Alteration of Fractional Anisotropy and Mean Diffusivity in Glaucoma: Novel Results of a Meta-Analysis of Diffusion Tensor Imaging Studies

Objectives

We hypothesized that a meta-analysis of existing studies may help to reveal significant changes on diffusion tensor imaging (DTI) in patients with glaucoma. Therefore, a meta-analysis was utilized to investigate the possibility that DTI can detect white matter damage in patients with glaucoma.

Methods

The study design and report adhered to the PRISMA Statement guidelines. DTI studies that compared glaucoma patients and controls were surveyed using PubMed, Web of Science and EMBASE (January 2008 to September 2013). Stata was used to analyze the decrease in fractional anisotropy (FA) and increase in mean diffusivity (MD) in the optic nerve and optic radiation in patients with glaucoma.

Results

Eleven DTI studies were identified through a comprehensive literature search, and 10 independent DTI studies of glaucoma patients were eligible for the meta-analysis. A random effects model revealed a significant FA reduction in the optic nerve and optic radiation, as well as a significant MD increase in the tracts. A heterogeneity analysis suggested that FA may be related to glaucoma severity.

Conclusions

Our findings revealed that the optic nerve and optic radiation were vulnerable regions in patients with glaucoma and that FA may be correlated with glaucoma severity and age. Furthermore, this study suggests that magnetic resonance imaging in patients with glaucoma may help to provide objective evidence to aid in the diagnosis and management of glaucoma.     

3.0T磁共振扩张量成像对腰椎间盘突出致神经根受压的诊断价值及其与Oswestry功能障碍指数及视觉模拟评分的相关性

目的:研究3.0T磁共振扩张量成像(DTI)对腰椎间盘突出致神经根受压的诊断价值及其与Oswestry功能障碍指数(ODI)及视觉模拟评分(VAS)的相关性。方法:纳入我院从2017年1月~2019年1月收治的腰椎间盘突出致神经根受压患者50例进行研究,记作研究组。另取同期我院收治的单纯腰椎间盘突出患者50例作为对照组。两组受试者均接受DTI扫描以及ODI、VAS评分。比较两组神经根不同层面的各向异性分数(FA)值、弥散系数(ADC)值、ODI、VAS评分,并作相关性分析。同时,以手术病理诊断为金标准,分析DTI诊断腰椎间盘突出致神经根受压的敏感性、特异性、准确度。结果:研究组患者神经根近层、中层、远层的FA值均显著低于对照组,而ADC值均显著高于对照组(均P<0.05)。以手术病理诊断为金标准,DTI诊断腰椎间盘突出致神经根受压的敏感性为94.00%、特异性为96.00%、准确度为95.00%。研究组ODI、VAS评分分别为(43.22±7.25)分、(6.68±1.92)分,相较于对照组的(28.56±6.22)分、(4.02±1.34)分显著更高(均P<0.05)。经Pearson相关性分析可得:腰椎间盘突出致神经根受压患者的FA值与ODI、VAS评分均呈负相关关系(均P<0.05),而ADC值与ODI、VAS评分无相关性(均P>0.05)。结论:DTI对腰椎间盘突出致神经根受压的诊断价值较高,且FA值与ODI、VAS均存在明显相关性。临床工作中可能将DTI的FA值作为量化神经根结构改变的重要参数,值得临床重点关注。     

Parallel Changes in Structural and Functional Measures of Optic Nerve Myelination after Optic Neuritis

IntroductionVisual evoked potential (VEP) latency prolongation and optic nerve lesion length after acute optic neuritis (ON) corresponds to the degree of demyelination, while subsequent recovery of latency may represent optic nerve remyelination. We aimed to investigate the relationship between multifocal VEP (mfVEP) latency and optic nerve lesion length after acute ON.MethodsThirty acute ON patients were studied at 1,3,6 and 12 months using mfVEP and at 1 and 12 months with optic nerve MRI. LogMAR and low contrast visual acuity were documented. By one month, the mfVEP amplitude had recovered sufficiently for latency to be measured in 23 (76.7%) patients with seven patients having no recordable mfVEP in more than 66% of segments in at least one test. Only data from these 23 patients was analysed further.ResultsBoth latency and lesion length showed significant recovery during the follow-up period. Lesion length and mfVEP latency were highly correlated at 1 (r = 0.94, p = <0.0001) and 12 months (r = 0.75, p < 0.001). Both measures demonstrated a similar trend of recovery. Speed of latency recovery was faster in the early follow-up period while lesion length shortening remained relatively constant. At 1 month, latency delay was worse by 1.76ms for additional 1mm of lesion length while at 12 months, 1mm of lesion length accounted for 1.94ms of latency delay.ConclusionA strong association between two putative measures of demyelination in early and chronic ON was found. Parallel recovery of both measures could reflect optic nerve remyelination.     

Optic Nerve Diffusion Tensor Imaging after Acute Optic Neuritis Predicts Axonal and Visual Outcomes

Background

Early markers of axonal and clinical outcomes are required for early phase testing of putative neuroprotective therapies for multiple sclerosis (MS).

Objectives

To assess whether early measurement of diffusion tensor imaging (DTI) parameters (axial and radial diffusivity) within the optic nerve during and after acute demyelinating optic neuritis (ON) could predict axonal (retinal nerve fibre layer thinning and multi-focal visual evoked potential amplitude reduction) or clinical (visual acuity and visual field loss) outcomes at 6 or 12 months.

Methods

Thirty-seven patients presenting with acute, unilateral ON were studied at baseline, one, three, six and 12 months using optic nerve DTI, clinical and paraclinical markers of axonal injury and clinical visual dysfunction.

Results

Affected nerve axial diffusivity (AD) was reduced at baseline, 1 and 3 months. Reduced 1-month AD correlated with retinal nerve fibre layer (RNFL) thinning at 6 (R=0.38, p=0.04) and 12 months (R=0.437, p=0.008) and VEP amplitude loss at 6 (R=0.414, p=0.019) and 12 months (R=0.484, p=0.003). AD reduction at three months correlated with high contrast visual acuity at 6 (ρ = -0.519, p = 0.001) and 12 months (ρ = -0.414, p=0.011). The time-course for AD reduction for each patient was modelled using a quadratic regression. AD normalised after a median of 18 weeks and longer normalisation times were associated with more pronounced RNFL thinning and mfVEP amplitude loss at 12 months. Affected nerve radial diffusivity (RD) was unchanged until three months, after which time it remained elevated.

Conclusions

These results demonstrate that AD reduces during acute ON. One month AD reduction correlates with the extent of axonal loss and persistent AD reduction at 3 months predicts poorer visual outcomes. This suggests that acute ON therapies that normalise optic nerve AD by 3 months could also promote axon survival and improve visual outcomes.     

Reduced Ventral Cingulum Integrity and Increased Behavioral Problems in Children with Isolated Optic Nerve Hypoplasia and Mild to Moderate or No Visual Impairment

Objectives

To assess the prevalence of behavioral problems in children with isolated optic nerve hypoplasia, mild to moderate or no visual impairment, and no developmental delay. To identify white matter abnormalities that may provide neural correlates for any behavioral abnormalities identified.

Patients and Methods

Eleven children with isolated optic nerve hypoplasia (mean age 5.9 years) underwent behavioral assessment and brain diffusion tensor imaging, Twenty four controls with isolated short stature (mean age 6.4 years) underwent MRI, 11 of whom also completed behavioral assessments. Fractional anisotropy images were processed using tract-based spatial statistics. Partial correlation between ventral cingulum, corpus callosum and optic radiation fractional anisotropy, and child behavioral checklist scores (controlled for age at scan and sex) was performed.

Results

Children with optic nerve hypoplasia had significantly higher scores on the child behavioral checklist (p<0.05) than controls (4 had scores in the clinically significant range). Ventral cingulum, corpus callosum and optic radiation fractional anisotropy were significantly reduced in children with optic nerve hypoplasia. Right ventral cingulum fractional anisotropy correlated with total and externalising child behavioral checklist scores (r = −0.52, p<0.02, r = −0.46, p<0.049 respectively). There were no significant correlations between left ventral cingulum, corpus callosum or optic radiation fractional anisotropy and behavioral scores.

Conclusions

Our findings suggest that children with optic nerve hypoplasia and mild to moderate or no visual impairment require behavioral assessment to determine the presence of clinically significant behavioral problems. Reduced structural integrity of the ventral cingulum correlated with behavioral scores, suggesting that these white matter abnormalities may be clinically significant. The presence of reduced fractional anisotropy in the optic radiations of children with mild to moderate or no visual impairment raises questions as to the pathogenesis of these changes which will need to be addressed by future studies.     

Positive Effects of bFGF Modified Rat Amniotic Epithelial Cells Transplantation on Transected Rat Optic Nerve

PurposeEffective therapy for visual loss caused by optic nerve injury or diseases has not been achieved even though the optic nerve has the regeneration potential after injury. This study was designed to modify amniotic epithelial cells (AECs) with basic fibroblast growth factor (bFGF) gene, preliminarily investigating its effect on transected optic nerve.MethodsA human bFGF gene segment was delivered into rat AECs (AECs/hbFGF) by lentiviral vector, and the gene expression was examined by RT-PCR and ELISA. The AECs/hbFGF and untransfected rat AECs were transplanted into the transected site of the rat optic nerve. At 28 days post transplantation, the survival and migration of the transplanted cells was observed by tracking labeled cells; meanwhile retinal ganglion cells (RGCs) were observed and counted by employing biotin dextran amine (BDA) and Nissl staining. Furthermore, the expression of growth associated protein 43 (GAP-43) within the injury site was examined with immunohistochemical staining.ResultsThe AECs/hbFGF was proven to express bFGF gene and secrete bFGF peptide. Both AECs/hbFGF and AECs could survive and migrate after transplantation. RGCs counting implicated that RGCs numbers of the cell transplantation groups were significantly higher than that of the control group, and the AECs/hbFGF group was significantly higher than that of the AECs group. Moreover GAP-43 integral optical density value in the control group was significantly lower than that of the cell transplantation groups, and the value in the AECs/hbFGF group was significantly higher than that of the AECs group.ConclusionsAECs modified with bFGF could reduce RGCs loss and promote expression of GAP-43 in the rat optic nerve transected model, facilitating the process of neural restoration following injury.     

The effect of fractionated gamma knife radiosurgery on visual acuity in patients with optic nerve tumor

BackgroundStereotactic radiosurgery (SRS) method has been considered the first-line treatment option to treat patients involved with pre-optic nerve tumors. However, studies have shown that using fractionated SRS, normal tissue sparing and tumor dose can be strongly increased simultaneously. Our main goal was to illustrate the effects of fractionated SRS approach in optic nerve tumor treatment and its adjacent sensitive structures.Materials and methods19 patients involved in optic nerve tumor with clinical symptoms of vision loss were treated with Gamma Knife radiosurgery in three sessions with 12 hours intervals between them. The prescribed dose was about 6.0 ± 1.2 Gy. Patient-related parameters including pre-treatment and after-treatment tumor size, visual acuity and visual field were evaluated using the Snell chart and MRI imaging. Patients were followed for about 14 months.ResultThe overall result showed vision improvement for patients with low and moderate visual loss. However, there was no significant improvement in patients with severe visual loss. Relative improvement was observed in blind patients, although poorly. There was no evidence of growth, recurrence, or new tumor after treatment in patients.ConclusionFractionated gamma knife radiosurgery offers a safe and effective alternative for benign lesions adjacent to the optic nerve.     

BMSCs移植对视神经损伤家猫RGCs损伤及BDNF表达的影响

目的:探讨玻璃体腔内注射移植体外培养的骨髓间充质干细胞(Bone marrow mesenchymal stem cells, BMSCs)对家猫视神经损伤后视网膜神经节细胞(Retinal ganglion cells, RGCs)的影响及其可能的作用机制。方法:参照标准化家猫外伤性视神经损伤动物模型建立的方法建立右眼视神经夹伤家猫模型,然后将其分为以下四组:(1)A组:右眼BMSCs注射移植组,玻璃体腔内接受注射移植BMSCs浓度为1×10~5细胞/μL的单细胞悬液0.1 m L;(2)B组:右眼PBS注射组,玻璃体腔内注射PBS缓冲液0.1 mL;(3)C组:假损伤控制组,BMSCs左眼组,仅暴露视神经而不损伤,不接受治疗;(4)D组:正常对照组,PBS左眼组,正常眼,不做任何处理。分别在移植后的3、7、14及28天,用免疫荧光染色双十八烷基四甲基吲哚羰基花青高氯酸盐染色标记法观察分离视网膜的RGCs存活率,用双抗体一步夹心法酶联免疫吸附试验方法检测分离视网膜的脑源性神经营养因子(Brain derived neurotrophic factor, BDNF)的含量。结果:术后3、7、14及28天,在周边区及中央区视网膜上RGCs密度均显著减少(周边区:P3d=0.0446, P7d=0.0011, P14d 0.001, P28d0.001;中央区:P3d=0.0437, P7d=0.0067, P14d0.001, P28d0.001)。7天、14天、28天后,A组RGCs密度及BDNF含量均显著高于B组(P0.05)。结论:BMSCs移植可以减缓外伤性视神经损伤家猫RGCs凋亡,可能与其增加BDNF表达有关。     

血府逐瘀汤对糖尿病视网膜病变患者视神经形态结构的影响

摘要 目的：探讨血府逐瘀汤对糖尿病视网膜病变患者视神经形态结构的影响。方法：2017年11月~2019年12月选择在本院就诊的糖尿病视网膜病变患者76例,根据随机信封抽签原则把患者分为观察组与对照组各38例。对照组给予康柏西普治疗,观察组在对照组治疗的基础上给予血府逐瘀汤治疗,两组都治疗观察2个月,记录视神经形态结构变化情况。结果：治疗后观察组的总有效率为97.37 %,显著高于对照组的78.95 %(P<0.05)。两组治疗后行空腹血糖(fasting blood glucose,FBG)与餐后2 h血糖(2 h postprandial blood glucose,2hPG),值都低于治疗前,观察组低于对照组(P<0.05)。两组治疗前的视盘周围视网膜神经纤维层(Retinal nerve fiber layer,RNFL)厚度在上象限、下象限、颞象限、鼻象限上对比无差异(P>0.05),两组治疗后各个象限的RNFL厚度均显著下降(P<0.05),且观察组各个象限的RNFL厚度均低于对照组(P<0.05)。观察组治疗后的红细胞聚集指数与纤维蛋白原低于治疗前,也低于对照组(P<0.05),对照组治疗前后对比无差异(P>0.05)。结论：血府逐瘀汤在糖尿病视网膜病变患者中的应用能改善视神经形态结构,促进降低血糖,改善患者的血液流变学状况,从而提高治疗效果。     

Comparison of the Deep Optic Nerve Head Structure between Normal-Tension Glaucoma and Nonarteritic Anterior Ischemic Optic Neuropathy

PurposeTo compare the deep optic nerve head (ONH) structure between normal-tension glaucoma (NTG) and nonarteritic anterior ischemic optic neuropathy (NAION) and also in healthy subjects as a control using enhanced depth imaging (EDI) spectral-domain optical coherence tomography (SD-OCT).MethodsThis prospective cross-sectional study included 21 NAION patients who had been diagnosed as NAION at least 6 months prior to study entry, and 42 NTG patients and 42 healthy controls who were matched with NAION patients in terms of age, intraocular pressure (IOP), and optic disc area. The retinal nerve fiber layer (RNFL) thickness in the affected sector was also matched between NAION and NTG patients. The ONH was imaged using SD-OCT with the EDI technique. The anterior lamina cribrosa surface depth (LCD) and average prelaminar tissue (PT) thickness were measured in a sector of interest in each eye and compared among the three groups.ResultsIn the sector-matched comparison, LCD was largest in NTG patients, followed by NAION patients, while PT was thinner in NTG patients than in NAION patients (all P < 0.001). NAION patients had a comparable LCD and a thinner PT relative to normal controls (P = 0.170 and < 0.001, respectively).ConclusionThe deep ONH configuration is strikingly different between NTG and NAION. The differing features provide comparative insight into the pathophysiology of the two diseases, and may be useful for differential diagnosis.     

Optic Disc Change during Childhood Myopic Shift: Comparison between Eyes with an Enlarged Cup-To-Disc Ratio and Childhood Glaucoma Compared to Normal Myopic Eyes

BackgroundProgressive disc tilting and the development or enlargement of peripapillary atrophy (PPA) are observed during a myopic shift in children. This could be related to the changes around the optic nerve head during eyeball elongation. If the biomechanical properties at or around the optic nerve head are changed after exposure to elevated intraocular pressure (IOP) in glaucoma eyes, different response of the disc tilting and PPA changes could take place during eyeball elongation by myopic shift. On the basis of this background, the aim of this study was to compare the morphological changes in the optic disc induced by a myopic shift during childhood between normal control eyes, eyes from disc suspects with an enlarged cup-to-disc ratio (CDR), and eyes with childhood glaucoma.MethodsTotal of 82 eyes from 82 subjects younger than 14 years of age were included in the study. Serial disc photographs were classified into one of two groups: eyes with an optic nerve head (ONH) or peripapillary atrophy (PPA) change or without an ONH/PPA change. Using ImageJ software, the outlines of the optic disc and PPA were plotted, and the vertical disc diameter (VDD), horizontal disc diameter (HDD), and maximum PPA width (PPW) were measured. The changes in the ratios of these parameters and the relationships between the degree of myopic shift or the ONH/PPA change were analyzed.ResultsTwenty-five eyes with normal optic disc appearance, 36 eyes with enlarged cup-to-disc ratio, and 21 eyes of glaucoma patients were analyzed. The initial intraocular pressure (IOP) at diagnosis was significantly different among the groups (P<0.001). The degree of myopic shift during follow-up period was not significantly different among the groups (P=0.612). However, the changes in the HDD/VDD and PPW/VDD ratios were significantly greater in the disc suspect group and significantly smaller in the glaucoma group. Among the 42 eyes with an ONH/PPA change, 16 (38.1%) were from the normal control group, 24 (57.1%) were from the disc suspect group, and 2 (4.8%) were from the glaucoma group (P < 0.001).

Conclusions and Relevance

The optic disc change during childhood myopic shift was different in eyes with various conditions. Eyes of childhood glaucoma showed less change in the disc morphology during myopic shift compared to eyes with normal disc or enlarged cup-to-disc ratio.     

Widespread Changes in White Matter Microstructure after a Day of Waking and Sleep Deprivation

BackgroundElucidating the neurobiological effects of sleep and waking remains an important goal of the neurosciences. Recently, animal studies indicated that sleep is important for cell membrane and myelin maintenance in the brain and that these structures are particularly susceptible to insufficient sleep. Here, we tested the hypothesis that a day of waking and sleep deprivation would be associated with changes in diffusion tensor imaging (DTI) indices of white matter microstructure sensitive to axonal membrane and myelin alterations.MethodsTwenty-one healthy adult males underwent DTI in the morning [7:30AM; time point (TP)1], after 14 hours of waking (TP2), and then after another 9 hours of waking (TP3). Whole brain voxel-wise analysis was performed with tract based spatial statistics.ResultsA day of waking was associated with widespread increases in white matter fractional anisotropy, which were mainly driven by radial diffusivity reductions, and sleep deprivation was associated with widespread fractional anisotropy decreases, which were mainly explained by reductions in axial diffusivity. In addition, larger decreases in axial diffusivity after sleep deprivation were associated with greater sleepiness. All DTI changes remained significant after adjusting for hydration measures.ConclusionsThis is the first DTI study of sleep deprivation in humans. Although previous studies have observed localized changes in DTI indices of cerebral microstructure over the course of a few hours, further studies are needed to confirm widespread DTI changes within hours of waking and to clarify whether such changes in white matter microstructure serve as neurobiological substrates of sleepiness.     

Dendrimers Target the Ischemic Lesion in Rodent and Primate Models of Nonarteritic Anterior Ischemic Optic Neuropathy

IntroductionPolyamidoamine dendrimer nanoparticles (~ 4 nanometers) are inert polymers that can be linked to biologically active compounds. These dendrimers selectively target and accumulate in inflammatory cells upon systemic administration. Dendrimer-linked compounds enable sustained release of therapeutic compounds directly at the site of damage. The purpose of this study was to determine if dendrimers can be used to target the optic nerve (ON) ischemic lesion in our rodent and nonhuman primate models of nonarteritic anterior ischemic optic neuropathy (NAION), a disease affecting >10,000 individuals in the US annually, and for which there currently is no effective treatment.MethodsNAION was induced in male Long-Evans rats (rNAION) and in one adult male rhesus monkey (pNAION) using previously described procedures. Dendrimers were covalently linked to near-infrared cyanine-5 fluorescent dye (D-Cy5) and injected both intravitreally and systemically (in the rats) or just systemically (in the monkey) to evaluate D-Cy5 tissue accumulation in the eye and optic nerve following induction of NAION.ResultsFollowing NAION induction, Cy-5 dendrimers selectively accumulated in astrocytes and circulating macrophages. Systemic dendrimer administration provided the best penetration of the ON lesion site when injected shortly after induction. Systemic administration 1 day post-induction in the pNAION model gave localization similar to that seen in the rats.ConclusionsDendrimers selectively target the ischemic ON lesion after induction of both rNAION and pNAION. Systemic nanoparticle-linked therapeutics thus may provide a powerful, targeted and safe approach to NAION treatment by providing sustained and focused treatment of the cells directly affected by ischemia.     

A dosimetric comparison of IMRT versus helical tomotherapy for brain tumors

Background and purposeHelical tomotherapy (HT) can deliver highly conformal, uniform doses to the target volume. However, HT can only be delivered in a coplanar mode.The purpose of this study was to perform a dosimetric comparison of HT versus coplanar (cIMRT) and non-coplanar (n-cIMRT) beam arrangements on a conventional linear accelerator in a diverse group of brain tumors.Materials and methodsA total of 45 treatment plans were calculated retrospectively for 15 cases. For each case, 3 different delivery techniques (n-cIMRT, cIMRT and HT) were used. The treatment plans were compared using the parameters of the target coverage (conformity index; CI) and homogeneity (HI) for the planning target volume (PTV) and the maximum and mean doses for organs at risk (OARs).ResultsMedian HI and CI were the best for HT plans and the worst for cIMRT. The largest reduction of maximum dose for lenses and mean dose for both eyes was achieved for n-cIMRT plans. Mean dose for chiasm and the ipsilateral optic nerve were the lowest for HT. The contralateral optic nerve was most spared with n-cIMRT. For D_1% in the brain stem, there was no significant difference between HT and the IMRT plans.ConclusionsBoth HT and n-cIMRT are capable of producing conformal and homogeneous treatment plans with a good sparing of OARs. However, due to the non-coplanar capabilities of IMRT, n-cIMRT led to a superior dose reduction to the lenses.     

Peripheral Nerve Diffusion Tensor Imaging: Assessment of Axon and Myelin Sheath Integrity

Purpose

To investigate the potential of diffusion tensor imaging (DTI) parameters as in-vivo biomarkers of axon and myelin sheath integrity of the median nerve in the carpal tunnel as validated by correlation with electrophysiology.

Methods

MRI examinations at 3T including DTI were conducted on wrists in 30 healthy subjects. After manual segmentation of the median nerve quantitative analysis of fractional anisotropy (FA) as well as axial, radial and mean diffusivity (AD, RD, and MD) was carried out. Pairwise Pearson correlations with electrophysiological parameters comprising sensory nerve action potential (SNAP) and compound muscle action potential (CMAP) as markers of axon integrity, and distal motor latency (dml) and sensory nerve conduction velocity (sNCV) as markers of myelin sheath integrity were computed. The significance criterion was set at P=0.05, Bonferroni corrected for multiple comparisons.

Results

DTI parameters showed a distinct proximal-to-distal profile with FA, MD, and RD extrema coinciding in the center of the carpal tunnel. AD correlated with CMAP (r=0.50, p=0.04, Bonf. corr.) but not with markers of myelin sheath integrity. RD correlated with sNCV (r=-0.53, p=0.02, Bonf. corr.) but not with markers of axon integrity. FA correlated with dml (r=-0.63, p=0.002, Bonf. corr.) and sNCV (r=0.68, p=0.001, Bonf. corr.) but not with markers of axon integrity.

Conclusion

AD reflects axon integrity, while RD (and FA) reflect myelin sheath integrity as validated by correlation with electrophysiology. DTI parameters consistently indicate a slight decrease of structural integrity in the carpal tunnel as a physiological site of median nerve entrapment. DTI is particularly sensitive, since these findings are observed in healthy participants. Our results encourage future studies to evaluate the potential of DTI in differentiating axon from myelin sheath injury in patients with manifest peripheral neuropathies.     

Microstructural White Matter Changes Underlying Cognitive and Behavioural Impairment in ALS – An In Vivo Study Using DTI

Background

A relevant fraction of patients with amyotrophic lateral sclerosis (ALS) exhibit a fronto-temporal pattern of cognitive and behavioural disturbances with pronounced deficits in executive functioning and cognitive control of behaviour. Structural imaging shows a decline in fronto-temporal brain areas, but most brain imaging studies did not evaluate cognitive status. We investigated microstructural white matter changes underlying cognitive impairment using diffusion tensor imaging (DTI) in a large cohort of ALS patients.

Methods

We assessed 72 non-demented ALS patients and 65 matched healthy control subjects using a comprehensive neuropsychological test battery and DTI. We compared DTI measures of fiber tract integrity using tract-based spatial statistics among ALS patients with and without cognitive impairment and healthy controls. Neuropsychological performance and behavioural measures were correlated with DTI measures.

Results

Patients without cognitive impairment demonstrated white matter changes predominantly in motor tracts, including the corticospinal tract and the body of corpus callosum. Those with impairments (ca. 30%) additionally presented significant white matter alterations in extra-motor regions, particularly the frontal lobe. Executive and memory performance and behavioural measures were correlated with fiber tract integrity in large association tracts.

Conclusion

In non-demented cognitively impaired ALS patients, white matter changes measured by DTI are related to disturbances of executive and memory functions, including prefrontal and temporal regions. In a group comparison, DTI is able to observe differences between cognitively unimpaired and impaired ALS patients.     

A novel animal model of partial optic nerve transection established using an optic nerve quantitative amputator

Background

Research into retinal ganglion cell (RGC) degeneration and neuroprotection after optic nerve injury has received considerable attention and the establishment of simple and effective animal models is of critical importance for future progress.

Methodology/Principal Findings

In the present study, the optic nerves of Wistar rats were semi-transected selectively with a novel optic nerve quantitative amputator. The variation in RGC density was observed with retro-labeled fluorogold at different time points after nerve injury. The densities of surviving RGCs in the experimental eyes at different time points were 1113.69±188.83 RGC/mm² (the survival rate was 63.81% compared with the contralateral eye of the same animal) 1 week post surgery; 748.22±134.75 /mm² (46.16% survival rate) 2 weeks post surgery; 505.03±118.67 /mm² (30.52% survival rate) 4 weeks post surgery; 436.86±76.36 /mm² (24.01% survival rate) 8 weeks post surgery; and 378.20±66.74 /mm² (20.30% survival rate) 12 weeks post surgery. Simultaneously, we also measured the axonal distribution of optic nerve fibers; the latency and amplitude of pattern visual evoke potentials (P-VEP); and the variation in pupil diameter response to pupillary light reflex. All of these observations and profiles were consistent with post injury variation characteristics of the optic nerve. These results indicate that we effectively simulated the pathological process of primary and secondary injury after optic nerve injury.

Conclusions/Significance

The present quantitative transection optic nerve injury model has increased reproducibility, effectiveness and uniformity. This model is an ideal animal model to provide a foundation for researching new treatments for nerve repair after optic nerve and/or central nerve injury.     

不同方向撕除内界膜方式对特发性黄斑裂孔术后视网膜位移的影响

目的:比较玻璃体切割切术中不同方向撕除内界膜对特发性黄斑裂孔愈合后视网膜位移、视功能的影响。方法:纳入特发性黄斑裂孔患者25例(25眼),按照术中内界膜(ILM)撕除方向,以1:1随机分为NS-TI组(13眼)和TI-NS组(12眼)。NS-TI组患者接受内界膜撕除方向为鼻上起瓣,向颞下方向撕除ILM;TI-NS组患者接受内界膜撕除方向为颞下起瓣,向鼻上方向撕除ILM。术前、术后1月、术后3月采集患者自发荧光照相,通过影像学上血管标记点或交叉点的位置计算黄斑视盘距离(FMD)、颞侧血管至视盘距离(T-OD)、鼻侧血管至视盘距离(N-OD)、黄斑区垂直血管距离(VIAD)、黄斑区水平血管距离(HIAD)、黄斑区面积(PMA)。对比两种撕膜方式后术后1月、3月视网膜位移(包括FMD、T-OD、N-OD、VIAD、HIAD、PMA)、裂孔闭合率,术后最佳矫正视力,分析两种撕膜方式的异同。结果:术后1月及3月,两组患者的视网膜皆向视盘方向偏移,表现为FMD、T-OD、N-OD、VIAD、HIAD、PMA五项指标均较术前增大(p 0.05)。术后1月及3月,NS-TI组和TI-NS组FMD、T-OD、N-OD、VIAD、HIAD、PMA、黄斑裂孔愈合率(皆100%)和最佳矫正视力比较差异均无统计学意义(P0.05)。结论:不同方向撕除内界膜不是特发性黄斑裂孔术后视网膜位移的影响因素。     

Laser Doppler Flare Imaging and Quantitative Thermal Thresholds Testing Performance in Small and Mixed Fiber Neuropathies

IntroductionSmall fiber neuropathy might be a part of typical mixed small and large fiber neuropathy, or a distinct entity, affecting exclusively small nerve fibers.ObjectivesExplore the utility of small nerve fiber testing in patients with clinical presentation suggesting small fiber neuropathy, with and without evidence for concomitant large fiber neuropathy.MethodsPatients attending the neuromuscular clinic from 2012 to 2015 with a clinical presentation suggesting small nerve fiber impairment, who had Laser Doppler flare imaging (LDI_Flare) and quantitative thermal testing (QTT) were evaluated for this study. Patients with clinical or electrophysiological evidence for concomitant large fiber neuropathy were not excluded.ResultsThe sensitivities of LDI_Flare, cooling and heat threshold testing were 64%, 36%, and 0% respectively for clinically highly suggestive small fiber neuropathy, 64%, 56%, and 19% respectively for mixed fiber neuropathy, and 86%, 79%, and 29% respectively for diabetic mixed fiber neuropathy.DiscussionLDI_Flare and cooling thresholds testing are non-invasive small nerve fiber testing modalities, with moderate performance in patients with small and mixed fiber neuropathy, and excellent performance in diabetic mixed fiber neuropathy.     

An Optic Nerve Crush Injury Murine Model to Study Retinal Ganglion Cell Survival

Injury to the optic nerve can lead to axonal degeneration, followed by a gradual death of retinal ganglion cells (RGCs), which results in irreversible vision loss. Examples of such diseases in human include traumatic optic neuropathy and optic nerve degeneration in glaucoma. It is characterized by typical changes in the optic nerve head, progressive optic nerve degeneration, and loss of retinal ganglion cells, if uncontrolled, leading to vision loss and blindness.The optic nerve crush (ONC) injury mouse model is an important experimental disease model for traumatic optic neuropathy, glaucoma, etc. In this model, the crush injury to the optic nerve leads to gradual retinal ganglion cells apoptosis. This disease model can be used to study the general processes and mechanisms of neuronal death and survival, which is essential for the development of therapeutic measures. In addition, pharmacological and molecular approaches can be used in this model to identify and test potential therapeutic reagents to treat different types of optic neuropathy.Here, we provide a step by step demonstration of (I) Baseline retrograde labeling of retinal ganglion cells (RGCs) at day 1, (II) Optic nerve crush injury at day 4, (III) Harvest the retinae and analyze RGC survival at day 11, and (IV) Representative result.Download video file.^{(53M, mov)}