Trans-synaptic spreading of alpha-synuclein pathology through sensory afferents leads to sensory nerve degeneration and neuropathic pain.

Pain is a common non-motor symptom of Parkinson's disease (PD), with current limited knowledge of its pathophysiology. Here, we show that peripheral inoculation of mouse alpha-synuclein (α-Syn) pre-formed fibrils, in a transgenic mouse model of PD, elicited retrograde trans-synaptic spreading of α-Syn pathology (pSer129) across sensory neurons and dorsal nerve roots, reaching central pain processing regions, including the spinal dorsal horn and the projections of the anterolateral system in the central nervous system (CNS). Pathological peripheral to CNS propagation of α-Syn aggregates along interconnected neuronal populations within sensory afferents, was concomitant with impaired nociceptive response, reflected by mechanical allodynia, reduced nerve conduction velocities (sensory and motor) and degeneration of small- and medium-sized myelinated fibers. Our findings show a link between the transneuronal propagation of α-Syn pathology with sensory neuron dysfunction and neuropathic impairment, suggesting promising avenues of investigation into the mechanisms underlying pain in PD.

An Analysis of Retinal Nerve Fiber Layer Thickness before and after Pituitary Adenoma Surgery and its Correlation with Visual Acuity.

INTRODUCTION: Pituitary adenomas comprise approximately 10% of all intracranial tumors. Initially, subtle changes occur in the field of vision, which are difficult to assess clinically. It has been seen that following surgery of pituitary macroadenoma, total recovery of normal vision occurs in 35% of the patients, improvement of vision occurs in 60%, and in the rest there is no change in vision. Retinal nerve fiber layer thickness (RNFLT) undergoes retrograde degeneration following compression of optic apparatus by pituitary tumor. We planned a study to evaluate RNFLT before and after pituitary adenoma surgery and its correlation with visual acuity. MATERIAL AND METHODS: Twenty patients (40 eyes) with diagnosed pituitary adenoma were included in the study. Preoperative visual acuity, fundus and RNFL thickness were calculated using spectral-domain OCT Optovue, Heidelberg Engineering, Heidelberg, Germany (RT 100 version 5.1), and postoperative measurement was done after 1 and 3 months. Four-quadrant mean of RNFLT was calculated. Results were tabulated and analyzed. STATISTICAL ANALYSIS: Results of the study were analyzed using IBM SPSS Statistics version 19.0. RESULTS: There was no significant change in RNFLT after pituitary adenoma surgery, and it was found that patients with RNFLT within normal range preoperatively showed improvement in visual acuity after pituitary surgery. On the other hand, patients who had thinned-out RNFLT preoperatively showed no improvement in visual acuity. It was also found that once optic disc pallor sets due to chronic compression, then chances of its reversion to normal depend on its grading: only mild pallor disc has some chance to revert to normal, whereas moderate and severe pallor do not revert to normal. CONCLUSION: RNFLT and optic disc can be used as prognostic factors for evaluation of visual outcome in pituitary adenoma surgery.

Survival of retinal ganglion cells after damage to the occipital lobe in humans is activity dependent.

Damage to the optic radiations or primary visual cortex leads to blindness in all or part of the contralesional visual field. Such damage disconnects the retina from its downstream targets and, over time, leads to trans-synaptic retrograde degeneration of retinal ganglion cells. To date, visual ability is the only predictor of retinal ganglion cell degeneration that has been investigated after geniculostriate damage. Given prior findings that some patients have preserved visual cortex activity for stimuli presented in their blind field, we tested whether that activity explains variability in retinal ganglion cell degeneration over and above visual ability. We prospectively studied 15 patients (four females, mean age = 63.7 years) with homonymous visual field defects secondary to stroke, 10 of whom were tested within the first two months after stroke. Each patient completed automated Humphrey visual field testing, retinotopic mapping with functional magnetic resonance imaging, and spectral-domain optical coherence tomography of the macula. There was a positive relation between ganglion cell complex (GCC) thickness in the blind field and early visual cortex activity for stimuli presented in the blind field. Furthermore, residual visual cortex activity for stimuli presented in the blind field soon after the stroke predicted the degree of retinal GCC thinning six months later. These findings indicate that retinal ganglion cell survival after ischaemic damage to the geniculostriate pathway is activity dependent.

Robust Visual Responses and Normal Retinotopy in Primate Lateral Geniculate Nucleus following Long-term Lesions of Striate Cortex.

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.

Sonography of Carpal Tunnel Syndrome According to Pathophysiologic Type: Conduction Block Versus Axonal Degeneration.

OBJECTIVES: The purpose of this study was to investigate sonographic findings according to the pathophysiologic type in patients with carpal tunnel syndrome. METHODS: We retrospectively reviewed the records of 80 patients (148 hands) with carpal tunnel syndrome. Patients were classified into 3 groups according to electrophysiologic findings: (1) conduction block and conduction delay; (2) axonal degeneration; and (3) mixed. We used sonographic evaluations to assess the cross-sectional area at the distal wrist crease and the distal forearm and the wrist-to-forearm ratio of the median nerve. RESULTS: Patients with axonal degeneration had significantly larger cross-sectional areas and wrist-to-forearm ratios than those with a conduction block (P < .05). The increased wrist-to-forearm ratio correlated with a reduced amplitude of the sensory nerve action potential, which reflects the degree of axonal degeneration. CONCLUSIONS: The cross-sectional area and wrist-to-forearm ratio were associated with the pathophysiologic type of carpal tunnel syndrome, with larger nerve swellings seen in patients with axonal degeneration compared with those with demyelinating lesions. In addition to helping in the localization of the nerve lesion, sonography may indicate the type of nerve lesion.

Trans-synaptic degeneration of motoneurons distal to chronic cervical spinal cord compression in cervical spondylotic myelopathy.

OBJECTIVE: To assess the effect of chronic cervical spinal cord compression upon remote motor unit function in patients with cervical spondylotic myelopathy (CSM). METHODS: Fifty-three CSM patients and 47 healthy subjects were included. Bilateral motor unit number estimations (MUNEs) were recorded from both abductor digiti minimi and abductor pollicis brevis, and bilateral flexor carpi radialis (FCR) H-reflexes were examined in all subjects along with the nine-hole peg test (NHPT). The main outcome measures included the number of motor units, the average single motor unit potential (SMUP) area, the FCR Hmax/Mmax ratios and the NHPT time. RESULTS: Statistically significant results compared to healthy controls included increased average SMUP area, increased FCR Hmax/Mmax ratio and increased NHPT time (p < 0.05). Abnormal SMUP was observed in 10/53 (18.9%) CSM patients along with reduced motor units in 3 of these 10 patients, while the FCR Hmax/Mmax ratios in the CSM patients with abnormal MUNE were higher than those in others (p < 0.05). There was a positive correlation between the NHPT time and the average SMUP area, and a negative correlation was noted between the NHPT time and the number of motor units (p < 0.05). CONCLUSION: In CSM patients, the motor units below the level of compression may exhibit dysfunction, which is likely a result of trans-synaptic degeneration. Both cervical spinal cord compressive injury and this trans-synaptic degeneration contribute to the impairment of fine motor ability in CSM patients. Therefore, treatment and rehabilitation efforts should account for these two dysfunctions.

Evaluation of retinal nerve fiber layer thickness measured by optical coherence tomography in Moroccan patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by focal inflammatory infiltrates, demyelinating lesions and axonal injury. The purpose of the study was to evaluate the retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) in Moroccan patients with MS and to assess the relationship between RNFL thickness and disease duration, Expanded Disability Status Scale (EDSS) score, visual acuity and automated visual field indices. MATERIALS AND METHODS: Thirty-one patients with definite MS and thirty-one disease-free controls were enrolled in the study. After neurologic consultation, ophthalmologic examination including visual acuity, automated visual field testing and OCT were performed. RESULTS: Significant differences between both groups were observed in OCT parameters (total, temporal and macular ganglion cell layer) with lower thickness in the MS group. In patients without a history of optic neuritis, there were statistically significant inverse correlations between total RNFL thickness and disease duration, neurologic disability evaluated by the EDSS, logMAR visual acuity and automated visual field indices. CONCLUSIONS: OCT seems to be a reproducible test to detect axonal loss of ganglion cells in MS. Further and larger longitudinal prospective studies would be valuable to assess the evolution over time of the RNFL measurements in Moroccan MS patients.

Axonal Terminals Exposed to Amyloid-ß May Not Lead to Pre-Synaptic Axonal Damage.

BACKGROUND: Synaptic deficits and neuronal loss are the major pathological manifestations of Alzheimer's disease. However, the link between the early synaptic loss and subsequent neurodegeneration is not entirely clear. Cell culture studies have shown that amyloid-ß (Aß) applied to axonal terminals can cause retrograde degeneration leading to the neuronal loss, but this process has not been demonstrated in live animals. OBJECTIVE: To test if Aß applied to retinal ganglion cell axonal terminals can induce axonal damage in the optic nerve and optic tract in mice. METHODS: Aß was injected into the terminal field of the optic tract, in the left lateral geniculate nucleus of wildtype C57BL/6 mice. Following the injection, monthly diffusion tensor imaging was performed. Three months after the injection, mice underwent visual evoked potential recordings, and then sacrificed for immunohistochemical examination. RESULTS: There were no significant changes seen with diffusion tensor imaging in the optic nerve and optic tract 3 months after the Aß injection. The myelin and axons in these regions remained intact according to immunohistochemistry. The only significant changes observed in this study were delayed transduction and reduced amplitude of visual evoked potentials, although both Aß and its reversed form caused similar changes. CONCLUSION: Despite the published in vitro studies, there was no significant axonal damage in the optic nerve and optic tract after injecting Aß onto retinal ganglion cell axonal terminals of wildtype C57BL/6 mice.

Lesions in the posterior visual pathway promote trans-synaptic degeneration of retinal ganglion cells.

OBJECTIVE: Retrograde trans-synaptic degeneration of retinal ganglion cell layer (GCL) has been proposed as one of the mechanisms contributing to permanent disability after visual pathway damage. We set out to test this mechanism taking advantage of the new methods for imaging the macula with high resolution by optical coherence tomography (OCT) in patients with lesions in the posterior visual pathway. Additionally, we explored the association between thinning of GCL as an imaging marker of visual impairment such as visual field defects. METHODS: Retrospective case note review of patients with retrogeniculate lesions studied by spectral domain OCT of the macula and quadrant pattern deviation (PD) of the visual fields. RESULTS: We analysed 8 patients with either hemianopia or quadrantanopia due to brain lesions (stroke  = 5; surgery  = 2; infection  = 1). We found significant thinning of the GCL in the projecting sector of the retina mapping to the brain lesion. Second, we found strong correlation between the PD of the visual field quadrant and the corresponding macular GCL sector for the right (R = 0.792, p<0.001) and left eyes (R = 0.674, p<0.001). CONCLUSIONS: The mapping between lesions in the posterior visual pathway and their projection in the macula GCL sector corroborates retrograde trans-synaptic neuronal degeneration after brain injury as a mechanism of damage with functional consequences. This finding supports the use of GCL thickness as an imaging marker of trans-synaptic degeneration in the visual pathway after brain lesions.

[Pathogenesis of spinal cord injuries and mechanisms of repair induced by olfactory ensheathing cells]. / Patogenia de la lesion medular y mecanismos de reparacion inducidos por las celulas de la glia envolvente olfatoria.

INTRODUCTION: Spinal cord injury is a catastrophic event with permanent consequences during the all life. Treatment research has been based in the development of therapies that reduce the discapacity, but since the nineties there has been an important advance and several cellular transplants have been tested in spinal cord animal models, like Schwann cells, astrocytes and olfactory and olfactory ensheathing cells (OEC). AIM: Detailed account of spinal cord injury pathogeny, primary and secondary, and the OEC mechanisms for the regeneration effects that have been described in the literature. DEVELOPMENT: After the trauma, spinal cord injury develops in two phases, the primary injury with characteristics compression lesions, and the secondary produce for several factors that occur in parallel and include: vascular, cellular and molecular factors, and glial scar formation. The most of spinal cord models and OEC transplants have been reported functional recovery, remielinization and axonal regeneration. These cells exert their action in a direct way by producing grow factors and in an indirect way inducing directly neuronal an axonal regeneration and remielinization. CONCLUSIONS: OEC are a therapeutic option in patients with spinal cord injury, because they induce in a direct or indirect way, neuronal and axonal regeneration, remielinization, decrease the glial scar and produce other effects that conduce a functional recovery.

TITLE: Patogenia de la lesion medular y mecanismos de reparacion inducidos por las celulas de la glia envolvente olfatoria.Introduccion. La lesion medular es un evento catastrofico, cuyas consecuencias persisten durante toda la vida del paciente. La investigacion en tratamiento se ha basado principalmente en el desarrollo de terapias que reduzcan la discapacidad, pero desde los anos noventa hay un avance significativo y se han probado varios trasplantes celulares en modelos animales de lesion medular, celulas de Schwann, astrocitos y celulas de la glia envolvente olfatoria (CGEO). Objetivo. Hacer un recuento detallado de la patogenia de la lesion medular primaria y secundaria y de los mecanismos por los cuales las CGEO inducirian sus posibles efectos regenerativos descritos en la bibliografia. Desarrollo. Despues del traumatismo, la lesion se desarrolla en dos fases, la primaria se caracteriza por las lesiones de compresion y la secundaria se produce por una serie de factores que se dan en paralelo y que incluyen factores vasculares, celulares, moleculares y formacion de cicatriz glial. La mayoria de los modelos de lesion medular y trasplante con CGEO han comunicado recuperacion funcional, remielinizacion y regeneracion axonal. Estas celulas ejercen su accion de manera indirecta a traves de la produccion de factores de crecimiento y de manera directa induciendo regeneracion neuronal, axonal y remielinizacion. Conclusiones. Las CGEO son una opcion terapeutica en pacientes con lesion medular debido a que inducen de modo directo o indirecto regeneracion neuronal, axonal, remielinizacion de axones, disminucion de cicatriz glial y otros efectos que conducen a la recuperacion funcional.

Retrograde and Wallerian axonal degeneration occur synchronously after retinal ganglion cell axotomy.

Axonal injury and degeneration are pivotal pathological events in diseases of the nervous system. In the past decade, it has been recognized that the process of axonal degeneration is distinct from somal degeneration and that axoprotective strategies may be distinct from those that protect the soma. Preserving the cell body via neuroprotection cannot improve function if the axon is damaged, because the soma is still disconnected from its target. Therefore, understanding the mechanisms of axonal degeneration is critical for developing new therapeutic interventions for axonal disease treatment. We combined in vivo imaging with a multilaser confocal scanning laser ophthalmoscope and in vivo axotomy with a diode-pumped solid-state laser to assess the time course of Wallerian and retrograde degeneration of unmyelinated retinal ganglion cell axons in living rats for 4 weeks after intraretinal axotomy. Laser injury resulted in reproducible axon loss both distal and proximal to the site of injury. Longitudinal polarization-sensitive imaging of axons demonstrated that Wallerian and retrograde degeneration occurred synchronously. Neurofilament immunostaining of retinal whole-mounts confirmed axonal loss and demonstrated sparing of adjacent axons to the axotomy site. In vivo fluorescent imaging of axonal transport and photobleaching of labeled axons demonstrated that the laser axotomy model did not affect adjacent axon function. These results are consistent with a shared mechanism for Wallerian and retrograde degeneration.

Failure of lower motor neuron radial outgrowth precedes retrograde degeneration in a feline model of spinal muscular atrophy.

Feline spinal muscular atrophy (SMA) is a fully penetrant, autosomal recessive lower motor neuron disease in domestic cats that clinically resembles human SMA Type III. A whole genome linkage scan identified a ∼140-kb deletion that abrogates expression of LIX1, a novel SMA candidate gene of unknown function. To characterize the progression of feline SMA, we assessed pathological changes in muscle and spinal cord from 3 days of age to beyond onset of clinical signs. Electromyographic (EMG) analysis indicating denervation occurred between 10 and 12 weeks, with the first neurological signs occurring at the same time. Compound motor action potential (CMAP) amplitudes were significantly reduced in the soleus and extensor carpi radialis muscles at 8-11 weeks. Quadriceps femoris muscle fibers from affected cats appeared smaller at 10 weeks; by 12 weeks atrophic fibers were more prevalent than in age-matched controls. In affected cats, significant loss of L5 ventral root axons was observed at 12 weeks. By 21 weeks of age, affected cats had 40% fewer L5 motor axons than normal. There was no significant difference in total L5 soma number, even at 21 weeks; thus degeneration begins distal to the cell body and proceeds retrogradely. Morphometric analysis of L5 ventral roots and horns revealed that 4 weeks prior to axon loss, motor axons in affected cats failed to undergo radial enlargement, suggesting a role for the putative disease gene LIX1 in radial growth of axons.

Mononeuritis múltiple en un paciente con síndrome de Churg-Strauss. Pseudobloqueos como expresión electroclínica temprana / Multiple mononeuritis in a patient with Churg-Strauss syndrome. Pseudo conduction block as an early electroclinical expression

Introducción. La mononeuritis múltiple es una de las manifestaciones más frecuentes del síndrome de Churg-Strauss. Caso clínico. En un varón de 53 años con síndrome de Churg-Strauss, se describe una mononeuritis múltiple aguda sensitivomotora de las cuatro extremidades. Mediante electrodiagnóstico en los primeros siete días se demostraron bloqueos de conducción en varios nervios. Los estudios posteriores objetivaron una polineuropatía axonal sensitivomotora difusa y bilateral con asimetrías, pero sin bloqueos. La electrofisiología y la histología, así como los estudios experimentales, indicaban que se trataba de una axonopatía secundaria a isquemia aguda. Conclusiones. Sólo en pocos casos, como en éste, y en estudios muy incipientes se han descrito bloqueos de conducción que, por su relación habitual con desmielinización, provocan confusión diagnóstica y pronóstica. La evolución suele demostrar una axonopatía por degeneración walleriana. Por tanto, en estos casos parece recomendable extremar la cautela y realizar estudios neurofisiológicos en las siguientes semanas para evitar inadecuados juicios diagnósticos y pronósticos (AU)

Introduction. Multiple mononeuritis is one of the most frequent manifestations of Churg-Strauss syndrome. Case report. We describe a case of acute sensory-motor multiple mononeuritis in all four limbs of a 53-year-old male with Churg-Strauss syndrome. Electrodiagnosis performed within the first seven days revealed conduction blocks in several nerves. Follow-up studies showed diffuse bilateral sensory-motor axonal polyneuropathy with symmetries, but without blocks. Electrophysiological and histological analyses, together with experimental studies, showed it to be an axonopathy secondary to acute ischaemia. Conclusions. In only a few cases, such as this one and in a small number of incipient studies, have there been reports of conduction blocks that, owing to the fact that they are commonly related with demyelination, give rise to confusion when it comes to diagnoses and prognoses. The condition usually displays axonopathy due to Wallerian degeneration. It therefore seems recommendable in these cases to proceed with caution and to perform neurophysiological studies in the following weeks in order to prevent inappropriate diagnostic and prognostic judgements from being formed (AU)

Differential involvement of perineuronal astrocytes and microglia in synaptic stripping after hypoglossal axotomy.

Following peripheral axotomy, the presynaptic terminals are removed from lesioned neurons, that is synaptic stripping. To elucidate involvement of astrocytes and microglia in synaptic stripping, we herein examined the motoneuron perineuronal circumference after hypoglossal nerve transection. As reported previously, axotomy-induced slow cell death occurred in C57BL/6 mice but not in Wistar rats. Synaptophysin labeling in the hypoglossal nucleus exhibited a minor reduction in both species after axotomy. Slice patch recording showed that the mean frequency of miniature postsynaptic currents in axotomized motoneurons was significantly lower in rats than in mice. We then estimated the relative coverage of motoneuron perineuronal circumference by line profile analysis. In the synaptic environment, axotomy-induced intrusion of astrocytic processes was significantly more extensive in rats than in mice, whereas microglial intrusion into the synaptic space was significantly more severe in mice than in rats. Interestingly, in the extrasynaptic environment, the prevalence of contact between astrocytic processes and lesioned motoneurons was significantly increased in rats, while no significant axotomy-induced alterations in astrocytic contact were observed in mice. These findings indicate that astrocytic, but not microglial, reaction may primarily mediate some anti-apoptotic effects through synaptic stripping after hypoglossal nerve axotomy. In addition, enlargement of astrocytic processes in the extrasynaptic environment may also be involved in neuronal protection via the increased uptake of excessive glutamate.

Neuropatía axonal motora aguda con hiperreflexia y desmielinización central asociada a anticuerpos anti-GA1 / Acute motor axonal neuropathy with hyperreflexia and central demyelination associated

Caso clínico. Varón de 37 años que presentó un cuadro de polirradiculoneuropatía axonal motora aguda que comenzó tres semanas después de un cuadro de gastroenteritis de tres días de evolución, y se asoció a rigidez de nuca, hiperreflexia y anticuerpos anti-GA1. El paciente desarrolló los síntomas en 12 horas, que comenzaron en la madrugada al despertarse con cefalea; en la mañana presentó debilidad generalizada y neuropatía craneal, por lo cual acudió al hospital. La exploración neurológica mostró una neuropatía craneal múltiple, cuadriparesia con hiperreflexia, Babinski bilateral y rigidez de nuca. Tras el tratamiento con metilprednisolona primero y gammaglobulina después, se logró detener la progresión de la enfermedad. Se descartó neuroinfección por punción lumbar, y se confirmó la polirradiculoneuropatía axonal motora aguda en un segundo estudio de neuroconducción a los siete días de su ingreso. La resonancia magnética mostró una zona de desmielinización en la sustancia blanca, y en la serología se detectó la presencia de anticuerpos anti-GA1. Dos años después el paciente realiza actividades de la vida diaria, camina con asistencia y ha reiniciado sus actividades laborales. Conclusión. La polirradiculoneuropatía axonal motora aguda con hiperreflexia, rigidez de nuca y desmielinización central se puede asociar a anticuerpos anti-GA1. El tratamiento con gammaglobulina parece detener la evolución del padecimiento (AU)

Case report. We report the case of a 37-year-old male who presented signs of acute motor axonal polyradiculoneuropathy that began three weeks after a three-day bout of gastroenteritis and was accompanied by a stiff neck, hyperreflexia and anti-GA1 antibodies. The symptoms developed within 12 hours, after beginning with the patient waking up in the middle of the night with a headache; the following morning he presented general weakness and cranial neuropathy and therefore decided to go to hospital. The neurological examination showed multiple cranial neuropathy, quadriparesis with hyperreflexia, bilateral Babinski and a stiff neck. Following treatment, first with methylprednisolone and then with gamma globulin, the development of the illness was halted. Neuroinfection due to lumbar puncture was ruled out and acute motor axonal polyradiculoneuropathy was confirmed in a second neuroconduction study performed seven days after admission. Magnetic resonance imaging revealed an area of demyelination in the white matter and the presence of anti-GA1 antibodies was detected in the serological analysis. Two years later, the patient performs activities of daily living, walks with assistance and has gone back to work. Conclusions. Acute motor axonal polyradiculoneuropathy with hyperreflexia, a stiff neck and central demyelination can be associated to anti-GA1 antibodies. Treatment with gamma globulin appears to curb development of the disease (AU)

Primary retinal pathology in multiple sclerosis as detected by optical coherence tomography.

Optical coherence tomography studies in multiple sclerosis have primarily focused on evaluation of the retinal nerve fibre layer. The aetiology of retinal changes in multiple sclerosis is thought to be secondary to optic nerve demyelination. The objective of this study was to use optical coherence tomography to determine if a subset of patients with multiple sclerosis exhibit primary retinal neuronopathy, in the absence of retrograde degeneration of the retinal nerve fibre layer and to ascertain if such patients may have any distinguishing clinical characteristics. We identified 50 patients with multiple sclerosis with predominantly macular thinning (normal retinal nerve fibre-layer thickness with average macular thickness < 5th percentile), a previously undescribed optical coherence tomography defined phenotype in multiple sclerosis, and compared them with 48 patients with multiple sclerosis with normal optical coherence tomography findings, 48 patients with multiple sclerosis with abnormal optical coherence tomography findings (typical for multiple sclerosis) and 86 healthy controls. Utilizing a novel retinal segmentation protocol, we found that those with predominant macular thinning had significant thinning of both the inner and outer nuclear layers, when compared with other patients with multiple sclerosis (P < 0.001 for both), with relative sparing of the ganglion cell layer. Inner and outer nuclear layer thicknesses in patients with non-macular thinning predominant multiple sclerosis were not different from healthy controls. Segmentation analyses thereby demonstrated extensive deeper disruption of retinal architecture in this subtype than may be expected due to retrograde degeneration from either typical clinical or sub-clinical optic neuropathy. Functional corroboration of retinal dysfunction was provided through multi-focal electroretinography in a subset of such patients. These findings support the possibility of primary retinal pathology in a subset of patients with multiple sclerosis. Multiple sclerosis-severity scores were also significantly increased in patients with the macular thinning predominant phenotype, compared with those without this phenotype (n = 96, P=0.006). We have identified a unique subset of patients with multiple sclerosis in whom there appears to be disproportionate thinning of the inner and outer nuclear layers, which may be occurring as a primary process independent of optic nerve pathology. In vivo analyses of retinal layers in multiple sclerosis have not been previously performed, and structural demonstration of pathology in the deeper retinal layers, such as the outer nuclear layer, has not been previously described in multiple sclerosis. Patients with inner and outer nuclear layer pathology have more rapid disability progression and thus retinal neuronal pathology may be a harbinger of a more aggressive form of multiple sclerosis.

Use of laser microdissection in the investigation of facial motoneuron and neuropil molecular phenotypes after peripheral axotomy.

The mechanism underlying axotomy-induced motoneuron loss is not fully understood, but appears to involve molecular changes within the injured motoneuron and the surrounding local microenvironment (neuropil). The mouse facial nucleus consists of six subnuclei which respond differentially to facial nerve transection at the stylomastoid foramen. The ventromedial (VM) subnucleus maintains virtually full facial motoneuron (FMN) survival following axotomy, whereas the ventrolateral (VL) subnucleus results in significant FMN loss with the same nerve injury. We hypothesized that distinct molecular phenotypes of FMN existed within the two subregions, one responsible for maintaining cell survival and the other promoting cell death. In this study, we used laser microdissection to isolate VM and VL facial subnuclear regions for molecular characterization. We discovered that, regardless of neuronal fate after injury, FMN in either subnuclear region respond vigorously to injury with a characteristic "regenerative" profile and additionally, the surviving VL FMN appear to compensate for the significant FMN loss. In contrast, significant differences in the expression of pro-inflammatory cytokine mRNA in the surrounding neuropil response were found between the two subnuclear regions of the facial nucleus that support a causative role for glial and/or immune-derived molecules in directing the contrasting responses of the FMN to axonal transection.

Estudio de la degeneración axonal a nivel de la capa de fibras nerviosas de la retina en pacientes con esclerosis múltiple / No disponible

No disponible

Degeneración axonal de la capa de fibras nerviosas de la retina en función del tratamiento recibido para la esclerosis múltiple / No disponible

No disponible