Paths to hippocampal damage in neuromyelitis optica spectrum disorders.

AIMS: Many patients with neuromyelitis optica spectrum disorders (NMOSD) suffer from cognitive impairment affecting memory, processing speed and attention and suffer from depressive symptoms. Because some of these manifestations could trace back to the hippocampus, several magnetic resonance imaging (MRI) studies have been performed in the past, with a number of groups describing volume loss of the hippocampus in NMOSD patients, whereas others did not observe such changes. Here, we addressed these discrepancies. METHODS: We performed pathological and MRI studies on the hippocampi of NMOSD patients, combined with detailed immunohistochemical analysis of hippocampi from experimental models of NMOSD. RESULTS: We identified different pathological scenarios for hippocampal damage in NMOSD and its experimental models. In the first case, the hippocampus was compromised by the initiation of astrocyte injury in this brain region and subsequent local effects of microglial activation and neuronal damage. In the second case, loss of hippocampal volume was seen by MRI in patients with large tissue-destructive lesions in the optic nerves or the spinal cord, and the pathological work-up of tissue derived from a patient with such lesions revealed subsequent retrograde neuronal degeneration affecting different axonal tracts and neuronal networks. It remains to be seen whether remote lesions and associated retrograde neuronal degeneration on their own are sufficient to cause extensive volume loss of the hippocampus, or whether they act in concert with small astrocyte-destructive, microglia-activating lesions in the hippocampus that escape detection by MRI, either due to their small size or due to the chosen time window for examination. CONCLUSIONS: Different pathological scenarios can culminate in hippocampal volume loss in NMOSD patients.

Optic Tract Shrinkage Limits Visual Restoration After Occipital Stroke.

Background and Purpose: Damage to the adult primary visual cortex (V1) causes vision loss in the contralateral visual hemifield, initiating a process of trans-synaptic retrograde degeneration. The present study examined functional implications of this process, asking if degeneration impacted the amount of visual recovery attainable from visual restoration training in chronic patients, and if restoration training impacted optic tract (OT) shrinkage. Methods: Magnetic resonance imaging was used to measure OT volumes bilaterally in 36 patients with unilateral occipital stroke. From OT volumes, we computed laterality indices (LI), estimating the stroke-induced OT shrinkage in each case. A subset of these chronic patients (n=14, 13±6 months poststroke) underwent an average of nearly 1 year of daily visual restoration training, which repeatedly stimulated vision in their blind field. The amount of visual field recovery was quantified using Humphrey perimetry, and post training magnetic resonance imaging was used to assess the impact of training on OT shrinkage. Results: OT LI was correlated with time since stroke: it was close to 0 (no measurable OT shrinkage) in subacute participants (<6 months poststroke) while chronic participants (>6 months poststroke) exhibited LI >0, but with significant variability. Visual training did not systematically alter LI, but chronic patients with baseline LI≈0 (no OT shrinkage) exhibited greater visual field recovery than those with LI>0. Conclusions: Unilateral OT shrinkage becomes detectable with magnetic resonance imaging by ≈7 months poststroke, albeit with significant interindividual variability. Although visual restoration training did not alter the amount of degeneration already sustained, OT shrinkage appeared to serve as a biomarker of the potential for training-induced visual recovery in chronic cortically blind patients.

Corticospinal tract involvement in spinocerebellar ataxia type 3: a diffusion tensor imaging study.

PURPOSE: The aim of this study was to evaluate the integrity of the corticospinal tracts (CST) in patients with SCA3 and age- and gender-matched healthy control subjects using diffusion tensor imaging (DTI). We also looked at the clinical correlates of such diffusivity abnormalities. METHODS: We assessed 2 cohorts from different Brazilian centers: cohort 1 (n = 29) scanned in a 1.5 T magnet and cohort 2 (n = 91) scanned in a 3.0 T magnet. We used Pearson's coefficients to assess the correlation of CST DTI parameters and ataxia severity (expressed by SARA scores). RESULTS: Two different results were obtained. Cohort 1 showed no significant between-group differences in DTI parameters. Cohort 2 showed significant between-group differences in the FA values in the bilateral precentral gyri (p < 0.001), bilateral superior corona radiata (p < 0.001), bilateral posterior limb of the internal capsule (p < 0.001), bilateral cerebral peduncle (p < 0.001), and bilateral basis pontis (p < 0.001). There was moderate correlation between CST diffusivity parameters and SARA scores in cohort 2 (Pearson correlation coefficient: 0.40-0.59). CONCLUSION: DTI particularly at 3 T is able to uncover and quantify CST damage in SCA3. Moreover, CST microstructural damage may contribute with ataxia severity in the disease.

[Retrograde degeneration of visual pathway]. / Retrogradnaya degeneratsiya zritel'nogo puti.

BACKGROUND: Optical coherence tomography (OCT) gives the opportunity to examine retrograde degeneration of visual pathway damaged at various levels. OBJECTIVE: To estimate OCT data on retrograde degeneration of visual pathway damaged at various levels. MATERIAL AND METHODS: Ganglion cell layer (GCL) thickness was measured by OCT in 79 patients with visual pathway damaged at various levels and known duration of visual disturbances. Twenty-One patients were diagnosed with traumatic lesions of the optic nerves and/or chiasma. Fifty-eight patients had retro-genicular visual pathway damage. Thirty-three patients were examined for postoperative homonymous hemianopia after surgery for drug-resistant temporal lobe epilepsy. Twenty-five patients were diagnosed with occipital lobe damage following stroke (12 patients), surgery for arteriovenous malformation (11 patients) and traumatic brain injury (2 patients). All patients underwent assessment of visual acuity, automatic static perimetry, MRI/CT of the brain. Retinal ganglion cell complex was analyzed during OCT. RESULTS: GCL thinning following anterior visual pathway damage was detected in 20 out of 21 patients after ≥22 days. In case of post-genicular visual pathway damage, GCL thinning was found in 25 out of 58 patients (9 out of 33 ones after surgery for temporal lobe epilepsy and 16 out of 25 patients with occipital lobe lesion). After surgery for temporal lobe epilepsy, minimum period until GCL thinning detection after previous visual pathway damage was 3 months, in case of occipital lobe lesion - 5 months. CONCLUSION: Retrograde visual pathway degeneration is followed by GCL thinning and depends on the level of visual pathway lesion.

Retrogeniculate Lesion of the Visual Pathways: Retinal Optical Coherence Tomography Angiography Shows Evidence of Transsynaptic Retrograde Degeneration.

Transsynaptic retrograde degeneration (TSRD) of the visual pathways is the loss of retinal ganglion cells occurring upstream from a posterior visual pathway lesion. We present a case of a 54-year-old woman with an epidermoid cyst at the right temporo-occipital junction, in whom retinal optical coherence tomography angiography showed a reduction of the superficial retinal capillary density consistent with TSRD. While this reduction has been described in chronic optic neuropathies and pregeniculate lesions, to our knowledge, this is the first case report showing how a reduction in the superficial retinal capillary density occurs also for a postgeniculate lesion.

Evaluation of Significance Maps and the Analysis of the Longitudinal Time Course of the Macular Ganglion Cell Complex Thicknesses in Acquired Occipital Homonymous Hemianopia Using Spectral-domain Optical Coherence Tomography.

The present study was performed to evaluate the ganglion cell complex (GCC) thickness as well as the significance map and analyse the time course of the change in GCC thickness in patients with homonymous hemianopia due to posterior cerebral artery (PCA) territory stroke using spectral-domain optical coherence tomography. This study included 40 control subjects and 11 patients with unilateral PCA territory stroke. The GCC parameters were quantified using a custom-built software programme. The GCC data, centred on the macula, was divided vertically into hemianopic and unaffected sides. GCC parameters were calculated using an average of those from both eyes. The relationship between the GCC parameters and the time after stroke was determined by regression analyses. The GCC parameters in the hemi-retinae corresponding to the affected hemifields significantly differed between the hemianopes and the control group. The area under the receiver operating characteristics curve of the GCC significance map areas was significantly high. A regression analysis revealed a significant relationship between the time after stroke and both the GCC significance map areas (r = 0.791, p = .004) and GCC thickness (r = -0.736, p = .010) on the hemianopic side. The GCC parameters on the hemianopic side were reduced in patients with acquired occipital homonymous hemianopia, and the reduction was slowly progressive probably due to transsynaptic retrograde degeneration of the retinal ganglion cells. A significance map analysis provides additional OCT parameters that could be used to investigate the effect of retrogeniculate lesions on the inner retina of patients.

Amyloid-beta induced retrograde axonal degeneration in a mouse tauopathy model.

White matter abnormalities, revealed by Diffusion Tensor Imaging (DTI), are observed in patients with Alzheimer's Disease (AD), representing neural network deficits that underlie gradual cognitive decline in patients. However, how DTI changes related to the development of Amyloid beta (Aß) and tau pathology, two key hallmarks of AD, remain elusive. We hypothesized that tauopathy induced by Aß could initiate an axonal degeneration, leading to DTI-detectable white matter abnormalities. We utilized the visual system of the transgenic p301L tau mice as a model system. Aß was injected in Lateral Geniculate Nucleus (LGN), where the Retinal Ganglion Cell (RGC) axons terminate. Longitudinal DTI was conducted to detect changes in the optic tract (OT) and optic nerve (ON), containing the distal and proximal segments of RGC axons, respectively. Our results showed DTI changes in OT (significant 13.2% reduction in axial diffusion, AxD vs. vehicle controls) followed by significant alterations in ON AxD and fractional anisotropy, FA. Histology data revealed loss of synapses, RGC axons and cell bodies resulting from the Aß injection. We further tested whether microtubule-stabilizing compound Epothilone D (EpoD) could ameliorate the damage. EpoD co-treatment with Aß was sufficient to prevent Aß-induced axon and cell loss. Using an acute injection paradigm, our data suggest that EpoD may mediate its protective effect by blocking localized, acute Aß-induced tau phosphorylation. This study demonstrates white matter disruption resulting from localized Aß, the importance of tau pathology induction to changes in white matter connectivity, and the use of EpoD as a potential therapeutic avenue to prevent the axon loss in AD.

Progression of Anterograde Trans-Synaptic Degeneration in the Human Retina Is Modulated by Axonal Convergence and Divergence.

In the visual pathway of patients with multiple sclerosis (MS), the inner nuclear layer (INL) of the retina is a tight barrier for retrograde trans-synaptic degeneration. In this observational, retrospective cross-sectional study, segmented macular spectral domain optical coherence tomography (OCT) volume scans were reviewed to investigate if this observation also holds true for anterograde trans-synaptic degeneration. Significant thinning was found in all retinal layers in patients with outer retinal diseases compared with the healthy controls, while there was no significant attenuation of the outer retina in patients with MS. In contrast to the tight barrier function observed with retrograde trans-synaptic degeneration, the INL appears to be more permissive for the propagation of anterograde trans-synaptic degeneration. We speculate that this may be due to the size of the area affected and be explained by convergence and divergence of axons within the retinal layers. These findings are likely relevant to future restorative stem cell treatment of the outer retinal layers, as time may matter.

Altered Retinal Nerve Fiber Layer Thickness and Choroid Thickness in Patients with Migraine.

BACKGROUND: Migraine is a chronic neurological disorder. However, its pathogenesis is still unclear. This study aimed to measure the posterior ocular structure in patients with migraine using enhanced depth imaging (EDI)-optical coherence tomography (OCT) and explore the probable pathogenesis of migraine. METHODS: A total of 115 patients diagnosed with migraine and 50 healthy volunteers were recruited. These participants underwent an ocular examination to exclude the ocular diseases. Retinal nerve fiber layer thickness, macular thickness, and choroid thickness were assessed using EDI-OCT. RESULTS: The nasal peripapillary retinal nerve fiber layer (pRNFL) was significantly thinner in the migraine with aura group (p = 0.001) than that in the control group. The inferior inner macular layer was thinner in the migraine with aura group (p = 0.005). The 3 subfields of choroid were significantly thinner in the migraine with aura group (p = 0.044, 0.008, and 0.029). However, there was no difference between the migraine without aura group and the control group. The nasal pRNFL in migraine with aura was negatively correlated with the product of duration (months) and number of attacks/month (p = 0.039). CONCLUSION: The changes in the ocular posterior structure may serve as evidence of the trigeminovascular system mechanism underlying migraine and transneuronal retrograde degeneration of the primary visual cortex, which reflects the cortical spreading depression.

Trans-synaptic Retrograde Degeneration Following Hemispherectomy in Childhood.

Trans-synaptic retrograde degeneration (TRD) in the human visual system has been established. However there are few studies demonstrating macular thinning of the Retinal Ganglion cell Layer and/or Inner Plexiform layer (RGCL-IPL), corresponding to an acquired homonymous hemianopia. We report a 17 year old with a homonymous hemianopia, secondary to a hemispherectomy for intractable epilepsy. Three years following hemispherectomy, Optical Coherence Tomography (OCT) revealed evidence of TRD, corresponding to his complete homonymous hemianopia. Macular maps of the RGCL-IPL thickness provides useful additional information to measurements of optic nerve Retinal Nerve Fibre Layer Thickness (RNFL) in identifying TRD in acquired homonymous hemianopia.

Sectoral analysis of the retinal nerve fiber layer thinning and its association with visual field loss in homonymous hemianopia caused by post-geniculate lesions using spectral-domain optical coherence tomography.

PURPOSE: To report a sectoral analysis of circumpapillary retinal nerve fiber layer (cpRNFL) thinning and its association with visual field loss using spectral-domain optical coherence tomography (SD-OCT) in patients with homonymous hemianopia following acquired post-geniculate visual pathway damage. PATIENTS AND METHODS: Seven patients with homonymous hemianopia due to unilateral acquired post-geniculate visual pathway lesions were studied. The average duration from the onset of brain lesions to the initial visit was 49.8 months. Forty-nine normal control subjects without visual field defects, as confirmed using a Humphrey visual field analyzer, were also enrolled. Measurement of the cpRNFL thickness was performed at the initial visit and 24 months using SD-OCT (RTVue-100® OCT). The cpRNFL thickness was divided into eight sectors (superior temporal: ST, temporal upper: TU, temporal lower: TI, inferior temporal: IT, inferior nasal: IN, nasal lower: NL, nasal upper: NU, superior nasal: SN). The eye on the same side as the occipital lobe lesions was defined as the ipsilateral eye, and the eye on the opposite side was defined as the contralateral eye. RESULTS: The average cpRNFL thickness in the homonymous hemianopic eyes was significantly reduced as compared with that seen in the normal controls, except for the ipsilateral eyes at the initial visit. Four of the eight sectors of the cpRNFL thickness in the homonymous hemianopic eyes were significantly reduced compared with that noted in the normal controls. In the ipsilateral eyes, the cpRNFL thickness in the ST, TU, TL, and IT sectors was significantly reduced at both the initial visit and 24 months. In the contralateral eyes, the cpRNFL thickness in the TU, TL, IT, and SN sectors was significantly reduced at both the initial visit and 24 months. The reduction of the quadrantic cpRNFL thickness significantly correlated with some of the visual field parameters, in accordance with the structure-function relationship. In the contralateral eyes, the T and I quadrant cpRNFL thickness correlated with the mean deviation and hemianopic field total deviation at 24 months. In the ipsilateral eyes, the S, T, and I quadrant cpRNFL thickness correlated with mean deviation. However, there were no correlations between the cpRNFL thickness and visual field parameters at the initial visit. CONCLUSIONS: A reduction of the cpRNFL thickness corresponding to the hemianopic visual field loss due to acquired post-geniculate visual pathway lesions was detected using SD-OCT, and the change was more evident at 24 months than at the initial visit. The latter finding suggests that this change is, at least partially, caused by transsynaptic retrograde degeneration.

Individual Assessment of Brain Tissue Changes in MS and the Effect of Focal Lesions on Short-Term Focal Atrophy Development in MS: A Voxel-Guided Morphometry Study.

We performed voxel-guided morphometry (VGM) investigating the mechanisms of brain atrophy in multiple sclerosis (MS) related to focal lesions. VGM maps detect regional brain changes when comparing 2 time points on high resolution T1-weighted (T1w) magnetic resonace imaging (MRI). Two T1w MR datasets from 92 relapsing-remitting MS patients obtained 12 months apart were analysed with VGM. New lesions and volume changes of focal MS lesions as well as in the surrounding tissue were identified by visual inspection on colour coded VGM maps. Lesions were dichotomized in active and inactive lesions. Active lesions, defined by either new lesions (NL) (volume increase > 5% in VGM), chronic enlarging lesions (CEL) (pre-existent T1w lesions with volume increase > 5%), or chronic shrinking lesions (CSL) (pre-existent T1w lesions with volume reduction > 5%) in VGM, were accompanied by tissue shrinkage in surrounding and/or functionally related regions. Volume loss within the corpus callosum was highly correlated with the number of lesions in its close proximity. Volume loss in the lateral geniculate nucleus was correlated with lesions along the optic radiation. VGM analysis provides strong evidence that all active lesion types (NL, CEL, and CSL) contribute to brain volume reduction in the vicinity of lesions and/or in anatomically and functionally related areas of the brain.

Macular Ganglion Cell Layer and Peripapillary Retinal Nerve Fibre Layer Thickness in Patients with Unilateral Posterior Cerebral Artery Ischaemic Lesion: An Optical Coherence Tomography Study.

The purpose of this study is to evaluate the macular ganglion cell layer (GCL) and peripapillary retinal nerve fibre layer (RNFL) thickness in patients with unilateral posterior cerebral artery (PCA) ischaemic lesions using spectral-domain optical coherence tomography (SD-OCT). A prospective, case-control study of patients with unilateral PCA lesion was conducted in the neuro-ophthalmology clinic of Centro Hospitalar Lisboa Central. Macular and peripapillary SD-OCT scans were performed in both eyes of each patient. Twelve patients with PCA lesions (stroke group) and 12 healthy normal controls were included in this study. Peripapillary RNFL comparison between both eyes of the same subject in the stroke group found a thinning in the superior-temporal (p = 0.008) and inferior-temporal (p = 0.023) sectors of the ipsilateral eye and nasal sector (p = 0.003) of the contralateral eye. Macular GCL thickness comparison showed a reduction temporally in the ipsilateral eye (p = 0.004) and nasally in the contralateral eye (p = 0.002). Peripapillary RNFL thickness was significantly reduced in both eyes of patients with PCA compared with controls, affecting all sectors in the contralateral eye and predominantly temporal sectors in the ipsilateral eye. A statistically significant decrease in macular GCL thickness was found in both hemiretinas of both eyes of stroke patients when compared with controls (p < 0.05). This study shows that TRD may play a role in the physiopathology of lesions of the posterior visual pathway.

Progressive nigrostriatal terminal dysfunction and degeneration in the engrailed1 heterozygous mouse model of Parkinson's disease.

Current research on Parkinson's disease (PD) pathogenesis requires relevant animal models that mimic the gradual and progressive development of neuronal dysfunction and degeneration that characterizes the disease. Polymorphisms in engrailed 1 (En1), a homeobox transcription factor that is crucial for both the development and survival of mesencephalic dopaminergic neurons, are associated with sporadic PD. This suggests that En1 mutant mice might be a promising candidate PD model. Indeed, a mouse that lacks one En1 allele exhibits decreased mitochondrial complex I activity and progressive midbrain dopamine neuron degeneration in adulthood, both features associated with PD. We aimed to further characterize the disease-like phenotype of these En1(+/-) mice with a focus on early neurodegenerative changes that can be utilized to score efficacy of future disease modifying studies. We observed early terminal defects in the dopaminergic nigrostriatal pathway in En1(+/-) mice. Several weeks before a significant loss of dopaminergic neurons in the substantia nigra could be detected, we found that striatal terminals expressing high levels of dopaminergic neuron markers TH, VMAT2, and DAT were dystrophic and swollen. Using transmission electron microscopy, we identified electron dense bodies consistent with abnormal autophagic vacuoles in these terminal swellings. In line with these findings, we detected an up-regulation of the mTOR pathway, concurrent with a downregulation of the autophagic marker LC3B, in ventral midbrain and nigral dopaminergic neurons of the En1(+/-) mice. This supports the notion that autophagic protein degradation is reduced in the absence of one En1 allele. We imaged the nigrostriatal pathway using the CLARITY technique and observed many fragmented axons in the medial forebrain bundle of the En1(+/-) mice, consistent with axonal maintenance failure. Using in vivo electrochemistry, we found that nigrostriatal terminals in the dorsal striatum were severely deficient in dopamine release and reuptake. Our findings support a progressive retrograde degeneration of En1(+/-) nigrostriatal neurons, akin to what is suggested to occur in PD. We suggest that using the En1(+/-) mice as a model will provide further key insights into PD pathogenesis, and propose that axon terminal integrity and function can be utilized to estimate dopaminergic neuron health and efficacy of experimental PD therapies.

Retinal Ganglion Cell Loss in X-linked Adrenoleukodystrophy with an ABCD1 Mutation (Gly266Arg).

The authors here report a single case of a 10-year-old male patient who presented with severe vision loss associated with progressive demyelination. The patient was diagnosed with X-linked childhood cerebral adrenoleukodystrophy (ALD). Genetic analysis demonstrated a missense mutation (Gly266Arg) in exon 1 of the ABCD1 gene. His corrected visual acuity confirmed the absolute lack of light perception in both eyes. Funduscopy revealed severe pallor of the optic disc in both eyes. Spectral-domain optical coherence tomography showed thinning of the retinal ganglion cell and inner plexiform layers (GCL and IPL). Thinning of the GCL and IPL may be due to transneuronal retrograde degeneration of ganglion cells secondary to optic tract demyelination.

Distinct alterations of retinal structure between thalamic and extra-thalamic subcortical infarction patients: A cross-sectional and longitudinal study.

AIMS: Cerebrovascular lesions in the primary visual cortex, the lateral geniculate nucleus, and the optic tract have been associated with retinal neurodegeneration via the retrograde degeneration (RD) mechanism. We aimed to use optical coherence tomography (OCT) to assess the effects of the strategic single subcortical infarction (SSI) location on retinal neurodegeneration and its longitudinal impacts. METHODS: Patients with SSI were enrolled and stratified by lesion location on cerebral MRI into the thalamic infarction group and extra-thalamic infarction group. Healthy controls from the native communities were also recruited. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) were quantified using OCT. Generalized estimating equation (GEE) models were used for cross-sectional analyses and linear mixed models for longitudinal analyses. P < 0.05 was considered statistically significant. RESULTS: We included a total of 283 eyes from 149 SSI patients. Of these, 115 eyes of 60 patients with follow-up were included in the longitudinal analyses. Cross-sectionally, thalamic-infarction patients had reduced retinal thickness compared with extra-thalamic infarction patients after adjustment for age, gender, disease duration, and vascular risk factors (p = 0.026 for RNFL, and p = 0.026 for GCIPL). Longitudinally, SSI patients showed greater retinal thinning compared with healthy controls over time (p = 0.040 for RNFL, and p < 0.001 for GCIPL), and thalamic infarction patients exhibited faster rates of GCIPL thinning in comparison with extra-thalamic infarction patients (p < 0.001). CONCLUSION: Our study demonstrates a distinct effect of subcortical infarction lesion site on the retina both at the early stage of disease and at the 1-year follow-up time. These results present evidence of significant associations between strategic infarction locations and retinal neurodegeneration. It may provide novel insights for further research on RD in stroke patients and ultimately facilitate individualized recovery therapeutic strategy.

Alterations of optic tract and retinal structure in patients after thalamic stroke.

Objectives: To investigate the association between degeneration of retinal structure and shrinkage of the optic tract in patients after thalamic stroke. Materials and methods: Patients with unilateral thalamic stroke were included. Structural magnetic resonance imaging (MRI) and optical coherence tomography (OCT) were performed to obtain parameters of optic tract shrinkage (lateral index) and retina structural thickness (retinal nerve fiber layer, RNFL; peripapillary retinal nerve fiber layer, pRNFL; ganglion cell-inner plexiform layer, GCIP), respectively. Visual acuity (VA) examination under illumination was conducted using Snellen charts and then converted to the logarithm of the minimum angle of resolution (LogMAR). We investigated the association between LI and OCT parameters and their relationships with VA. Results: A total of 33 patients and 23 age-sex matched stroke-free healthy controls were enrolled. Patients with thalamic stroke showed altered LI compared with control participants (P = 0.011) and a significantly increased value of LI in the subgroup of disease duration more than 6 months (P = 0.004). In these patients, LI were significantly associated with pRNFL thickness (ß = 0.349, 95% confidence interval [CI]: 0.134-0.564, P = 0.002) after adjusting for confounders (age, sex, hypertension, diabetes, dyslipidemia, and lesion volume). LI and pRNFL were both significantly associated with VA in all patients (LI: ß = -0.275, 95% CI: -0.539 to -0.011, P = 0.041; pRNFL: ß = -0.023, 95% CI: -0.046 to -0.001, P = 0.040) and in subgroup of disease duration more than 6 months (LI: ß = -0.290, 95% CI: -0.469 to -0.111, P = 0.002; pRNFL: ß = -0.041, 95% CI: -0.065 to -0.017, P = 0.003). Conclusion: Shrinkage of the optic tract can be detected in patients with thalamic stroke, especially after 6 months of stroke onset. In these patients, the extent of optic tract atrophy is associated with pRNFL thickness, and they are both related to visual acuity changes.

Secondary damage and neuroinflammation in the spinal dorsal horn mediate post-thalamic hemorrhagic stroke pain hypersensitivity: SDF1-CXCR4 signaling mediation.

Central post-stroke pain (CPSP) is an intractable neuropathic pain, which can be caused by primary lesion of central somatosensory system. It is also a common sequelae of the thalamic hemorrhagic stroke (THS). So far, the underlying mechanisms of CPSP remain largely unknown. Our previous studies have demonstrated that SDF1-CXCR4 signaling in the hemorrhagic region contributes to the maintenance of the THS pain hypersensitivity via mediation of the thalamic neuroinflammation. But whether the spinal dorsal horn, an initial point of spinothalamic tract (STT), suffers from retrograde axonal degeneration from the THS region is still unknown. In this study, neuronal degeneration and loss in the spinal dorsal horn were detected 7 days after the THS caused by intra-thalamic collagenase (ITC) injection by immunohistochemistry, TUNEL staining, electron microscopy, and extracellular multi-electrode array (MEA) recordings, suggesting the occurrence of secondary apoptosis and death of the STT projecting neuronal cell bodies following primary THS via retrograde axonal degeneration. This retrograde degeneration was accompanied by secondary neuroinflammation characterized by an activation of microglial and astrocytic cells and upregulation of SDF1-CXCR4 signaling in the spinal dorsal horn. As a consequence, central sensitization was detected by extracellular MEA recordings of the spinal dorsal horn neurons, characterized by hyperexcitability of both wide dynamic range and nociceptive specific neurons to suprathreshold mechanical stimuli. Finally, it was shown that suppression of spinal neuroinflammation by intrathecal administration of inhibitors of microglia (minocycline) and astrocytes (fluorocitrate) and antagonist of CXCR4 (AMD3100) could block the increase in expression levels of Iba-1, GFAP, SDF1, and CXCR4 proteins in the dorsal spinal cord and ameliorate the THS-induced bilateral mechanical pain hypersensitivity, implicating that, besides the primary damage at the thalamus, spinal secondary damage and neuroinflammation also play the important roles in maintaining the central post-THS pain hypersensitivity. In conclusion, secondary neuronal death and neuroinflammation in the spinal dorsal horn can be induced by primary thalamic neural damage via retrograde axonal degeneration process. SDF1-CXCR4 signaling is involved in the mediation of secondary spinal neuroinflammation and THS pain hypersensitivity. This finding would provide a new therapeutic target for treatment of CPSP at the spinal level.

Magnetic resonance tractography exhibiting retrograde degeneration of the corticospinal tract in a patient with a unilateral spinal cord tumor.

BACKGROUND: Transection-induced axonal retrograde degeneration, in contrast to Wallerian degeneration, has not been widely recognized in clinical practice. AIMS OF THE STUDY: To assess a potential of corticospinal tractography for detecting axonal retrograde degeneration. METHODS: We assessed the corticospinal tractography of a 74-year-old woman with monoplegia of the lower limb due to a unilateral thoracic spinal cord tumor. RESULTS: The tractography revealed integrity reduction of the corticospinal tract in the cerebra contralateral to the spinal cord tumor. CONCLUSIONS: The present report supports that magnetic resonance tractography has the potential for detecting this under-recognized phenomenon.

Homonymous thinning on macular optical coherence tomography indicating retrograde trans-synaptic degeneration from occipital infarctions.

Inner retinal thinning on optical coherence tomography (OCT) occurring through retrograde trans-synaptic degeneration is an increasingly recognized phenomenon, even in acquired retro-chiasmal brain lesions. We describe a man with stable visual field defects from multiple bilateral posterior circulation infarctions, who had ganglion cell complex (GCC) thinning on macular OCT that corresponded precisely with his visual field defects. In contrast to previous reports indicating that peripapillary retinal nerve fiber layer (RNFL) changes are important in detecting this phenomenon, the peripapillary RFNL thickness and the optic disc appearance of our patient were relatively unaffected. Our case contributes to the growing body of evidence that retrograde trans-synaptic degeneration can manifest as isolated macular OCT findings.