RESUMO
Patients with adult Refsum Disease (ARD) have retinitis pigmentosa and thus nyctalopia, anosmia, sensorineural deafness, polyneuropathy, and ataxia. Upon physical examination, patients with ARD have congenital short metacarpals, metatarsals, and cardiac arrhythmias. Manifestations due to the lack of phytanoyl-CoA hydroxylase in peroxisomes needed for alpha-oxidation of phytanic acid lead patients to accumulate phytanic acid in their body tissues. To our knowledge, no consensus for clinical diagnostic criteria for patients with ARD has been published. Our patient had nyctalopia, retinal findings, and visual field results compatible with retinitis pigmentosa. Additionally, the patient had decreased macular thickness and volume in both eyes, the findings being worse in the left eye. The patient had undergone hand surgery due to chronic pain in both hands, as well as his fourth and fifth metatarsal bones were shortened. Interestingly, audiology evaluation showed mild hearing loss in the right ear and mild to moderate hearing loss in the left ear. Inheritance patterns in patients with ARD have been described. Physical examination, phytanic acid evaluation, and genetic studies may all help reach an ARD diagnosis. This is the first report of adult Refsum disease in Puerto Rico.
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BACKGROUND: The present study aimed to assess the gait capacity of youths with Charcot Marie Tooth disease (CMT), considering the different foot postures as a grouping variable. METHODS: The total distance, the predicted distance, and gait velocity obtained during the six-minute walking test (6MWT) were compared between participants with and without CMT. In addition, part of the CMT group completed a 12-month follow-up. The study evaluated 63 participants (CMT group = 31; Non-CMT group = 32) aged 6 to 18, both sexes. Data included anthropometric measures, foot posture index (FPI), the distance (D6), percentage of predicted distance (%D6), and walking velocity(V) in 6MWT. RESULTS: The D6% presented no significant difference between the types of feet in CMT or Non-CMT (p < 0.05, Kruskal Wallis test). CMT presented reduced values of D6, %D6, and V when compared to Non-CMT. CONCLUSIONS: These findings indicate that gait performance was decreased in youths with CMT in comparison to non-CMT. Contrary to what was expected, the cavus foot type did not show lower gait capacity than the flatfoot, suggesting that the types of feet alone did not determine differences in gait capacity within the CMT group.
Assuntos
Doença de Charcot-Marie-Tooth , Adolescente , Feminino , Pé , Marcha , Humanos , Masculino , Teste de Caminhada , CaminhadaRESUMO
Abstract Background: Charcot-Marie-Tooth disease type 2Q (CMT2Q) is a rare disorder (< 1/1,000,000 individuals worldwide) linked to chromosome 10p14 in the DHTKD1 gene. This phenotype is characterized by an adolescent or adulthood-onset, slowly progressive distal muscle weakness and symmetrical atrophy associated with reduced or absent deep tendon reflexes. Currently, only two familiar cases from China have been reported: one familiar case of eight individuals affected by isolated DHTKD1 gene mutation and one familiar case of two individuals affected by DHTKD1 gene mutation and GJB1 gene mutation. Case report: We present the case of a 10-year-old male patient with obesity, frequent falls, swollen legs and thighs, and pain in the lower and upper limbs. We performed the clinical evaluation and a clinical targeted exome test, which reported mutations on DHTKD1 y NTRK2 genes. Conclusions: Due to scientific and technological advances, genetic dysfunctions that can cause different diseases have been identified with greater sensitivity. Globally, this is the eleventh case reported of DHTKD1 gene mutation linked to CMT2Q. Moreover, this is the first case related to NTRK2 gene mutation (linked to obesity, hyperphagia, and delayed development). The patient showed an atypical CMT2Q phenotype additional to obesity. Therefore, we propose to study metabolic disorders linked to hereditary peripheral neuropathies.
Resumen Introducción: La enfermedad de Charcot-Marie-Tooth tipo 2Q (CMT2Q) es una alteración poco frecuente (< 1/1,000,000 habitantes en todo el mundo) condicionada por mutaciones en el gen DHTKD1, localizado en el cromosoma 10p14. El padecimiento inicia en la adolescencia o la edad adulta de manera lenta y progresiva, con debilidad muscular y atrofia distal simétrica, y afecta predominantemente las extremidades inferiores y los reflejos tendinosos profundos, que se encuentran reducidos o ausentes. Solo se ha reportado un caso familiar de ocho personas afectadas con la mutación aislada en el gen DHTKD1 y un caso familiar de dos personas afectadas con mutaciones en los genes DHTKD1 y GJB1, ambas familias de China. Caso clínico: Se presenta el caso de un paciente de sexo masculino de 10 años y 11 meses de edad con obesidad, caídas frecuentes, edema de miembros pélvicos y dolor en las extremidades inferiores y superiores. Se realizaron valoración clínica y estudio genético molecular de exoma dirigido, el cual reportó mutaciones en los genes DHTKD1 y NTRK2. Conclusiones: Gracias al avance científico y tecnológico se han podido identificar con mayor precisión las alteraciones genéticas causantes de diferentes enfermedades. Este es el undécimo caso reportado en el mundo de una mutación en el gen DHTKD1 asociada con la enfermedad de CMT2Q. También es el primer caso relacionado con una mutación del gen NTRK2 (asociada con obesidad, hiperfagia y retraso en el desarrollo). El paciente presentó un cuadro clínico atípico de enfermedad de CMT2Q agregado a obesidad. Por ello, se sugiere estudiar a fondo la conexión entre trastornos metabólicos y neuropatías periféricas hereditarias.
RESUMO
Background: Charcot-Marie-Tooth disease type 2Q (CMT2Q) is a rare disorder (< 1/1,000,000 individuals worldwide) linked to chromosome 10p14 in the DHTKD1 gene. This phenotype is characterized by an adolescent or adulthood-onset, slowly progressive distal muscle weakness and symmetrical atrophy associated with reduced or absent deep tendon reflexes. Currently, only two familiar cases from China have been reported: one familiar case of eight individuals affected by isolated DHTKD1 gene mutation and one familiar case of two individuals affected by DHTKD1 gene mutation and GJB1 gene mutation. Case report: We present the case of a 10-year-old male patient with obesity, frequent falls, swollen legs and thighs, and pain in the lower and upper limbs. We performed the clinical evaluation and a clinical targeted exome test, which reported mutations on DHTKD1 y NTRK2 genes. Conclusions: Due to scientific and technological advances, genetic dysfunctions that can cause different diseases have been identified with greater sensitivity. Globally, this is the eleventh case reported of DHTKD1 gene mutation linked to CMT2Q. Moreover, this is the first case related to NTRK2 gene mutation (linked to obesity, hyperphagia, and delayed development). The patient showed an atypical CMT2Q phenotype additional to obesity. Therefore, we propose to study metabolic disorders linked to hereditary peripheral neuropathies.
Introducción: La enfermedad de Charcot-Marie-Tooth tipo 2Q (CMT2Q) es una alteración poco frecuente (< 1/1,000,000 habitantes en todo el mundo) condicionada por mutaciones en el gen DHTKD1, localizado en el cromosoma 10p14. El padecimiento inicia en la adolescencia o la edad adulta de manera lenta y progresiva, con debilidad muscular y atrofia distal simétrica, y afecta predominantemente las extremidades inferiores y los reflejos tendinosos profundos, que se encuentran reducidos o ausentes. Solo se ha reportado un caso familiar de ocho personas afectadas con la mutación aislada en el gen DHTKD1 y un caso familiar de dos personas afectadas con mutaciones en los genes DHTKD1 y GJB1, ambas familias de China. Caso clínico: Se presenta el caso de un paciente de sexo masculino de 10 años y 11 meses de edad con obesidad, caídas frecuentes, edema de miembros pélvicos y dolor en las extremidades inferiores y superiores. Se realizaron valoración clínica y estudio genético molecular de exoma dirigido, el cual reportó mutaciones en los genes DHTKD1 y NTRK2. Conclusiones: Gracias al avance científico y tecnológico se han podido identificar con mayor precisión las alteraciones genéticas causantes de diferentes enfermedades. Este es el undécimo caso reportado en el mundo de una mutación en el gen DHTKD1 asociada con la enfermedad de CMT2Q. También es el primer caso relacionado con una mutación del gen NTRK2 (asociada con obesidad, hiperfagia y retraso en el desarrollo). El paciente presentó un cuadro clínico atípico de enfermedad de CMT2Q agregado a obesidad. Por ello, se sugiere estudiar a fondo la conexión entre trastornos metabólicos y neuropatías periféricas hereditarias.
Assuntos
Doença de Charcot-Marie-Tooth , Cetona Oxirredutases , Adolescente , Adulto , Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/genética , Criança , China , Humanos , Complexo Cetoglutarato Desidrogenase , Cetona Oxirredutases/genética , Masculino , Glicoproteínas de Membrana , Mutação , Fenótipo , Receptor trkBRESUMO
This study aimed to describe the clinical, genetic, and epidemiological features of Charcot-Marie-Tooth disease (CMT) in Brazilian patients from a tertiary center, and to compare our data with previously published findings. This retrospective observational study conducted between February 2015 and July 2020 evaluated 503 patients (94 families and 192 unrelated individuals), diagnosed with CMT. Clinical and neurophysiological data were obtained from electronic medical records and blood samples were used for genetic analyses. Multiplex ligation-dependent probe amplification was used to assess duplications/deletions in PMP22. Sanger sequencing of GJB1 was performed in cases of suspected demyelinating CMT. Targeted gene panel sequencing was used for the remaining negative demyelinating cases and all axonal CMT cases. The first decade of life was the most common period of disease onset. In all, 353 patients had demyelinating CMT, 39 had intermediate CMT, and 111 had axonal CMT. Pathogenic or likely pathogenic variants were identified in 197 index cases. The most common causative genes among probands were PMP22 (duplication) (n = 116, 58.88%), GJB1 (n = 23, 11.67%), MFN2 (n = 12, 6.09%), GDAP1 (n = 7, 3.55%), MPZ (n = 6, 3.05%), PMP22 (point mutation) (n = 6, 3.05%), NEFL (n = 3, 1.52%), SBF2 (n = 3, 1.52%), and SH3TC2 (n = 3, 1.52%). Other identified variants were ≤1% of index cases. This study provides further data on the frequency of CMT subtypes in a Brazilian clinical-based population and highlights the importance of rarer and previously undiagnosed variants in clinical practice.
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Doença de Charcot-Marie-Tooth , Doença de Charcot-Marie-Tooth/epidemiologia , Doença de Charcot-Marie-Tooth/genética , Perfil Genético , Testes Genéticos , Humanos , Reação em Cadeia da Polimerase Multiplex , Mutação/genética , Proteínas/genética , Estudos RetrospectivosRESUMO
Hereditary sensory neuropathies (HSN) are a group of rare neurological disorders with heterogeneous clinical and genetic characteristics. Although at least 17 different genes have already been associated with HSN, the epidemiology of the disorder in Brazil is still unknown. Performing whole genome sequencing (WGS) in 23 unrelated Brazilian families diagnosed with HSN, we detected pathogenic variants in ATL3, SPTLC2, and SCN9A in 12 patients belonging to five unrelated families. Clinical features associated with heterozygous mutations in ATL3 (c.575A > G; p.(Tyr192Cys)) and SPTLC2 (c.529A > G; p.(Asn177Asp)) were sensory deficits, neuropathic pain, and recurrent ulcerations. Presenting as congenital insensitivity to pain, three unrelated probands carried biallelic loss-of-function mutations in SCN9A. The so far undescribed stop mutation c.2106G > A (p.(Trp702Ter)) and the likewise novel splicing variant c.3319-1G > A were found in compound-heterozygosity with, respectively, the known pathogenic variants c.2908G > T (p.Trp970Ter) and c.2690G > A (p.Glu897Ter). In total, we identified pathogenic mutations in 21.7% of our families, which suggests that most of the cases could be explained by yet to be discovered genes or unusual alleles. Our study represents the first mutational screen in a Brazilian HSN cohort, enabling additional insights for genotype-phenotype correlations, reducing misdiagnoses, and providing early treatment considerations.
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Neuropatias Hereditárias Sensoriais e Autônomas , Insensibilidade Congênita à Dor , Brasil , GTP Fosfo-Hidrolases/genética , Neuropatias Hereditárias Sensoriais e Autônomas/genética , Heterozigoto , Humanos , Mutação/genética , Canal de Sódio Disparado por Voltagem NAV1.7/genética , Insensibilidade Congênita à Dor/genética , Serina C-PalmitoiltransferaseRESUMO
The relationship between Parkinson Disease (PD) and peripheral neuropathy (PN) has gained attention in recent years. There is increasing evidence of a-synuclein deposition and pointing to a form of small fiber neuropathy intrinsic to PD, medium-large fiber PN is also a relatively frequent and potentially severe complication in advanced levodopa-treated PD, but degenerative factors and vitamin deficiency were related. Objective: To determine the neurophysiological characteristics of patients with PD and the clinical manifestations of suspected PN. Methods: We performed a cross-sectional study between January 2014 and December 2017, of 36 patients diagnosed with PD who were referred for electrodiagnostic studies (EDX) with suspected clinical PN. We performed electromyography of five muscle or more (brachial biceps, first dorsal interosseous, thumb abductor, anterior tibial, medial gastrocnemius and short finger extensor), and nerve conduction/velocity studies on fibular and tibial nerves (motor) sural and superficial fibular nerves (sensory) and median and ulnar, (both motor and sensory). Results: Twenty-one females (58.3%) with an average age of 69.6 years and fifteen males (41.7%) with an average age of 68.0 years who were submitted for EDX were included in this study. All had a tremor and the average evolution of PD was 5 years. Thirty-two patients were receiving oral levodopa treatment. EDX of twenty-two patients demonstrated neuropathy abnormalities, and in 90.9% of these patients, sensory neuropathy was confirmed. The most common nerve found to be compromised was the superficial fibular nerve (55.0%), followed by the sural (50.0%). Conclusions: Sensory neuropathy was the main finding. Diagnosing PN based on symptom prevalence assessed by checklists and questionnaire has a risk of overestimating the prevalence of PN. The age and the time of disease evolution were factors related to neuropathy. In our study we found that 39% of the patients did not have neuropathic alterations despite clinical suspicion, which opens up new questions about the mechanisms of PD neuropathy and the possibility of fine fiber neuropathy in these patients, motivating further research.
Assuntos
Doença de Parkinson/complicações , Doenças do Sistema Nervoso Periférico/epidemiologia , Doenças do Sistema Nervoso Periférico/etiologia , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
BACKGROUND: Diabetic neuropathy (DN) is a frequent and debilitating manifestation of diabetes mellitus, to which there are no effective therapeutic approaches. Mesenchymal stem/stromal cells (MSC) have a great potential for the treatment of this syndrome, possibly through regenerative actions on peripheral nerves. Here, we evaluated the therapeutic effects of MSC on spinal neuroinflammation, as well as on ultrastructural aspects of the peripheral nerve in DN-associated sensorial dysfunction. METHODS: C57Bl/6 mice were treated with bone marrow-derived MSC (1 × 106), conditioned medium from MSC cultures (CM-MSC) or vehicle by endovenous route following the onset of streptozotocin (STZ)-induced diabetes. Paw mechanical and thermal nociceptive thresholds were evaluated by using von Frey filaments and Hargreaves test, respectively. Morphological and morphometric analysis of the sciatic nerve was performed by light microscopy and transmission electron microscopy. Mediators and markers of neuroinflammation in the spinal cord were measured by radioimmunoassay, real-time PCR, and immunofluorescence analyses. RESULTS: Diabetic mice presented behavioral signs of sensory neuropathy, mechanical allodynia, and heat hypoalgesia, which were completely reversed by a single administration of MSC or CM-MSC. The ultrastructural analysis of the sciatic nerve showed that diabetic mice exhibited morphological and morphometric alterations, considered hallmarks of DN, such as degenerative changes in axons and myelin sheath, and reduced area and density of unmyelinated fibers. In MSC-treated mice, these structural alterations were markedly less commonly observed and/or less pronounced. Moreover, MSC transplantation inhibited multiple parameters of spinal neuroinflammation found in diabetic mice, causing the reduction of activated astrocytes and microglia, oxidative stress signals, galectin-3, IL-1ß, and TNF-α production. Conversely, MSC increased the levels of anti-inflammatory cytokines, IL-10, and TGF-ß. CONCLUSIONS: The present study described the modulatory effects of MSC on spinal cord neuroinflammation in diabetic mice, suggesting new mechanisms by which MSC can improve DN.
Assuntos
Transplante de Medula Óssea/métodos , Citocinas/metabolismo , Neuropatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/cirurgia , Células-Tronco Mesenquimais/fisiologia , Medula Espinal/patologia , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Meios de Cultivo Condicionados/farmacologia , Citocinas/genética , Neuropatias Diabéticas/induzido quimicamente , Modelos Animais de Doenças , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Hiperalgesia/etiologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Células-Tronco Mesenquimais/química , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas dos Microfilamentos/metabolismo , Atividade Motora/efeitos dos fármacos , Nitritos/metabolismo , Nervo Isquiático/patologia , Nervo Isquiático/ultraestrutura , Medula Espinal/ultraestrutura , Estreptozocina/toxicidadeRESUMO
OBJETIVO: Realizar uma revisão sobre o pé cavo, sua fisiopatologia, avaliação clínica, diagnósticos diferenciais com ênfase na doença de Charcot-Marie-Tooth e tratamento. MÉTODO: Revisão não sistemática de artigos abordando a fisiopatologia do pé cavo, avaliação clínica, diagnósticos diferenciais e tratamento. RESULTADOS E DISCUSSÃO: Foram utilizados 33 artigos de língua inglesa e 02 artigos em português para a confecção desta revisão. CONCLUSÃO: O pé cavo é geralmente secundário a doenças neurológicas, em especial a doença de Charcot-Marie-Tooth e raramente é originado por doenças não neurológicas. O diagnóstico etiológico do pé cavo permite um melhor tratamento, cirúrgico ou não, com adequada orientação ao paciente quanto ao prognóstico e eficácia da terapia.
OBJECTIVE: We realize a review about cavus foot, discussing pathophysiology, clinical evaluation, differential diagnosis with emphasis on Charcot-Marie-Tooth Disease and treatment. METHOD: We perform a non-systematic review of articles about cavus foot pathophysiology, physical examination, etiology and treatment. RESULTS AND DISCUSSION: We used 33 articles in english and 02 articles in portuguese for this review. CONCLUSION: The cavus foot is mostly a consequence of neurological etiologies, in particular Charcot-Marie-Tooth disease and rarely is caused by non-neurological diseases. The correct diagnosis allows better treatment, conservative or surgical, with appropriate guidance to patients in terms of prognosis and therapy effectiveness.
Assuntos
Humanos , Doença de Charcot-Marie-Tooth/complicações , Pé Cavo/cirurgia , Pé Cavo/diagnóstico , Pé Cavo/fisiopatologia , Literatura de Revisão como Assunto , Diagnóstico Diferencial , Limitação da Mobilidade , Pé Cavo/etiologiaRESUMO
Sensory neuronopathies or ganglionopathies, or dorsal root ganglion disorders, represent a subgroup of peripheral nervous system diseases, frequently associated with dysinmune or neoplastic disorders and with toxic agents. A degeneration of both central and peripheral sensory proyections is present. Patients typically show early ataxia, loss of deep tendon reflexes and positive sensory symptoms present both in proximal and distal sites of the body. We retrospectively studied 10 cases with a final diagnosis of sensory neuronopathy. Sensory neuropathy was the presenting symptom and the course was subacute in all cases. Paresthesias in upper limbs were a predominant manifestation (100%). Other manifestations included: hypoesthesia (10/10), gait ataxia (8/10), autonomic symptoms (3/10) and perioral paresthesias (3/10). Electrophysiology showed sensory axonal neuronal pattern, with normal motor responses. Final diagnosis was acquired sensory neuronopathy in all patients, associated with Sjögren's syndrome in 2, with lupus erythematosus in 1, with rheumatoid arthritis in 1, with a cancer in 2 (paraneoplastic) and idiopathic in 4. In paraneoplastic cases, the tumor was small cell lung cancer in 1 (with positive anti-Hu antibodies), and epidermoid lung cancer in the other. Eight patients were treated with immunotherapy, high dose intravenous methylprednisolone and/or intravenous immunoglobulin; with poor response in 4 cases, neurologic improvement in 5, and without any change in 1 patient. The present work shows the typical clinical and electrophysiological pattern of subacute sensory neuronopathy, and the relevance of early treatment.
Assuntos
Ataxia/diagnóstico , Ataxia/tratamento farmacológico , Carcinoma de Células Escamosas/complicações , Neoplasias Pulmonares/complicações , Carcinoma de Pequenas Células do Pulmão/complicações , Tempo para o Tratamento , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/uso terapêutico , Artrite Reumatoide/complicações , Ataxia/complicações , Evolução Fatal , Feminino , Marcha Atáxica/diagnóstico , Marcha Atáxica/tratamento farmacológico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Parestesia/diagnóstico , Parestesia/tratamento farmacológico , Estudos Retrospectivos , Síndrome de Sjogren/complicaçõesRESUMO
Las neuronopatías o ganglionopatías sensitivas, o enfermedades del ganglio dorsal, representan un subgrupo de enfermedades del sistema nervioso periférico, frecuentemente asociadas a trastornos disinmunes o paraneoplásicos, y a agentes tóxicos. Los pacientes típicamente presentan ataxia temprana, pérdida de los reflejos osteotendinosos y síntomas sensitivos positivos, presentes tanto en partes proximales como distales del cuerpo. Estudiamos retrospectivamente 10 casos con un diagnóstico final de neuronopatía sensitiva. El síntoma de presentación fue el de una neuropatía sensitiva de curso subagudo en todos los casos, con parestesias en el 100% de los casos. Otras manifestaciones fueron: hipoestesia (10/10), ataxia de la marcha (8/10), síntomas autonómicos (3/10) y parestesias periorales (3/10). La electrofisiología mostró un patrón de compromiso sensitivo axonal, con respuestas motoras normales. El diagnóstico final fue neuronopatía sensitiva adquirida en todos, asociada a síndrome de Sjögren en dos, a lupus eritematoso en uno, a artritis reumatoidea en uno, a cáncer en dos (paraneoplásica) e idiopática en cuatro. En los casos paraneoplásicos, los tumores fueron un carcinoma de pulmón de células pequeñas (con anticuerpos anti-Hu positivos) y un carcinoma epidermoide de pulmón. Ocho pacientes fueron tratados con inmunoterapia, con altas dosis de metilprednisolona endovenosa y/o con inmunoglobulina endovenosa; con pobre respuesta en cuatro casos, mejoría neurológica en cinco, y sin cambios en uno. El presente trabajo muestra el patrón clinico y electrofisiológico de las neuronopatías sensitivas subagudas, y la relevancia de un tratamiento temprano.
Sensory neuronopathies or ganglionopathies, or dorsal root ganglion disorders, represent a subgroup of peripheral nervous system diseases, frequently associated with dysinmune or neoplastic disorders and with toxic agents. A degeneration of both central and peripheral sensory proyections is present. Patients typically show early ataxia, loss of deep tendon reflexes and positive sensory symptoms present both in proximal and distal sites of the body. We retrospectively studied 10 cases with a final diagnosis of sensory neuronopathy. Sensory neuropathy was the presenting symptom and the course was subacute in all cases. Paresthesias in upper limbs were a predominant manifestation (100%). Other manifestations included: hypoesthesia (10/10), gait ataxia (8/10), autonomic symptoms (3/10) and perioral paresthesias (3/10). Electrophysiology showed sensory axonal neuronal pattern, with normal motor responses. Final diagnosis was acquired sensory neuronopathy in all patients, associated with Sjögren’s syndrome in 2, with lupus erythematosus in 1, with rheumatoid arthritis in 1, with a cancer in 2 (paraneoplastic) and idiopathic in 4. In paraneoplastic cases, the tumor was small cell lung cancer in 1 (with positive anti-Hu antibodies), and epidermoid lung cancer in the other. Eight patients were treated with immunotherapy, high dose intravenous methylprednisolone and/or intravenous immunoglobulin; with poor response in 4 cases, neurologic improvement in 5, and without any change in 1 patient. The present work shows the typical clinical and electrophysiological pattern of subacute sensory neuronopathy, and the relevance of early treatment.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Ataxia/diagnóstico , Ataxia/tratamento farmacológico , Carcinoma de Células Escamosas/complicações , Carcinoma de Pequenas Células do Pulmão/complicações , Neoplasias Pulmonares/complicações , Parestesia/diagnóstico , Artrite Reumatoide/complicações , Ataxia/complicações , Síndrome de Sjogren/complicações , Imunoglobulinas Intravenosas/uso terapêutico , Evolução Fatal , Marcha Atáxica/diagnóstico , Marcha Atáxica/tratamento farmacológico , Anti-Inflamatórios/uso terapêuticoRESUMO
OBJECTIVE: Several distinctive clinical features of patients with familial dysautonomia (FD) including dysarthria and dysphagia suggest a developmental defect in brainstem reflexes. Our aim was to characterize the neurophysiological profile of brainstem reflexes in these patients. METHODS: We studied the function of sensory and motor trigeminal tracts in 28 patients with FD. All were homozygous for the common mutation in the IKAP gene. Each underwent a battery of electrophysiological tests including; blink reflexes, jaw jerk reflex, masseter silent periods and direct stimulation of the facial nerve. Responses were compared with 25 age-matched healthy controls. RESULTS: All patients had significantly prolonged latencies and decreased amplitudes of all examined brainstem reflexes. Similar abnormalities were seen in the early and late components. In contrast, direct stimulation of the facial nerve revealed relative preservation of motor responses. CONCLUSIONS: The brainstem reflex abnormalities in FD are best explained by impairment of the afferent and central pathways. A reduction in the number and/or excitability of trigeminal sensory axons is likely the main problem. SIGNIFICANCE: These findings add further evidence to the concept that congenital mutations of the elongator-1 protein (or IKAP) affect the development of afferent neurons including those carrying information for the brainstem reflex pathways.
Assuntos
Tronco Encefálico/fisiopatologia , Disautonomia Familiar/fisiopatologia , Neurônios Aferentes/fisiologia , Reflexo/fisiologia , Adolescente , Adulto , Estimulação Elétrica , Eletromiografia , Nervo Facial/fisiopatologia , Feminino , Humanos , Masculino , Músculo Masseter/fisiopatologia , Adulto JovemRESUMO
In 2002, Spring et al reported a family with an autosomal dominant form of hereditary sensory neuropathy; patients also presented adult onset of gastroesophageal reflux and cough. Since then, no further families have been described. Objective: To study a new Portuguese family with these characteristics. Method: To describe the clinical and neurophysiologic characteristics of one family with features of sensory neuropathy associated with cough and gastroesophageal erflux. Results: Three of five siblings presented a similar history of paroxysmal cough (5th decade). About a decade later they experienced numbness and paraesthesia in the feets and in all cases there was evidence of an axonal sensory neuropathy. A history of gastroesophageal reflux of variable severity and age of onset was also present. Discussion: Molecular genetic studies have demonstrated genetic heterogeneity between the hereditary sensory neuropathy type 1 subtypes. The identification of these families is of major importance because further work is required to identify the underlying genetic defect. .
Em 2002, Spring et al descreveram uma família com uma combinação de polineuropatia sensitiva hereditária, doença do refluxo gastroesofágico e tosse paroxística. Desde então não foram descritos outros casos. Objectivo: Estudar uma nova família portuguesa com essas características. Método: Caracterização clínica e neurofisiológica de uma família com a referida combinação de patologias. Resultados: Três, de cinco irmãos, apresentam uma história semelhante de tosse paroxística com início na 5a década. Cerca de uma década mais tarde iniciam quadro de parestesias em ambos os pés, com evidência de neuropatia sensitiva axonal. Todos os casos apresentam também uma história de doença do refluxo gastroesofágico de gravidade variável. Discussão: Nos últimos anos, os estudos de genética molecular permitiram evidenciar a heterogeneidade genética dos vários subtipos de polineuropatia sensitiva hereditária tipo 1. A identificação das famílias afectadas reveste-se de grande importância, nomeadamente na tentativa de caracterização da alteração genética deste subtipo. .
Assuntos
Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Tosse/etiologia , Refluxo Gastroesofágico/diagnóstico , Neuropatias Hereditárias Sensoriais e Autônomas/diagnóstico , Idade de Início , Tosse/genética , Tosse/fisiopatologia , Refluxo Gastroesofágico/genética , Refluxo Gastroesofágico/fisiopatologia , Neuropatias Hereditárias Sensoriais e Autônomas/genética , Neuropatias Hereditárias Sensoriais e Autônomas/fisiopatologia , Mutação , Condução Nervosa , Linhagem , PortugalRESUMO
La notalgia parestésica es una neuropatía sensorial caracterizada clínicamente por una mancha hiperpigmentada bien circunscrita localizada en la espalda, que afecta las áreas correspondientes a los dermatomos D2 a D6. El prurito es el síntoma más común, aunque algunos pacientes describen otras sensaciones, incluyendo ardor, parestesia, hiperestesia o dolor. Los hallazgos histopatológicos son inespecíficos. Su etiología no ha sido claramente demostrada, pero en algunos casos existe una llamativa correlación con patología de la columna vertebral, incluyendo cambios degenerativos y/o hernias del núcleo pulposo. El diagnóstico diferencial incluye la neurodermitis y la amiloidosis macular. No existe un tratamiento definitivo para la enfermedad. Se han empleado diversas terapias incluyendo capsaicina tópica, bloqueo anestésico para vertebral, oxcarbazepina, gabapentina y toxina botulínica.
Notalgia paresthetica is a sensory neuropathy characterizd clinically by a well-circumscribed hyperpigmented patch located on the back, affecting the areas corresponding to dermatomes D2-D6. Pruritus is its most common symptom, but some patients describe other sensations including burning, paresthesia, hypeesthesia or pain. Histopathological findings are not specific. The etiology of this condition has not be en clearly demonstrated but in some cases there exists a striking correlation with spinal pathology, including degenerative changes or a herniated nucleous pulposus. Differential diagnoses include neurodermitis and maclular amyloidosis There is no definitive treatment for the disease diverse therapies have been employed including topical capsaicin paravertebral local anesthetic block, oxcarbazepine, gabapentir and botulinum toxin type A.
Assuntos
Humanos , Dermatopatias/diagnóstico , Dermatopatias/tratamento farmacológico , Parestesia/diagnóstico , Parestesia/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Capsaicina/uso terapêutico , Diagnóstico Diferencial , Dor nas Costas/etiologia , Dermatopatias/etiologia , Dermatopatias/patologia , Hiperpigmentação , Parestesia/etiologia , Parestesia/patologia , Toxinas Botulínicas/uso terapêuticoRESUMO
BACKGROUND: Trigeminal sensory neuropathy (TSN) describes a heterogeneous group of disorders manifesting as facial numbness. OBJECTIVE: We report the case of a patient who had TSN associated with contact dermatitis due to Anthurium sp. METHOD/RESULTS: A 21-year-old female patient developed left hemifacial contact dermatitis after exposure to the anthurium plant. The patient had paresthesias and pain in the V2 and V3 divisions of the left trigeminal nerve. Eight days after its onset the dermatitis resolved, but numbness developed in the V2 and V3 divisions of the left trigeminal nerve. Cranial CT scan and MRI, as well as CSF and extensive work-up exams, were normal. After one month the symptoms disappeared completely. CONCLUSION: Anthurium sp, an indoor ornamental plant that contains calcium oxalate crystals, and can causes contact dermatitis. To our knowledge, this is the first report associating TSN with contact dermatitis due to Anthurium sp.
INTRODUÇÃO: A neuropatia trigeminal sensitiva (NTS) representa um grupo heterogêneo de doenças, cuja manifestação clínica é a presença de dormência na região facial. OBJETIVO: Relatamos o caso de paciente que apresenta NTS associada com dermatite de contato (DC) devido à planta Anthurium sp. MÉTODO/RESULTADOS: Uma paciente com 21 anos desenvolveu DC na região hemi-facial esquerda, após exposição à planta Anthurium sp. Após a resolução do quadro de dermatite, a referida paciente apresentou dormência e parestesias no território do segundo e terceiro ramos do nervo trigêmeo esquerdo. Um mês após o início do quadro houve resolução completa dos sintomas. CONCLUSÃO: O Anthurium é uma planta ornamental que contém cristas de oxalato de cálcio, que podem causar DC. Para o nosso conhecimento este é o primeiro relato associando NTS e dermatite de contato devido à exposição ao Anthurium sp.