RESUMO
We developed an immunoassay platform for the detection of human Thyroglobulin (Tg) to be integrated with fine-needle aspiration biopsy for early detection of lymph node metastases in thyroid cancer patients. The sensing platform detects Tg by a sandwich immunoassay involving a self-assembled surface-enhanced Raman scattering (SERS) substrate assisted by functionalized gold nanoparticles that provide additional Raman signal amplification and improved molecular specificity. Specifically, the SERS-active substrates were functionalized with Tg Capture antibodies and fabricated either on-chip or on optical fiber tips by nanosphere lithography. Gold nanoparticles were functionalized with Detection antibodies and conjugated with 4-mercaptobenzoic acid, which serves as a Raman reporter. The sandwich assay platform was validated in the planar configuration and a detection limit as low as 7 pg/mL was successfully achieved. Careful morphological examination of the SERS substrates before and after Tg measurements further assessed the effective capture of nanoparticles and correlated the average nanoparticle coverage with the Tg concentration obtained by SERS measurements. The sandwich assay was successfully demonstrated on washout fluids of fine needle aspiration biopsies from cancer patients and confirmed the high specificity of the proposed methodology when complex biological matrices are considered. Finally, SERS optrodes were fabricated and successfully used to detect Tg concentration by applying the same bio-recognition strategy and Raman interrogation through an optical fiber. This opens the possibility of transferring the Tg detection approach to the optical fiber tip to develop point-of-care platforms that can be directly integrated into fine needle aspiration biopsies.
Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Humanos , Nanopartículas Metálicas/química , Tireoglobulina , Ouro/química , Técnicas Biossensoriais/métodos , Imunoensaio/métodos , Análise Espectral Raman/métodosRESUMO
A major problem of current biomedical implants is the bacterial colonization and subsequent biofilm formation, which seriously affects their functioning and can lead to serious post-surgical complications. Intensive efforts have been directed toward the development of novel technologies that can prevent bacterial colonization while requiring minimal antibiotics doses. To this end, biocompatible materials with intrinsic antifouling capabilities are in high demand. Silk fibroin, widely employed in biotechnology, represents an interesting candidate. Here, we employ a soft-lithography approach to realize micro- and nanostructured silk fibroin substrates, with different geometries. We show that patterned silk film substrates support mammal cells (HEK-293) adhesion and proliferation, and at the same time, they intrinsically display remarkable antifouling properties. We employ Escherichia coli as representative Gram-negative bacteria, and we observe an up to 66% decrease in the number of bacteria that adhere to patterned silk surfaces as compared to control, flat silk samples. The mechanism leading to the inhibition of biofilm formation critically depends on the microstructure geometry, involving both a steric and a hydrophobic effect. We also couple silk fibroin patterned films to a biocompatible, optically responsive organic semiconductor, and we verify that the antifouling properties are very well preserved. The technology described here is of interest for the next generation of biomedical implants, involving the use of materials with enhanced antibacterial capability, easy processability, high biocompatibility, and prompt availability for coupling with photoimaging and photodetection techniques.
Assuntos
Incrustação Biológica/prevenção & controle , Nanoestruturas/química , Seda/química , Aderência Bacteriana/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Materiais Biocompatíveis/farmacologia , Biofilmes/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Células HEK293 , Humanos , Interações Hidrofóbicas e Hidrofílicas , Propriedades de SuperfícieRESUMO
Self-assembly offers a unique resource for the preparation of discrete structures at the nano- and microscale, which are either not accessible by other fabrication techniques or require highly expensive and technologically demanding processes. The possibility of obtaining spontaneous organization of separated components, whether they are molecules, polymers, nano- or micro-objects, into a larger functional unit, enables the development of ready-to-use plug and play devices and components at lower costs. Expanding the applicability of self-assembly approaches at the nanoscale to non-conventional substrates would open up new avenues towards multifunctional platforms customized for specific applications. Recently, the combination of the amazing morphological and optical features of self-assembled patterns with the intrinsic properties of optical fibers to conduct light to a remote location has demonstrated the potentiality to open up new intriguing scenarios featuring unprecedented functionalities and performances. The integration of advanced materials and structures at the nanoscale with optical fiber substrates is the idea behind the so-called lab-on-fiber technology, which is an emerging technology at the forefront of nanophotonics and nanotechnology research. Self-assembly processes can have a key role in implementing cost-effective solutions suitable for the mass production of technologically advanced platforms based on optical fibers towards their real market exploitation. Novel lab-on-fiber optrodes would arise from the sustainable integration of functional materials at the nano- and microscale onto optical fiber substrates. Such devices are able to be easily integrated in hypodermic needles and catheters for in vivo theranostics and point-of-care diagnostics, opening up new frontiers in multidisciplinary technological development to be exploited in life science applications. This work is conceived to provide an overview of the latest strategies, based on self-assembly processes, which have been implemented for the realization of lab-on-fiber optrodes with particular emphasis on the perspectives and challenges that lie ahead. We discuss the main fabrication techniques and strategies aimed at developing new multifunctional optical fiber nanoprobes and their application in real scenarios. Finally, we highlight some of the other self-assembly processes that have not yet been applied to optical fiber sensors, but have the potentiality to be exploited in the fabrication of future lab-on-fiber devices.
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Mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo A) is a neurodegenerative lysosomal storage disorder caused by the deficiency of sulphamidase enzyme (SGSH) leading to accumulation of heparan sulfate (HS). We quantitatively and structurally characterize primary stored HS and other glycosaminoglycans (GAGs) possibly accumulated through a secondary storage in brain, liver, kidney and lung of MPS IIIA mouse model. This analysis was also performed in MPS IIIA mice upon the intravenous treatment with an engineered human sulphamidase (chimeric hSGSH) capable to increase its secretion from the liver and to cross the blood-brain barrier. MPS IIIA animals showed a huge accumulation of HS, from ~15 up to ~24-times higher than wild type and also of hyaluronic acid (HA) (from 2.5 up to ~5.0-times more) and chondroitin sulfate (CS)/dermatan sulfate (DS) (from ~2 up to ~5-times more) in all studied organs. We also observed a significant increase in the overall HS charge density and in particular of 2-O-sulfation in MPS IIIA mice organs. 8 months after a systemic treatment with an engineered SGSH, the enzyme was highly efficient in the reduction of all accumulated GAGs in liver, brain and lung up to values of wild type mice. On the contrary, even if reduced, GAGs levels still remained significantly elevated in kidney. Overall data obtained by this detailed analysis of GAGs in the different organs of affected and treated animals with chimeric hSGSH may have implications for the evaluation of an effective therapeutic option of MPS IIIA and for the reduction of related neuropathology.
Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Glicosaminoglicanos/metabolismo , Hidrolases/farmacologia , Mucopolissacaridose III/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Modelos Animais de Doenças , Glicosaminoglicanos/sangue , Camundongos , Mucopolissacaridose III/sangue , Mucopolissacaridose III/genéticaRESUMO
Mucopolysaccharidoses (MPS) are characterized by mental retardation constantly present in the severe forms of Hurler (MPS I), Hunter (MPS II) and Sanfilippo (MPS III) diseases. On the contrary, mental retardation is absent in Morquio (MPS IV) and Maroteaux-Lamy (MPS VI) diseases and absent or only minimal in the attenuated forms of MPS I, II and III. Considering that MPS patients affected by mental disease accumulate heparan sulfate (HS) due to specific enzymatic defects, we hypothesized a possible correlation between urinary HS-derived glucosamine (GlcN) accumulated in tissues and excreted in biological fluids and mental retardation. 83 healthy subjects were found to excrete HS in the form of fragments due to the activity of catabolic enzymes that are absent or impaired in MPS patients. On the contrary, urinary HS in 44 patients was observed to be composed of high molecular weight polymer and fragments of various lengths depending on MPS types. On this basis we correlated mental retardation with GlcN belonging to high and low molecular weight HS. We demonstrate a positive relationship between the accumulation of high molecular weight HS and mental retardation in MPS severe compared to attenuated forms. This is also supported by the consideration that accumulation of other GAGs different from HS, as in MPS IV and MPS VI, and low molecular weight HS fragments do not impact on central nervous system disease.
Assuntos
Glucosamina/urina , Heparitina Sulfato/urina , Deficiência Intelectual/genética , Deficiência Intelectual/metabolismo , Mucopolissacaridoses/genética , Mucopolissacaridoses/psicologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Glucosamina/química , Heparitina Sulfato/química , Humanos , Lactente , Masculino , Peso Molecular , Mucopolissacaridose I/genética , Mucopolissacaridose I/psicologia , Mucopolissacaridose III/genética , Mucopolissacaridose III/psicologia , Valores de Referência , Adulto JovemRESUMO
OBJECTIVES: The aim of this study was to compare the effects of Animal-Assisted Therapy (AAT) with a standard treatment protocol in children and adolescents admitted to the psychiatry hospital for acute mental disorders. We used a methodology involving high quality standards for AAT research. DESIGN: A pre-post experimental design with a randomized controlled trial (RCT) in 34 hospitalized patients (17 treatment, 17 control) was carried out. MAIN OUTCOME MEASURES: The study focused on improvement in clinical status including, global functioning measured by the Children Global Assessment Scale (C GAS), format of care and ordinary school attendance measured by a rating scale. RESULTS: Our results indicate a statistically significant improvement in global functioning, reduction in format of care and increased ordinary school attendance in the treatment group, but not in the control group. CONCLUSIONS: Our results verify that AAT can have significant positive effects on therapeutic progress and the recovery process.
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Terapia Assistida com Animais , Transtornos Mentais/terapia , Doença Aguda , Adolescente , Animais , Criança , Cães , Feminino , Humanos , Masculino , Transtornos Mentais/epidemiologiaRESUMO
Conjugated polyelectrolytes (CPEs) have recently emerged as label-free materials for biosensing due to their intrinsic ability to transduce an amplified optical signal in response to interactions with different analytes. Herein, the conformational change of an anionic oligothiophene is exploited to generate a unique fluorescent response upon interaction with myristoylcholine (MyrCh). The variations observed in spectroscopic signals are explained in terms of a synergistic combination of hydrophobic and electrostatic forces involving the oligothiophene chains and MyrCh molecules, inducing the disassembling of oligothiophene chains. The enzyme acetylcholinesterase (AChE) is able to reverse this effect by catalyzing the hydrolysis of MyrCh; hence, its enzymatic activity can be monitored through the variation of fluorescence emission of the system. The oligothiophene sensing probe retains its conformational sensitivity with regard to the AChE-mediated cleavage of MyrCh upon immobilization onto a quartz substrate, which is accomplished by a "grafting onto" approach based on click chemistry. These results are encouraging for the further development of such a label-free system towards the fabrication of sensing devices that would incorporate CPEs and would be potentially useful for the specific detection of a wide range of bioanalytes.
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The GISTs are rare tumours but even rarer is the localization in some districts. We reported two GISTs of the duodenum, two of the omentum and peritoneum, one of the rectum and one of a Meckel's diverticulum. These exceptional locations are confirmed by the relative difficult diagnosis, obtained in some cases only by the surgical treatment despite the CT and MR. The endoscopy is useful in hemorrhagic and duodenum forms, only for the diagnosis and for the control of blood loss. Surgical treatment in all cases was decisive without the need to make use of adjuvant therapy, with positive long-term results, which excluded the disappearance of relapses or secondary lesions.
Assuntos
Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/cirurgia , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Duodenais/diagnóstico , Neoplasias Duodenais/cirurgia , Feminino , Humanos , Neoplasias do Íleo/diagnóstico , Neoplasias do Íleo/cirurgia , Masculino , Divertículo Ileal/diagnóstico , Divertículo Ileal/cirurgia , Pessoa de Meia-Idade , Omento/patologia , Omento/cirurgia , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/cirurgia , Neoplasias Retais/diagnóstico , Neoplasias Retais/cirurgia , Resultado do TratamentoRESUMO
AIM: To assess the predictive value of fluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) in early assessing response during neo-adjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer. MATERIALS AND METHODS: A systematic review was performed by search of MEDLINE Library for the following terms: "rectal carcinoma OR rectal cancer", "predictive OR prediction OR response assessment OR response OR assessment", "early OR ad interim", "therapy", "FDG OR (18)F-FDG", "PET OR PET/CT". Articles performed by the use of stand-alone PET scanners were excluded. RESULTS: 10 studies met the inclusion criteria, including 302 patients. PET/CT demonstrated a good early predictive value in the global cohort (mean sensitivity = 79%; mean specificity = 78%). SUV and its percentage decrease (response index = RI) were calculated in all studies. A higher accuracy was demonstrated for RI (mean sensitivity = 82%; pooled specificity = 85%) with a mean cut-off of 42%. The mean time point to perform PET scan during CRT resulted to be at 1.85 weeks. Some PET parameters resulted to be both predictive and not statistical predictive of response, maybe due to the small population and few studies bias. CONCLUSION: PET showed high accuracy in early prediction response during preoperative CRT, increased with the use of RI as parameter. In the era of tailored treatment, the precocious assessment of non-responder patients allows modification of the subsequent strategy especially the timing and the type of surgical approach.
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Carcinoma/diagnóstico por imagem , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Neoplasias Retais/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Carcinoma/patologia , Carcinoma/terapia , Quimiorradioterapia Adjuvante , Fluordesoxiglucose F18 , Humanos , Terapia Neoadjuvante , Prognóstico , Compostos Radiofarmacêuticos , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Resultado do TratamentoRESUMO
Pain is a subjective condition that cannot be objectively measured; for this reason, self patient-perspective is crucial. Recently, several screening tools to discriminate between nociceptive and neuropathic pain have been developed. We aimed at assessing the consistence and discrepancy of two widely used screening tools, The Douleur Neuropathique 4 (DN4) and the 6-item questionnaire (ID-Pain), by comparing their ability in discriminating neuropathic from nociceptive pain. DN4 and ID-Pain were administered to 392 Italian patients attending 16 outpatient services for peripheral nerve diseases. Based on medical history, clinical findings and diagnostic tools, patients were divided into two groups (neuropathic and nociceptive). Globally, ID-Pain identified neuropathic pain in 60 % of patients (38 % probable, 22 % likely). Interestingly also DN4 diagnosed neuropathic pain in 60 % of cases. A discrepancy was observed in 16 % of cases. DN4 and ID-Pain resulted to be highly interrelated in the identification of neuropathic pain. Sensitivity of DN4 was 82 % and specificity was 81 %, while ID-Pain (considering both probable and likely groups) showed sensitivity 78 % and specificity 74 %. Reliable screening tools for neuropathic pain are well related between them; hence, they are available for researchers and clinicians who may choose the most appropriate for their activity. Since the gold standard for the diagnosis and treatment of neuropathic pain cannot do without a neurological evaluation, perhaps DN4, that includes physician objective measures, may help reducing the percentage of dubious cases. Conversely, when needing a more agile tool (not needing a physician) ID-Pain may be adopted.
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Neuralgia/classificação , Neuralgia/diagnóstico , Medição da Dor/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: There is good evidence that radiotherapy is beneficial in advanced rectal cancer, but its application in Italy has not been investigated. METHODS: We conducted a nationwide survey among members of the Italian Society of Colo-Rectal Surgery (SICCR) on the use of radiation therapy for rectal cancer in the year 2005. Demographic, clinical and pathologic data were retrospectively collected with an online database. Italy was geographically divided into 3 regions: north, center and south which included the islands. Hospitals performing 30 or more surgeries per year were considered high volume. Factors related to radiotherapy delivery were identified with multivariate analysis. RESULTS: Of 108 centers, 44 (41%) responded to the audit. We collected data on 682 rectal cancer patients corresponding to 58% of rectal cancers operated by SICCR members in 2005. Radiotherapy was used in 307/682 (45.0%) patients. Preoperative radiotherapy was used in 236/682 (34.6%), postoperative radiotherapy in 71/682 (10.4%) cases and no radiotherapy in 375 (55.0%) cases. Of the 236 patients who underwent preoperative radiotherapy, only 24 (10.2%) received short-course radiotherapy, while 212 (89.8%) received long-course radiotherapy. Of the 339 stage II-III patients, 159 (47%) did not receive any radiotherapy. Radiotherapy was more frequently used in younger patients (P < 0.0001), in patients undergoing abdominoperineal resection (APR) (P < 0.01) and in the north and center of Italy (P < 0.001). Preoperative radiotherapy was more frequently used in younger patients (P < 0.001), in large volume centers (P < 0.05), in patients undergoing APR (P < 0.005) and in the north-center of Italy (P < 0.05). CONCLUSION: Our study first identified a treatment disparity among different geographic Italian regions. A more systematic audit is needed to confirm these results and plan adequate interventions.
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Auditoria Médica/métodos , Terapia Neoadjuvante , Neoplasias Retais/mortalidade , Neoplasias Retais/radioterapia , Idoso , Análise de Variância , Colectomia/métodos , Feminino , Seguimentos , Pesquisas sobre Atenção à Saúde , Humanos , Itália , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Razão de Chances , Dosagem Radioterapêutica , Radioterapia Adjuvante , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
In patients with distal symmetric polyneuropathy we assessed non-nociceptive Abeta- and nociceptive Adelta-afferents to investigate their role in the development of neuropathic pain. We screened 2240 consecutive patients with sensory disturbances and collected 150 patients with distal symmetric polyneuropathy (68 with pain and 82 without). All patients underwent the Neuropathic Pain Symptom Inventory to rate ongoing, paroxysmal and provoked pains, a standard nerve conduction study (NCS) to assess Abeta-fibre function, and laser-evoked potentials (LEPs) to assess Adelta-fibre function. Patients with pain had the same age (P>0.50), but a longer delay since symptom onset than those without (P<0.01). Whereas the LEP amplitude was significantly lower in patients with pain than in those without (P<0.0001), NCS data did not differ between groups (P>0.50). LEPs were more severely affected in patients with ongoing pain than in those with provoked pain (P<0.0001). Our findings indicate that the impairment of Abeta-fibres has no role in the development of ongoing or provoked pain. In patients with ongoing pain the severe LEP suppression and the correlation between pain intensity and LEP attenuation may indicate that this type of pain reflects damage to nociceptive axons. The partially preserved LEPs in patients with provoked pain suggest that this type of pain is related to the abnormal activity arising from partially spared and sensitised nociceptive terminals. Because clinical and neurophysiological abnormalities followed similar patterns regardless of aetiology, pain should be classified and treated on mechanism-based grounds.
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Neuralgia/diagnóstico , Neuralgia/etiologia , Neurofisiologia/métodos , Medição da Dor/métodos , Polineuropatias/complicações , Idoso , Potenciais Evocados/fisiologia , Feminino , Humanos , Lasers , Masculino , Pessoa de Meia-Idade , Condução Nervosa/fisiologia , Neuralgia/classificação , Exame Neurológico , Tempo de Reação/fisiologia , Estudos RetrospectivosRESUMO
Laser-evoked potentials (LEPs) are brain responses to laser radiant heat pulses and reflect the activation of Adelta nociceptors. LEPs are to date the reference standard technique for studying nociceptive pathway function in patients with neuropathic pain. To find out whether LEPs also provide a useful neurophysiological tool for assessing antinociceptive drug efficacy, in this double-blind placebo-controlled study we measured changes induced by the analgesic tramadol on LEPs in 12 healthy subjects. We found that tramadol decreased the amplitude of LEPs, whereas placebo left LEPs unchanged. The opioid antagonist naloxone partially reversed the tramadol-induced LEP amplitude decrease. We conclude that LEPs may be reliably used in clinical practice and research for assessing the efficacy of antinociceptive drugs.
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Analgésicos/uso terapêutico , Potenciais Evocados/efeitos dos fármacos , Lasers , Medição da Dor/métodos , Dor/diagnóstico , Dor/tratamento farmacológico , Adulto , Analgésicos/antagonistas & inibidores , Analgésicos Opioides/antagonistas & inibidores , Analgésicos Opioides/uso terapêutico , Estudos Cross-Over , Método Duplo-Cego , Eletroencefalografia/efeitos dos fármacos , Feminino , Humanos , Masculino , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Tramadol/antagonistas & inibidores , Tramadol/uso terapêuticoRESUMO
Carpal tunnel syndrome (CTS), a common entrapment neuropathy involving the median nerve at the wrist, frequently manifests with neuropathic pain. We sought information on pain mechanisms in CTS. We studied 70 patients with a diagnosis of CTS (117 CTS hands). We used the DN4 questionnaire to select patients with neuropathic pain, and the Neuropathic Pain Symptom Inventory (NPSI) to assess the intensity of the various qualities of neuropathic pain. All patients underwent a standard nerve conduction study (NCS) to assess the function of non-nociceptive Abeta-fibres, and the cutaneous silent period (CSP) after stimulation of the IIIrd and Vth digits, to assess the function of nociceptive Adelta-fibres. In 40 patients (75 CTS hands) we also recorded laser-evoked potentials (LEPs) in response to stimuli delivered to the median nerve territory and mediated by nociceptive Adelta-fibres. We sought possible correlations between neurophysiological data and the various qualities of neuropathic pain as assessed by the NPSI. We found that the median nerve sensory conduction velocity correlated with paroxysmal pain and abnormal sensations, whereas LEP amplitude correlated with spontaneous constant pain. Our findings suggest that whereas paroxysmal pain and abnormal sensations reflect demyelination of non-nociceptive Abeta-fibres, spontaneous constant pain arises from damage to nociceptive Adelta-fibres.
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Síndrome do Túnel Carpal/complicações , Fibras Nervosas Mielinizadas/classificação , Fibras Nervosas Mielinizadas/fisiologia , Neuralgia/etiologia , Neuralgia/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Potenciais Evocados/fisiologia , Feminino , Humanos , Lasers , Masculino , Pessoa de Meia-Idade , Condução Nervosa/fisiologia , Estudos Retrospectivos , Estatísticas não Paramétricas , Inquéritos e Questionários , Adulto JovemRESUMO
Although many patients with multiple sclerosis (MS) complain of trigeminal neuralgia (TN), its cause and mechanisms are still debatable. In a multicentre controlled study, we collected 130 patients with MS: 50 patients with TN, 30 patients with trigeminal sensory disturbances other than TN (ongoing pain, dysaesthesia, or hypoesthesia), and 50 control patients. All patients underwent pain assessment, trigeminal reflex testing, and dedicated MRI scans. The MRI scans were imported and normalised into a voxel-based, 3D brainstem model that allows spatial statistical analysis. The onset ages of MS and trigeminal symptoms were significantly older in the TN group. The frequency histogram of onset age for the TN group showed that many patients fell in the age range of classic TN. Most patients in TN and non-TN groups had abnormal trigeminal reflexes. In the TN group, 3D brainstem analysis showed an area of strong probability of lesion (P<0.0001) centred on the intrapontine trigeminal primary afferents. In the non-TN group, brainstem lesions were more scattered, with the highest probability for lesions (P<0.001) in a region involving the subnucleus oralis of the spinal trigeminal complex. We conclude that the most likely cause of MS-related TN is a pontine plaque damaging the primary afferents. Nevertheless, in some patients a neurovascular contact may act as a concurring mechanism. The other sensory disturbances, including ongoing pain and dysaesthesia, may arise from damage to the second-order neurons in the spinal trigeminal complex.
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Esclerose Múltipla/patologia , Fibras Nervosas Mielinizadas/patologia , Ponte/patologia , Nervo Trigêmeo/patologia , Neuralgia do Trigêmeo/patologia , Núcleos do Trigêmeo/patologia , Adulto , Idade de Início , Artéria Basilar/patologia , Artéria Basilar/fisiopatologia , Mapeamento Encefálico , Descompressão Cirúrgica/normas , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/fisiopatologia , Ponte/fisiopatologia , Estudos Prospectivos , Estudos Retrospectivos , Rizotomia/normas , Nervo Trigêmeo/fisiopatologia , Neuralgia do Trigêmeo/etiologia , Neuralgia do Trigêmeo/fisiopatologia , Núcleos do Trigêmeo/fisiopatologia , Degeneração Walleriana/etiologia , Degeneração Walleriana/patologia , Degeneração Walleriana/fisiopatologia , Adulto JovemRESUMO
In this study we investigate whether the cutaneous silent period (CSP)-an inhibitory response evoked in hand muscles by painful digital nerve stimulation-is useful for assessing nociceptive pathway function in patients with neuropathic pain. In 40 patients with peripheral neuropathy (21 without and 19 with neuropathic pain) we recorded the CSP in the abductor digiti minimi after fifth digit stimulation and also recorded laser evoked potentials (LEPs) after stimulation applied to the ulnar territory of the hand. Although the LEP amplitude was significantly lower in patients with pain than in those without (P < 0.005), the CSP duration did not differ between groups (P > 0.50). Pain intensity correlated significantly with LEP amplitudes (P < 0.005) but not with CSP duration (P > 0.5). Our findings indicate that the CSP is not useful for assessing nociceptive pathway function in patients with neuropathic pain.
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Potenciais Evocados/efeitos da radiação , Lasers/efeitos adversos , Músculo Esquelético/fisiologia , Neuralgia/fisiopatologia , Pele/inervação , Adulto , Idoso , Potenciais Evocados/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/efeitos da radiação , Neuralgia/diagnóstico , Estudos Prospectivos , Tempo de Reação/fisiologia , Tempo de Reação/efeitos da radiação , Pele/fisiopatologiaRESUMO
Postherpetic neuralgia is an exceptionally drug-resistant neuropathic pain. To investigate the pathophysiological mechanisms underlying postherpetic neuralgia we clinically investigated sensory disturbances, pains and itching, with an 11-point numerical rating scale in 41 patients with ophthalmic postherpetic neuralgia. In all the patients we recorded the blink reflex, mediated by non-nociceptive myelinated Abeta-fibers, and trigeminal laser evoked potentials (LEPs) related to nociceptive myelinated Adelta- and unmyelinated C-fiber activation. We also sought possible correlations between clinical sensory disturbances and neurophysiological data. Neurophysiological testing yielded significantly abnormal responses on the affected side compared with the normal side (P<0.001). The blink reflex delay correlated with the intensity of paroxysmal pain, whereas the Adelta- and C-LEP amplitude reduction correlated with the intensity of constant pain (P<0.01). Allodynia correlated with none of the neurophysiological data. Our study shows that postherpetic neuralgia impairs all sensory fiber groups. The neurophysiological-clinical correlations suggest that constant pain arises from a marked loss of nociceptive afferents, whereas paroxysmal pain is related to Abeta-fiber demyelination. These findings might be useful for a better understanding of pain mechanisms in postherpetic neuralgia.
Assuntos
Piscadela/fisiologia , Lasers , Neuralgia Pós-Herpética/diagnóstico , Neuralgia Pós-Herpética/fisiopatologia , Nervo Oftálmico/fisiopatologia , Medição da Dor/métodos , Doenças do Nervo Trigêmeo/diagnóstico , Doenças do Nervo Trigêmeo/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Doenças Desmielinizantes/patologia , Doenças Desmielinizantes/fisiopatologia , Doenças Desmielinizantes/virologia , Potenciais Somatossensoriais Evocados/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Nervosas Mielinizadas/fisiologia , Fibras Nervosas Amielínicas/fisiologia , Condução Nervosa/fisiologia , Neuralgia Pós-Herpética/etiologia , Neurofisiologia/instrumentação , Neurofisiologia/métodos , Nociceptores/fisiologia , Valor Preditivo dos Testes , Tempo de Reação/fisiologia , Doenças do Nervo Trigêmeo/etiologiaRESUMO
Although laser pulses activate concomitantly Adelta and C fibres, the corresponding brain evoked responses remain strictly limited to the Adelta component, without any potential consistent with C-fibre activation. To investigate whether this phenomenon depends on the order of arrival to the cortex ("first come first served" hypothesis) or is simply explained by A-to-C inhibition and/or lower energy associated with the desynchronised C-fibre input, we devised an experiment where the physiological order of arrival to the cortex was artificially inverted. Following a conditioning C-pulse, the cortical response to a second laser stimulus was significantly attenuated, whether it was Adelta or C. Thus, a C-volley was able to depress the response to a subsequent Adelta stimulus, in support of the "first come first served" hypothesis. However, the conditioning C-fibre stimulus attenuated significantly more a subsequent C-volley than a subsequent Adelta-volley, indicating that the suppression effect does not depend solely on the order of arrival to the cortex, but also on the ratio of energy per unit time conveyed by the successive inputs. This supports the notion that cortical evoked potentials to laser pulses (and probably to other sensory stimuli) reflect networks detecting rapid energy changes relative to a preceding baseline. The output of such networks should depend both on the time elapsed between successive inputs and on the relative energy per unit time conveyed by successive volleys. Such dedicated networks aimed at detecting energy changes may be related to orienting reactions, and can be dissociated from subjective perception.
Assuntos
Vias Aferentes/fisiologia , Córtex Cerebral/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Lasers , Inibição Neural/fisiologia , Fenômenos Fisiológicos da Pele , Sensação Térmica/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Limiar da Dor/fisiologia , Pele/inervaçãoRESUMO
Contact heat stimuli have been reported to excite mechano-thermal nociceptors and to evoke brain potentials (CHEPs) from the limbs. We investigated whether contact heat evokes reproducible CHEPs from the trigeminal territory and may prove a reliable diagnostic tool in facial neuropathic pain. We applied contact heat stimuli to the perioral and supraorbital regions; CHEPs were recorded from the vertex in 20 controls and 2 patients with facial neuropathic pains, and reflex responses from the orbicularis oculi and masticatory muscles in 5 controls. We studied the correlation between CHEP data and perceptive ratings, site of stimulation, and age. Finally, we compared CHEPs with laser evoked potentials (LEPs). Contact heat stimuli at 51 degrees C evoked vertex potentials consisting of an NP complex similar to that elicited by laser pulses, though with a latency some 100-ms longer. Perioral stimulation yielded higher pain intensity ratings, shorter latency and larger amplitude CHEPs than supraorbital stimulation. CHEP data correlated significantly with age. Contact heat stimuli at 53 degrees C evoked a blink-like response in the relaxed orbicularis oculi muscle and a silent period in the contracted masseter muscle. In patients with facial neuropathic pain the CHEP abnormalities paralleled those seen with LEPs. We were unable to achieve reproducible signals related to C-receptor stimulation by contact heat stimuli at 41 degrees C in the ten subjects in whom they were tested. Contact heat stimulation, as well as laser stimulation, easily yields large-amplitude brain potentials and nociceptive reflexes, both related to the Adelta input. However CHEPs are not suitable for C-fibres potentials recording.
Assuntos
Técnicas de Diagnóstico Neurológico , Dor Facial/diagnóstico , Dor Facial/fisiopatologia , Temperatura Alta , Fibras Nervosas , Tempo de Reação , Nervo Trigêmeo/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Potenciais Somatossensoriais Evocados , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) is a rare primary headache whose origins are unclear. To seek information on its pathophysiology, we studied the trigeminal Abeta and Adelta pathways by recording trigeminal reflexes and laser evoked potentials (LEPs) in patients with SUNCT. METHODS: Trigeminal reflexes and LEPs were recorded in 11 consecutive patients. Ten patients had neuroimaging evidence documenting idiopathic SUNCT and one had a posterior fossa tumour that compressed the trigeminal nerve thus causing symptomatic SUNCT. RESULTS: Whereas the patients with idiopathic SUNCT had normal trigeminal reflex and LEP responses, the patient with symptomatic SUNCT had abnormal responses. CONCLUSIONS: Our neurophysiological findings show that idiopathic SUNCT spares the trigeminal sensory pathways whereas symptomatic SUNCT does not. SIGNIFICANCE: Neurophysiological testing can easily differentiate the idiopathic and symptomatic forms of SUNCT. It also suggests that the two forms are pathophysiologically distinct entities.