophagy controllers (TECPR2). Monogenic disorders provoke hereditary sensory and autonomic neuropathies. Their clinical pictures are extremely variable, and a precise classification has yet to be established. Additionally, pain insensitivity is described in diverse numerical and structural chromosomal abnormalities, such as Angelman syndrome, Prader Willy syndrome, Chromosome 15q duplication syndrome, and Chromosome 4 interstitial deletion. Studying these conditions could be a practical strategy to better understand the mechanisms of nociception and investigate potential therapeutic targets against pain.

A Novel de novo KIF1A Mutation in a Patient with Autism, Hyperactivity, Epilepsy, Sensory Disturbance, and Spastic Paraplegia.

Heterozygous mutations in KIF1A have been reported to cause syndromic intellectual disability or pure spastic paraplegia. However, their genotype-phenotype correlations have not been fully elucidated. We herein report a man with autism and hyperactivity along with sensory disturbance and spastic paraplegia, carrying a novel de novo mutation in KIF1A [c.37C>T (p.R13C)]. Autism and hyperactivity have only previously been reported in a patient with c.38 G>A (R13H) mutation. This case suggests that alterations in this arginine at codon 13 might lead to a common clinical spectrum and further expand the genetic and clinical spectra associated with KIF1A mutations.

ATL3, a cargo receptor for reticulophagy.

The endoplasmic reticulum (ER) is the largest membranous organelle, and its turnover ensures cellular homeostasis. The selective macroautophagy/autophagy of the ER (reticulophagy) guarantees the balance of ER turnover. However, the mechanism and physiological relevance of reticulophagy is largely unknown. Recently, we identified ATL3 (atlastin GTPase 3), generally considered to mediate ER fusion, as a receptor for reticulophagy. ATL3 specifically interacts with the GABARAP subfamily proteins of the Atg8-family, and this association is crucial for ATL3's role as a receptor for reticulophagy. Moreover, 2 hereditary sensory and autonomic neuropathies type 1 (HSANI)-associated mutations of ATL3 (Tyr192Cys and Pro338Arg) impair ATL3's binding to GABARAP and function in reticulophagy. Therefore, we illuminate a new function of ATL3 in reticulophagy and the potential physiological relevance of reticulophagy in neurodegenerative diseases.

F-waves persistence in peripheral sensory syndromes / Persistência das ondas-F nas síndromes sensitivas periféricas

Abstract Background The distinction between sensory neuronopathies (SN), which is by definition purely sensory, and sensory polyneuropathies (SP) and sensory multineuropathies (SM) is important for etiologic investigation and prognosis estimation. However, this task is often challenging in clinical practice. We hypothesize that F-wave assessment might be helpful, since it is able to detect subtle signs of motor involvement, which are found in SP and SM, but not in SN. Objective The aim of the present study was to determine whether F-waves are useful to distinguish SN from SP and SM. Methods We selected 21 patients with SP (12 diabetes mellitus, 4 transthyretin familial amyloid polyneuropathy, 4 others), 22 with SM (22 leprosy), and 26 with SN (13 immune-mediated, 10 idiopathic, 3 others) according to clinical-electrophysiological-etiological criteria. For every subject, we collected data on height and performed 20 supramaximal distal stimuli in median, ulnar, peroneal, and tibial nerves, bilaterally, to record F-waves. Latencies (minimum and mean) and persistences were compared across groups using the Kruskal-Wallis and Bonferroni tests. P-values < 0.05 were considered significant. Results All groups were age, gender, and height-matched. Overall, there were no significant between-group differences regarding F-wave latencies. In contrast, F-wave persistence was able to stratify the groups. Peroneal F-wave persistence was higher, bilaterally, in the SN group compared to SM and SP (p < 0.05). In addition, F-waves persistence of the ulnar and tibial nerves was also helpful to separate SN from SP (p < 0.05). Conclusion F-wave persistence of the peroneal nerves might be an additional and useful diagnostic tool to differentiate peripheral sensory syndromes.

Resumo Antecedentes A distinção entre neuronopatias sensitivas (SN) e polineuropatias sensitivas (SP) e multineuropatias sensitivas (SM) é importante para a investigação etiológica e para o prognóstico. Contudo, esta tarefa é desafiadora na prática clínica. Hipotetizou-se que a avaliação das ondas-F pode ser útil, por ser capaz de detectar envolvimento motor nas SP e SM, mas não nas SN. Objetivo Determinar se as ondas-F podem ajudar a distinguir entre SN, SP e SM. Métodos Selecionou-se 21 pacientes com SP (12 diabetes mellitus, 4 ATTR-FAP e 4 com outras neuropatias), 22 com SM (22 hanseníases) e 26 com SN (13 imunomediadas, 10 idiopáticas e 3 com outras neuronopatias), de acordo com critérios clínicos, etiológicos e eletrofisiológicos. Para cada indivíduo, foi aferida a altura e foram aplicados 20 estímulos distais supramáximos nos nervos mediano, ulnar, fibular e tibial, bilateralmente, para registrar as ondas-F. Uma comparação foi feita, por grupo, das latências (mínimas e médias) e persistências pelos testes Kruskal-Wallis e Bonferroni. Valores de p < 0.05 foram considerados estatisticamente significativos. Resultados Todos os grupos foram pareados por idade, sexo e altura. Não houve diferença estatística significativa entre os grupos quanto às latências das ondas-F. A persistência da onda-F foi capaz de estratificar os grupos, sendo as dos nervos fibulares bilateralmente maiores no grupo SN que nos grupos SM e SP (p < 0.05). Adicionalmente, a persistência das ondas-F dos nervos ulnares e tibiais também foi útil para distinguir SN de SP (p < 0.05). Conclusão A persistência das ondas-F dos nervos fibulares pode ser uma ferramenta adicional e útil para diferenciar síndromes sensitivas periféricas.