ObjectiveUncontrolled studies of mesenchymal stem cells (MSCs) in multiple sclerosis suggested some beneficial effect. In this randomized, double-blind, placebo-controlled, crossover phase II study we investigated their safety and efficacy in relapsing-remitting multiple sclerosis patients. Efficacy was evaluated in terms of cumulative number of gadolinium-enhancing lesions (GEL) on magnetic resonance imaging (MRI) at 6 months and at the end of the study.MethodsPatients unresponsive to conventional therapy, defined by at least 1 relapse and/or GEL on MRI scan in past 12 months, disease duration 2 to 10 years and Expanded Disability Status Scale (EDSS) 3.0–6.5 were randomized to receive IV 1–2×106 bone-marrow-derived-MSCs/Kg or placebo. After 6 months, the treatment was reversed and patients were followed-up for another 6 months. Secondary endpoints were clinical outcomes (relapses and disability by EDSS and MS Functional Composite), and several brain MRI and optical coherence tomography measures. Immunological tests were explored to assess the immunomodulatory effects.ResultsAt baseline 9 patients were randomized to receive MSCs (n = 5) or placebo (n = 4). One patient on placebo withdrew after having 3 relapses in the first 5 months. We did not identify any serious adverse events. At 6 months, patients treated with MSCs had a trend to lower mean cumulative number of GEL (3.1, 95% CI = 1.1–8.8 vs 12.3, 95% CI = 4.4–34.5, p = 0.064), and at the end of study to reduced mean GEL (−2.8±5.9 vs 3±5.4, p = 0.075). No significant treatment differences were detected in the secondary endpoints. We observed a non-significant decrease of the frequency of Th1 (CD4+ IFN-γ+) cells in blood of MSCs treated patients.ConclusionBone-marrow-MSCs are safe and may reduce inflammatory MRI parameters supporting their immunomodulatory properties.ClinicalTrials.gov NCT01228266

ObjectiveRetrograde trans-synaptic degeneration of retinal ganglion cell layer (GCL) has been proposed as one of the mechanisms contributing to permanent disability after visual pathway damage. We set out to test this mechanism taking advantage of the new methods for imaging the macula with high resolution by optical coherence tomography (OCT) in patients with lesions in the posterior visual pathway. Additionally, we explored the association between thinning of GCL as an imaging marker of visual impairment such as visual field defects.MethodsRetrospective case note review of patients with retrogeniculate lesions studied by spectral domain OCT of the macula and quadrant pattern deviation (PD) of the visual fields.ResultsWe analysed 8 patients with either hemianopia or quadrantanopia due to brain lesions (stroke  = 5; surgery  = 2; infection  = 1). We found significant thinning of the GCL in the projecting sector of the retina mapping to the brain lesion. Second, we found strong correlation between the PD of the visual field quadrant and the corresponding macular GCL sector for the right (R = 0.792, p<0.001) and left eyes (R = 0.674, p<0.001).ConclusionsThe mapping between lesions in the posterior visual pathway and their projection in the macula GCL sector corroborates retrograde trans-synaptic neuronal degeneration after brain injury as a mechanism of damage with functional consequences. This finding supports the use of GCL thickness as an imaging marker of trans-synaptic degeneration in the visual pathway after brain lesions.

Colour vision impairment is associated with greater MS severity.

Background: Effective management of multisymptomatic chronic diseases such as multiple sclerosis (MS) requires a multimodal, interdisciplinary approach. At MS clinics, numerous healthcare specialties are coordinated to provide patients with quality clinical care for all aspects of their disease. Settings and resource availability may vary between countries. Four specific specialty services from different EU countries are examined in more detail. Summary: The multidisciplinary neurorehabilitation team in Rennes, France, provides specialized consultations (e.g. spasticity, urodynamic unit, devices), inpatient and outpatient intensive rehabilitation programs and therapeutic education. Management approaches are based on a patient's level of impairment as assessed by the Expanded Disability Status Scale. In Girona, Spain, neuropsychologists perform assessments as part of the neurological protocol for all patients with MS. Depending on the level of impairment and patients' characteristics (e.g. working or not working), cognitive deficits may be treated at home or at a neurorehabilitation center. In Barcelona, Spain, neuro-ophthalmologists are involved in the differential diagnosis and follow-up care of MS patients with visual disturbances; particular attention is given to patients' vision-related quality of life. Pain specialists at the Marianne Strauß Klinik in Berg, Germany, have developed a system for classifying MS pain syndromes and differentiating MS-related pain from non MS-related pain. Chronic pain management involves numerous disciplines and requires active engagement by patients in developing treatment plans. Key Messages: MS affects several body systems and patients invariably require specialized interdisciplinary support. Insight into services provided by various specialties and their fit within multidisciplinary care models at MS centers may facilitate the design or refinement of care models in other locations.

Changes in the thickness of different layers of the retina occur early in the course of AION and evolve over time, resulting in the atrophy of the GCL and RNFL. ONL thickening at baseline is associated with visual dysfunction. Thinning of the GCL after 1 month correlates with poorer VF and BCVA at 1 month after acute AION.

We performed an in-depth study of the neuro-ophthalmologic signs and symptoms of a rare but fatal disease known as primary diffuse leptomeningeal gliomatosis (PDLG). Two new cases of PDLG are described, and 22 published cases reviewed. Papilledema and sixth nerve palsy are the most common neuro-ophthalmic findings. Other abnormalities include third and fourth nerve palsies, nystagmus, and vision loss. Involvement of the visual system may be part of the initial presentation of PDLG.

A 57-year-old-man treated with deep brain stimulation (DBS) of both subthalamic nuclei for advanced Parkinson disease developed a brain hemorrhage near the site of one of the DBS electrodes 9 months after implantation. The hemorrhage caused vertical diplopia from skew deviation. Examination also disclosed evidence of ipsiversive binocular torsion and a right head tilt, constituting an ocular tilt reaction (OTR). Fourteen months later, he was still symptomatic from diplopia. An OTR has not previously been reported as a delayed complication of DBS.

The most common ophthalmological pathology in POEMS syndrome is papilledema, the etiology of which could be infiltrative, intracranial hypertension, inflammation or an increase of the vascular permeability. The correct diagnosis and treatment of papilledema, depending on its etiology, should permit an acceptable visual outcome to be achieved.