The effect of levodopa treatment on vascular endothelial function in Parkinson's disease.

OBJECTIVE: There has been increasing awareness that micro-vascular alteration or vascular inflammation has been associated with levodopa-induced dyskinesia in PD. Vascular endothelial function assessed by flow mediated dilation (FMD) is known to reflect early microvascular change. We compare the impact of levodopa or dopamine agonist treatment on the change of FMD in de novo PD patients. METHODS: This retrospective study used a selected sample from registry. We identified de-novo PD patients who underwent FMD at baseline, and follow-up FMD after 1 year (± 2 month) of levodopa (n = 18) or dopamine agonist (n = 18) treatment. RESULTS: FMD decreased after levodopa (8.60 ± 0.46 to 7.21 ± 0.4, p = 0.002) but there were no significant changes after DA treatment (8.33 ± 0.38 to 8.22 ± 0.33, p = 0.26). Homocysteine rose (11.52 ± 0.45 to 14.33 ± 0.68, p < 0.05) during levodopa treatment, but dopamine agonist had no effect (10.59 ± 0.38 to 11.38 ± 0.67, p = 0.184). Correlation analysis revealed that the changes in homocysteine level had non-significant correlation with FMD change (r = - 0.30, p = 0.06). FMD change was not associated with age (p = 0.47), disease duration (p = 0.81), baseline motor UPDRS (p = 0.43), motor UPDRS change (p = 0.64), levodopa equivalent dose change (p = 0.65). CONCLUSIONS: We found that 1-year levodopa treatment may adversely affect vascular endothelial function in de novo PD. Further studies are needed to clarify the exact pathogenesis and clinical implication of levodopa-induced endothelial dysfunction in PD.

Real-world efficacy of galcanezumab for the treatment of migraine in Korean patients.

BACKGROUND AND OBJECTIVE: We aimed to provide real-world data on the effectiveness of an anti-calcitonin gene-related peptide monoclonal antibody administered for treating migraine in Korean patients. METHODS: We prospectively recruited patients with migraine who received galcanezumab treatment at a single university hospital from June 2020 to April 2021. The treatment response was assessed after three consecutive monthly injections. A 50% responder rate was evaluated based on ≥50% reduction in the number of moderate/severe headache days. RESULTS: Overall, 87 patients were included in the analysis. Most patients were women (83.9%). They had a mean age of 41.7 ± 12.3 years (range 17-72). Sixty-five patients (74.7%) had chronic migraine, 35 patients (40.2%) had a history of medication-overuse headache, and 32 patients (36.8%) were previously unresponsive to or found intolerable five classes of preventive medication. After three months of treatment, mean changes in numbers of monthly headache days, moderate/severe headache days, crystal clear days, and days of acute medication use were -7.2 ± 8.43, -4.3 ± 9.76, 7.3 ± 8.50, and -4.1 ± 7.93, respectively. The 50% responder rates were 58.3%, 44.2%, and 40.6% for patients with unsuccessful previous use of 0-1, 2-4, and 5 preventive medication classes, respectively. Headache Impact Test-6 and Migraine Disability Assessment Test scores also decreased (-4.4 ± 8.09 and -32.9 ± 77.04, respectively). CONCLUSION: In our cohort, the effectiveness and safety of galcanezumab were comparable with those reported in clinical trials, whereas a higher response rate was observed in the difficult-to-treat patient subset than that reported in trials. We provide real-world evidence of galcanezumab treatment benefits in Asian patients with migraine.

Effect of caffeine and caffeine cessation on cerebrovascular reactivity in patients with migraine.

OBJECTIVE: To investigate the effect of chronic caffeine use and caffeine cessation on vasodilatory function in the posterior circulation in patients with migraine. BACKGROUND: Studies regarding cerebrovascular reactivity (CVR) using vasodilatory stimuli in patients with migraine have yielded conflicting results. We postulated that CVR may not be static, and caffeine might negatively affect vasodilatory function via its vasoconstrictive effect. METHODS: In this prospective longitudinal observation study, we recruited patients with episodic migraine who were 18-50 years of age and free of vascular risk factors at the Samsung Medical Center between August 2015 and March 2020. Patients were classified into caffeine users and non-users at baseline, and caffeine users were instructed to discontinue caffeine intake. We measured the mean breath-holding index (BHI) of bilateral posterior cerebral arteries (PCA) using transcranial Doppler in all the included patients at baseline and followed up after 3 months. We compared breath-holding indices cross-sectionally between caffeine users and non-users and analyzed BHI changes according to caffeine cessation. RESULTS: In total, 84 patients completed the study protocol. Cross-sectional analysis showed that the baseline BHI of PCA was lower in caffeine users (n = 56, 1.1 [interquartile range (IQR) 0.8-1.3]) than that in nonusers (n = 28, 1.3 [IQR 1.0-1.5], p = 0.030). In the longitudinal analysis, caffeine quitters showed a significant improvement in BHI in PCA (baseline 1.1 [IQR 0.8-1.2], follow-up 1.3 [IQR 1.0-1.4], p = 0.034), whereas continuous users and non-users did not. Multivariable analysis showed an independent effect of caffeine cessation on the changes in BHI of PCA (unstandardized ß = 0.27, 95% confidence interval 0.01-0.53, p = 0.044). CONCLUSION: In patients with migraine, caffeine use is associated with reduced CVR in the posterior circulation, and caffeine cessation might be beneficial in improving CVR.

Characteristics of pre-cluster symptoms in cluster headache: A cross-sectional multicentre study.

BACKGROUND: Contrary to pre-attack symptoms before an individual cluster headache attack, little is known about the pre-cluster symptoms before the onset of cluster bouts. We previously described pre-attack symptoms before cluster headache attacks. The aim of this study was to investigate characteristics of pre-cluster symptoms in patients with episodic cluster headache. METHODS: In this multicentre study, 184 patients with episodic cluster headache were recruited between October 2018 and December 2020. They were interviewed by investigators and completed a structured questionnaire. To investigate pre-cluster and pre-attack symptoms, we assessed 20 symptoms and signs using the questionnaire. RESULTS: The upcoming cluster bout was predictable in 35.3% (n = 65/184) of the patients. When present, pre-cluster symptoms occurred at a median duration of 7 days (interquartile range, 2.3-14 days) before the onset of the cluster bout. Patients with pre-cluster symptoms showed a higher proportion of women, prevalence of pre-attack symptoms and seasonal rhythmicity, frequency of cluster headache attacks per day, and total number of cluster bouts compared to patients without pre-cluster symptoms. In univariable and multivariable logistic regression analyses, female sex was associated with the predictability of pre-cluster symptoms (odds ratio = 2.297, p = 0.016). CONCLUSIONS: The upcoming cluster bout was predicted in approximately 35% of patients with episodic cluster headache, which may allow for an earlier preventive treatment and help understand the pathophysiology.

RCVS-TCH score can predict reversible cerebral vasoconstriction syndrome in patients with thunderclap headache.

Reversible cerebral vasoconstriction syndrome (RCVS) is one of the most important differential diagnosis in patients with thunderclap headache (TCH). We aimed to develop a new scoring system for RCVS in patients with TCH. We retrospectively analyzed 72 patients enrolled in the prospective study of TCH conducted in 2015-2016 (derivation set). We identified possible predictors for the diagnosis of RCVS and constructed a prediction model (RCVS-TCH score) using the multivariable logistic regression model. Diagnostic performance was validated to an independent validation set from our headache registry. The derivation set comprised 41 patients with RCVS and 31 with non-RCVS, and the validation set included 253 patients with TCH (165 with RCVS and 88 with non-RCVS). The RCVS-TCH score (range: 0-12) contained four predictors: recurrent TCHs, female sex, triggering factor for TCH (single or multi) and blood pressure surge. The C-index of RCVS-TCH score was 0.929 (95% CI = 0.874-0.984). The RCVS-TCH score ≥ 7 had a sensitivity of 80% and a specificity of 97% in discriminating RCVS from non-RCVS. In the validation set, RCVS-TCH score showed a C-index of 0.861 (95% CI = 0.815-0.908). In our study, the RCVS-TCH showed good performance, which may aid the diagnosis of RCVS among patients with TCH.

The Clinical Usefulness of Targeted Temperature Management in Acute Ischemic Stroke with Malignant Trait After Endovascular Thrombectomy.

BACKGROUND/OBJECTIVE: Targeted temperature management (TTM) may be more beneficial after endovascular treatment (EVT) in patients with a large ischemic core. Therefore, we assessed the usefulness of TTM for such patients from a multicenter endovascular registry. METHODS: Anterior circulation stroke patients who underwent endovascular recanalization were included; acute ischemic stroke with malignant traits was designated as (1) baseline Alberta Stroke Program Early CT Score (ASPECTS) below 6 and (2) diffusion-weighted imaging (DWI) lesion volume measurement (> 82 ml) or National Institutes of Health Stroke Scale score > 20 and item Ia > 0. TTM (34.5 °C) was maintained for at least 48 h. RESULTS: We evaluated baseline demographics, risk factors, EVT parameters, and clinical outcomes between the TTM and non-TTM groups. Among the 548 patients, the TTM group (n = 91) significantly had a lower baseline ASPECTS (p < 0.001) and a higher DWI volume (p < 0.001) than the non-TTM group (n = 457). TTM group had a lower prevalence of favorable outcome (0-2 of modified Rankin Scale at 3 months; p = 0.008) than the non-TTM group. In a subgroup analysis of malignant trait patients (n = 80), TTM patients (n = 28) had more favorable outcome (32.1% vs. 7.7% p = 0.009) and less hemorrhagic transformation (none vs. any hemorrhage, p = 0.007) than non-TTM patients (n = 52). After adjusting for potential outcome predictors, TTM (odds ratio [OR] 4.63; confidence interval [CI] 1.20-17.89; p = 0.026) and hypertension (OR 0.18; CI 0.04-0.74; p = 0.018) were found to be independent determinants. CONCLUSIONS: Our data suggest that TTM attenuates impending hemorrhagic transformation and leads to favorable clinical outcomes in EVT patients with malignant trait.

Neurological Complications Resulting from Non-Oral Occupational Methanol Poisoning.

Methanol poisoning results in neurological complications including visual disturbances, bilateral putaminal hemorrhagic necrosis, parkinsonism, cerebral edema, coma, or seizures. Almost all reported cases of methanol poisoning are caused by oral ingestion of methanol. However, recently there was an outbreak of methanol poisoning via non-oral exposure that resulted in severe neurological complications to a few workers at industrial sites in Korea. We present 3 patients who had severe neurological complications resulting from non-oral occupational methanol poisoning. Even though initial metabolic acidosis and mental changes were improved with hemodialysis, all of the 3 patients presented optic atrophy and ataxia or parkinsonism as neurological complications resulting from methanol poisoning. In order to manage it adequately, as well as to prevent it, physicians should recognize that methanol poisoning by non-oral exposure can cause neurologic complications.