RESUMO
BACKGROUND: Following spinal cord injury (SCI), disease processes spread gradually along the spinal cord forming a spatial gradient with most pronounced changes located at the lesion site. However, the dynamics of this gradient in SCI patients is not established. OBJECTIVE: This study tracks the spatiotemporal dynamics of remote anterograde and retrograde spinal tract degeneration in the upper cervical cord following SCI over two years utilizing quantitative MRI. METHODS: Twenty-three acute SCI patients (11 paraplegics, 12 tetraplegics) and 21 healthy controls were scanned with a T1-weighted sequence for volumetry and a FLASH sequence for myelin-sensitive magnetization transfer saturation (MTsat) of the upper cervical cord. We estimated myelin content from MTsat maps within the corticospinal tracts (CST) and dorsal columns (DC) and measured spinal cord atrophy by means of left-right width (LRW) and anterior-posterior width (APW) on the T1-weighted images across cervical levels C1-C3. MTsat in the CST and LRW were considered proxies for retrograde degeneration, while MTsat in the DC and APW provided evidence for anterograde degeneration, respectively. Using regression models, we compared the temporal and spatial trajectories of these MRI readouts between tetraplegics, paraplegics, and controls over a 2-year period and assessed their associations with clinical improvement. RESULTS: Linear rates and absolute differences in myelin-sensitive MTsat indicated retrograde and anterograde neurodegeneration in the CST and DC, respectively. Changes in MTsat within the CST and in LRW progressively developed over time forming a gradient towards lower cervical levels by 2 years after injury, especially in tetraplegics (change per cervical level in MTsat: -0.247 p.u./level, p = 0.034; in LRW: -0.323 mm/level, p = 0.024). MTsat within the DC was already decreased at cervical levels C1-C3 at baseline (1.5 months after injury) in both tetra- and paraplegics, while linear decreases in APW over time were similar across C1-C3, preserving the spatial gradient. The relative improvement in light touch score was associated with MTsat within the DC at baseline (rs = 0.575, p = 0.014). CONCLUSION: Rostral and remote to the injury, the CST and DC show ongoing structural changes, indicative of myelin reductions and atrophy within 2 years after SCI. While anterograde degeneration in the DC was already detectable uniformly at C1-C3 early following SCI, retrograde degeneration in the CST developed over time revealing specific spatial and temporal neurodegenerative gradients. Disentangling and quantifying such dynamic pathological processes may provide biomarkers for regenerative and remyelinating therapies along entire spinal pathways.
Assuntos
Degeneração Retrógrada , Traumatismos da Medula Espinal , Humanos , Estudos Longitudinais , Degeneração Retrógrada/complicações , Degeneração Retrógrada/patologia , Traumatismos da Medula Espinal/patologia , Medula Espinal/patologia , Tratos Piramidais/patologia , Atrofia/patologiaRESUMO
BACKGROUND: Loss of retinal ganglion cells after occipital lobe damage is known to occur through transsynaptic retrograde degeneration in congenital lesions; however, studies of this phenomenon in acquired pathology, such as strokes affecting postgenicular visual pathway, are scant. We studied a cohort of adult patients with known onset of occipital lobe stroke to look for the presence, rate, and timing of macular ganglion cell loss on optical coherence tomography. METHODS: Retrospective review of patients seen in tertiary neuro-ophthalmology practice with homonymous hemianopia secondary to occipital lobe stroke of known onset. Optical coherence tomography of the macular ganglion cell complex (GCC) was performed, and hemifields corresponding to the side of the visual field (VF) defect were compared with the control retinal hemifield. RESULTS: Fifteen patients with homonymous VF defects were included in the study, and 8 of these (53.3%) demonstrated GCC hemifield thickness of less than 90% on the side corresponding to VF loss including 2/9 (22%) patients who had a stroke less than 2.5 years ago and 6/6 (100%) patients who had a stroke longer than 2.5 years ago. The amount of hemifield atrophy correlated to the logarithm of time since stroke onset ( P =0.030) but not age ( P = 0.95) or mean deviation on VF ( P = 0.19). Three patients with longitudinal data showed GCC thinning rates of 1.99, 5.13, and 5.68 µm per year. CONCLUSION: Transsynaptic retrograde degeneration occurs after occipital lobe stroke as early as 5.5 months after injury and was observed in all patients 2.5 years after stroke.
Assuntos
Degeneração Retrógrada , Acidente Vascular Cerebral , Humanos , Adulto , Degeneração Retrógrada/complicações , Degeneração Retrógrada/patologia , Fibras Nervosas/patologia , Vias Visuais/patologia , Testes de Campo Visual , Transtornos da Visão , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Infarto Cerebral/complicações , Lobo Occipital/diagnóstico por imagem , Lobo Occipital/patologia , Tomografia de Coerência Óptica/métodosRESUMO
Lesions of striate cortex (V1) trigger massive retrograde degeneration of neurons in the LGN. In primates, these lesions also lead to scotomas, within which conscious vision is abolished. Mediation of residual visual capacity within these regions (blindsight) has been traditionally attributed to an indirect visual pathway to the extrastriate cortex, which involves the superior colliculus and pulvinar complex. However, recent studies have suggested that preservation of the LGN is critical for behavioral evidence of blindsight, raising the question of what type of visual information is channeled by remaining neurons in this structure. A possible contribution of LGN neurons to blindsight is predicated on two conditions: that the neurons that survive degeneration remain visually responsive, and that their receptive fields continue to represent the region of the visual field inside the scotoma. We tested these conditions in male and female marmoset monkeys (Callithrix jacchus) with partial V1 lesions at three developmental stages (early postnatal life, young adulthood, old age), followed by long recovery periods. In all cases, recordings from the degenerated LGN revealed neurons with well-formed receptive fields throughout the scotoma. The responses were consistent and robust, and followed the expected eye dominance and retinotopy observed in the normal LGN. The responses had short latencies and preceded those of neurons recorded in the extrastriate middle temporal area. These findings suggest that the pathway that links LGN neurons to the extrastriate cortex is physiologically viable and can support residual vision in animals with V1 lesions incurred at various ages.SIGNIFICANCE STATEMENT Patients with a lesion of the primary visual cortex (V1) can retain certain visually mediated behaviors, particularly if the lesion occurs early in life. This phenomenon ("blindsight") not only sheds light on the nature of consciousness, but also has implications for studies of brain circuitry, development, and plasticity. However, the pathways that mediate blindsight have been the subject of debate. Recent studies suggest that projections from the LGN might be critical, but this finding is puzzling given that the lesions causes severe cell death in the LGN. Here we demonstrate in monkeys that the surviving LGN neurons retain a remarkable level of visual function and could therefore be the source of the visual information that supports blindsight.
Assuntos
Corpos Geniculados/fisiopatologia , Degeneração Retrógrada/fisiopatologia , Escotoma/fisiopatologia , Córtex Visual/fisiopatologia , Percepção Visual , Animais , Callithrix , Feminino , Corpos Geniculados/crescimento & desenvolvimento , Masculino , Degeneração Retrógrada/complicações , Escotoma/etiologia , Visão Ocular , Córtex Visual/crescimento & desenvolvimento , Vias Visuais/crescimento & desenvolvimento , Vias Visuais/fisiopatologiaRESUMO
Initial clinical recognition of "paralysis agitans" by James Parkinson was expanded by Jean-Martin Charcot, who recognized additional clinical findings of his own, such as slowness (distinct from paralysis), rigidity (distinct from spasticity) and characteristic countenance. Charcot assembled these findings under the umbrella of "Parkinson disease (PD)". This purely clinical concept was so prescient and penetrating that subsequent neuropathological and biochemical evidences were ordered along this axis to establish the nigra-central trinity of PD (dopamine depletion, nigral lesion with Lewy bodies: LBs). Although dramatic efficacy of levodopa boosted an enthusiasm for this nigra-centralism, extranigral lesions were identified, especially after identification of alpha-synuclein (αS) as a major constituent of LBs. Frequent αS lesions in the lower brainstem with their presumed upward spread were coupled with the self-propagating property of αS molecule, as a molecular template, to constitute the prion-Braak hypothesis. This hybrid concept might expectedly explain clinical, structural and biochemical features of PD/dementia with Lewy bodies (DLB) as if they were stereotypic. In spite of this ordered explanation, recent studies have demonstrated unexpectedly that αS lesions in the human brain, as well as their corresponding clinical manifestations, are much more disordered. Even with such a chaos of LB disorders, affected neuronal groups are uniformly characterized by hyperbranching axons, which may facilitate distal-dominant degeneration and retrograde progression of LB-related degeneration along axons as a fundamental structural order to template LB disorders. This "structural template" hypothesis may explain why: (i) some selective groups are prone to develop Lewy pathology; (ii) their clinical manifestations (especially non-motor components) are vague and generalized without somatotopic accentuation; (iii) distal axons and terminals are preferentially affected early, which is clinically detectable as reduced myocardial uptake of meta-iodobenzylguanidine in PD/DLB. Because each Lewy-prone system develops LBs independently, their isolated presentation as "focal LB disease" or their whatever combinations as "multifocal LB disease" are a more plausible framework to explain clinicopathological diversities of LB disorders. Clinical criteria are now being revised to integrate these clinicopathological disorders of PD/DLB. To gain closer access to the reality of the human brain, it is necessary to facilitate more interactions between clinicopathological and experimental fields so that both are mutually critical and complementary for improved diagnosis and treatment.
Assuntos
Axônios/patologia , Encéfalo/patologia , Doença por Corpos de Lewy/patologia , Doença de Parkinson/patologia , Degeneração Retrógrada/complicações , Idoso , Idoso de 80 Anos ou mais , Encéfalo/metabolismo , Progressão da Doença , Feminino , Humanos , Doença por Corpos de Lewy/complicações , Doença por Corpos de Lewy/metabolismo , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/metabolismo , Substância Negra/patologia , alfa-Sinucleína/metabolismoRESUMO
OBJECTIVE: Pathogenesis of pseudohypertrophy of the inferior olivary nucleus (PH-IO) was analyzed based on immunohistochemical study. METHODS: Immunostained medullas with PH-IO were observed with confocal laser microscopy. RESULTS: αB-crystallin (αBC) was frequently expressed in the neurons and co-localized with microtubule-associated protein 2 (MAP2). The neurons were occasionally positive for SMI-31. αBC and SMI-31 were co-localized in some neurons. Synaptophysin (SYP)-immunoreactive dots were present around MAP2-positive hypertrophic neurons and hypertrophic thick neurites. Periphery-stained Lys-Asp-Glu-Leu (KDEL)-positive neurons were shown. Central chromatolytic neurons were found with Klüver-Barrera staining, which indicated that the rough endoplasmic reticulum (ER) was distributed to the periphery of the cytoplasm. CONCLUSIONS: αBC prevents microtubule disassembly and phosphorylation of the neurofilaments under stressful conditions. Our results indicated that αBC protected microtubules and neurofilaments in PH-IO. The retrograde transport of KDEL receptors from the Golgi complex to the ER is increased under stressful conditions. We considered that KDEL receptors were retro-transported to ER, and then the ER containing KDEL receptors was distributed to the periphery of the cytoplasm. PH-IO showed various immunohistochemical changes due to trans-synaptic degeneration.
Assuntos
Núcleo Olivar/metabolismo , Núcleo Olivar/patologia , Retículo Endoplasmático/fisiologia , Complexo de Golgi/fisiologia , Humanos , Hipertrofia/etiologia , Hipertrofia/metabolismo , Hipertrofia/patologia , Microscopia Confocal , Receptores de Peptídeos/metabolismo , Degeneração Retrógrada/complicações , Degeneração Retrógrada/metabolismo , Degeneração Retrógrada/patologia , Cadeia B de alfa-Cristalina/metabolismoAssuntos
Parto Obstétrico/efeitos adversos , Plexo Hipogástrico/lesões , Perna (Membro) , Debilidade Muscular/etiologia , Condução Nervosa , Recuperação de Função Fisiológica , Degeneração Retrógrada/complicações , Axônios/fisiologia , Eletromiografia , Feminino , Humanos , Plexo Hipogástrico/fisiopatologia , Debilidade Muscular/fisiopatologia , Gravidez , Degeneração Retrógrada/diagnóstico , Degeneração Retrógrada/fisiopatologia , Adulto JovemRESUMO
We report a 40-year-old man with myotonic dystrophy who survived for 5 years after pontine infarction. Serial MRI detected abnormal T2 elongation of the corticospinal tract at the cerebral peduncle 4 years after the infarction. An autopsy confirmed the existence of retrograde degeneration extending from the pons to the internal capsule, evidence that retrograde degeneration in the corticospinal tract occurs above the pontine level. MRI was suggested to be useful for detection of the degenerative process.
Assuntos
Infarto Encefálico/complicações , Ponte/patologia , Tratos Piramidais/patologia , Degeneração Retrógrada/complicações , Adulto , Humanos , Imageamento por Ressonância Magnética/métodos , MasculinoRESUMO
We report a case of a 23-year-old woman with progressive hemifacial atrophy. She showed an atrophic change on the left side of her face for 8 years. A skin biopsy obtained from the lesion revealed the fibrotic changes in the deep dermis and adipose tissue with infiltrations of lymphocytes and plasma cells. She underwent the augmentation using a deepithelialized anteromedial thigh flap with endoscopic assistance. A specimen of the peripheral facial nerve taken from the region adjacent to the skin lesion during the operation showed atrophy of neurofibers with vacuole degeneration. On an electron microscopic examination, a high degree of degeneration of myelinated and unmyelinated axons was observed. These findings may provide direct evidence that atrophic changes of nerve fibers are closely related with the pathology of this disease.