Parkinson's disease (PD) is a prevalent neurodegenerative disorder, and levodopa (L-dopa) remains the most efficacious drug treatment for PD and a gold-standard for symptom control. Nonetheless, a significant majority of PD patients develop motor fluctuations over their disease course, with a significant impact on quality-of-life, meaning control of such complications translates into a fundamental clinical need. Catechol-O-methyl transferase (COMT) inhibitors (COMT-i) are used as first-line adjuvant therapy to L-dopa for endof-dose (EoD) motor fluctuations, since they increase L-dopa availability in the brain by inhibiting its peripheral metabolism. Opicapone (OPC), a once-daily, long-acting COMT-i, is the most recent and potent of its class, having been licensed in Europe in 2016 as an add-on to preparations of L-dopa/DOPA decarboxylase inhibitors in PD patients with EoD motor fluctuations. More recently, it has also received approval in the USA and Japan in 2020. Two high-quality positive efficacy studies (double-blind Phase III clinical trials) established OPC efficacy with significant reduction in OFF time (average 60 minutes vs placebo), without concomitant increase of distressing dyskinesias during ON time. These beneficial effects were sustained in open-label extension studies, without unexpected safety issues or adverse events, with dyskinesia having been the most frequent complaint. OPC also avoids liver toxicity and gastrointestinal issues compared with previous COMT-i. In this review, we aimed to cover OPC's lifecycle (synthesis to commercialization), its clinical pharmacological data, safety, tolerability and pharmacovigilance evidence, and discuss its role in the management of motor fluctuations in PD as well as its emerging place in international recommendations.
Cerebral amyloid angiopathy (CAA) is characterized by progressive deposition of Aβ protein in the walls of small-to medium-sized leptomeningeal and cortical blood vessels. 1 Clinical manifestations include symptomatic acute lobar intracerebral hemorrhage, chronic progressive cognitive decline and transient focal neurological episodes, with widespread cortical microbleeds in brain MRI. 1 Rarely, it can present as cerebral amyloid angiopathy-related inflammation (CAA-ri) in which there is a perivascular inflammation around amyloid-laden vessels, along with rapid clinical progression and adding cortico-subcortical T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities in brain MRI. Parkinsonism as a presentation of CAA is extremely rare.We report a case of periodic spasms and rapidly progressive parkinsonism caused by probable CAA, ameliorated by corticosteroids.
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