RESUMEN
The aim of this study was to describe the results of a Brazilian Consensus on Small Fiber Neuropathy (SFN). Fifteen neurologists (members of the Brazilian Academy of Neurology) reviewed a preliminary draft. Eleven panelists got together in the city of Fortaleza to discuss and finish the text for the manuscript submission. Small fiber neuropathy can be defined as a subtype of neuropathy characterized by selective involvement of unmyelinated or thinly myelinated sensory fibers. Its clinical picture includes both negative and positive manifestations: sensory (pain/dysesthesias/pruritus) or combined sensory and autonomic complaints, associated with an almost entirely normal neurological examination. Standard electromyography is normal. A growing list of medical conditions is associated with SFN. The classification of SFN may also serve as a useful terminology to uncover minor discrepancies in the normal values from different neurophysiology laboratories. Several techniques may disclose sensory and/or autonomic impairment. Further studies are necessary to refine these techniques and develop specific therapies.
Asunto(s)
Neuropatía de Fibras Pequeñas/diagnóstico , Neuropatía de Fibras Pequeñas/patología , Vías Autónomas/patología , Biopsia , Brasil , Electromiografía/métodos , Humanos , Fibras Nerviosas Amielínicas/patología , Piel/patología , Neuropatía de Fibras Pequeñas/etiología , Neuropatía de Fibras Pequeñas/fisiopatologíaRESUMEN
ABSTRACT The aim of this study was to describe the results of a Brazilian Consensus on Small Fiber Neuropathy (SFN). Fifteen neurologists (members of the Brazilian Academy of Neurology) reviewed a preliminary draft. Eleven panelists got together in the city of Fortaleza to discuss and finish the text for the manuscript submission. Small fiber neuropathy can be defined as a subtype of neuropathy characterized by selective involvement of unmyelinated or thinly myelinated sensory fibers. Its clinical picture includes both negative and positive manifestations: sensory (pain/dysesthesias/pruritus) or combined sensory and autonomic complaints, associated with an almost entirely normal neurological examination. Standard electromyography is normal. A growing list of medical conditions is associated with SFN. The classification of SFN may also serve as a useful terminology to uncover minor discrepancies in the normal values from different neurophysiology laboratories. Several techniques may disclose sensory and/or autonomic impairment. Further studies are necessary to refine these techniques and develop specific therapies.
RESUMO O objetivo deste estudo é descrever os resultados de um Consenso Brasileiro sobre Neuropatia de Fibras Finas (NFF). Quinze neurologistas (membros da Academia Brasileira de Neurologia) revisaram uma versão preliminar do artigo. Onze panelistas se reuniram na cidade de Fortaleza para discutir e terminar o texto para a submissão do manuscrito. NFF pode ser definida como um subtipo de neuropatia caracterizada pelo envolvimento seletivo de fibras sensitivas amielínicas ou pouco mielinizadas. Seu quadro clínico inclui manifestações negativas e positivas: sensitivas (dor/disestesias/prurido) ou queixas sensitivas e autonômicas combinadas, associadas a exame neurológico quase totalmente normal. A eletromiografia convencional é normal. Uma lista crescente de condições médicas causa NFF. NFF também pode servir como uma terminologia útil para referenciar pequenas discrepâncias nos valores normais de diferentes laboratórios de neurofisiologia. Diferentes técnicas podem evidenciar anormalidades sensitivas e/ou autonômicas. São necessários mais estudos para refiná-las e para o desenvolvimento de terapias específicas.
Asunto(s)
Humanos , Neuropatía de Fibras Pequeñas/diagnóstico , Neuropatía de Fibras Pequeñas/patología , Piel/patología , Biopsia , Brasil , Vías Autónomas/patología , Fibras Nerviosas Amielínicas/patología , Electromiografía/métodos , Neuropatía de Fibras Pequeñas/etiología , Neuropatía de Fibras Pequeñas/fisiopatologíaRESUMEN
BACKGROUND/AIMS: Micrurus is one of the four snake genera of medical importance in Brazil. Coral snakes have a broad geographic distribution from the southern United States to Argentina. Micrurine envenomation is characterized by neurotoxic symptoms leading to dyspnea and death. Moreover, various local manifestations, including edema formation, have been described in patients bitten by different species of Micrurus. Thus, we investigated the ability of Micrurus lemniscatus venom (MLV) to induce local edema. We also explored mechanisms underlying this effect, focusing on participation of neuropeptides and mast cells. METHODOLOGY/PRINCIPAL FINDINGS: Intraplantar injection of MLV (1-10 µg/paw) in rats caused dose- and time-dependent edema with a peak between 15 min and 1 h after injection. MLV also induced degranulation of peritoneal mast cells (MCs). MC depletion by compound 48/80 markedly reduced MLV-induced edema. Pre-treatment (30 min) of rats with either promethazine a histamine H1 receptor antagonist or methysergide, a nonselective 5-HT receptor antagonist, reduced MLV-induced edema. However, neither thioperamide, a histamine H3/H4 receptor antagonist, nor co-injection of MLV with HOE-140, a BK2 receptor antagonist, altered the response. Depletion of neuropeptides by capsaicin or treatment of animals with NK1- and NK2-receptor antagonists (SR 140333 and SR 48968, respectively) markedly reduced MLV-induced edema. CONCLUSIONS/SIGNIFICANCE: In conclusion, MLV induces paw edema in rats by mechanisms involving activation of mast cells and substance P-releasing sensory C-fibers. Tachykinins NKA and NKB, histamine, and serotonin are major mediators of the MLV-induced edematogenic response. Targeting mast cell- and sensory C-fiber-derived mediators should be considered as potential therapeutic approaches to interrupt development of local edema induced by Micrurus venoms.
Asunto(s)
Edema/metabolismo , Venenos Elapídicos/toxicidad , Mediadores de Inflamación/metabolismo , Mastocitos/metabolismo , Neuropéptidos/metabolismo , Animales , Degranulación de la Célula , Serpientes de Coral , Edema/inducido químicamente , Edema/patología , Venenos Elapídicos/antagonistas & inhibidores , Masculino , Mastocitos/efectos de los fármacos , Mastocitos/patología , Fibras Nerviosas Amielínicas/metabolismo , Fibras Nerviosas Amielínicas/patología , Ratas Wistar , p-Metoxi-N-metilfenetilamina/farmacologíaRESUMEN
El diagnóstico de la Neuropatía Diabética Periférica es tardío. Identificar maniobras semiológicas que permitan el diagnóstico precoz de la neuropatía diabética. Estudio de casos, analítico, transversal y operacional: personas sanas, prediabéticos, diabéticos de reciente diagnóstico y diabéticos de más de 5 años de diagnóstico. Se realizaron 2 evaluaciones: la primera por dos investigadores a ciegas que evaluaron: sensibilidad mecánica, reflejos osteotendinosos y palestesia. También se evaluación de la córnea con Rosa de Bengala y se aplicó el Cuestionario DN4. Segunda Evaluación: von Frey. Biopsia de Piel: será tratada con inmunohistoquímica de campo claro. Muestra de 25 personas. El DN4, obtuvo 14 personas con dolor neuropático. La tinción con Rosa de Bengala obtuvo 7 pacientes con ojo seco y una diabética con más de 5 años de diagnóstico con alteración corneal. En la evaluación con von Frey hubo 3 pacientes con zonas sin respuesta al microfilamento de 10 g. La inmunohistoquímica demostró que el número y densidad de fibras nerviosas tuvo un promedio de 7 fibras/campo en sanos y a partir de los prediabéticos disminuyó desde 4,4 fibras/campo. El ojo seco justifica la evaluación periódica del internista. La evaluación de la sensibilidad con los filamentos de von Frey señala que el monofilamento utilizado individualmente tiene menor eficiencia diagnóstica. La biopsia demostró una capacidad diagnóstica precoz de esta, aún en ausencia de síntomas. La biopsia de piel con cuantificación del número y densidad de fibras, es útil en la identificación temprana de lesión de fibras C y se comporta como método de pesquisa.
The diagnosis of Diabetic Peripheral Neuropathy is made lately. To identify semiological maneuvres that allow early diagnosis of diabetic neuropathy. Case studie, analitic, transversal and operational, without therapeutic intervention in healthy, prediabetic, diabetic and newly diagnosed diabetes over 5 years of diagnosis. The First Assessment was: conducted by two blinded researchers measuring mechanical sensitivity, tendon reflexes, and palesthesia. Von Frey 3) Skin biopsy: the cornea Bengal Rose and DN4 Questionnaire. The second assessment was done with brightfield immunohistochemistry. The sample consisted of 25 persons. The DN4 had 14 people with neuropathic pain. Staining with Rose Bengal scored 7 persons. The second Assessment was done in patients with dry eye and over 5 years of diagnosis of corneal disorder. The evaluation with von Frey 3 patients with no response areas were obtained at 10 g microfilament. Immunohistochemistry showed that the number and density of nerve fibers had an average of 7 fibers in healthy and from prediabetic decreased to 4.4 fibers. The Dry eye justifies the periodic evaluation by the internist. The evaluation of sensitivity with von Frey hairs used indicate that the monofilament has a lower diagnostic efficiency individually. The biopsy revealed an early diagnostic capacity in this condition in the absence of symptoms. Skin biopsy with quantification of the number and density of nerve fibers is useful in early identification of C fiber damage and behaves like screening method.
Asunto(s)
Humanos , Masculino , Femenino , Biopsia/métodos , Diabetes Mellitus , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Fibras Nerviosas Amielínicas/patología , Neuropatías Diabéticas/diagnóstico , Medicina Interna , NeurologíaRESUMEN
Neuropsychiatric syndromes are highly prevalent in Alzheimer's disease (AD), but their neurobiology is not completely understood. New methods in functional magnetic resonance imaging, such as intrinsic functional connectivity or "resting-state" analysis, may help to clarify this issue. Using such approaches, alterations in the default-mode and salience networks (SNs) have been described in Alzheimer's, although their relationship with specific symptoms remains unclear. We therefore carried out resting-state functional connectivity analysis with 20 patients with mild to moderate AD, and correlated their scores on neuropsychiatric inventory syndromes (apathy, hyperactivity, affective syndrome, and psychosis) with maps of connectivity in the default mode network and SN. In addition, we compared network connectivity in these patients with that in 17 healthy elderly control subjects. All analyses were controlled for gray matter density and other potential confounds. Alzheimer's patients showed increased functional connectivity within the SN compared with controls (right anterior cingulate cortex and left medial frontal gyrus), along with reduced functional connectivity in the default-mode network (bilateral precuneus). A correlation between increased connectivity in anterior cingulate cortex and right insula areas of the SN and hyperactivity syndrome (agitation, irritability, aberrant motor behavior, euphoria, and disinhibition) was found. These findings demonstrate an association between specific network changes in AD and particular neuropsychiatric symptom types. This underlines the potential clinical significance of resting state alterations in future diagnosis and therapy.
Asunto(s)
Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/psicología , Descanso/fisiología , Anciano , Enfermedad de Alzheimer/patología , Mapeo Encefálico , Humanos , Imagen por Resonancia Magnética , Fibras Nerviosas Amielínicas/patología , Fibras Nerviosas Amielínicas/fisiología , Vías Nerviosas/fisiopatología , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Análisis de RegresiónRESUMEN
OBJECTIVE: Cortical and subcortical gray matter abnormalities have been reported in individuals at high genetic risk for bipolar disorder, but the findings are inconsistent. The aim of this study was to review the available literature to identify common findings that could represent brain structural vulnerability factors for bipolar disorder and to discuss challenges for the advancement of the field. METHOD: A systematic search was conducted using the PubMed database to identify all original articles investigating cortical or subcortical gray matter abnormalities in first-degree relatives of bipolar disorder patients. RESULTS: Very few findings were replicated, with the exception of larger insular cortex volumes in adult first-degree relatives and larger right inferior frontal gyrus in offspring of probands with bipolar disorder, both when compared with healthy controls. Isolated findings included decreased gray matter density in the left thalamus, decreased gray matter volumes in the left hippocampus and parahippocampal gyrus, and thicker right hippocampus in unaffected first-degree relatives. Genetic liability for bipolar disorder was associated with gray matter volumes in regions of the anterior cingulate cortex, ventral striatum, medial frontal gyrus, right precentral gyrus, right insular cortex, and medial orbital gyrus. Some studies found no evidence for gray matter abnormalities in first-degree relatives of bipolar disorder patients. CONCLUSIONS: Possible reasons for the discrepancies of findings across studies include small samples sizes, small effect size of susceptibility genes, the phenotypic heterogeneity of bipolar disorder, and the possible confounding effect of other Axis I psychopathologies among the relatives of patients. Future multisite, prospective, large studies with more homogeneous samples would be a key strategy to advance the field. The ultimate benefit would be an understanding of how to use brain imaging tools to identify individuals at increased risk for bipolar disorder and develop preventive strategies for that population.
Asunto(s)
Trastorno Bipolar/patología , Encéfalo/patología , Fibras Nerviosas Amielínicas/patología , Adulto , Trastorno Bipolar/etiología , Trastorno Bipolar/genética , Predisposición Genética a la Enfermedad , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Neuroimagen , Factores de RiesgoRESUMEN
Nearly one-third of patients with obsessive-compulsive disorder (OCD) fail to respond to adequate therapeutic approaches such as serotonin reuptake inhibitors and/or cognitive-behavioral therapy (CBT). This study investigated structural magnetic resonance imaging (MRI) correlates as potential pre-treatment brain markers to predict treatment response in treatment-naïve OCD patients randomized between trials of fluoxetine or CBT. Treatment-naïve OCD patients underwent structural MRI scans before randomization to a 12-week clinical trial of either fluoxetine or group-based CBT. Voxel-based morphometry was used to identify correlations between pretreatment regional gray matter volume and changes in symptom severity on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Brain regional correlations of treatment response differed between treatment groups. Notably, symptom improvement in the fluoxetine treatment group (n=14) was significantly correlated with smaller pretreatment gray matter volume within the right middle lateral orbitofrontal cortex (OFC), whereas symptom improvement in the CBT treatment group (n=15) was significantly correlated with larger pretreatment gray matter volume within the right medial prefrontal cortex (mPFC). No significant a priori regional correlations of treatment response were identified as common between the two treatment groups when considering the entire sample (n=29). These findings suggest that pretreatment gray matter volumes of distinct brain regions within the lateral OFC and mPFC were differentially correlated to treatment response to fluoxetine versus CBT in OCD patients. This study further implicates the mPFC in the fear/anxiety extinction process and stresses the importance of lateral portions of the OFC in mediating fluoxetine's effectiveness in OCD. Clinical registration information: http://clinicaltrials.gov-NCT00680602.
Asunto(s)
Terapia Cognitivo-Conductual , Fluoxetina/uso terapéutico , Fibras Nerviosas Amielínicas/patología , Trastorno Obsesivo Compulsivo/patología , Trastorno Obsesivo Compulsivo/terapia , Corteza Prefrontal/patología , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Adulto , Atrofia/patología , Femenino , Humanos , Masculino , Neuroimagen , Pruebas Neuropsicológicas , Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Valor Predictivo de las Pruebas , Corteza Prefrontal/efectos de los fármacos , Psicoterapia de Grupo , Resultado del TratamientoRESUMEN
Most of the reports about an altered baroreflex attribute this condition to the diabetic efferent neuropathy of the aortic depressor nerve (ADN) (afferent arm of the baroreflex less explored). We evaluated the ADN ultrastructural alterations caused by long term experimental diabetes and the effects of insulin treatment. Wistar rats (N=14) received a single intravenous injection of streptozotocin (40 mg/kg) 12 weeks before the experiment. Control animals (N=9) received vehicle (citrate buffer). Insulin treated animals (N=8) received a single subcutaneous injection of insulin daily. Under pentobarbital anesthesia the ADNs were isolated and had their spontaneous activity recorded. Afterwards, proximal and distal segments of the nerves were prepared for transmission electron microscopy study. Morphometry of the unmyelinated fibers was carried out with the aid of computer software. ADN of the diabetic animals showed axonal atrophy for myelinated fibers, with more pronounced alterations of the myelin sheath, such as myelin infolding and out folding, presence of myelin balls and very thin myelin sheath in relation to the axonal size, particularly for the small myelinated fibers becoming evident. No differences were observed in myelinated fiber number and their density, as well as on the fascicular area. Unmyelinated fiber number was significantly larger in the diabetic group while fiber diameter was significantly smaller compared to control. This result suggests axonal atrophy or, if associated to the larger number of fibers present in this group, could indicate fiber sprouting. These alterations were more evident in the distal segments of the nerves and were moderated by insulin treatment.
Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/patología , Neuropatías Diabéticas/tratamiento farmacológico , Neuropatías Diabéticas/patología , Corazón/inervación , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Nervios Periféricos/patología , Animales , Glucemia/metabolismo , Presión Sanguínea/fisiología , Peso Corporal , Interpretación Estadística de Datos , Frecuencia Cardíaca/fisiología , Masculino , Microscopía Electrónica de Transmisión , Fibras Nerviosas Amielínicas/patología , Fibras Nerviosas Amielínicas/ultraestructura , Nervios Periféricos/ultraestructura , Ratas , Ratas WistarRESUMEN
Animal models for mechanical pressure or heat nociception usually only measure the threshold response latency. In this study, the effect of typical sensitising treatments on the lasting nocifensive behaviour elicited after a supra-threshold heating stimulus - the hyperpathic component of hypernociception - was assessed. Male Wistar rats received either intra-plantar (i.pl.) injection of 350ng PGE(2) (50microL) or topical application (t.a.) of 100% dimethylsulfoxide (DMSO), and 10mM capsaicin. One hour after the paw treatments the number of nocifensive events (NNE) was scored hourly (6h), for 5min, immediately after a hind paw immersion in hot water (50 degrees C/7s). PGE(2), DMSO and capsaicin increased the NNE -induced by the supra-threshold stimuli. Indomethacin (2.5mg/kg i.p.), given 30min before paw treatments, completely inhibited NNE in all groups (P<0.01). However, indomethacin given 60min after PGE(2) did not reverse this sensitisation. PGE(2) and DMSO did not lower the heat threshold in the paw withdrawal test, although carrageenan and capsaicin were effective (P<0.05). Capsaicin neonatal treatment (CNT) (50mg/kg) reduced the sensitisation induced by DMSO and capsaicin (P<0.01), but not that induced by PGE(2). These data suggest that the heat-induced lasting nociception is probably conveyed by Aeth nociceptors, and PGE(2) seems to be more selective to induce this phenomenon than the thermal threshold lowering. In addition, this hyperpathic effect induced by DMSO and capsaicin seems to be indirectly mediated by PGE(2) and C-fibres.
Asunto(s)
Dinoprostona/farmacología , Calor , Hiperalgesia/patología , Fibras Nerviosas Mielínicas/patología , Dolor/fisiopatología , Animales , Antiinflamatorios no Esteroideos/farmacología , Capsaicina/antagonistas & inhibidores , Capsaicina/farmacología , Dimetilsulfóxido/antagonistas & inhibidores , Dimetilsulfóxido/farmacología , Dinoprostona/antagonistas & inhibidores , Indometacina/farmacología , Masculino , Fibras Nerviosas Mielínicas/fisiología , Fibras Nerviosas Amielínicas/efectos de los fármacos , Fibras Nerviosas Amielínicas/patología , Nociceptores/efectos de los fármacos , Dolor/inducido químicamente , Dimensión del Dolor , Umbral del Dolor/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
We have demonstrated that phrenic nerves' large myelinated fibers in streptozotocin (STZ)-induced diabetic rats show axonal atrophy, which is reversed by insulin treatment. However, studies on structural abnormalities of the small myelinated and the unmyelinated fibers in the STZ-model of neuropathy are limited. Also, structural changes in the endoneural vasculature are not clearly described in this model and require detailed study. We have undertaken morphometric studies of the phrenic nerve in insulin-treated and untreated STZ-diabetic rats and non-diabetic control animals over a 12-week period. The presence of neuropathy was assessed by means of transmission electron microscopy, and morphometry of the unmyelinated fibers was performed. The most striking finding was the morphological evidence of small myelinated fiber neuropathy due to the STZ injection, which was not protected or reversed by conventional insulin treatment. This neuropathy was clearly associated with severe damage of the endoneural vessels present on both STZ groups, besides the insulin treatment. The STZ-diabetes model is widely used to investigate experimental diabetic neuropathies, but few studies have performed a detailed assessment of either unmyelinated fibers or capillary morphology in this animal model. The present study adds useful information for further investigations on the ultrastructural basis of nerve function in diabetes.