Neurology最新文献

Background and objectives: Calcitonin gene-related peptide (CGRP) inhibitors have entered widespread use in the United States for treatment of migraine, but data on their cardiovascular risk profile are lacking. The objective of this study was to determine whether exposure to a CGRP inhibitor is associated with cardiovascular events in patients with migraine.

Methods: A retrospective, observational, cohort study was conducted using computerized claims data from a proprietary, insurance-based registry, MarketScan (by Merative). Beneficiaries with at least one claim related to a migraine diagnosis and continuous coverage for at least 12 months before migraine diagnosis were included. Using a sequential trial framework, the rate of cardiovascular events was computed in those who did and did not initiate a CGRP inhibitor, using both crude estimates and those derived in propensity score overlap-weighted cohorts. Adjusted hazard ratios (HR) and corresponding 95% CI were computed. The principal exposure was initiation of any CGRP inhibitor. The primary end point was a composite of myocardial infarction (MI), cerebral ischemic stroke, revascularization, peripheral arterial disease, or central retinal artery occlusion (CRAO). Secondary end points included each component individually. A falsification end point (humeral fracture) was included.

Results: In total, 900,370 beneficiaries (median age 41 [Q1, Q3: 31, 51] years; 77.8% female) were included, of whom 58,679 initiated a CGRP inhibitor and 841,691 did not initiate a CGRP inhibitor during the study period. Beneficiaries initiating a CGRP inhibitor exhibited a greater degree of cardiovascular morbidity at baseline than noninitiators. In the overlap-weighted analysis, there was a higher rate of the primary end point among beneficiaries who initiated a CGRP inhibitor (8.77 events/1,000 person-years vs 6.76 events/1,000 person-years; aHR 1.26 [95% CI 1.10-1.45]). Initiation of a CGRP inhibitor was associated with a significantly higher rate of one secondary end point (ischemic stroke [aHR 1.26 (95% CI 1.07-1.49)]) but not 4 other secondary end points: MI, revascularization, CRAO, and intracranial hemorrhage.

Discussion: In a nationwide cohort study, initiation of a CGRP inhibitor was associated with an increased risk of a composite of cardiovascular events; however, the magnitude of the increased risk was low.

Classification of evidence: This study provides Class II evidence that in patients with migraine, initiation of a CGRP inhibitor was associated with a modestly increased risk of a composite of cardiovascular events.

We present a case of reversible leukoencephalopathy and parkinsonism associated with type III mixed cryoglobulinemic vasculitis in a patient who initially presented with systemic vasculitic symptoms such as rash and arthralgias. Neither hepatitis C nor monoclonal gammopathy-typical triggers of cryoglobulinemia-was identified. The neurologic syndrome evolved with tremor, rigidity, significant cognitive decline, and extensive white matter abnormalities on MRI, mimicking primary neurodegenerative conditions such as multiple system atrophy. Diagnostic workup ruled out infectious, metabolic, autoimmune, and drug-related etiologies. After immunosuppressive therapy with methotrexate and steroids, the patient experienced marked clinical and radiologic improvement, paralleled by a decline in serum neurofilament levels. This case highlights the importance of recognizing inflammatory CNS involvement as a potentially reversible cause of rapidly progressive parkinsonism and cognitive impairment. Prompt identification and timely immunosuppressive treatment may reverse symptoms and prevent permanent neurologic damage.

We report the case of a 27-year-old man with a history of speech delay and chronic, progressive movement disorder. He first developed gait difficulty at the age of 12. Given clinical signs of bradykinesia and resting tremor, he received a clinical diagnosis of childhood-onset parkinsonism. Treatment with oral levodopa initially improved symptoms, but after 2 years, he developed motor fluctuations and dyskinesias. Additional signs of spasticity and brain MRI showing a thin corpus callosum prompted genetic testing that identified a heterozygous pathogenic variant in the PRKN gene. However, he exhibited a progressive loss of response to chronic dopaminergic therapy, first with oral and later with continuous levodopa-carbidopa intestinal gel infusion, with disease progression over 7 years. This progression led to further genetic testing and the diagnosis of hereditary spastic paraplegia type 15 (SPG 15). Advancing motor symptoms prompted deep brain stimulation and botulinum toxin injections, although these had limited benefit. This case highlights the challenges of diagnosing and managing juvenile-onset parkinsonism and the value of comprehensive genetic analysis in evaluating genotypic-phenotypic correlations. Hereditary spastic paraplegias (HSPs) are a rare group of neurodegenerative disorders with diverse clinical and genetic features. They can be inherited in autosomal dominant, recessive, X-linked, or mitochondrial patterns. The SPG15 subtype (or HSP-ZFYVE26), caused by pathogenic variants in the ZFYVE26 gene, is a common form of autosomal recessive HSP. Presenting symptoms vary but commonly include cognitive impairment with a history of speech delay or learning disability and balance impairment or clumsiness from spasticity of the lower limbs.