Background and purpose
Alemtuzumab, a monoclonal CD52 antibody, is a high‐efficacy disease‐modifying‐therapy in relapsing‐remitting multiple sclerosis (RRMS). Recently, intracerebral hemorrhage (ICH) ...was reported as a possible treatment‐related adverse event. Arterial hypertension during infusion was suggested as a potential cause, although platelet or endothelial dysfunction may also contribute. This study aimed to screen for occult hemorrhagic cerebral lesions after alemtuzumab treatment and to further elucidate risk factors.
Methods
We included 30 RRMS patients who received alemtuzumab treatment at Ghent University Hospital or Sint‐Jan Bruges Hospital. Retrospective data concerning vital signs, adverse effects and thrombocyte levels during treatment were collected. The occurrence of occult intracranial hemorrhagic lesions was assessed by magnetic resonance imaging with susceptibility‐weighted imaging (SWI).
Results
The mean (standard deviation SD) systolic blood pressure (SBP) during the morning, afternoon and evening was 120 (3.38) mmHg during first administration and 114 (4.40) mmHg during second administration (N = 13). There was no significant increase in SBP when comparing morning, afternoon and evening per day, nor was there a significant difference in daily mean SBP between consecutive administration days. Thrombocyte count during treatment cycles ranged between 107 × 109/L and 398 × 109/L, with a mean (SD) absolute reduction of 59.3 × 109/L (50.65) or a mean (SD) relative reduction of 25.0 (12.84)% (N = 20). No patient had ICH, nor did SWI show any cerebral microbleeds or other hemorrhagic lesions post‐treatment (N = 23).
Conclusions
In our patient population, alemtuzumab treatment was not associated with arterial hypertension, ICH or occult microbleeds. Possible differences in administration regimen (ambulatory vs. in‐hospital setting) and patient population (cardiovascular risk) might explain an increased risk in different populations.
Arterial hypertension and intracerebral hemorrhages were recently reported as adverse events in alemtuzumab‐treated multiple sclerosis patients. In our cohort, retrospective analysis did not show a significant increase in systolic blood pressure during alemtuzumab infusions. Magnetic resonance imaging with susceptibility‐weighted imaging (SWI) sequences did not show any signs of hemorrhage or (occult) microbleeds post‐treatment.
Aseptic meningitis is a rare, but possible severe side effect after SARS-CoV-2 Pfizer/BioNTech vaccination.
Recently, a first case of aseptic meningitis after the first shot of mRNA-BNT162b2 ...SARS-CoV-2 (Pfizer/BioNTech) vaccine was reported. We present the first case of a 34-year-old woman without relevant medical history developing aseptic meningitis after her 2
Pfizer/BioNTech vaccination. She was admitted with severe headache and fever for 5 days prior to her presentation at the emergency department. An extensive work-up of the clinical problem could narrow the differential diagnosis. Symptoms resolved after methylprednisolone therapy.
This case highlights a rare but important side effect after vaccination that primary physicians and neurologists should be aware of in order to identify and efficiently manage these patients.
Aseptic meningitis is a rare, but possible severe side effect after SARS-CoV-2 Pfizer/BioNTech vaccination.
Recently, a first case of aseptic meningitis after the first shot of mRNA-BNT162b2 ...SARS-CoV-2 (Pfizer/BioNTech) vaccine was reported. We present the first case of a 34-year-old woman without relevant medical history developing aseptic meningitis after her 2
nd
Pfizer/BioNTech vaccination. She was admitted with severe headache and fever for 5 days prior to her presentation at the emergency department. An extensive work-up of the clinical problem could narrow the differential diagnosis. Symptoms resolved after methylprednisolone therapy.
This case highlights a rare but important side effect after vaccination that primary physicians and neurologists should be aware of in order to identify and efficiently manage these patients.
According to the neurotrophin deprivation hypothesis, diminished retrograde delivery of neurotrophic support during an early stage of glaucoma pathogenesis is one of the main triggers that induce ...retinal ganglion cell (RGC) degeneration. Therefore, interfering with neurotrophic signaling seems an attractive strategy to achieve neuroprotection. Indeed, exogenous neurotrophin administration to the eye has been shown to reduce loss of RGCs in animal models of glaucoma; however, the neuroprotective effect was mostly insufficient for sustained RGC survival. We hypothesized that treatment at the level of neurotrophin-releasing brain areas might be beneficial, as signaling pathways activated by target-derived neurotrophins are suggested to differ from pathways that are initiated at the soma membrane. In our study, first, the spatiotemporal course of RGC degeneration was characterized in mice subjected to optic nerve crush (ONC) or laser induced ocular hypertension (OHT). Subsequently, the well-known neurotrophin brain-derived neurotrophic factor (BDNF) was chosen as the lead molecule, and the levels of BDNF and its high-affinity receptor, tropomyosin receptor kinase B (TrkB), were examined in the mouse retina and superior colliculus (SC) upon ONC and OHT. Both models differentially influenced BDNF and TrkB levels. Next, we aimed for RGC protection through viral vector-mediated upregulation of collicular BDNF, thought to boost the retrograde neurotrophin delivery. Although the previously reported temporary neuroprotective effect of intravitreally delivered recombinant BDNF was confirmed, viral vector-induced BDNF overexpression in the SC did not result in protection of the RGCs in the glaucoma models used. These findings most likely relate to decreased neurotrophin responsiveness upon vector-mediated BDNF overexpression. Our results highlight important insights concerning the complexity of neurotrophic factor treatments that should surely be considered in future neuroprotective strategies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Glaucoma is characterized by a progressive loss of retinal ganglion cells (RGCs) in the eye, which ultimately results in visual impairment or even blindness. Because current therapies often fail to ...halt disease progression, there is an unmet need for novel neuroprotective therapies to support RGC survival. Various research lines suggest that visual target centers in the brain support RGC functioning and survival. Here, we explored whether increasing neuronal activity in one of these projection areas could improve survival of RGCs in a mouse glaucoma model. Prolonged activation of an important murine RGC target area, the superior colliculus (SC), was established via a novel optogenetic stimulation paradigm. By leveraging the unique channel kinetics of the stabilized step function opsin (SSFO), protracted stimulation of the SC was achieved with only a brief light pulse. SSFO-mediated collicular stimulation was confirmed by immunohistochemistry for the immediate-early gene c-Fos and behavioral tracking, which both demonstrated consistent neuronal activity upon repeated stimulation. Finally, the neuroprotective potential of optogenetic collicular stimulation was investigated in mice of either sex subjected to a glaucoma model and a 63% reduction in RGC loss was found. This work describes a new paradigm for optogenetic collicular stimulation and a first demonstration that increasing target neuron activity can increase survival of the projecting neurons.
Despite glaucoma being a leading cause of blindness and visual impairment worldwide, no curative therapies exist. This study describes a novel paradigm to reduce retinal ganglion cell (RGC) degeneration underlying glaucoma. Building on previous observations that RGC survival is supported by the target neurons to which they project and using an innovative optogenetic approach, we increased neuronal activity in the mouse superior colliculus, a main projection target of rodent RGCs. This proved to be efficient in reducing RGC loss in a glaucoma model. Our findings establish a new optogenetic paradigm for target stimulation and encourage further exploration of the molecular signaling pathways mediating retrograde neuroprotective communication.
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