Optical coherence tomography-based assessment of retinal vascular pathology in cerebral small vessel disease.

BACKGROUND: Cerebral small vessel disease (CSVD) is a disorder of brain vasculature that causes various structural changes in the brain parenchyma, and is associated with various clinical symptoms such as cognitive impairment and gait disorders. Structural changes of brain arterioles cannot be visualized with routine imaging techniques in vivo. However, optical coherence tomography (OCT) is thought to be a "window to the brain". Thus, retinal vessel parameters may correlate with CSVD characteristic brain lesions and cerebrospinal fluid biomarkers (CSF) of the neuropathological processes in CSVD like endothelial damage, microglial activation and neuroaxonal damage. METHODS: We applied OCT-based assessment of retinal vessels, magnetic resonance imaging (MRI), and CSF biomarker analysis in a monocentric prospective cohort of 24 patients with sporadic CSVD related stroke and cognitive impairment. MRI lesions were defined according to the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE). Biomarkers were assessed using commercially available ELISA kits. Owing to the unavailability of an age-matched control-group lacking MRI-characteristics of CSVD, we compared the retinal vessel parameters in CSVD patients (73.8 ± 8.5 years) with a younger group of healthy controls (51.0 ± 16.0 years) by using an age- and sex-adjusted multiple linear regression analysis model. RESULTS: Among the parameters measured with OCT, the Wall to Lumen Ratio (WLR) but not Mean Wall Thickness (MWT) of the superior branch of the retinal artery correlated significantly with the volume of white matter hyperintensities on MRI (rs = - 0.5) and with CSF-levels of Chitinase 3 like 1 protein (rs = - 0.6), zona occludens 1 protein (rs = - 0.5) and GFAP (rs = - 0.4). MWT and WLR were higher in CSVD than in controls (28.9 µm vs. 23.9 µm, p = 0.001 and 0.32 vs. 0.25, p = 0.001). CONCLUSIONS: In this exploratory study, WLR correlated with the volume of white matter hyperintensities, and markers of vascular integrity, microglial activation, and neuroaxonal damage in CSVD. Further prospective studies should clarify whether retinal vessel parameters and CSF biomarkers may serve to monitor the natural course and treatment effects in clinical studies on CSVD.

In vivo assessment of retinal vessel pathology in amyotrophic lateral sclerosis.

BACKGROUND: Changes in skin and muscle small blood vessels (SBVs) and microvascular structures of the brain have been reported in patients with amyotrophic lateral sclerosis (ALS). A direct assessment of brain SBVs in vivo is currently not feasible. Retinal vessels are considered a "mirror" of brain SBVs. In this study, we used optic coherence tomography (OCT)-based measurements to detect changes in retinal blood vessels of ALS patients compared to those of healthy controls. METHODS: We analysed Spectralis-OCT images of 34 ALS patients and 20 HCs. The inner wall thickness (IWT), outer wall thickness (OWT), and lumen diameter (LD) of retinal vessels were assessed using intensity-based measurements. In addition, the different retinal layers were analysed using automated segmentation software. The correlations between the various retinal layers and clinical parameters [e.g., disease duration and revised ALS functional rating scale (ALS-FRS-R)] were examined. RESULTS: The OWT of retinal vessels was higher in ALS patients than in HCs (p = 0.04). There were no differences in the IWT, LD. ALS patients showed a thinning of the outer nuclear layer (ONL) compared to HCs (median 1.63 vs. 1.77, p = 0.002). The whole retinal thickness negatively correlated with the ALS-FRS scale (r = 0.3, p = 0.03). CONCLUSION: Our study reports retinal vessel pathology in ALS patients. These changes may be related to those observed in SBVs in skin and muscle biopsies. Furthermore, we report a thinning of the ONL in ALS, revealing a possible affection of rods and cones function in ALS.

[Amyotrophic lateral sclerosis. Multisystem degeneration]. / Amyotrophe Lateralsklerose. Eine Multisystemdegeneration.

BACKGROUND: There is increasing evidence that amyotrophic lateral sclerosis (ALS) has to be regarded as multisystem degeneration rather than as purely a motor neuron disease, as it also includes various dnonmotor symptoms. This modern view has been confirmed by neuropathological and imaging findings. OBJECTIVES: To review recent findings supporting the idea of multisystem degeneration and to describe the implications for diagnostics and therapy. METHODS: A discussion of recent clinical, imaging, and neuropathological findings is presented. RESULTS: Symptoms of ALS include not only motor symptoms but also cognitive impairment, oculomotor abnormalities, and extrapyramidal and sensory symptoms. As a neuropathological correlate, a systematic spreading of "transactive response DNA binding protein 43 kDa" (TDP-43) over functionally connected cortical structures has been described. CONCLUSIONS: Nonmotor symptoms are regularly seen in ALS, although they usually do not dominate the clinical picture. Recent neuropathological findings offer new perspectives for diagnostics and therapy in ALS.

[Optical Coherence Tomography (OCT)--a new diagnostic tool in psychiatry?]. / Optische Kohärenztomografie (OCT)--ein neues diagnostisches Instrument in der Psychiatrie?

Optical coherence tomography (OCT) is a non-invasive, contact-less imaging method which provides an "in vivo" representation of the retina. It allows the quantitative measurement of retinal nerve fibre layer thickness (RNFLT) and macula thickness (MT) and, in addition, is suitable to measure volumes (e.g., macula volume/MV). In the research of neurodegenerative diseases, OCT has been increasingly used and has shown its potential as a possible diagnostic tool over the course of the last few years. In recent years, the hypothesis that mental disorders like schizophrenia or unipolar depressive disorder have a degenerative component was established through a variety of volumetric MRI studies. This review article aims to present the method of OCT, to display its recent use in medicine and psychiatry, as well as to examine possible additional applications in the field of psychiatry.

[Botulinum toxin for the treatment of major depressive disorder]. / Botulinumtoxin bei der Behandlung depressiver Störungen.

OBJECTIVE: Botulinum toxin (BTX) plays an important role in the treatment and prophylaxis of migraine and is also used for the treatment of focal dystonia, spasm, hypersalivation, and hyperhydrosis. Recent clinical trials suggest that BTX treatment of muscles involved in the development of negative emotions may also have an antidepressant effect. This article gives a systematic review of the literature regarding BTX in the treatment of major depression. METHODS: We screened the databases of Medline and Scopus using the search terms [("botulinum toxin" OR "botox") AND ("antidepressant" OR "depression" OR "depressed")]. The website www.clinicaltrials.gov was screened with the same search terms in order to detect current studies. RESULTS: As of April 2013, we identified 3 studies that evaluated the antidepressant effects of BTX in the treatment of major depression. An improvement in mood after treatment with BTX was seen in a case series of 10 depressed patients. In a randomised, placebo-controlled study of thirty patients assigned to a verum (BTX, n = 15) or placebo (saline, n = 15) group, treatment with BTX has also shown a positive effect on mood. Another prospective, open-label study evaluated the antidepressive effect of BTX in 25 subjects with major depression. On www.clinicaltrials.gov we identified 2 ongoing studies, which are currently investigating the antidepressant effect of BTX. CONCLUSION: Recently published studies have shown a reduction of depressive symptoms after treatment of the glabellar frown lines with BTX injections. Further clinical studies in larger patient samples are necessary to prove the efficacy and safety of BTX injections used for the treatment of depressive disorders.

[The eye as a window to the pathophysiology in Parkinson's syndromes]. / Das Auge als Zugang zur Pathophysiologie von Parkinson-Syndromen.

Although dysfunction of the visual system and dysfunctional eye movements during sporadic Parkinson's disease have been reported for more than 40 years, they have never been the focus of early and/or differential diagnosis. To date Parkinson's disease-related α-synuclein aggregates, i.e., Lewy pathology, are not known to develop either in the retina or in other components of the visual system. In a clinical context it is currently possible to test the involvement of the respective functional systems by means of optical coherence tomography and video oculography. Moreover, non-motor-related abnormalities are detectable both during psychophysical testing of visuospatial function as well as in the form of measurable deficits of color perception. These deficits of the visual and oculomotor systems could prove to be suitable candidates for diagnosing sporadic Parkinson's disease in its early phase in a non-invasive manner. This article is intended to provide an overview of the fundamental pathophysiological principles and clinical aspects of visual system involvement in sporadic Parkinson's disease together with currently available differential diagnostic options.

Fully automated atlas-based MR imaging volumetry in Huntington disease, compared with manual volumetry.

BACKGROUND AND PURPOSE: The atrophy of the caudate is considered the hallmark of HD-associated neurodegeneration and has high potential as a biomarker in structural MR imaging. This study aimed at comparing automated and manual caudate volumetry. MATERIALS AND METHODS: In this cross-sectional volumetric study in 40 patients with HD and 30 healthy controls, a fully automated caudate measurement by ABV was used for the first time in HD and was directly compared with manual delineation as the generally accepted criterion standard of volumetry. RESULTS: It could be shown that both techniques were able to separate patients and controls to a similar degree. The differences between the 2 volumetric measurements ranged within the limits of agreement; the systematically lower values by manual volumetry were caused by the different assessment of the dorsal caudate tail, which is hard to delineate manually. CONCLUSIONS: ABV may be used instead of manual volumetry to quantify caudate volume loss. Additionally, the ABV technique has the advantage of being much faster, is less laborious, and is free of a subjective region-of interest definition. ABV might serve as a tool in potential future clinical trials of disease-modifying treatments in HD.

Is spinal epidural lipomatosis an MRI-based diagnosis with clinical implications? A retrospective analysis.

OBJECTIVES: Magnetic resonance imaging (MRI) is considered the most sensitive modality for evaluating spinal epidural lipomatosis (SEL) in vivo. The aim of this study was to compare the existing MRI classifications of SEL and to reevaluate the clinico-radiological correlation of SEL as a pathological entity. MATERIALS AND METHODS: Measurements of the cervical, thoracic and lumbar spine were performed in a retrospective setting within 1406 data sets from the digital MRI archives. RESULTS: It could be shown that the existing MRI classifications developed for different spinal regions complemented each other. However, there was no distinct correlation of these MRI findings with clinical symptoms because other morphological changes existed that probably caused the patients' complaints. CONCLUSION: Existing SEL classifications developed either for the lumbar or the thoracic spine were found to be applicable to both regions, but the very vague association with clinical symptoms should caution against premature conclusions with respect to the clinical significance of SEL.