Visual signs and symptoms of multiple system atrophy

Multiple system atrophy (MSA) is a rare movement disorder and a member of the 'parkinsonian syndromes', which also include Parkinson's disease (PD), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB) and corticobasal degeneration (CBD). Multiple system atrophy is a complex syndrome, in which patients exhibit a variety of signs and symptoms, including parkinsonism, ataxia and autonomic dysfunction. It can be difficult to separate MSA from the other parkinsonian syndromes but if ocular signs and symptoms are present, they may aid differential diagnosis. Typical ocular features of MSA include blepharospasm, excessive square-wave jerks, mild to moderate hypometria of saccades, impaired vestibular-ocular reflex (VOR), nystagmus and impaired event-related evoked potentials. Less typical features include slowing of saccadic eye movements, the presence of vertical gaze palsy, visual hallucinations and an impaired electroretinogram (ERG). Aspects of primary vision such as visual acuity, colour vision or visual fields are usually unaffected. Management of the disease to deal with problems of walking, movement, daily tasks and speech problems is important in MSA. Optometrists can work in collaboration with the patient and health-care providers to identify and manage the patient's visual deficits. A more specific role for the optometrist is to correct vision to prevent falls and to monitor the anterior eye to prevent dry eye and control blepharospasm.

Neurophysiological evaluation of convergent afferents innervating the human esophagus and area of referred pain on the anterior chest wall

Noxious stimuli in the esophagus cause pain that is referred to the anterior chest wall because of convergence of visceral and somatic afferents within the spinal cord. We sought to characterize the neurophysiological responses of these convergent spinal pain pathways in humans by studying 12 healthy subjects over three visits (V1, V2, and V3). Esophageal pain thresholds (Eso-PT) were assessed by electrical stimulation and anterior chest wall pain thresholds (ACW-PT) by use of a contact heat thermode. Esophageal evoked potentials (EEP) were recorded from the vertex following 200 electrical stimuli, and anterior chest wall evoked potentials (ACWEP) were recorded following 40 heat pulses. The fear of pain questionnaire (FPQ) was administered on V1. Statistical data are shown as point estimates of difference +/- 95% confidence interval. Pain thresholds increased between V1 and V3 [Eso-PT: V1-V3 = -17.9 mA (-27.9, -7.9) P < 0.001; ACW-PT: V1-V3 = -3.38 degrees C (-5.33, -1.42) P = 0.001]. The morphology of cortical responses from both sites was consistent and equivalent [P1, N1, P2, N2 complex, where P1 and P2 are is the first and second positive (downward) components of the CEP waveform, respectively, and N1 and N2 are the first and second negative (upward) components, respectively], indicating activation of similar cortical networks. For EEP, N1 and P2 latencies decreased between V1 and V3 [N1: V1-V3 = 13.7 (1.8, 25.4) P = 0.02; P2: V1-V3 = 32.5 (11.7, 53.2) P = 0.003], whereas amplitudes did not differ. For ACWEP, P2 latency increased between V1 and V3 [-35.9 (-60, -11.8) P = 0.005] and amplitudes decreased [P1-N1: V1-V3 = 5.4 (2.4, 8.4) P = 0.01; P2-N2: 6.8 (3.4, 10.3) P < 0.001]. The mean P1 latency of EEP over three visits was 126.6 ms and that of ACWEP was 101.6 ms, reflecting afferent transmission via Adelta fibers. There was a significant negative correlation between FPQ scores and Eso-PT on V1 (r = -0.57, P = 0.05). These data provide the first neurophysiological evidence of convergent esophageal and somatic pain pathways in humans.

Oculo-visual changes and clinical considerations affecting older patients with dementia

Purpose: Dementia is associated with various alterations of the eye and visual function. Over 60% of cases are attributable to Alzheimer's disease, a significant proportion of the remainder to vascular dementia or dementia with Lewy bodies, while frontotemporal dementia, and Parkinson's disease dementia are less common. This review describes the oculo-visual problems of these five dementias and the pathological changes which may explain these symptoms. It further discusses clinical considerations to help the clinician care for older patients affected by dementia. Recent findings: Visual problems in dementia include loss of visual acuity, defects in colour vision and visual masking tests, changes in pupillary response to mydriatics, defects in fixation and smooth and saccadic eye movements, changes in contrast sensitivity function and visual evoked potentials, and disturbance of complex visual functions such as in reading ability, visuospatial function, and the naming and identification of objects. Pathological changes have also been reported affecting the crystalline lens, retina, optic nerve, and visual cortex. Clinically, issues such as cataract surgery, correcting the refractive error, quality of life, falls, visual impairment and eye care for dementia have been addressed. Summary: Many visual changes occur across dementias, are controversial, often based on limited patient numbers, and no single feature can be regarded as diagnostic of any specific dementia. Nevertheless, visual hallucinations may be more characteristic of dementia with Lewy bodies and Parkinson's disease dementia than Alzheimer's disease or frontotemporal dementia. Differences in saccadic eye movement dysfunction may also help to distinguish Alzheimer's disease from frontotemporal dementia and Parkinson's disease dementia from dementia with Lewy bodies. Eye care professionals need to keep informed of the growing literature in vision/dementia, be attentive to signs and symptoms suggestive of cognitive impairment, and be able to adapt their practice and clinical interventions to best serve patients with dementia.

Retinal nerve fiber layer analysis using GDx® in 49 patients with chronic phase DUSN

To describe retinal nerve fiber layer changes in late-stage diffuse unilateral subacute neuroretinitis eyes and compare these results with healthy eyes observed through nerve fiber analyzer (GDx®). Methods: This is a retrospective case-control study in which 49 eyes in late-stage diffuse unilateral subacute neuroretinitis were examined from May/97 to December/ 01. First, eyes with diffuse unilateral subacute neuroretinitis and healthy contralateral eyes (Control Group I) were statistically matched. Subsequently, eyes with diffuse unilateral subacute neuroretinitis were compared with eyes of healthy patients (Control Group II). Results: Eyes from Control Groups I and II had higher relative frequency of “within normal limits” status. Eyes from the diffuse unilateral subacute neuroretinitis (DUSN) Group had higher frequency of “outside normal limits” and “borderline” status. Control Groups I and II had absolute values different from the DUSN Group regarding all parameters (p<0.05), except for Symmetry in Control Groups I and II, Average thickness and Superior Integral in control group II. Conclusion: Patients with late-stage diffuse unilateral subacute neuroretinitis presented presumed decrease in nerve fiber layer thickness shown by GDx®. Retinal zones with larger vascular support and larger amount of nerve fibers presented higher decrease in the delay of the reflected light measured by the nerve fiber analyzer

Retinal nerve fiber layer analysis using GDx® in 49 patients with chronic phase DUSN

To describe retinal nerve fiber layer changes in late-stage diffuse unilateral subacute neuroretinitis eyes and compare these results with healthy eyes observed through nerve fiber analyzer (GDx®). Methods: This is a retrospective case-control study in which 49 eyes in late-stage diffuse unilateral subacute neuroretinitis were examined from May/97 to December/ 01. First, eyes with diffuse unilateral subacute neuroretinitis and healthy contralateral eyes (Control Group I) were statistically matched. Subsequently, eyes with diffuse unilateral subacute neuroretinitis were compared with eyes of healthy patients (Control Group II). Results: Eyes from Control Groups I and II had higher relative frequency of “within normal limits” status. Eyes from the diffuse unilateral subacute neuroretinitis (DUSN) Group had higher frequency of “outside normal limits” and “borderline” status. Control Groups I and II had absolute values different from the DUSN Group regarding all parameters (p<0.05), except for Symmetry in Control Groups I and II, Average thickness and Superior Integral in control group II. Conclusion: Patients with late-stage diffuse unilateral subacute neuroretinitis presented presumed decrease in nerve fiber layer thickness shown by GDx®. Retinal zones with larger vascular support and larger amount of nerve fibers presented higher decrease in the delay of the reflected light measured by the nerve fiber analyzer

Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury.

Electrical neuromodulation of lumbar segments improves motor control after spinal cord injury in animal models and humans. However, the physiological principles underlying the effect of this intervention remain poorly understood, which has limited the therapeutic approach to continuous stimulation applied to restricted spinal cord locations. Here we developed stimulation protocols that reproduce the natural dynamics of motoneuron activation during locomotion. For this, we computed the spatiotemporal activation pattern of muscle synergies during locomotion in healthy rats. Computer simulations identified optimal electrode locations to target each synergy through the recruitment of proprioceptive feedback circuits. This framework steered the design of spatially selective spinal implants and real-time control software that modulate extensor and flexor synergies with precise temporal resolution. Spatiotemporal neuromodulation therapies improved gait quality, weight-bearing capacity, endurance and skilled locomotion in several rodent models of spinal cord injury. These new concepts are directly translatable to strategies to improve motor control in humans.

Incidencia de hipoacusia y su relación con factores de riesgo, en pacientes del servicio de neonatología, Hospital Latinoamericano, Cuenca-Ecuador. 2015

ANTECEDENTES: Conocer el funcionamiento del sistema auditivo es de interés para los profesionales, por esto la detección temprana de hipoacusia es importante. OBJETIVO GENERAL: Determinar la incidencia de hipoacusia y su relación con factores de riesgo, en pacientes del Servicio de Neonatología, Hospital Latinoamericano, Cuenca - Ecuador, 2015. METODOLOGÍA: Es un estudio prospectivo analítico, la muestra de 50 pacientes cumplieron los criterios de inclusión y exclusión, los factores de riesgo se recolectaron en un formulario elaborado por los autores. Para la formulación y análisis de tablas estadísticas se utilizó Microsoft Office Excel 2007 y SPSS. Medidas Estadísticas: Riesgo Relativo, Índice de Confianza, y valor de P. RESULTADOS: La incidencia de hipoacusia detectada por OEA fue de 20 (40%) de 50 pacientes. El grupo etario con mayor incidencia de hipoacusia fueron pacientes entre 1 y 5 días de nacidos. Los factores de riesgo más frecuentes fueron PREMATURIDAD y APGAR al minuto deprimido, ambos con 28 casos (56%). El sexo MASCULINO con un 60% del total de hipoacusias detectadas fue el de mayor incidencia. Los factores de riesgo estadísticamente significativos, fueron MANIFESTACIONES NEUROLÓGICAS, con un RR=3.31 (IC95%: 2.10 – 5.21) y valor p = 0.001 y MALFORMACIONES CONGENITAS con un RR=2.88 (IC95%: 1.94 – 4.27) y valor p=0.021. CONCLUSIONES: Determinar la incidencia de hipoacusia mediante OEA es importante para llegar a un diagnóstico definitivo mediante la prueba de Potenciales Evocados y lograr un tratamiento temprano y adecuado, además de un control epidemiológico propio para detectar factores de riesgo asociados

Les interactions vestibulo-corticales qui sous-tendent le contrôle de la posture chez les sujets sains

Le système vestibulaire et le cortex moteur participent au contrôle de la posture, mais la nature de leurs interactions est peu documentée. Afin de caractériser les interactions vestibulo-corticales qui sous-tendent le contrôle de l’équilibre en position debout, l’activité électromyographique (EMG) du soléaire (SOL), du tibial antérieur (TA) et du péronier long (PERL) de la jambe droite a été enregistrée chez 14 sujets sains. La stimulation galvanique vestibulaire (GVS) a été appliquée avec la cathode derrière l’oreille droite ou gauche à différents intervalles inter-stimulus (ISIs) avant ou après la stimulation magnétique transcrânienne induisant des potentiels moteurs évoqués (MEPs) au niveau des muscles enregistrés. Lorsque que la cathode était à droite, une inhibition des MEPs a été observée au niveau du SOL à un ISI de 40 et 130 ms et une facilitation des MEPS a été observée au niveau TA à un ISI de 110 ms. Lorsque la cathode était à gauche, une facilitation des MEPs a été observée au niveau du SOL, du TA et du PERL à un ISI de 50, -10 et 0 ms respectivement. L’emplacement de ces interactions sur l’axe neural a été estimé en fonction des ISIs et en comparant l’effet de la GVS sur les MEPs à son effet sur l’EMG de base et sur le réflexe-H. Selon ces analyses, les modulations observées peuvent avoir lieu au niveau spinal ou au niveau supraspinal. Ces résultats suggèrent que les commandes de la voie corticospinale peuvent être modulées par le système vestibulaire à différents niveaux de l’axe neuronal.

Les interactions vestibulo-corticales qui sous-tendent le contrôle de la posture chez les sujets sains

Le système vestibulaire et le cortex moteur participent au contrôle de la posture, mais la nature de leurs interactions est peu documentée. Afin de caractériser les interactions vestibulo-corticales qui sous-tendent le contrôle de l’équilibre en position debout, l’activité électromyographique (EMG) du soléaire (SOL), du tibial antérieur (TA) et du péronier long (PERL) de la jambe droite a été enregistrée chez 14 sujets sains. La stimulation galvanique vestibulaire (GVS) a été appliquée avec la cathode derrière l’oreille droite ou gauche à différents intervalles inter-stimulus (ISIs) avant ou après la stimulation magnétique transcrânienne induisant des potentiels moteurs évoqués (MEPs) au niveau des muscles enregistrés. Lorsque que la cathode était à droite, une inhibition des MEPs a été observée au niveau du SOL à un ISI de 40 et 130 ms et une facilitation des MEPS a été observée au niveau TA à un ISI de 110 ms. Lorsque la cathode était à gauche, une facilitation des MEPs a été observée au niveau du SOL, du TA et du PERL à un ISI de 50, -10 et 0 ms respectivement. L’emplacement de ces interactions sur l’axe neural a été estimé en fonction des ISIs et en comparant l’effet de la GVS sur les MEPs à son effet sur l’EMG de base et sur le réflexe-H. Selon ces analyses, les modulations observées peuvent avoir lieu au niveau spinal ou au niveau supraspinal. Ces résultats suggèrent que les commandes de la voie corticospinale peuvent être modulées par le système vestibulaire à différents niveaux de l’axe neuronal.

Late onset spinal cord ischemia after thoracoabdominal aortic aneurysm open repair

The aim of this study is to evaluate if spinal cord ischemia (SCI), especially its late presentation, and can be correlated to the results of intraoperative evoked potential monitoring (IOM). Methods. This study is a physician-initiated, retrospective, single-center, non-randomized study. Data from all patients undergoing a thoracoabdominal aortic aneurysm surgical repair (TAAA SR) between January 2016 and March 2020 IOM was collected and analyzed. Results. During the study period, 261 patients underwent TAAA SR with MEP/SSEPs monitoring [190 males, 73%; median age 65 (57-71)]. Thirty-seven patients suffered from SCI, for an overall rate of 14% (permanent 9%). When stratifying patients according to the SCI onset, 18 patients presented with an early (11 permanent) and 19 with a late SCI (<24h) (11 permanent). Of 261 patients undergoing TAAA SR with IOM, 15 were excluded due to changes in the upper extremity motor evoked potentials. For the remaining 246, the association between SCI and IOM was investigated: only irreversible IOM loss without peripheral changes have been found to be a risk factor for late onset SCI (p=.006). Furthermore, given that no statistical differences were found between the two groups when no IOM changes were recorded (p=.679), this situation cannot reliably rule out any SCI in our cohort. Independent risk factors for late spinal cord ischemia onset found at multivariate analysis were smoking history (p=.008), BMI>28 (p=.048) and TAAA extent II (p=.009). The irreversible MEP change without peripheral showed a trend of significance (p=.052). Conclusions. Evoked potential intraoperative monitoring is an important adjunct during thoracoabdominal aortic open repair to predict and possibly prevent spinal cord ischemia. Irreversible IOM loss without peripheral changes was predictive of late SCI, therefore more attention should be paid to the postoperative management of this subgroup of patients.

Nuclear calcium signaling evoked by cholinergic stimulation in hippocampal CA1 pyramidal neurons

The cholinergic system is thought to play an important role in hippocampal-dependent learning and memory. However, the mechanism of action of the cholinergic system in these actions in not well understood. Here we examined the effect of muscarinic receptor stimulation in hippocampal CA1 pyramidal neurons using whole-cell recordings in acute brain slices coupled with high-speed imaging of intracellular calcium. Activation of muscarinic acetylcholine receptors by synaptic stimulation of cholinergic afferents or application of muscarinic agonist in CA1 pyramidal neurons evoked a focal rise in free calcium in the apical dendrite that propagated as a wave into the soma and invaded the nucleus. The calcium rise to a single action potential was reduced during muscarinic stimulation. Conversely, the calcium rise during trains of action potentials was enhanced during muscarinic stimulation. The enhancement of free intracellular calcium was most pronounced in the soma and nuclear regions. In many cases, the calcium rise was distinguished by a clear inflection in the rising phase of the calcium transient, indicative of a regenerative response. Both calcium waves and the amplification of action potential-induced calcium transients were blocked the emptying of intracellular calcium stores or by antagonism of inositol 1,4,5-trisphosphate receptors with heparin or caffeine. Ryanodine receptors were not essential for the calcium waves or enhancement of calcium responses. Because rises in nuclear calcium are known to initiate the transcription of novel genes, we suggest that these actions of cholinergic stimulation may underlie its effects on learning and memory.

Tone-evoked ABR in full-term and preterm neonates with normal hearing

This study was designed to investigate the feasibility of applying tone-ABRs in the nursery and neonatal intensive care unit (NICU), and to provide normative tone-ABR data from neonates. Normative tone-ABR latency data were determined. The study obtained intensity series of tone-ABRs from thirty preterm neonates and twenty fullterm neonates who had confirmed normal peripheral auditory function after passing both an OAE and ABR screening examination. ABRs were collected in response to 500, 1500, and 4000 Hz tone bursts at 70, 50, 30, and 20 dB nHL. Mean wave V latencies were compared between groups, ears, and by gender. Responses to tone bursts of 20 and 30 dB nHL were detected in 97% and 100% of all ears respectively, in addition to responses to the higher-intensity stimuli. Preterm neonates` ABRs showed significantly longer latencies than those of the full-term infants. Tone-ABR evaluation was found to be both feasible and reliable as a measure of auditory function in neonates.

Quantifying network properties in multi-electrode recordings: spatiotemporal characterization and inter-trial variation of evoked gamma oscillations in mouse somatosensory cortex in vitro.

Linking the structural connectivity of brain circuits to their cooperative dynamics and emergent functions is a central aim of neuroscience research. Graph theory has recently been applied to study the structure-function relationship of networks, where dynamical similarity of different nodes has been turned into a "static" functional connection. However, the capability of the brain to adapt, learn and process external stimuli requires a constant dynamical functional rewiring between circuitries and cell assemblies. Hence, we must capture the changes of network functional connectivity over time. Multi-electrode array data present a unique challenge within this framework. We study the dynamics of gamma oscillations in acute slices of the somatosensory cortex from juvenile mice recorded by planar multi-electrode arrays. Bursts of gamma oscillatory activity lasting a few hundred milliseconds could be initiated only by brief trains of electrical stimulations applied at the deepest cortical layers and simultaneously delivered at multiple locations. Local field potentials were used to study the spatio-temporal properties and the instantaneous synchronization profile of the gamma oscillatory activity, combined with current source density (CSD) analysis. Pair-wise differences in the oscillation phase were used to determine the presence of instantaneous synchronization between the different sites of the circuitry during the oscillatory period. Despite variation in the duration of the oscillatory response over successive trials, they showed a constant average power, suggesting that the rate of expenditure of energy during the gamma bursts is consistent across repeated stimulations. Within each gamma burst, the functional connectivity map reflected the columnar organization of the neocortex. Over successive trials, an apparently random rearrangement of the functional connectivity was observed, with a more stable columnar than horizontal organization. This work reveals new features of evoked gamma oscillations in developing cortex.

Event-related potentials and changes of brain rhythm oscillations during working memory activation in patients with first-episode psychosis.

Background: Earlier contributions have documented significant changes in sensory, attention-related endogenous event-related potential (ERP) components and θ band oscillatory responses during working memory activation in patients with schizophrenia. In patients with first-episode psychosis, such studies are still scarce and mostly focused on auditory sensory processing. The present study aimed to explore whether subtle deficits of cortical activation are present in these patients before the decline of working memory performance. Methods: We assessed exogenous and endogenous ERPs and frontal θ event-related synchronization (ERS) in patients with first-episode psychosis and healthy controls who successfully performed an adapted 2-back working memory task, including 2 visual n-backworking memory tasks as well as oddball detection and passive fixation tasks. Results: We included 15 patients with first-episode psychosis and 18 controls in this study. Compared with controls, patients with first-episode psychosis displayed increased latencies of early visual ERPs and phasic θ ERS culmination peak in all conditions. However, they also showed a rapid recruitment of working memory-related neural generators, even in pure attention tasks, as indicated by the decreased N200 latency and increased amplitude of sustained θ ERS in detection compared with controls. Limitations: Owing to the limited sample size, no distinction was made between patients with first-episode psychosis with positive and negative symptoms. Although we controlled for the global load of neuroleptics, medication effect cannot be totally ruled out. Conclusion: The present findings support the concept of a blunted electroencephalographic response in patients with first-episode psychosis who recruit the maximum neural generators in simple attention conditions without being able to modulate their brain activation with increased complexity of working memory tasks.

Age-related differences on event-related potentials and brain rhythm oscillations during working memory activation.

Previous functional imaging studies have pointed to the compensatory recruitment of cortical circuits in old age in order to counterbalance the loss of neural efficiency and preserve cognitive performance. Recent electroencephalographic (EEG) analyses reported age-related deficits in the amplitude of an early positive-negative working memory (PN(wm)) component as well as changes in working memory (WM)-load related brain oscillations during the successful performance of the n-back task. To explore the age-related differences of EEG activation in the face of increasing WM demands, we assessed the PN(wm) component area, parietal alpha event-related synchronization (ERS) as well as frontal theta ERS in 32 young and 32 elderly healthy individuals who successfully performed a highly WM demanding 3-back task. PN(wm) area increased with higher memory loads (3- and 2-back > 0-back tasks) in younger subjects. Older subjects reached the maximal values for this EEG parameter during the less WM demanding 0-back task. They showed a rapid development of an alpha ERS that reached its maximal amplitude at around 800 ms after stimulus onset. In younger subjects, the late alpha ERS occurred between 1,200 and 2,000 ms and its amplitude was significantly higher compared with elders. Frontal theta ERS culmination peak decreased in a task-independent manner in older compared with younger cases. Only in younger individuals, there was a significant decrease in the phasic frontal theta ERS amplitude in the 2- and 3-back tasks compared with the detection and 0-back tasks. These observations suggest that older adults display a rapid mobilization of their neural generators within the parietal cortex to manage very low demanding WM tasks. Moreover, they are less able to activate frontal theta generators during attentional tasks compared with younger persons.