Intravitreal allogeneic mesenchymal stem cells: a non-randomized phase II clinical trial for acute non-arteritic optic neuropathy.

BACKGROUND: An effective treatment for acute non-arteritic ischemic optic neuropathy (NA-AION) has not been known or proven yet. Previous studies have suggested a neuroprotective effect of allogeneic bone marrow-derived mesenchymal stem cells. This study aims to report the results of a clinical trial on patients with acute non-arteritic optic neuropathy (NA-AION) treated with an intravitreal injection of allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) (MSV®). METHODS: We conducted a prospective, non-randomized, clinical phase-II study (Eudra CT number 2016-003029-40; ClinicalTrials.gov Registry NCT03173638) that included 5 patients with acute unilateral NA-AION diagnosed within 2 weeks after symptom onset and who received an intravitreal injection of allogeneic BM-MSCs (0.05 ml; cell concentration: 1.5 × 106cells/mL). The patients underwent regular ophthalmological examinations and were followed for one year. RESULTS: In this trial, allogeneic BM-MSCs appeared to be safe as no patients developed signs of acute nor chronic intraocular inflammation or a significant change in intraocular pressure, although an epiretinal membrane was developed in one patient. A retrolental aggregate formed shortly after the injection spontaneously disappeared within a few weeks in another phakic patient, leaving a subcapsular cataract. Visual improvement was noted in 4 patients, and amplitudes of P100 on the visually evoked potentials recordings increased in three patients. The retinal nerve fiber layer and macular ganglion cell layer thicknesses significantly decreased during the follow-up. CONCLUSIONS: Besides the development of an epiretinal membrane in one patient, the intravitreal application of allogeneic BM-MSCs appeared to be intraocularly well tolerated. Consequently, not only NA-AION but also BM-MSCs deserve more clinical investigational resources and a larger randomized multicenter trial that would provide stronger evidence both about safety and the potential therapeutic efficacy of intravitreally injected allogeneic BM-MSCs in acute NA-AION. TRIAL REGISTRATION: Safety Assessment of Intravitreal Mesenchymal Stem Cells for Acute Non-Arteritic Anterior Ischemic Optic Neuropathy (NEUROSTEM). NCT03173638. Registered June 02, 2017 https://clinicaltrials.gov/ct2/show/NCT03173638 .

Headache as a crucial symptom in the etiology of convexal subarachnoid hemorrhage.

BACKGROUND: Convexal subarachnoid hemorrhage has been associated with different diseases, reversible cerebral vasoconstriction syndrome and cerebral amyloid angiopathy being the 2 main causes. OBJECTIVE: To investigate whether headache at onset is determinant in identifying the underlying etiology for convexal subarachnoid hemorrhage. METHODS: After searching in the database of our hospital, 24 patients were found with convexal subarachnoid hemorrhage in the last 10 years. The mean age of the sample was 69.5 years. We recorded data referring to demographics, symptoms and neuroimaging. RESULTS: Cerebral amyloid angiopathy patients accounted for 46% of the sample, 13% were diagnosed with reversible cerebral vasoconstriction syndrome, 16% with several other etiologies, and in 25%, the cause remained unknown. Mild headache was present only in 1 (9%) of the 11 cerebral amyloid angiopathy patients, while severe headache was the dominant feature in 86% of cases of the remaining etiologies. CONCLUSION: Headache is a key symptom allowing a presumptive etiological diagnosis of convexal subarachnoid hemorrhage. While the absence of headache suggests cerebral amyloid angiopathy as the more probable cause, severe headache obliges us to rule out other etiologies, such as reversible cerebral vasoconstriction syndrome.