Cerebral Tumefactive Inflammatory Lesion Occurrence During Ixekizumab Treatment in a Patient With Active Psoriatic Arthritis.

INTRODUCTION: Ixekizumab is an anti-interleukin-17A (IL-17A) humanized monoclonal antibody approved for the treatment of moderate-to-severe plaque psoriasis, active psoriatic arthritis, and ankylosing spondylitis. Central nervous system inflammatory manifestations are atypical during therapy with IL-17A inhibitors, with only one case of myelitis described to date. CASE REPORT: A 72-year-old man with a medical history of active psoriatic arthritis was admitted to our department owing to the acute onset of left face numbness 1 month after the first ixekizumab administration. Magnetic resonance imaging of the brain displayed a large T2-hyperintense infratentorial lesion involving the root of the fifth and seventh left cranial nerves. A thorough laboratoristic and instrumental work-up did not show elements suggestive of extracerebral neoplasms or infections. Therefore, neuronavigation-assisted brain biopsy was performed, and histologic analysis of the lesion revealed the presence of wide aggregates of foamy histiocytes diffusely infiltrating the brain parenchyma, in the absence of malignant tissue or histologic elements suggestive of central nervous system infections or primary histiocytoses. Steroid treatment (dexamethasone 8 mg/daily) was then administered with subsequent clinical amelioration. One month after hospital discharge, a brain magnetic resonance imaging showed a nearly complete resolution of the lesion. CONCLUSION: This is the first case of a cerebral inflammatory lesion occurring during treatment with ixekizumab. Although very rare, neurological complications may occur during anti-IL-17A therapies, thus leading to the need for careful monitoring of patients exposed to these drugs.

Successful treatment of ruptured multiple fusiform middle cerebral artery aneurysms with Silk Vista Baby flow diverter in a 10-month-old infant.

We report the successful treatment of multiple ruptured fusiform middle cerebral artery (MCA) aneurysms in a 10-month-old girl. This previously healthy infant presented with subarachnoid hemorrhage and was found to have multiple irregular dilatations of the superior division branch of the right MCA. Cerebral angiography was performed and confirmed the presence of multiple fusiform aneurysms of the MCA. After discussion with the multidisciplinary team, it was decided to treat the aneurysms with a endovascular approach, using a flow diverter. Microsurgical clipping was deemed risky because of the high likelihood of parent artery occlusion, and expectant management was also considered inappropriate because of the risk of rebleeding. Dual antiplatelet therapy was started, and a flow diverter was successfully delivered in the superior division branch of the right MCA. The postoperative course was uneventful, MRI at 12 months did not show any sign of recurrence, and at 3 years of age the patient had a normal neurological examination.

Modification of MRI pattern of high-grade glioma pseudoprogression in regorafenib therapy.

Pseudoprogression (PP) is a diagnostic dilemma in the follow-up of brain high grade gliomas (HGG), and the introduction of new therapies has further complicated its identification in Magnetic Resonance Imaging (MRI). We report a case of pseudoprogression after intraoperative radiotherapy (ioRT) and Regorafenib therapy in a patient with anaplastic astrocytoma recurrence. A 65-year-old man, treated in August 2017 for a right frontal anaplastic astrocytoma, with surgical resection and following radiotherapy and Temozolomide, in October 2019 was again treated for peri-surgical bed recurrence with resection and ioRT followed by Regorafenib therapy, interrupted in February 2020, after the onset of adverse reactions. MRI examination showed a large irregular alteration posterior to the surgical bed, T2 weighted hypointense featuring strong diffusion restriction (low ADC values), with an irregular contrast-enhancement (CE) pattern, and surrounded by a vast vasogenic oedema; Dynamic Susceptibility Contrast (DSC) perfusion imaging (PWI) showed no increase of relative cerebral blood volume (rCBV). Particularly, lesion appeared markedly hypointense and dusty-like on susceptibility weighted images (SWI) probably due to a constant hemorrhagic diapedesis promoted by Regorafenib. Therefore, pseudoprogression was suspected. Follow-up MRI exams showed gradual reduction of SWI and CE abnormalities, but a persistent DWI restriction. Unfortunately, the last MRI control showed a secondary cerebellar localisation of the disease. New therapies are changing MRI pattern in HGG imaging and this case underlines how a multimodality approach is increasingly necessary. In particular, when using anti-VEGF drugs, SWI can have a crucial role in identifying therapy-related haemorrhagic changes.

Republished: Successful treatment of ruptured multiple fusiform middle cerebral artery aneurysms with silk vista baby flow diverter in a 10-months-old infant.

We report the successful treatment of multiple ruptured fusiform middle cerebral artery (MCA) aneurysms in a 10-month-old girl. This previously healthy infant presented with subarachnoid haemorrhage and was found to have multiple irregular dilatations of the superior division branch of the right MCA. Cerebral angiography was performed and confirmed the presence of multiple fusiform aneurysms of the MCA. After multidisciplinary team discussion, it was decided to treat the aneurysms with endovascular approach, using a flow-diverter. Microsurgical clipping was deemed risky because of the high likelihood of parent artery occlusion and expectant management was also considered inappropriate because of the risk of re-bleeding. Dual antiplatelet therapy was started, and a flow-diverter was successfully delivered in the superior division branch of the right MCA. The post-operative course was uneventful, MRI at 12 months did not show any sign of recurrence and at 3 years of age the patient had a normal neurological examination.

Combined HSV-TK/IL-2 gene therapy in patients with recurrent glioblastoma multiforme: biological and clinical results.

Following our pilot clinical study of combined IL-2/HSV-TK gene therapy for recurrent glioblastoma multiforme (GBM), we extended the protocol to a larger population of patients and evaluated safety, feasibility, and biological activity of treatment. A total of 12 patients received intratumor injection of retroviral vector-producing cells (RVPCs), followed by intravenous ganciclovir (GCV). Treatment was well tolerated with only minor adverse events. Transduction of tumor cells was demonstrated in tumor biopsies. A marked and persistent increase of intratumor and plasma Th1 cytokine levels was demonstrated after RVPC injection. At magnetic resonance imaging evaluation, two patients had a partial response (including a patient showing disappearance of a distant noninjected tumor mass), four had a minor response, four had stable disease, and two had progressive disease. The 6- and 12-month progression-free survival rates were 47 and 14%, respectively. The 6- and 12-month overall survival rates were 58 and 25%, respectively. In conclusion, the results of our clinical protocol of gene therapy for recurrent GBM, based on combined delivery of a suicide and a cytokine gene, demonstrate that intratumor injection of RVPCs was safe, provided effective transduction of the therapeutic genes to target tumor cells, and activated a systemic cytokine cascade, with tumor responses in 50% of cases.