Cytokines profile in pure neural leprosy.

Introduction: Pure Neural Leprosy (PNL) is a form of this long time known disease that affects only the peripheral nervous system. Since it is a rare form of the disease, its pathophisiology is still poorly understood. Objective: Describe the cytokines profile in patients with PNL. Methods: 30 Patients diagnosed with PNL in the Souza Araujo Outpatient Clinic and with cytokines evaluated were selected. They were evaluated by neurologists and diagnosed after a nerve biopsy. Serum levels of IL-1 ß, IL-6, IL-10, IL-17, TNF, CCL-2/MCP-1, IFN-ϒ, CXCL-10/IP-10 and TGF-ß were evaluates at the moment of the diagnosis. Results: Neural thickening was a common clinical finding in this groups of patients. Small and medium sensitive fibers signs and symptoms were present in 92% of the patients and motor involvement in 53%. 43% of patients presented neuropathic pain and no one had neuritis TGF-beta, IL-17, CCl-2 and IP-10. CCL-2 levels were associated with demyelinating patters and IP-10 and IL-1o were associated with axonal patterns at NCS. Discussion: PNL patients' cytokine profile appears to be different of other clinical forms of leprosy, with the presence of cytokines described in both tuberculoid and lepromatous leprosy. High levels of CCl-2 may be related to the presence of silent neuritis as well as the presence of IL-10. PNL is unique a form of leprosy, therefore, understanding its immunological profiles essential to better understand the disease itself.

Case report: Injected corticosteroids for treating leprosy isolated neuritis.

One of the main manifestations of leprosy is peripheral nerve impairment. Early diagnosis and treatment are important to reduce the impact of neurological impairment, which can cause deformities and physical disabilities. Leprosy neuropathy can be acute or chronic, and neural involvement can occur before, during, or after multidrug therapy, and especially during reactional episodes when neuritis occurs. Neuritis causes loss of function in the nerves and can be irreversible if left untreated. The recommended treatment is corticosteroids, usually through an oral regimen at an immunosuppressive dose. However, patients with clinical conditions that restrict corticosteroid use or that have focal neural involvement may benefit from the use of ultrasound-guided perineural injectable corticosteroids. In this study, we report two cases that demonstrate how the treatment and follow-up of patients with neuritis secondary to leprosy, using new techniques, can be provided in a more individualized way. Nerve conduction studies in association with neuromuscular ultrasound were used to monitor the response to treatment with injected steroids, focusing on neural inflammation. This study provides new perspectives and options for this profile of patients.

Evidencing leprosy neuronal inflammation by 18-Fluoro-deoxy-glucose.

BACKGROUND: Leprosy is caused by multiple interactions between Mycobacterium leprae (M. leprae) and the host's peripheral nerve cells. M. leprae primarily invades Schwann cells, causing nerve damage and consequent development of disabilities. Despite its long history, the pathophysiological mechanisms of nerve damage in the lepromatous pole of leprosy remain poorly understood. This study used the findings of 18F-FDG PET/CT on the peripheral nerves of eight lepromatous patients to evaluate the degree of glucose uptake by peripheral nerves and compared them with clinical, electrophysiological, and histopathological evaluations. METHODS: Eight patients with lepromatous leprosy were included in this study. Six patients were evaluated up to three months after leprosy diagnosis using neurological examination, nerve conduction study, 18F-FDG PET/CT, and nerve biopsy. Two others were evaluated during an episode of acute neuritis, with clinical, neurophysiological, and PET-CT examinations to compare the images with the first six. RESULTS: Initially, six patients already had signs of peripheral nerve injury, regardless of symptoms; however, they did not present with signs of neuritis, and there was little or no uptake of 18F-FDG in the clinically and electrophysiologically affected nerves. Two patients with signs of acute neuritis had 18F-FDG uptake in the affected nerves. CONCLUSIONS: 18F-FDG uptake correlates with clinical neuritis in lepromatous leprosy patients but not in silent neuritis patients. 18F-FDG PET-CT could be a useful tool to confirm neuritis, especially in cases that are difficult to diagnose, such as for the differential diagnosis between a new episode of neuritis and chronic neuropathy.

Progressive neuropathy in patients with lepromatous leprosy after multidrug therapy.

BACKGROUND: The lepromatous pole is a stigmatising prototype for patients with leprosy. Generally, these patients have little or no symptoms of peripheral nerve involvement at the time of their diagnosis. However, signs of advanced peripheral neuropathy would be visible during the initial neurological evaluation and could worsen during and after multidrug therapy (MDT). Disabilities caused by peripheral nerve injuries greatly affect these patients' lives, and the pathophysiological mechanisms underlying nerve damage remain unclear. OBJECTIVES: To evaluate the outcome of peripheral neuropathy in patients with lepromatous leprosy (LL) and persistent neuropathic symptoms years after completing MDT. METHODS: We evaluated the medical records of 14 patients with LL who underwent nerve biopsies due to worsening neuropathy at least four years after MDT. FINDINGS: Neuropathic pain developed in 64.3% of the patients, and a neurological examination showed that most patients had alterations in the medium- and large-caliber fibers at the beginning of treatment. Neurological symptoms and signs deteriorated despite complete MDT and prednisone or thalidomide use for years. Nerve conduction studies showed that sensory nerves were the most affected. MAIN CONCLUSIONS: Patients with LL can develop progressive peripheral neuropathy, which continues to develop even when they are on long-term anti-inflammatory and immunosuppressive therapy.

Gene Expression Profile of Mycobacterium leprae Contribution in the Pathology of Leprosy Neuropathy.

Peripheral neuropathy is the main cause of physical disability in leprosy patients. Importantly, the extension and pattern of peripheral damage has been linked to how the host cell will respond against Mycobacterium leprae (M. leprae) infection, in particular, how the pathogen will establish infection in Schwann cells. Interestingly, viable and dead M. leprae have been linked to neuropathology of leprosy by distinct mechanisms. While viable M. leprae promotes transcriptional modifications that allow the bacteria to survive through the use of the host cell's internal machinery and the subvert of host metabolites, components of the dead bacteria are associated with the generation of a harmful nerve microenvironment. Therefore, understanding the pathognomonic characteristics mediated by viable and dead M. leprae are essential for elucidating leprosy disease and its associated reactional episodes. Moreover, the impact of the viable and dead bacteria in Schwann cells is largely unknown and their gene signature profiling has, as yet, been poorly explored. In this study, we analyzed the early differences in the expression profile of genes involved in peripheral neuropathy, dedifferentiation and plasticity, neural regeneration, and inflammation in human Schwann cells challenged with viable and dead M. leprae. We substantiated our findings by analyzing this genetic profiling in human nerve biopsies of leprosy and non-leprosy patients, with accompanied histopathological analysis. We observed that viable and dead bacteria distinctly modulate Schwann cell genes, with emphasis to viable bacilli upregulating transcripts related to glial cell plasticity, dedifferentiation and anti-inflammatory profile, while dead bacteria affected genes involved in neuropathy and pro-inflammatory response. In addition, dead bacteria also upregulated genes associated with nerve support, which expression profile was similar to those obtained from leprosy nerve biopsies. These findings suggest that early exposure to viable and dead bacteria may provoke Schwann cells to behave differentially, with far-reaching implications for the ongoing neuropathy seen in leprosy patients, where a mixture of active and non-active bacteria are found in the nerve microenvironment.

Correlation Between Single-Pulse and Pulse-Train Stimulation During Neuromonitoring of Thoracic Pedicle Screws in Scoliosis Surgery.

BACKGROUND: The use of thoracic pedicle screws (TPSs) during scoliosis surgery entails an inherent risk of neurological deficit. Triggered electromyography (t-EMG) is an accurate neuromonitoring test for detection of malpositioned TPSs. However, single-pulse (SP) t-EMG stimulation has shown variable capability for detecting medial pedicle breaches, while pulse-train (PT) t-EMG could be more accurate. The aim of this study was to analyze the correlation between SP t-EMG and PT t-EMG. METHODS: This retrospective study included 20 patients who underwent scoliosis correction with 294 TPSs placed. A total of 588 tests with both SP t-EMG and PT t-EMG were performed, analyzed, and compared. The results of both t-EMG techniques were stratified into 3 different groups according to threshold obtained: group 1 (≤6 mA), group 2 (6.1-11.9 mA), and group 3 (12 mA). A generalized linear model was used to analyze the correlation between the methods. RESULTS: SP t-EMG elicited response in 5 screws (1.7%) at ≤6 mA, 28 screws (9.5%) at 6.1-11.9 mA, and 261 screws (88.8%) at 12 mA. PT t-EMG elicited response in 16 screws (5.4%) at ≤6 mA, 30 screws (10.2%) at 6.1-11.9mA, and 248 screws (84.4%) at 12 mA. There is a strong positive and significant association between SP t-EMG and PT t-EMG with a decrease ratio of 2% (95% confidence interval 1% to 3%). CONCLUSIONS: SP t-EMG and PT t-EMG stimulation techniques had similar results when the stimuli were applied to TPSs, but PT t-EMG may have better efficacy in low-threshold group.

Leprosy Reactions and Neuropathic Pain in Pure Neural Leprosy in a Reference Center in Rio de Janeiro - Brazil.

Introduction: Leprosy reactions are complications that can occur before, during, or after multidrug therapy (MDT) and are considered a major cause of nerve damage. Neuritis is an inflammatory process that causes nerve function impairment associated with pain and tenderness along the nerve. Neuritis can be found in both type 1 and type 2 reactions and may also be the sole manifestation of a leprosy reaction. The objective of this study is to describe the incidence of leprosy reactions and its association with neuropathic pain in pure neural leprosy (PNL) patients. Methods: We selected 52 patients diagnosed with PNL and 67 patients with other clinical forms of leprosy. During the MDT the patients visited the clinic monthly to take their supervised dose. The patients were instructed to return immediately if any new neurological deficit or skin lesions occurred during or after the MDT. Results: Of the PNL patients, 23.1% had a leprosy reaction during or after the MDT, while this was 59.7% for patients with the other clinical forms of leprosy. There was an association between having PNL and not having any reaction during and after the MDT, as well as having PNL and having neuritis after the MDT.There was also an association between having previous neuritis and having neuropathic pain in the other clinical forms of leprosy group, although this association was not present in the PNL group. Discussion: Our data suggest that PNL is a different form of the disease, which is immunologically more stable. In addition, PNL patients have more neuritis than the classical leprosy skin reactions. In PNL there was no association between acute neuritis and neuropathic pain, suggesting that these patients may have had silent neuritis. Understanding and identifying neuritis is essential to reduce disability and the impact on public health.

Ultrasonography as a diagnostic tool for Neural Pain in Leprosy.

Leprosy is still a prevalent disease in Brazil, representing 93% of all occurrences in the Americas. Leprosy neuropathy is one of the most worrying manifestations of the disease. Acute neuropathy usually occurs during reaction episodes and is called neuritis. Twenty-two leprosy patients were included in this study. These patients had neural pain associated with ulnar sensory neuropathy, with or without adjunct motor involvement. The neurological picture began within thirty days of the clinical evaluation. The patients underwent a nerve conduction study and the demyelinating findings confirmed the diagnosis of neuritis. Ultrasonographic study (US) of the ulnar nerve was performed in all patients by a radiologist who was blinded to the clinical or neurophysiological results. Morphological characteristics of the ulnar nerve were analyzed, such as echogenicity, fascicular pattern, transverse cross-sectional area (CSA), aspect of the epineurium, as well as their anatomical relationships. The volume of selected muscles referring to the ulnar nerve, as well as their echogenicity, was also examined. Based on this analysis, patients with increased ulnar nerve CSA associated with loss of fascicular pattern, epineurium hyperechogenicity and presence of power Doppler flow were classified as neuritis. Therefore, patients initially classified by the clinical-electrophysiological criteria were reclassified by the imaging criteria pre-established in this study as with and without neuritis. Loss of fascicular pattern and flow detection on power Doppler showed to be significant morphological features in the detection of neuritis. In 38.5% of patients without clinical or neurophysiological findings of neuritis, US identified power Doppler flow and loss of fascicular pattern. The US is a method of high resolution and portability, and its low cost means that it could be used as an auxiliary tool in the diagnosis of neuritis and its treatment, especially in basic health units.

Kynurenines in the Pathogenesis of Peripheral Neuropathy During Leprosy and COVID-19.

Inflammatory disorders are associated with the activation of tryptophan (TRYP) catabolism via the kynurenine pathway (KP). Several reports have demonstrated the role of KP in the immunopathophysiology of both leprosy and coronavirus disease 19 (COVID-19). The nervous system can be affected in infections caused by both Mycobacterium leprae and SARS-CoV-2, but the mechanisms involved in the peripheral neural damage induced by these infectious agents are not fully understood. In recent years KP has received greater attention due the importance of kynurenine metabolites in infectious diseases, immune dysfunction and nervous system disorders. In this review, we discuss how modulation of the KP may aid in controlling the damage to peripheral nerves and the effects of KP activation on neural damage during leprosy or COVID-19 individually and we speculate its role during co-infection.

Follow-up assessment of patients with Pure Neural Leprosy in a reference center in Rio de Janeiro-Brazil.

INTRODUCTION: Pure Neural Leprosy (PNL) is a rare clinical form of leprosy in which patients do not present with the classical skin lesions but have a high burden of the disability associated with the disease. Clinical characteristics and follow up of patients in PNL are still poorly described in the literature. OBJECTIVE: This paper aims to describe the clinical, electrophysiological and histopathological characteristics of PNL patients, as well as their evolution after multidrug therapy (MDT). METHODS: Fifty-two PNL patients were selected. Clinical, nerve conduction studies (NCS), histopathological and anti-PGL-1serology were evaluated. Patients were also assessed monthly during the MDT. At the end of the MDT, all of the patients had a new neurological examination and 44 were submitted to another NCS. RESULTS: Paresthesia was the complaint most frequently reported by patients, and in the neurological examination the most common pattern observed was impairment in sensory and motor examination and a mononeuropathy multiplex. Painful nerve enlargement, a classical symptom of leprosy neuropathy, was observed in a minority of patients and in the motor NCS axonal injuries, alone or in combination with demyelinating features, were the most commonly observed. 88% of the patients did not present any leprosy reaction during MDT. There was no statistically significant difference between the neurological examinations, nor the NCS pattern, performed before and after the MDT. DISCUSSION: The classical hallmarks of leprosy neuropathy are not always present in PNL making the diagnosis even more challenging. Nerve biopsy is an important tool for PNL diagnosis as it may guide therapeutic decisions. This paper highlights unique characteristics of PNL in the spectrum of leprosy in an attempt to facilitate the diagnosis and management of these patients.

Progressive neuropathy in patients with lepromatous leprosy after multidrug therapy

BACKGROUND The lepromatous pole is a stigmatising prototype for patients with leprosy. Generally, these patients have little or no symptoms of peripheral nerve involvement at the time of their diagnosis. However, signs of advanced peripheral neuropathy would be visible during the initial neurological evaluation and could worsen during and after multidrug therapy (MDT). Disabilities caused by peripheral nerve injuries greatly affect these patients' lives, and the pathophysiological mechanisms underlying nerve damage remain unclear. OBJECTIVES To evaluate the outcome of peripheral neuropathy in patients with lepromatous leprosy (LL) and persistent neuropathic symptoms years after completing MDT. METHODS We evaluated the medical records of 14 patients with LL who underwent nerve biopsies due to worsening neuropathy at least four years after MDT. FINDINGS Neuropathic pain developed in 64.3% of the patients, and a neurological examination showed that most patients had alterations in the medium- and large-caliber fibers at the beginning of treatment. Neurological symptoms and signs deteriorated despite complete MDT and prednisone or thalidomide use for years. Nerve conduction studies showed that sensory nerves were the most affected. MAIN CONCLUSIONS Patients with LL can develop progressive peripheral neuropathy, which continues to develop even when they are on long-term anti-inflammatory and immunosuppressive therapy.

Gene expression profile of Mycobacterium leprae contribution in the pathology of leprosy neuropathy

Peripheral neuropathy is the main cause of physical disability in leprosy patients.Importantly, the extension and pattern of peripheral damage has been linked to how the host cell will respond against Mycobacterium leprae (M. leprae) infection, in particular, how the pathogen will establish infection in Schwann cells. Interestingly, viable and dead M. leprae have been linked to neuropathology of leprosy by distinct mechanisms. While viable M. leprae promotes transcriptional modifications that allow the bacteria to survive through the use of the host cell's internal machinery and the subvert of host metabolites, components of the dead bacteria are associated with the generation of a harmful nerve microenvironment. Therefore, understanding the pathognomonic characteristics mediated by viable and dead M. leprae are essential for elucidating leprosy disease and its associated reactional episodes. Moreover, the impact of the viable and dead bacteria in Schwann cells is largely unknown and their gene signature profiling has, as yet, been poorly explored. In this study, we analyzed the early differences in the expression profile of genes involved in peripheral neuropathy, dedifferentiation and plasticity, neural regeneration, and inflammation in human Schwann cells challenged with viable and dead M. leprae. We substantiated our findings by analyzing this genetic profiling in human nerve biopsies of leprosy and non-leprosy patients, with accompanied histopathological analysis. We observed that viable and dead bacteria distinctly modulate Schwann cell genes, with emphasis to viable bacilli upregulating transcripts related to glial cell plasticity, dedifferentiation and anti-inflammatory profile, while dead bacteria affected genes involved in neuropathy and pro-inflammatory response. In addition, dead bacteria also upregulated genes associated with nerve support, which expression profile was similar to those obtained from leprosy nerve biopsies. These findings suggest that early exposure to viable and dead bacteria may provoke Schwann cells to behave differentially, with far-reaching implications for the ongoing neuropathy seen in leprosy patients, where a mixture of active and non-active bacteria are found in the nerve microenvironment.

The red flags of ulnar neuropathy in leprosy.

The diagnosis of pure neural leprosy is more challenging because patients share characteristics with other common pathologies, such as ulnar compression, which should be taken into consideration for differential diagnosis. In this study, we identify ulnar nerve conduction characteristics to aid in the differential diagnosis of ulnar neuropathy (UN) in leprosy and that of non-leprosy etiology. In addition, we include putative markers to better understand the inflammatory process that may occur in the nerve. Data were extracted from a database of people affected by leprosy (leprosy group) diagnosed with UN at leprosy diagnosis. A non-leprosy group of patients diagnosed with mechanical neuropathy (compressive, traumatic) was also included. Both groups were submitted to clinical, neurological, neurophysiological and immunological studies. Nerve enlargement and sensory impairment were significantly higher in leprosy patients than in patients with compressive UN. Bilateral impairment was significantly higher in the leprosy group than in the non-leprosy group. Leprosy reactions were associated to focal demyelinating lesions at the elbow and to temporal dispersion (TD). Clinical signs such as sensory impairment, nerve enlargement and bilateral ulnar nerve injury associated with eletrodiagnostic criteria such as demyelinating finds, specifically temporal dispersion, could be tools to help us decided on the best conduct in patients with elbow ulnar neuropathy and specifically decide if we should perform a nerve biopsy for diagnosis of pure neural leprosy.

Serosurvey of antibodies against zoonotic pathogens in free-ranging wild canids (Cerdocyon thous and Lycalopex gymnocercus) from Southern Brazil.

The expansion of urbanization on natural areas is increasing contact between human populations with wild animals. Wild carnivores can act as sentinel hosts or environmental health indicators. Thus, the aim of this work was to investigate the exposure of two major species of wild canids from Southern Brazil to selected pathogens. For that, we live-trapped free-ranging Cerdocyon thous and Lycalopex gymnocercus in five localities and determined the frequency of animals with antibodies against Toxoplasma gondii, Trypanosoma cruzi, Leishmania infantum, Neospora caninum, and Leptospira spp. Among the canids sampled, 23% (12/52) (95%CI: 13-36%) had antibodies against T. gondii, with titers ranging from 64 to 512. For T. cruzi, 28% (15/52) (95%CI: 18-42%) of sampled canids were seropositive, with titers ranging from 8 to 64. Concerning the protozoan pathogen N. caninum, a total of 5% (3/52) (95%CI: 2-15%) of wild canids had antibodies against it. None of the sampled canids showed the presence of antibodies against L. infantum. On the other hand, 44% (23/52) (95%CI: 31-57%) of the wild canids showed antibodies against Leptospira spp. The set of results presented here, show that free-ranging neotropical wild canids are exposed and have antibodies against to T. gondii, T. cruzi, Leptospira spp., and to a lesser degree to N. caninum. We found no evidence of L. infantum circulation among the studied populations. These results highlight some of the major pathogens which may represent risks for populations of these wild canids. DATA AVAILABILITY STATEMENT: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Clinical prediction rules for the diagnosis of neuritis in leprosy.

BACKGROUND: Diagnosing neuritis in leprosy patients with neuropathic pain or chronic neuropathy remains challenging since no specific laboratory or neurophysiological marker is available. METHODS: In a cross-sectional study developed at a leprosy outpatient clinic in Rio de Janeiro, RJ, Brazil, 54 individuals complaining of neural pain (single or multiple sites) were classified into two groups ("neuropathic pain" or "neuritis") by a neurological specialist in leprosy based on anamnesis together with clinical and electrophysiological examinations. A neurologist, blind to the pain diagnoses, interviewed and examined the participants using a standardized form that included clinical predictors, pain features, and neurological symptoms. The association between the clinical predictors and pain classifications was evaluated via the Pearson Chi-Square or Fisher's exact test (p < 0.05). RESULTS: Six clinical algorithms were generated to evaluate sensitivity and specificity, with 95% confidence intervals, for clinical predictors statistically associated with neuritis. The most conclusive clinical algorithm was: pain onset at any time during the previous 90 days, or in association with the initiation of neurological symptoms during the prior 30-day period, necessarily associated with the worsening of pain upon movement and nerve palpation, with 94% of specificity and 35% of sensitivity. CONCLUSION: This algorithm could help physicians confirm neuritis in leprosy patients with neural pain, particularly in primary health care units with no access to neurologists or electrophysiological tests.

Morphometric analysis of nerve fibers in neural leprosy.

BACKGROUND: The present study assesses the contributions of axonal degeneration and demyelination in leprosy nerve damage. New clinical strategies can emerge from an in-depth understanding of the pathogenesis of neural leprosy (NL). METHODS: Morphometric analysis of myelinated nerve fibers was performed on 44 nerve biopsy samples collected from leprosy patients. Measures of density, diameter distribution, g-ratios, and the counting of axonal ovoids on the myelinated fibers were taken and compared to those in the control group. RESULTS: The proportion of small myelinated fibers increased in the leprosy group while large fiber frequency decreased. Indicative of axonal atrophy, the g-ratio was lower in the leprosy group. The frequency of axonal ovoids was identical to that found in the non-leprosy neuropathies. CONCLUSIONS: Axonal atrophy, Wallerian degeneration, and demyelination coexist in NL. Axonal degeneration predominates over demyelination in the chronic course of the disease; however, this may change during leprosy reactive episodes. This study regards demyelination and axon degeneration as concurrent mechanisms of damage to nerve fibers in leprosy. It also calls into question the view that demyelination is the primary and predominant mechanism in the complex pathogeny of NL.

Detection of Bartonella sp. and a novel spotted fever group Rickettsia sp. in Neotropical fleas of wild rodents (Cricetidae) from Southern Brazil.

The Neotropical region shows a great diversity of fleas, comprising more than 50 genera. The importance of the study of fleas is linked to their potential role as disease vectors. The aim of this study is to investigate the presence of Rickettsia spp. and Bartonella spp. in Neotropical fleas collected from wild rodents in Southern Brazil. From 350 rodents captured, 30 were parasitized by fleas. A total of 61 fleas belonging to two genera and six different species were collected (Craneopsylla minerva minerva, Polygenis occidentalis occidentalis, Polygenis platensis, Polygenis pradoi, Polygenis rimatus, and Polygenis roberti roberti). In 13 % of fleas of three different species (C. minerva, P. platensis, and P. pradoi) Rickettsia sp. DNA was found. Phylogenetic analysis of concatenated sequences of gltA, htrA, and ompA genes showed that Rickettsia sp. found in rodent fleas (referred as strain Taim) grouped together with Spotted Fever Group Rickettsia. In reference to Bartonella spp., five genotypes were identified in seven fleas of two species (C. minerva and P. platensis) and in five rodent spleens. Also, 207 frozen samples of wild rodents were screened for these pathogens: while none was positive for Rickettsia spp.; five rodent spleens were PCR-positive for Bartonella spp.. Herein, we show the detection of potential novel variants of Bartonella sp. and Rickettsia sp. in fleas collected of wild rodents from Southern Brazil. Further studies are needed to fully characterize these microorganisms, as well as to improve the knowledge on the potential role of Neotropical flea species as diseases vectors.

Evidence and practices of the use of next generation sequencing in patients with undiagnosed autosomal dominant cerebellar ataxias: a review / Evidências e práticas do uso do sequenciamento de nova geração em pacientes com ataxias cerebelares autossômicas dominantes não diagnosticadas: uma revisão

ABSTRACT Autosomal dominant cerebellar ataxias (ADCA) are heterogeneous diseases with a highly variable phenotype and genotype. They can be divided into episodic ataxia and spinocerebellar ataxia (SCA); the latter is considered the prototype of the ADCA. Most of the ADCA are caused by polyglutamine expansions, mainly SCA 1, 2, 3, 6, 7, 17 and Dentatorubral-pallidoluysian atrophy (DRPLA). However, 30% of patients remain undiagnosed after testing for these most common SCA. Recently, several studies have demonstrated that the new generation of sequencing methods are useful for the diagnose of these patients. This review focus on searching evidence on the literature, its usefulness in clinical practice and future perspectives.

RESUMO As ataxias cerebelares autossômicas dominantes (ACAD) são doenças heterogêneas com fenótipo e genótipo altamente variáveis. Podem ser divididas em ataxia episódica e ataxia espinocerebelar (SCA), sendo este último considerado o protótipo do ACAD. A maior parte das ACAD são causadas por expansões de poliglutaminas, principalmente SCA 1, 2, 3, 6, 7, 17 e atrofia dentatorubro-palidoluisiana (DRPLA). No entanto, 30% dos pacientes permanecem sem diagnóstico após o teste para essas SCA mais comuns. Recentemente, vários estudos têm demonstrado que a nova geração de métodos de sequenciamento são ferramentas úteis para o diagnóstico desses pacientes. Esta é uma revisão sistemática da literatura, com foco em sua utilidade na prática clínica e em perspectivas futuras.