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Doenças Mitocondriais/diagnóstico por imagem , Nervos Periféricos/fisiopatologia , Doenças do Sistema Nervoso Periférico/diagnóstico por imagem , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Mitocondriais/diagnóstico , Doenças Mitocondriais/fisiopatologia , Nervos Periféricos/diagnóstico por imagem , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/fisiopatologia , UltrassonografiaRESUMO
INTRODUCTION: Use of peripheral nerve ultrasound alongside standard electrodiagnostic tests may help to gain insight into the pathophysiology of peripheral nerve involvement in type 2 spinocerebellar ataxia (SCA2). METHODS: Twenty-seven patients with SCA2 underwent ultrasound cross-sectional area (CSA) measurement of median, ulnar, sural and tibial nerves, and motor (median, ulnar, tibial) and sensory (median, ulnar, radial, sural) nerve conduction studies. RESULTS: Twenty patients had pathologically small-nerve CSAs, suggestive of sensory neuronopathy. In these patients, electrophysiology showed non-length-dependent sensory neuropathy (14 of 20), "possible sensory neuropathy" (1 of 20), or normal findings (5 of 20). Four different patients had length-dependent sensory neuropathy on electrophysiology, and 1 had enlarged nerve CSAs. Regression analysis showed an inverse relationship between ataxia scores and upper limb nerve CSA (P < 0.03). DISCUSSION: Our findings suggest that a majority of patients with SCA2 (74%) have a sensory neuronopathy and this correlates with disability. A minority of patients have findings consistent with axonal neuropathy (18%). Muscle Nerve, 2019.
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Nervos Periféricos/fisiopatologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Ataxias Espinocerebelares/fisiopatologia , Extremidade Superior/fisiopatologia , Adulto , Idoso , Ataxia Cerebelar/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/metabolismo , Condução Nervosa/fisiologia , Doenças do Sistema Nervoso Periférico/diagnóstico , Transtornos de Sensação/fisiopatologia , Ultrassonografia/métodosRESUMO
Patients with congestive myelopathy due to spinal dural arteriovenous fistula (SDAVF) typically present with progressive sensory and motor disturbance in association with sphincter dysfunction. Spinal MRI usually shows longitudinally extensive T2 signal change. Here, we report four patients with progressive myelopathy due to SDAVF who also presented with findings on cerebrospinal fluid (CSF) examination suggestive of an inflammatory aetiology. Such CSF findings in SDAVF are important to recognise, to avoid the erroneous diagnosis of an inflammatory myelitis and inappropriate treatment with immunosuppression. SDAVF can be difficult to detect and may require repeated investigation, with formal angiography as the gold standard.
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INTRODUCTION: Sensory impairment in Friedreich ataxia (FRDA) is generally accepted as being due to a ganglionopathy. The degree of contribution from axonal pathology remains a matter of debate. Nerve ultrasound may be able to differentiate these processes. METHODS: The ultrasound cross-sectional area of median, ulnar, tibial, and sural nerves of 8 patients with FRDA was compared with 8 age- and gender-matched healthy controls and with reference values in our population. RESULTS: The nerves of the patients with FRDA were significantly larger than those of healthy controls at all upper limb sites (P < 0.05) but not significantly different in the lower limbs. DISCUSSION: Our findings add additional weight to the theory that dorsal root ganglionopathy is not the sole cause of peripheral sensory loss in FRDA. Peripheral neuropathic processes are also likely to play a role. Muscle Nerve 57: 852-856, 2018.
Assuntos
Ataxia de Friedreich/diagnóstico por imagem , Nervos Periféricos/diagnóstico por imagem , Ultrassonografia Doppler/métodos , Adulto , Idoso , Estudos de Casos e Controles , Avaliação da Deficiência , Feminino , Ataxia de Friedreich/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa/fisiologia , Nova Zelândia , Estatísticas não ParamétricasRESUMO
INTRODUCTION: Oxaliplatin-based chemotherapy has become the standard treatment for colorectal cancer and other gastrointestinal tumor types. Oxaliplatin-induced neurotoxicity is a major treatment-limiting side effect that compromizes the delivery of cancer treatment and causes long-standing neurological deficits that negatively impact upon patient quality of life Areas covered: The prevention of oxaliplatin-induced neurotoxicity represents an important opportunity for new therapeutic product development to address this major unmet medical need. In this article, we describe a phase Ib clinical trial design, and study procedures and protocols, that we have developed and now propose for the early clinical evaluation of investigational therapeutics for preventing oxaliplatin-induced neurotoxicity. Expert opinion: Recently, several advances have been made in the development of research methodologies applicable to the clinical evaluation of investigational drugs for preventing oxaliplatin-induced neurotoxicity. As we gain better understanding of the mechanisms of oxaliplatin-induced neurotoxicity, we will be able to use these methods to develop and test more effective and targeted neuroprotective agents that may not only improve patients' quality of life but also improve treatment delivery and survival outcomes.
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Síndromes Neurotóxicas/prevenção & controle , Compostos Organoplatínicos/efeitos adversos , Projetos de Pesquisa , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Ensaios Clínicos Fase I como Assunto/métodos , Estudos Cross-Over , Método Duplo-Cego , Neoplasias Gastrointestinais/tratamento farmacológico , Humanos , Síndromes Neurotóxicas/etiologia , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto/métodosRESUMO
BACKGROUND AND PURPOSE: There have been few recent population-based studies reporting the incidence (first ever) and attack rates (incident and recurrent) of transient ischemic attack (TIA). METHODS: The fourth Auckland Regional Community Stroke study (ARCOS IV) used multiple overlapping case ascertainment methods to identify all hospitalized and nonhospitalized cases of TIA that occurred in people ≥16 years of age usually resident in Auckland (population ≥16 years of age is 1.12 million), during the 12 months from March 1, 2011. All first-ever and recurrent new TIAs (any new TIA 28 days after the index event) during the study period were recorded. RESULTS: There were 785 people with TIA (402 [51.2%] women, mean [SD] age 71.5 [13.8] years); 614 (78%) of European origin, 84 (11%) Maori/Pacific, and 75 (10%) Asian/Other. The annual incidence of TIA was 40 (95% confidence interval, 36-43), and attack rate was 63 (95% confidence interval, 59-68), per 100 000 people, age standardized to the World Health Organization world population. Approximately two thirds of people were known to be hypertensive or were being treated with blood pressure-lowering agents, half were taking antiplatelet agents and just under half were taking lipid-lowering therapy before the index TIA. Two hundred ten (27%) people were known to have atrial fibrillation at the time of the TIA, of whom only 61 (29%) were taking anticoagulant therapy, suggesting a failure to identify or treat atrial fibrillation. CONCLUSIONS: This study describes the burden of TIA in an era of aggressive primary and secondary vascular risk factor management. Education programs for medical practitioners and patients around the identification and management of atrial fibrillation are required.
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Ataque Isquêmico Transitório/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Sistema de Registros , Adulto JovemRESUMO
Previous reports of ocular abnormalities in Huntington's disease (HD) have detailed eye movement disorders. The objective of this case-control study was to investigate optic nerve and macular morphology in HD using optical coherence tomography (OCT). A total of 26 HD patients and 29 controls underwent a thorough ophthalmic examination including spectral domain OCT scans of the macula and peripapillary retinal nerve fibre layer (RNFL). Genetic testing results, disease duration, HD disease burden scores and Unified HD Rating Scale motor scores were acquired for HD patients. Temporal RNFL thickness was significantly reduced in the HD group (62.3 vs. 69.8 µm, p = 0.005), and there was a significant negative correlation between temporal RNFL thickness and disease duration (R (2) = -0.51, p = 0.04). Average peripapillary RNFL thickness was not significantly different between the HD and control groups. There was a significant negative correlation between macular volume and disease duration (R (2) = -0.71, p = 0.002), and motor scores (R (2) = -0.56, p = 0.01). Colour vision was significantly poorer in the HD group. Temporal RNFL is preferentially thinned in HD patients, possibly implicating mitochondrial dysfunction as the temporal RNFL is reduced in the patients with some mitochondrial disorders, including Leber's hereditary optic neuropathy. The correlation between the decrease in macular volume and temporal RNFL, and increasing disease severity suggests that OCT may be a useful biomarker for disease progression in HD. Larger, longitudinal studies are required.
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Doença de Huntington/patologia , Macula Lutea/metabolismo , Fibras Nervosas/patologia , Doenças Retinianas/patologia , Neurônios Retinianos/patologia , Tomografia de Coerência Óptica/métodos , Adulto , Idoso , Biomarcadores , Estudos de Casos e Controles , Feminino , Humanos , Doença de Huntington/complicações , Masculino , Pessoa de Meia-Idade , Doenças Retinianas/etiologiaRESUMO
PURPOSE: We investigated the relationship between corneal subbasal nerve (SBN) plexus density, corneal sensitivity, and peripheral and cardiac autonomic neuropathy in patients with type 1 diabetes mellitus. METHODS: We recruited 53 patients with type 1 diabetes mellitus and 40 normal control participants. Corneal in vivo confocal microscopy (IVCM) and sensitivity testing were performed on one eye of each subject. Autonomic function testing was done and an overall neuropathy score obtained from a combination of a symptomatic neuropathy score, clinical assessment, biothesiometry, and nerve conduction tests. RESULTS: The corneal SBN density (P < 0.001) and corneal sensitivity (P < 0.001) were significantly lower in subjects with diabetes compared to controls. A modest negative correlation between total neuropathy score and SBN density was observed (r = -0.33, P = 0.01). A negative correlation between corneal sensitivity and expiration/inspiration component of the autonomic nerve analysis (ANS-EI) also was noted (r = -0.36, P = 0.008). Corneal SBN density was abnormal in 50% of diabetic subjects classified as "Normal" by the clinical and electrophysiological based tests of total neuropathy score. CONCLUSIONS: The correlation of corneal SBN density with total neuropathy score suggests that reduced corneal nerve density reflects peripheral neuropathy in diabetes. Corneal SBN changes precede other clinical and electrophysiology tests of neuropathy supporting a possible role for corneal IVCM and corneal sensitivity testing as surrogate markers in the assessment of diabetic peripheral and cardiac autonomic neuropathy.
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Doenças do Sistema Nervoso Autônomo/patologia , Córnea/inervação , Diabetes Mellitus Tipo 1/patologia , Neuropatias Diabéticas/patologia , Cardiopatias/patologia , Microscopia Confocal/métodos , Doenças do Sistema Nervoso Periférico/patologia , Adolescente , Adulto , Idoso , Sistema Nervoso Autônomo/patologia , Doenças do Sistema Nervoso Autônomo/etiologia , Diabetes Mellitus Tipo 1/complicações , Feminino , Cardiopatias/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/etiologia , Reprodutibilidade dos Testes , Adulto JovemRESUMO
Posterior reversible encephalopathy syndrome (PRES) is characterised clinically by encephalopathy, headache, visual disturbance and/or focal neurological symptoms. Bilateral cerebral oedema on T2 MRI sequences within the posterior cerebral white matter is the radiological hallmark, although involvement of the frontal lobe, basal ganglia and brainstem can occur. PRES with spinal cord involvement has been rarely reported and is under-recognised due to lack of myelopathic features in nearly half of the reported cases. We report a patient with PRES with spinal cord involvement and review the literature.
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Síndrome da Leucoencefalopatia Posterior/diagnóstico , Adulto , Tronco Encefálico/patologia , Vértebras Cervicais/patologia , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância Magnética , Masculino , Síndrome da Leucoencefalopatia Posterior/patologiaRESUMO
PURPOSE: To compare tear film metrics in patients with type 1 diabetes mellitus (DM) and healthy controls and investigate the association between peripheral neuropathy and ocular surface quality. METHODS: Dry eye symptoms were quantified in 53 patients with type 1 DM and 40 age-matched controls. Ocular examination included tear film lipid layer thickness grading, tear film stability and quantity measurement, and retinal photography. DM individuals additionally underwent a detailed neuropathy assessment. RESULTS: Neither mean age nor dry eye symptom scores differed significantly between the DM and control groups (P = 0.12 and P = 0.33, resp.). Tear lipid thickness (P = 0.02), stability (P < 0.0001), and quantity (P = 0.01) were significantly lower in the DM group. Corneal sensitivity was also reduced in the DM group (P < 0.001) and tear film stability was inversely associated with total neuropathy score (r = -0.29, P = 0.03). CONCLUSION: The DM group exhibited significantly reduced tear film stability, secretion, and lipid layer quality relative to the age-matched control group. The negative correlation between tear film parameters and total neuropathy score suggests that ocular surface abnormalities occur in parallel with diabetic peripheral neuropathy.
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Diabetes Mellitus Tipo 1/complicações , Neuropatias Diabéticas/etiologia , Síndromes do Olho Seco/etiologia , Aparelho Lacrimal/metabolismo , Lágrimas/metabolismo , Adulto , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/diagnóstico , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/fisiopatologia , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a recently recognized neurodegenerative ganglionopathy. Prompted by the presence of symptomatic postural hypotension in two patients with CANVAS, we hypothesized that autonomic dysfunction may be an associated feature of the syndrome. We assessed symptoms of autonomic dysfunction and performed autonomic nervous system testing among 26 patients from New Zealand. After excluding three patients with diabetes mellitus, 83% had evidence of autonomic dysfunction; all patients had at least one autonomic symptom and 91% had more than two symptoms. We also found a higher rate of downbeat nystagmus (65%) than previously described in CANVAS. We confirmed that sensory findings on nerve conduction tests were consistent with a sensory ganglionopathy and describe two patients with loss of trigeminal sensation consistent with previous pathological descriptions of trigeminal sensory ganglionopathy. Our results suggest that autonomic dysfunction is a major feature of CANVAS. This has implications for the management of patients with CANVAS as the autonomic symptoms may be amenable to treatment. The findings also provide an important differential diagnosis from multiple system atrophy for patients who present with ataxia and autonomic failure.
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Doenças do Sistema Nervoso Autônomo/fisiopatologia , Ataxia Cerebelar/fisiopatologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Doenças Vestibulares/fisiopatologia , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Doenças do Sistema Nervoso Autônomo/complicações , Ataxia Cerebelar/complicações , Tontura/fisiopatologia , Feminino , Força da Mão/fisiologia , Frequência Cardíaca/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Nova Zelândia , Nistagmo Patológico/etiologia , Nistagmo Patológico/fisiopatologia , Doenças do Sistema Nervoso Periférico/complicações , Reflexo Vestíbulo-Ocular/fisiologia , Síndrome , Manobra de Valsalva , Doenças Vestibulares/etiologia , Testes de Função Vestibular , Vitamina E/sangue , Adulto JovemRESUMO
BACKGROUND: Calcium and magnesium (Ca/Mg) infusions have been suggested as an effective intervention for preventing oxaliplatin-induced neurotoxicity, but the effects of Ca/Mg infusions on oxaliplatin pharmacokinetics, motor nerve hyperexcitability and acute neurotoxicity symptoms are unclear. METHODS: In this double blind crossover study, colorectal cancer patients undergoing oxaliplatin-based chemotherapy were randomised to receive Ca/Mg (1g Ca Gluconate plus 1g MgSO4) on cycle 1 and placebo (vehicle alone) on cycle 2, or to receive the same treatments in the opposite sequence. Study endpoints included plasma pharmacokinetics of intact oxaliplatin and free platinum; electromyography (EMG) detection of abnormal spontaneous high-frequency motor unit action potential discharges; and patient-reported acute neurotoxicity symptoms and their preferred study treatment for reducing these symptoms. RESULTS: Nineteen of 20 enrolled patients completed the study. Plasma pharmacokinetics of intact oxaliplatin and free platinum were similar when oxaliplatin was given with Ca/Mg or placebo (ratio of geometric means of AUC0-t with Ca/Mg or placebo: intact oxaliplatin, 0.95 (90% CI, 0.90 - 1.01); free platinum, 0.99 (90% CI, 0.94 - 1.05)). EMG motor nerve hyperexcitability scores were similar with Ca/Mg and placebo (mean difference in EMG score between Ca/Mg and placebo: -0.3 (95% CI, -2.2 - 1.6)). Patient-reported acute neurotoxicity symptoms were similar in frequency with Ca/Mg and placebo. For reducing neurotoxic symptoms, fewer patients preferred Ca/Mg than placebo or neither treatment (26% versus 74%; P<0.01). CONCLUSIONS: Ca/Mg infusions do not alter the clinical pharmacokinetics of oxaliplatin and do not seem to reduce its acute neurotoxicity. TRIAL REGISTRATION: Trial registration identifier ACTRN12611000738921.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cálcio/administração & dosagem , Neoplasias Colorretais/complicações , Neoplasias Colorretais/tratamento farmacológico , Magnésio/administração & dosagem , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Adulto , Idoso , Neoplasias Colorretais/patologia , Estudos Cross-Over , Interações Medicamentosas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/farmacocinética , Compostos Organoplatínicos/toxicidade , Oxaliplatina , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/fisiopatologia , Resultado do TratamentoRESUMO
We present a case of Moyamoya disease presenting as hemifacial spasm due to compression of the facial nerve by a vascular loop related to compensatory enlargement of the posterior circulation vessels.
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Espasmo Hemifacial/diagnóstico , Doença de Moyamoya/diagnóstico , Adulto , Espasmo Hemifacial/etiologia , Humanos , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Masculino , Doença de Moyamoya/complicaçõesRESUMO
OBJECTIVE: Mutations in SCN9A have been reported in (1) congenital insensitivity to pain (CIP); (2) primary erythromelalgia; (3) paroxysmal extreme pain disorder; (4) febrile seizures and recently (5) small fibre sensory neuropathy. We sought to investigate for SCN9A mutations in a clinically well-characterised cohort of patients with CIP and erythromelalgia. METHODS: We sequenced all exons of SCN9A in 19 clinically well-studied cases including 6 CIP and 13 erythromelalgia (9 with family history, 10 with small-fibre neuropathy). The identified variants were assessed in dbSNP135, 1K genome, NHLBI-Exome Sequencing Project (5400-exomes) databases, and 768 normal chromosomes. RESULTS: In erythromelalgia case 7, we identified a novel Q10>K mutation. In CIP case 6, we identified a novel, de novo splicing mutation (IVS8-2A>G); this splicing mutation compounded with a nonsense mutation (R523>X) and abolished SCN9A mRNA expression almost completely compared with his unaffected father. In CIP case 5, we found a variant (P610>T) previously considered causal for erythromelalgia, supporting recently raised doubt on its causal nature. We also found a splicing junction variant (IVS24-7delGTTT) in all 19 patients, this splicing variant was previously considered casual for CIP, but IVS24-7delGTTT was in fact the major allele in Caucasian populations. CONCLUSIONS: Two novel SCN9A mutations were identified, but frequently polymorphism variants are found which may provide susceptibility factors in pain modulation. CIP and erythromelalgia are defined as genetically heterogeneous, and some SCN9A variants previously considered causal may only be modifying factors.
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Eritromelalgia/genética , Mutação/genética , Canal de Sódio Disparado por Voltagem NAV1.7/genética , Insensibilidade Congênita à Dor/genética , Adolescente , Adulto , Idade de Início , Processamento Alternativo , Biópsia , Criança , Pré-Escolar , Estudos de Coortes , Bases de Dados Genéticas , Eritromelalgia/patologia , Éxons/genética , Feminino , Frequência do Gene , Humanos , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Exame Neurológico , Insensibilidade Congênita à Dor/patologia , Linhagem , Polimorfismo de Nucleotídeo Único , Pele/patologia , Nervo Sural/patologia , Adulto JovemRESUMO
OBJECTIVE: Facial onset sensorimotor neuronopathy (FOSMN) is a recently described neurological syndrome characterized by slow onset of facial sensory abnormalities and subsequent development of motor deficits. Except for 1 patient, FOSMN has so far been identified only in men. METHODS: We describe a case series of 3 women with FOSMN. We report their clinical, laboratory, and neurophysiological findings. RESULTS: The age of onset ranged from 39 to 72 years (mean, 60 years) with presentation 4-7 years after symptom onset. The first symptom was slowly progressive facial numbness, which was followed years later by dysphagia and impaired corneal reflexes. Dysarthria occurred in 2 patients, and mild arm weakness was noted in 2. Muscle stretch reflexes were increased in 1 patient, and in another case, arm sensation was reduced. Laboratory studies were unremarkable, and magnetic resonance imaging of the brain in 3 patients and of the cervical spine in 2 patients was normal. Nerve conduction studies showed reduced leg compound muscle action potential amplitudes in 1 patient and asymmetrically reduced arm sensory nerve action potentials in another case. In 2 patients, electromyography showed widespread active denervation in arm muscles in conjunction with the involvement of leg muscles in 1 case and the tongue in the other patient. We identified chronic neurogenic motor unit action potentials in the genioglossus muscle of all 3 cases while facial EMG performed in case 3 showed similar findings. Blink reflexes were abnormal in all patients. We treated 1 patient with high-dose intravenous methylprednisolone followed by intravenous immunoglobulin without any improvement, and she required percutaneous endoscopic gastrostomy (PEG) tube placement. CONCLUSIONS: This is the first case series describing 3 women with the FOSMN syndrome. We expand phenotype of FOSMN to include upper motor neuron signs and normal arm sensory nerve action potentials.
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Doenças do Nervo Facial/complicações , Transtornos Neurológicos da Marcha/etiologia , Condução Nervosa/fisiologia , Idoso , Piscadela/fisiologia , Creatina Quinase/metabolismo , Doenças do Nervo Facial/patologia , Feminino , Transtornos Neurológicos da Marcha/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Neurônios Motores/patologia , Músculo Esquelético/fisiopatologia , Língua/fisiopatologiaRESUMO
We report here a unique amyloidoma of the radial nerve which could not be subtyped by available techniques, including immunohistochemistry and standard clinical and laboratory evaluation. In order to identify the amyloid monomer, we developed a novel preparative procedure designed to optimize conditions for liquid chromatography tandem mass spectrometry analysis of formalin-fixed/paraffin-embedded (FFPE) tissue. Subsequent mass spectrometric analysis clearly identified kappa light chain as the monomer, with no evidence of lambda light chain. Manual interpretation of the matched spectra revealed no evidence of polyclonality. This study also enabled detailed characterisation of twelve likely amyloid matrix components. Finally, our analysis revealed extensive hydroxylation of collagen type I but, unexpectedly, an almost complete lack of hydroxylated residues in the normally heavily-hydroxylated collagen type VI chains, pointing to structural/functional alterations of collagen VI in this matrix that could have contributed to the pathogenesis of this very unusual tumour. Given the high quality of the data here acquired using a standard quadrupole-time of flight tandem mass spectrometer of modest performance, the robust and straightforward preparative method described constitutes a competitive alternative to more involved approaches using state-of-the-art equipment.
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Amiloidose/patologia , Placa Amiloide/patologia , Nervo Radial/patologia , Espectrometria de Massas em Tandem/métodos , Sequência de Aminoácidos , Amiloidose/metabolismo , Cromatografia Líquida de Alta Pressão , Colágeno Tipo VI/química , Colágeno Tipo VI/metabolismo , Feminino , Fixadores , Secções Congeladas , Humanos , Hidroxilação , Cadeias kappa de Imunoglobulina/química , Cadeias kappa de Imunoglobulina/metabolismo , Pessoa de Meia-Idade , Dados de Sequência Molecular , Inclusão em Parafina , Placa Amiloide/metabolismo , Nervo Radial/metabolismo , Fixação de TecidosRESUMO
AIMS: To create awareness of adult-onset carnitine palmitoyltransferase II (CPT II) deficiency by describing the clinical, biochemical, and genetic features of three New Zealand patients with this disorder. METHODS: Review of case notes, creatine kinase (CK) values, CPT II assay results, genetic mutation analyses, and the literature. RESULTS: Three patients with CPT II deficiency were encountered by the authors over a 7-year period. Onset of symptoms was between ages 10 and 17 years. Each patient reported exertional myalgia, and had had at least two episodes of myoglobinuria following exertion or infection. Interictal neurological examinations, CK values, and routine muscle histology were normal. CPT II activities ranged from 3.8 to 9.7 pmol/min/mg protein (normal+/-SD=162.9+/-51.0 pmol/min/mg protein). Genetic analysis showed that one patient was homozygous and two were heterozygous for S113L, the common mutation in CPT II deficiency. CONCLUSIONS: CPT II deficiency should be suspected in patients with persistent exertional myalgia who have one or more episodes of myoglobinuria. The diagnosis is confirmed using a combination of enzyme assay and genetic testing.