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2.
Brain ; 140(10): 2557-2569, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28969380

RESUMO

Non-freezing cold injury develops after sustained exposure to cold temperatures, resulting in tissue cooling but not freezing. This can result in persistent sensory disturbance of the hands and feet including numbness, paraesthesia and chronic pain. Both vascular and neurological aetiologies of this pain have been suggested but remain unproven. We prospectively approached patients referred for clinical assessment of chronic pain following non-freezing cold injury between 12 February 2014 and 30 November 2016. Of 47 patients approached, 42 consented to undergo detailed neurological evaluations including: questionnaires to detail pain location and characteristics, structured neurological examination, quantitative sensory testing, nerve conduction studies and skin biopsy for intraepidermal nerve fibre assessment. Of the 42 study participants, all had experienced non-freezing cold injury while serving in the UK armed services and the majority were of African descent (76.2%) and male (95.2%). Many participants reported multiple exposures to cold. The median time between initial injury and referral was 3.72 years. Pain was principally localized to the hands and the feet, neuropathic in nature and in all study participants associated with cold hypersensitivity. Clinical examination and quantitative sensory testing were consistent with a sensory neuropathy. In all cases, large fibre nerve conduction studies were normal. The intraepidermal nerve fibre density was markedly reduced with 90.5% of participants having a count at or below the 0.05 centile of published normative controls. Using the Neuropathic Pain Special Interest Group of the International Association for the Study of Pain grading for neuropathic pain, 100% had probable and 95.2% definite neuropathic pain. Chronic non-freezing cold injury is a disabling neuropathic pain disorder due to a sensory neuropathy. Why some individuals develop an acute painful sensory neuropathy on sustained cold exposure is not yet known, but individuals of African descent appear vulnerable. Screening tools, such as the DN4 questionnaire, and treatment algorithms for neuropathic pain should now be used in the management of these patients.


Assuntos
Lesão por Frio/complicações , Neuralgia/etiologia , Limiar da Dor/fisiologia , Adulto , Feminino , Humanos , Hiperalgesia/fisiopatologia , Masculino , Condução Nervosa/fisiologia , Neuralgia/psicologia , Exame Neurológico , Medição da Dor , Nervos Periféricos/fisiopatologia , Qualidade de Vida/psicologia , Pele/inervação , Pele/patologia , Inquéritos e Questionários , Adulto Jovem
3.
Ann Neurol ; 82(1): 44-56, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28598015

RESUMO

OBJECTIVE: To determine the utility of skin biopsies as a biomarker of disease severity in subjects with amyloid neuropathy. METHODS: Five groups of patients were studied: (1) transthyretin (TTR) familial amyloidotic polyneuropathy (FAP; n = 20), (2) TTR mutation carriers without peripheral neuropathy (TTR-noPN; n = 10), (3) healthy controls (n = 20), (4) diabetic neuropathy disease controls (n = 20), and (5) patients with light-chain (AL) amyloid (n = 2). All subjects underwent neurological examination and 3mm skin biopsies. Sections were stained with anti-PGP9.5, anti-TTR, and Congo red. Intraepidermal (IENFD), sweat gland (SGNFD), and pilomotor nerve fiber densities (PMNFD) were measured. Correlations between the amount of amyloid present (amyloid burden), fiber subtype, and Neuropathy Impairment Score in the Lower Limbs (NIS-LL) were evaluated. RESULTS: IENFD, SGNFD, and PMNFD were all significantly reduced in TTR-FAP patients versus healthy controls, whereas TTR-noPN subjects had intermediate reductions. Lower nerve fiber densities were associated with NIS-LL (p < 0.001). Congo red staining revealed brilliant red amyloid deposits confirmed by apple-green birefringence within dermal collagen, sweat glands, and arrector pili that engulfed axons. The diagnostic sensitivity and specificity to detect amyloid in skin were 70% and 100%. Both AL amyloidosis and 2 of 10 TTR-noPN subjects were Congo red-positive. Amyloid burden correlated with IENFD (r = -0.63), SGNFD (r = -0.67), PMNFD (r = -0.50), and NIS-LL (r = -0.57). Wild-type TTR staining was less prominent in TTR-FAP patients. INTERPRETATION: Cutaneous amyloid was detected in 70% of TTR-FAP and 20% of TTR-noPN subjects. Amyloid burden correlated strongly with reductions in IENFD, SGNFD, PMNFD, and NIS-LL. Skin is an attractive tissue to establish an amyloid diagnosis, and amyloid burden has potential as a biomarker to detect treatment effect in TTR-FAP drug trials. Ann Neurol 2017;82:44-56.


Assuntos
Neuropatias Amiloides Familiares/metabolismo , Neuropatias Amiloides Familiares/patologia , Amiloide/metabolismo , Fibras Nervosas/patologia , Pele/metabolismo , Pele/patologia , Glândulas Sudoríparas/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neuropatias Amiloides Familiares/genética , Biomarcadores/metabolismo , Estudos de Casos e Controles , Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/patologia , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Pré-Albumina/genética , Índice de Gravidade de Doença , Adulto Jovem
4.
Pain ; 157(12): 2843-2853, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27776012

RESUMO

We compared patterns of intraepidermal nerve fibers and mechanoreceptors from affected and unaffected plantar skin from patients with pachyonychia congenita (PC) and control subjects. Plantar biopsies from 10 genetically confirmed patients with PC (with a mutation in KRT6A) were performed at the ball of the foot (affected skin) and the arch (unaffected) and were compared to biopsies from corresponding locations in 10 control subjects. Tissue was processed to visualize intraepidermal nerve fibers (IENF) (PGP9.5), subsets of IENF (CGRP, substance P, tyrosine hydroxylase), myelinated nerve fiber (neurofilament H, NFH), blood vessels (CD31), Meissner corpuscles, and Merkel cells (MCs). Structures were quantified using stereology or validated quantification methods. We observed that PC-affected plantar skin had significantly lower sweat gland innervation (sweat gland nerve fiber density) and reduced numbers of Meissner corpuscles compared to PC-unaffected or anatomically matched control skin. In contrast, Merkel cell densities and blood vessel counts were higher in PC-affected skin compared to either control or PC-unaffected skin. There were no differences in myelinated nerve fiber densities, SP, or CGRP between the groups. Pressure pain thresholds in PC-affected skin were lower compared to PC-unaffected and anatomically matched control skin. Additionally, MC densities in callused plantar skin from healthy runners with callus and one subject with a nonpainful palmoplantar keratoderma (AQP5 mutation) were similar to PC-unaffected and control skin consistent with callus alone not being sufficient to increase MC number. These findings suggest that alterations in PC extend beyond keratinocytes and may provide strategies to study neuropathic pain in PC.


Assuntos
Fibras Nervosas Mielinizadas/patologia , Paquioníquia Congênita/complicações , Doenças do Sistema Nervoso Periférico/etiologia , Doenças do Sistema Nervoso Periférico/patologia , Adulto , Idoso , Animais , Aquaporina 5/genética , Biópsia , Feminino , Humanos , Queratina-20/metabolismo , Queratina-6/genética , Masculino , Células de Merkel/patologia , Pessoa de Meia-Idade , Mutação/genética , Fibras Nervosas Mielinizadas/metabolismo , Proteínas de Neurofilamentos/metabolismo , Paquioníquia Congênita/genética , Limiar da Dor/fisiologia , Pele/inervação , Pele/metabolismo , Ubiquitina Tiolesterase/metabolismo
5.
Int J Vasc Med ; 2012: 187872, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22489269

RESUMO

The management of atherosclerotic carotid occlusive disease for stroke prevention has entered a time of dramatic change. Improvements in medical management have begun to challenge traditional interventional approaches to asymptomatic carotid stenosis. Simultaneously, carotid artery stenting (CAS) has emerged as an alternative to carotid endarterectomy (CE). Finally, multiple factors beyond degree of stenosis and symptom status now mitigate clinical decision making. These factors include brain perfusion, plaque morphology, and patency of intracranial collaterals (circle of Willis). With all of these changes, it seems prudent to review the role of carotid duplex ultrasonography in the management of atherosclerotic carotid occlusive disease for stroke prevention. Carotid duplex ultrasonography (CDU) for initial and serial imaging of the carotid bifurcation remains an essential component in the management of carotid bifurcation disease. However, correlative axial imaging modalities (computer tomographic angiography (CTA) and contrast-enhanced magnetic resonance angiography (CE-MRA)) increasingly aid in the assessment of individual stroke risk and are important in treatment decisions. The purpose of this paper is twofold: (1) to discuss foundations and advances in CDU and (2) to evaluate the current role of CDU, in light of other imaging modalities, in the clinical management of carotid atherosclerosis.

6.
Am Surg ; 77(9): 1117-30, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21944619

RESUMO

The role of carotid artery stenting (CAS) as an alternative to carotid endarterectomy for the treatment of extracranial carotid occlusive disease for stroke prevention continues to evolve. Although technical and device refinements aimed at making CAS safer continue to this day, safety as measured by 30-day and 1-year outcomes has been the primary recipient of regulatory and practice attention. Relatively less emphasis has been placed on the incidence of recurrent stenosis after CAS and the efficacy of CAS in late stroke prevention. Data on late outcomes of CAS, including factors of potential influence, have been emerging and are addressed in this review.


Assuntos
Implante de Prótese Vascular/instrumentação , Estenose das Carótidas/cirurgia , Stents , Acidente Vascular Cerebral/prevenção & controle , Estenose das Carótidas/complicações , Humanos , Incidência , Desenho de Prótese , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Resultado do Tratamento , Estados Unidos/epidemiologia
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