Normal Ganglia Research Articles

Effects of Anatomical Variation on Ganglion Cell and Nerve Fibre Layer Evaluation by Optical Coherence Tomography

Background/Objectives: The automated analyses of optical coherence tomography (OCT) scans of the retina occasionally suggest the presence of tissue deficits when no visual field defects can be detected. This study was made to find the sources of such alerts. Methods: Data from a population-based cohort of 360 participants aged 30–80 years was analysed for the anatomical sources of alerts after the extensive exclusion of participants where any suspicion of abnormality could be raised. An analysis was made of 12 × 9 mm volume scans centred between the disc and the fovea. The exclusions comprised 107 eyes with definite or borderline abnormal visual fields or other potentially confounding characteristics. A statistical analysis of the thickness patterns was made using the manufacturer’s proprietary algorithm. The analysis comprised alerts corresponding to local layer thickness values in the lower 5th percentile of an independent reference population. Results: Of the 613 eligible healthy eyes, thickness deficit alerts were seen in 391. They were related to the angle between the temporal nerve fibre ridges being wider, narrower, or rotated compared to the reference template in 174 eyes and to the variations in the size of the macula in 207 eyes. The source was unidentifiable in 28 eyes. The common sources were a thin papillomacular nerve fibre layer accompanied by arcuate nerve fibre ridges spaced far apart and a thinly, but wider than the normal macular ganglion cell layer. Conclusions: Anatomical variation in the retinal nerve fibre and ganglion cell layers was the source of more than 90% of the thickness deficit alerts in the eyes with normal visual fields.

Does Length of Extended Resection Beyond Transition Zone Change Clinical Outcome for Hirschsprung Pull-Through?

IntroductionA proximal resection margin greater than 5 cm from the intra-operative histologically determined transition zone has been deemed necessary to minimize the risk of transition zone pull-through. This extended resection may require the sacrifice of vascular supply and even further bowel resection. The impact of extended proximal resection margin on post-operative complications and functional outcomes is unclear. MethodsA retrospective chart review of patients who underwent primary pull-through for Hirschsprung disease at a single institution between January 2008 and December 2022 was performed. An adequate proximal margin was defined by a circumferential normally ganglionated ring and absence of hypertrophic nerves. The extended margin was defined as the total length of proximal colon with normal ganglion cells and without hypertrophic nerves. Fecal incontinence severity was assessed with the Pediatric Fecal Incontinence Severity Score (PFISS). ResultsEighty seven patients met criteria for inclusion. Median age at primary pull-through was 17 days (IQR 10–92 days), 55% (n = 48) of patients had an extended proximal margin (EPM) ≤ 5 cm, and 45% (n = 39) had an EPM > 5 cm. An EPM ≤5 cm was not associated with increased rates of Hirschsprung associated enterocolitis (≤5 cm 43%, >5 cm 39%, P = 0.701), diversion post pull-through (≤5 cm 10%, >5 cm 5%, P = 0.367) or reoperation for transition zone pull-through (≤5 cm 3%, >5 cm 0%, P = 0.112). EPM ≤5 cm had more frequent involuntary daytime bowel movements (P = 0.041) and more frequent voluntary bowel movements (P = 0.035). There were no differences in other measures of fecal incontinence severity. ConclusionsShorter proximal extended margins beyond the adequate ganglionated margin do not significantly impact post-operative complication rates and have an unclear effect on fecal incontinence. Type of StudyCase Control. Level of EvidenceLevel III.

Chorea following SARS-CoV-2 infection and vaccination: a systematic review of reported cases

ObjectivesChorea following SARS-CoV-2 infection and vaccination, has been increasingly recognized. We aimed to synthesize clinical and paraclinical characteristics, treatment responses, and outcomes of this neurologic complication. MethodsWe systematically reviewed LitCOVID, the World Health Organization database on COVID-19, and MedRxiv up to March 2023, following a published protocol. ResultsWe included 14 chorea cases in patients with SARS-CoV-2 infection and eight following COVID-19 vaccination. Acute or subacute chorea preceded COVID-19 symptoms within 1-3 days or developed up to 3 months after infection. Frequently it was generalized (85.7%), with associated neurological manifestations (encephalopathy 35.7%; other movement disorders 7.1%). After vaccination, chorea had a sudden onset (87.5%) within 2 weeks (75%); 87.5% of cases presented hemichorea, with hemiballismus (37.5%) or other movement disorders; 12.5% presented additional neurological findings. Cerebrospinal fluid was normal in 50% of infected individuals but abnormal in all vaccinated cases. Brain magnetic resonance imaging detected normal basal ganglia in 51.7% of infection cases and 87.5% following vaccination. ConclusionIn SARS-CoV-2 infection, chorea may present several pathogenic mechanisms: autoimmune response to infection, direct infection-related injury, or an infection-related complication (i.e., acute disseminated encephalomyelitis, cerebral venous sinus thrombosis, hyperglycemia); also, previous Sydenham chorea may relapse. After COVID-19 vaccination, chorea could be due to an autoimmune reaction or other mechanisms (vaccine-induced hyperglycemia, stroke).

Reoperative and Non Reoperative Hirschsprung’s Disease in Associated with Clinicopathological Profile of the Proximal End of Resection in the Department of Anatomical Pathology, FMUI/CMH 2015-2019

Background
 Hirschsprung’s disease (HD) is a developmental disorder of the enteric nervous system, which is characterized by the absence of ganglion cells in the submucosal and myenteric plexuses. The success of surgery is influenced by many factors, one of which is the presence of histopathological abnormalities in the proximal part of the HD rectosigmoid resection. The aim of this study is to determine whether there are any histological characteristics associated with Hirschsprung's disease that would necessitate reoperation at the Department of Anatomical Pathology Faculty of Medicine Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital (FMUI/CMH).
 Methods
 This was an analytical study using a cross-sectional design and secondary data from the Department of Anatomical Pathology Faculty of Medicine Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital (FMUI/CMH) archives between 2015 and 2019. At the proximal end, histopathological examinations were performed to determine mature ganglion, nerve thickening, normal ganglion number, perineural inflammation, and serositis. The patient's age at the time of surgery, gender, the type of surgery, and the patient's age at the time of reoperation were all recorded.
 Results
 From the 64 resection cases, 15 reoperation resection cases and 49 non-reoperation resection cases were obtained. Of the 15 reoperation cases, the histopathological investigation revealed fifteen cases of mature ganglion, ten cases of nerve thickening, and fourteen cases of normal ganglion. There was no perineural inflammation in fifteen cases, and no serositis in fourteen cases. A p value of 0.026 was obtained for the patient's age at the time of the operation.
 Conclusion
 There are several factors that determine pasients with Hirschsprung disease who undergo reoperation after resection. The age of the patient at the time of resection is one of the factors that can affect the occurence of reoperation in patients with Hirschsprung disease.

Single-nucleus transcriptome analysis reveals transcriptional profiles of circadian clock and pain related genes in human and mouse trigeminal ganglion.

Clinical studies have revealed the existence of circadian rhythms in pain intensity and treatment response for chronic pain, including orofacial pain. The circadian clock genes in the peripheral ganglia are involved in pain information transmission by modulating the synthesis of pain mediators. However, the expression and distribution of clock genes and pain-related genes in different cell types within the trigeminal ganglion, the primary station of orofacial sensory transmission, are not yet fully understood. In this study, data from the normal trigeminal ganglion in the Gene Expression Omnibus (GEO) database were used to identify cell types and neuron subtypes within the human and mouse trigeminal ganglion by single nucleus RNA sequencing analysis. In the subsequent analyses, the distribution of the core clock genes, pain-related genes, and melatonin and opioid-related genes was assessed in various cell clusters and neuron subtypes within the human and mouse trigeminal ganglion. Furthermore, the statistical analysis was used to compare the differences in the expression of pain-related genes in the neuron subtypes of trigeminal ganglion. The present study provides comprehensive transcriptional profiles of core clock genes, pain-related genes, melatonin-related genes, and opioid-related genes in different cell types and neuron subtypes within the mouse and human trigeminal ganglion. A comparative analysis of the distribution and expression of the aforementioned genes was conducted between human and mouse trigeminal ganglion to investigate species differences. Overall, the results of this study serve as a primary and valuable resource for exploring the molecular mechanisms underlying oral facial pain and pain rhythms.

Intraocular Pressure-Lowering and Retina-Protective Effects of Exosome-Rich Conditioned Media from Human Amniotic Membrane Stem Cells in a Rat Model of Glaucoma.

Glaucoma is one of the most devastating eye diseases, since the disease can develop into blindness and no effective therapeutics are available. Although the exact mechanisms and causes of glaucoma are unknown, increased intraocular pressure (IOP) has been demonstrated to be an important risk factor. Exosomes are lipid nanoparticles secreted from functional cells, including stem cells, and have been found to contain diverse functional molecules that control body function, inhibit inflammation, protect and regenerate cells, and restore damaged tissues. In the present study, exosome-rich conditioned media (ERCMs) were attained via hypoxic culture (2% O2) of human amniotic membrane mesenchymal stem cells (AMMSCs) and amniotic membrane epithelial stem cells (AMESCs) containing 50 times more exosome particles than normoxic culture (20% O2) medium (NCM). The exosome particles in ERCM were confirmed to be 77 nm in mean size and contain much greater amounts of growth factors (GFs) and neurotrophic factors (NFs) than those in NCM. The glaucoma-therapeutic effects of ERCMs were assessed in retinal cells and a hypertonic (1.8 M) saline-induced high-IOP animal model. CM-DiI-labeled AMMSC exosomes were found to readily penetrate the normal and H2O2-damaged retinal ganglion cells (RGCs), and AMMSC-ERCM not only facilitated retinal pigment epithelial cell (RPEC) proliferation but also protected against H2O2- and hypoxia-induced RPEC insults. The IOP of rats challenged with 1.8 M saline increased twice the normal IOP (12-17 mmHg) in a week. However, intravitreal injection of AMMSC-ERCM or AMESC-ERCM (3.9-4.5 × 108 exosomes in 10 μL/eye) markedly recovered the IOP to normal level in 2 weeks, similar to the effect achieved with platelet-derived growth factor-AB (PDGF-AB, 1.5 μg), a reference material. In addition, AMMSC-ERCM, AMESC-ERCM, and PDGF-AB significantly reversed the shrinkage of retinal layers, preserved RGCs, and prevented neural injury in the glaucoma eyes. It was confirmed that stem cell ERCMs containing large numbers of functional molecules such as GFs and NFs improved glaucoma by protecting retinal cells against oxidative and hypoxic injuries in vitro and by recovering IOP and retinal degeneration in vivo. Therefore, it is suggested that stem cell ERCMs could be a promising candidate for the therapy of glaucoma.

Primary open-angle glaucoma in patients with obstructive sleep apnoea in a Colombian population: a cross-sectional study

ObjectiveDetermine the prevalence, functional and structural alterations of primary open-angle glaucoma (POAG) in patients with obstructive sleep apnoea (OSA).DesignCross-sectional.SettingTertiary hospital associated with specialised center in ophthalmologic images in Bogota, Colombia.Participants150...

Dichotomous activity and function of neurons with low- and high-frequency discharge in the external globus pallidus of non-human primates

To date, there is a consensus that there are at least two neuronal populations in the non-human primate (NHP) external globus pallidus (GPe): low-frequency discharge (LFD) and high-frequency discharge (HFD) neurons. Nevertheless, almost all NHP physiological studies have neglected the functional importance of LFD neurons. This study examined the discharge features of these two GPe neuronal subpopulations recorded in four NHPs engaged in a classical conditioning task with cues predicting reward, neutral and aversive outcomes. The results show that LFD neurons tended to burst, encoded the salience of behavioral cues, and exhibited correlated spiking activity. By contrast, the HFD neurons tended to pause, encoded cue valence, and exhibited uncorrelated spiking activity. Overall, these findings point to the dichotomic organization of theNHP GPe, which is likely to be critical to the implementation of normal basal ganglia functions and computations.

Huntington-associated protein 1 inhibition contributes to neuropathic pain by suppressing Cav1.2 activity and attenuating inflammation.

Although pain dysfunction is increasingly observed in Huntington disease, the underlying mechanisms still unknown. As a crucial Huntington-associated protein, Huntington-associated protein 1 (HAP1) is enriched in normal spinal dorsal horn and dorsal root ganglia (DRG) which are regarded as "primary sensory center," indicating its potential functions in pain process. Here, we discovered that HAP1 level was greatly increased in the dorsal horn and DRG under acute and chronic pain conditions. Lack of HAP1 obviously suppressed mechanical allodynia and hyperalgesia in spared nerve injury (SNI)-induced and chronic constriction injury-induced pain. Its deficiency also greatly inhibited the excitability of nociceptive neurons. Interestingly, we found that suppressing HAP1 level diminished the membrane expression of the L-type calcium channel (Cav1.2), which can regulate Ca 2+ influx and then influence brain-derived neurotrophic factor (BDNF) synthesis and release. Furthermore, SNI-induced activation of astrocytes and microglia notably decreased in HAP1-deficient mice. These results indicate that HAP1 deficiency might attenuate pain responses. Collectively, our results suggest that HAP1 in dorsal horn and DRG neurons regulates Cav1.2 surface expression, which in turn reduces neuronal excitability, BDNF secretion, and inflammatory responses and ultimately influences neuropathic pain progression.

Interactions between gut microbiota and Parkinson's disease: The role of microbiota-derived amino acid metabolism.

Non-motor symptoms (NMS) of Parkinson's disease (PD), such as constipation, sleep disorders, and olfactory deficits, may emerge up to 20 years earlier than motor symptoms. A series of evidence indicates that the pathology of PD may occur from the gastrointestinal tract to the brain. Numerous studies support that the gut microbiota communicates with the brain through the immune system, special amino acid metabolism, and the nervous system in PD. Recently, there is growing recognition that the gut microbiota plays a vital role in the modulation of multiple neurochemical pathways via the "gut microbiota-brain axis" (GMBA). Many gut microbiota metabolites, such as fatty acids, amino acids, and bile acids, convey signaling functions as they mediate the crosstalk between gut microbiota and host physiology. Amino acids' abundance and species alteration, including glutamate and tryptophan, may disturb the signaling transmission between nerve cells and disrupt the normal basal ganglia function in PD. Specific amino acids and their receptors are considered new potential targets for ameliorating PD. The present study aimed to systematically summarize all available evidence on the gut microbiota-derived amino acid metabolism alterations associated with PD.

Caractéristiques du complexe de cellules ganglionnaires chez le sujet normal à Lomé

To determine the features of the macular ganglion cell complex and its correlations in normal black subjects in Lomé. We conducted a descriptive, analytical, retrospective study over 32 months from November 2014 to June 2017. This study was based on records of healthy patients with normal IOP, optic discs and ganglion cell complexes (GCC). The 3D-OCT 2000 (Topcon Corporation, Tokyo, Japan) was used with standard image acquisition protocols. RNFL and the GCC parameters were analyzed. Univariate linear regression tests were used, with the Pearson correlation coefficient (r2) to assess correlations between the various parameters. A total of 277 eyes of 155 patients were examined-146 right eyes and 131 left eyes. The mean age of the patients was 37.7±15.2 (5-60) years. The mean RNFL thickness was 108.3±7.1μm, 134.8±11.1μm in the lower quadrant, 128.3±13.8μm in the upper, 92.2±12.8μm in the nasal and 77.9±11.6μm in the temporal quadrant. There was 6% asymmetry in the macular fibers, with a mean thickness of 33.1±3.5μm superiorly and 35.3±3.8μm inferiorly. There was 2% asymmetry in the macular cells, with a mean thickness of 71.6±5.7μm superiorly and 70.5±5.2μm inferiorly. The macular GCC thickness showed 1% asymmetry, with a mean thickness of 105.0±7.1μm superiorly and 106.1±6.7μm inferiorly. The thickness of the superior macular GCC was strongly correlated with the inferior (r2=0.8; p <0.05). The thickness of the macular GCC was weakly correlated with age (r2=0.05; p =0.0003), gender (r2=0.01; p =0.2), optic nerve head surface area (r2=0.2; p < 0.05) and RNFL thickness (r2=0.15; p <0.05) CONCLUSION: The results of this study will help to establish a normative database for GCC parameters in normal black Africans.

Antiphospholipid‐Related Chorea: Two Case Reports and Role of Metabolic Imaging

ABSTRACTBackgroundAntiphospholipid syndrome (APS) is a complex acquired autoimmune disease with a wide clinical spectrum. Chorea is a rare neurological manifestation of APS.CasesWe report two elderly patients with APS‐related chorea in whom functional imaging (18F‐FDG positron emission tomography, FDG‐PET) supported the diagnosis and compare our findings with existing literature.Literature ReviewAmong 142 clinical cases of antiphospholipid‐related chorea found in literature, only 10 had undergone brain metabolic imaging. Striatal hypermetabolism was evident in all cases (6) that underwent FDG‐PET cerebral imaging. Cerebral perfusion single photon emission computed tomography (SPECT) was normal in two cases, while the other two presented with basal ganglia hypoperfusion.ConclusionsBrain FDG‐PET usually shows striatal hypometabolism in neurodegenerative types of chorea as opposed to striatal hypermetabolism observed in most cases of chorea from reversible etiologies, such as APS‐related chorea. When a patient's clinical presentation is not clearly suggestive of either a neurodegenerative or autoimmune chorea, and first‐line investigations are normal, FDG‐PET may help in the differential diagnosis, especially in the presence of striatal hypermetabolism. SPECT data are less numerous and show either normal scans or basal ganglia hypoperfusion.

Early neonatal heart rate variability patterns in different subtypes of perinatal hypoxic-ischemic brain injury.

This study aims to compare the longitudinal changes in heartrate variability (HRV) during therapeutic hypothermia in neonates with different subtypes of hypoxic-ischemic brain injury. HRV was computed from 1 hour time-epochs q6 hours for the first 48 hours. Primary outcome was brain-injury pattern on MRI at 4(3-5) days. We fitted linear mixed-effect regression models with HRV metric, brain injury subtype and postnatal age. Among 89 term neonates, 40 neonates had abnormal brain MRI (focal infarct 15 (38%), basal-ganglia predominant 8 (20%), watershed-predominant 5 (13%), and mixed pattern 12 (30%)). There was no significant difference in the HRV metrics between neonates with normal MRI, focal infarcts and basal ganglia pattern. At any given postnatal age, the degree of HRV suppression(HRV measure in the brain-injury subtype group/HRV measure in Normal MRI group) was significant in neonates with watershed pattern (SDNN(0.63, p = 0.08), RMSSD(0.74, p = 0.04)) and mixed pattern injury (SDNN (0.64, p < 0.001), RMSSD (0.75, p = 0.02)). HRV suppression was most profound at the postnatal age of 24-30 h in all brain injury subtypes. Neonates with underlying watershed injury with or without basal-ganglia injury demonstrates significant HRV suppression during first 48 hour of hypothermia therapy. Our study suggests that suppression of heartrate variability in neonates during therapeutic hypothermia varies according to the pattern of underlying hypoxic-ischemic brain injury. Neonates with watershed predominant pattern and mixed pattern of brain injury have the most severe suppression of heartrate variability measures. Heartrate variability monitoring may provide early insights into the pattern of hypoxic-ischemic brain injury in neonates undergoing therapeutic hypothermia earlier than routine clinical MRI.

Expression of the axon guidance factor Slit2 and its receptor Robo1 in patients with Hirschsprung disease: An observational study.

Hirschsprung disease (HD) is a common form of digestive tract malformation in children. However, the pathogenesis of HD is not very clear. This study aimed to investigate the expression of slit guidance ligand 2 (Slit2) and roundabout 1 (Robo1) in patients with HD.From January 2018 to January 2019, 30 colon specimens from children with HD undergoing surgical resection at the Department of Surgery in Qilu Children's Hospital of Shandong University were obtained. These specimens were divided into the normal segment group, the transitional segment group and the spastic segment group. Immunohistochemical staining, Western blotting, and real-time polymerase chain reaction were used to measure the expression of Slit2 and Robo1 in the intestinal walls of normal, transitional, and spastic segments.Immunohistochemical staining and Western blot analyses showed high levels of the Slit2 and Robo1 proteins in normal ganglion cells in children with HD, lower levels in transitional ganglion cells, and no expression in spastic segments, with significant differences between groups (P < .05). Similarly, the real-time polymerase chain reaction results were consistent with the Western blot analysis results.The expression of Slit2 and Robo1 decreases significantly in the spastic segment of the intestinal tract in patients with HD.

Long-term outcomes in children with Hirschsprung's disease and transition zone bowel pull-through: impact of surgical techniques and role for conservative approach.

Presence of transition zone (TZ) in the pulled colon can impact the outcome of surgery in children with Hirschsprung's disease. There is a wide variation in terminology used to define TZ and its management. We present our series of managing 11 such children with considerations for conservative management. Eleven of 114 children operated for Hirschsprung's disease had features of TZ on the 4-quadrant doughnut assessment of proximal anastomosing margin. They were followed up for development of obstructive symptoms, failure of pull-through procedure or bowel-related complications. Intervention done were observation with laxatives, dilatation, Botox injection and redo pull-through. Of the 11 children, 6 underwent Duhamel's procedure and 5, transanal endorectal pull-through (TERP). Features identified on HPE were presence of hypertrophic nerve bundles involving 2 or 3 quadrants in the circumferential doughnut biopsy of proximal anastomosing margin. Observed symptoms included constipation, enterocolitis, increased bowel frequency and soiling. Intervention done were use of laxatives with bowel management program in six and Botox injections in four. Only one child with TZ in 3 quadrants required redo surgery. Mean follow-up was 5.2years with resolution of symptoms in most. This study highlights the role of conservative management with good outcomes in children with TZ bowel pull-through having hypertrophic nerve fibers and normal ganglion pattern. Children who underwent Duhamel's procedure had little impact with the presence of TZ at anastomotic margin and majority of those undergoing TERP benefitted from Botox injection. Conservative management can be attempted successfully to prevent redo surgical interventions as they can lead to poorer outcomes. Only those children not responding to conservative measures need to be planned for revision surgery.

Corticostriatal Hypermetabolism in Moyamoya Disease-Induced Hemichorea: Two Case Reports and a Literature Review

Moyamoya disease (MMD) is a rare cause of chorea, and its pathophysiological mechanism remains unclear. We explore the use of cerebral positron emission tomography (PET) to study brain functional connectivity in 2 patients with MMD-induced hemichorea. Abnormal metabolism of brain was analyzed by 18F-fluorodeoxyglucose (18F-FDG) PET images. Dopamine transporters (DAT) PET evaluated the integrity of the cerebral dopamine system. A comprehensive systemic literature search of the PubMed database was also conducted. The 18F-FDG imaging of our patients showed no responsible hypometabolism in affected brain areas, while hypermetabolism in the affected caudate nucleus, putamen and fronto-parietal areas could be seen. DAT PET imaging was normal in patient 1 (a 23-year-old woman), while remarkably reduced DAT binding was seen in the left striatum of patient 2 (a 48-year-old woman). The literature review of 9 publications revealed that 11 patients who underwent single photon emission computed tomography (SPECT) showed cerebral hypoperfusion in the cortex and subcortical area; 18F-FDG PET was performed in 3 cases, which revealed hypermetabolism in the affected striatum in 2 cases. These findings suggest that the striatal and cortical hypermetabolism in the first patient result from underactivity in indirect pathway from basal ganglia-thalamocortical circuits, causing increased activity of excitatory glutamatergic thalamostriatal and thalamocortical projection neurons. The collateral vessels in the basal ganglia might lead to disruption of normal basal ganglia signaling. A dominant left hemisphere with corpus callosal connections to the right basal ganglia resulting into left hemichorea is the most probable explanation for the second patient. We have identified abnormal functional connectivity in basal ganglia-thalamocortical circuits in patients with MMD-induced chorea highlighting the corticostriatal pathway plays an important role in the pathogenesis of MMD-induced chorea.

High-Frequency Oscillations in the Pallidum: A Pathophysiological Biomarker in Parkinson's Disease?

Abnormal oscillatory neural activity in the beta-frequency band (13-35 Hz) is thought to play a role in Parkinson's disease (PD); however, increasing evidence points to alterations in high-frequency ranges (>100 Hz) also having pathophysiological relevance. Studies have found that power in subthalamic nucleus (STN) high-frequency oscillations is increased with dopaminergic medication and during voluntary movements, implicating these brain rhythms in normal basal ganglia function. The objective of this study was to investigate whether similar signaling occurs in the internal globus pallidus (GPi), a nucleus increasingly used as a target for deep brain stimulation (DBS) for PD. Spontaneous and movement-related GPi field potentials were recorded from DBS leads in 5 externalized PD patients on and off dopaminergic medication, as well as from 3 rhesus monkeys before and after the induction of parkinsonism with the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine. In the parkinsonian condition, we identified a prominent oscillatory peak centered at 200-300 Hz that increased during movement. In patients the magnitude of high-frequency oscillation modulation was negatively correlated with bradykinesia. In monkeys, high-frequency oscillations were mostly absent in the naive condition but emerged after the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine. In patients, spontaneous high-frequency oscillations were significantly attenuated on-medication. Our findings provide evidence in support of the hypothesis that exaggerated, movement-modulated high-frequency oscillations in the GPi are pathophysiological features of PD. These findings suggest that the functional role(s) of high-frequency oscillations may differ between the STN and GPi and motivate additional investigations into their relationship to motor control in normal and diseased states.

Homonymous visual field defects in patients with multiple sclerosis: results of computerised perimetry and optical coherence tomography.

Visual dysfunction is frequent in multiple sclerosis, usually resulting from retrobulbar optic neuritis or papillitis. Less frequently, demyelinating lesions can affect the retrochiasmal pathways. There are few reports of homonymous visual field defects (HVFD) in multiple sclerosis and little is known about their evolution. The purpose of this study was to better define both the clinical profile and the evolution of HVFD in patients with multiple sclerosis. We performed a retrospective study of all multiple sclerosis patients who presented HVFD and were examined by automated static perimetry. A subset of patients benefited from macular assessment with optical coherence tomography (OCT). We also reviewed the worldwide literature on the subject. Twenty patients were retrieved from the neuro-ophthalmology database of the H&ocirc;pital Ophtalmique Jules-Gonin. There were 11 women and 9 men, and their average age was 35 &plusmn; 11 years. The relapsing-remitting form of multiple sclerosis was most common (18/20; 90%), the primary progressive form (1/20; 5%) and the secondary progressive form (1/20; 5%) were rare. HVFD were the presenting symptom of multiple sclerosis in seven patients (35%). The recovery was complete in 12/20 patients (60%), and the median time to recovery was 10 weeks (2-13 weeks). An incomplete recovery was found in 5/20 subjects (25%) and no recovery occurred in 3/20 subjects (15%). Magnetic resonance imaging disclosed a definite lesion explaining the HVFD in 7/11 patients: five within the optic radiations (71.4%), one within the optic tract (14.3%) and one within the lateral geniculate nucleus (14.3%). Our results were comparable to those compiled from our literature search (29 publications, totalling 70 cases). A recurrent episode of HVFD occurred in three patients (15%). OCT was performed in 10/20 patients. Retinal ganglion cell layer thickness was assessed and revealed a homonymous thinning in three patients, diffuse unilateral or bilateral thinning (resulting from previous episodes of optic neuritis) in six patients, and normal retinal ganglion cell layer thickness in one patient. HVFD in multiple sclerosis are found mostly in young patients with relapsing-remitting multiple sclerosis, which is consistent with the epidemiology of multiple sclerosis. HVFD can be the first manifestation of multiple sclerosis and have a relatively good prognosis. Like optic neuritis, HVFD can recur. The incidence of HVFD in multiple sclerosis is unknown, as it is probably underdiagnosed. Systematic automated static perimetry and OCT could help to determine the true incidence of HVFD in multiple sclerosis. &nbsp.

Challenges in management and prognosis of pediatric intestinal pseudo-obstruction.

Pediatric intestinal pseudo-obstruction (PIPO) is the most severe form of intestinal dysmotility in children. This study aims to present the cases of PIPO to discuss its diagnosis, management, and prognosis. We retrospectively analyzed the medical records of the patients with PIPO between 2010 and 2018. A total of 7 patients were included. The admission age was 3 days-10 years. The complaints were abdominal distention and constipation in all the patients. All the patients had passed meconium in the first 48 hours of their life. An upper gastrointestinal (GI) series revealed slow transit in 6 patients and malrotation in 2 patients. Full-thickness rectum biopsies revealed normal ganglion cells. Neurological examination revealed postinfectious pandysautonomy in 1 patient. Furthermore, 2 patients are under follow-up with ileostomy and TPN, 1 patient is with enteral feeding and ileostomy, and 3 patients are stable with pyridostigmine, enemas. Moreover, 1 patient died because of sepsis. The prognosis was not significantly correlated with initial presentation time, lag time, and presence of extraintestinal manifestations (p>0.05). The prognosis was significantly better when fewer number of operations were performed (p=0.029) Conclusion: PIPO is a broad-spectrum disease group that is difficult to diagnose and treat. It is mandatory to rule out the secondary causes of diagnosis. Medical and surgical treatments are used to support the nutritional status, prevent sepsis, and restore the intestinal motility. The prognosis was better when the secondary causes were identified and fewer operations were performed.

Circular RNA DGKB Promotes the Progression of Neuroblastoma by Targeting miR-873/GLI1 Axis.

Accumulated evidences suggested that circular RNAs (circRNA) played critical roles in tumorigenesis and progression. To our knowledge, no study reported the function of circular RNA DGKB (circDGKB, circRNA ID: hsa_circ_0133622) on progression of neuroblastoma (NB). Here, we showed that circDGKB was upregulated in NB tissues compared to the normal dorsal root ganglia. Moreover, the expression level of circDGKB was negatively correlated with the survival rate of NB patients. Mechanically, overexpression of circDGKB promoted the proliferation, migration, invasion, and tumorigenesis of NB cells and reduced cell apoptosis, and vice versa. In addition, qRT-PCR and/or Western blot results showed that circDGKB overexpression inhibited the expression level of miR-873 and enhanced GLI1 expression. Moreover, miR-873 functioned an opposite role to circDGKB and significantly weakened circDGKB role in promoting NB progression. Furthermore, GLI1 upregulation also rescued the miR-873 role in inhibiting NB progression. In conclusion, our work proved that circDGKB promoted NB progression via targeting miR-873/GLI1 axis in vitro and in vivo. Our study provided a new target for NB treatment and indicated that circDGKB could act as a novel diagnostic marker for NB.