Effectiveness of janus kinase inhibitors in relapsing giant cell arteritis in real-world clinical practice and review of the literature.

BACKGROUND: A substantial proportion of patients with giant cell arteritis (GCA) relapse despite standard therapy with glucocorticoids, methotrexate and tocilizumab. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway is involved in the pathogenesis of GCA and JAK inhibitors (JAKi) could be a therapeutic alternative. We evaluated the effectiveness of JAKi in relapsing GCA patients in a real-world setting and reviewed available literature. METHODS: Retrospective analysis of GCA patients treated with JAKi for relapsing disease at thirteen centers in Spain and one center in United States (01/2017-12/2022). Outcomes assessed included clinical remission, complete remission and safety. Clinical remission was defined as the absence of GCA signs and symptoms regardless of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values. Complete remission was defined as the absence of GCA signs and symptoms along with normal ESR and CRP values. A systematic literature search for other JAKi-treated GCA cases was conducted. RESULTS: Thirty-five patients (86% females, mean age 72.3) with relapsing GCA received JAKi therapy (baricitinib, n = 15; tofacitinib, n = 10; upadacitinib, n = 10). Before JAKi therapy, 22 (63%) patients had received conventional synthetic immunosuppressants (e.g., methotrexate), and 30 (86%) biologics (e.g., tocilizumab). After a median (IQR) follow-up of 11 (6-15.5) months, 20 (57%) patients achieved and maintained clinical remission, 16 (46%) patients achieved and maintained complete remission, and 15 (43%) patients discontinued the initial JAKi due to relapse (n = 11 [31%]) or serious adverse events (n = 4 [11%]). A literature search identified another 36 JAKi-treated GCA cases with clinical improvement reported for the majority of them. CONCLUSIONS: This real-world analysis and literature review suggest that JAKi could be effective in GCA, including in patients failing established glucocorticoid-sparing therapies such as tocilizumab and methotrexate. A phase III randomized controlled trial of upadacitinib is currently ongoing (ClinicalTrials.gov ID NCT03725202).

Steroid-Responsive Parkinsonism and Encephalopathy: A Case Report.

We describe a patient who presented with rapidly progressive parkinsonism and encephalopathy and was diagnosed with seronegative autoimmune encephalitis (AE). Subacute parkinsonism as a manifestation of seronegative AE is uncommon with only a handful of similar cases published in literature. A 71-year-old man presented with severe flu like symptoms, rapidly progressive cognitive decline and was found to have parkinsonian features on examination. Initial brain magnetic resonance imaging (MRI) was unremarkable however, cerebrospinal fluid (CSF) analysis revealed a lymphocytic pleocytosis and elevated protein level. Thorough searches for neural antibodies and infectious pathogens were negative. His symptoms fluctuated initially but markedly improved within days of starting prednisone and dramatically worsened after prednisone was tapered off. His CSF pleocytosis also improved on prednisone. Relapses again resolved with resumption of prednisone. The scope of autoimmune neurology Is constantly evolving, and physicians should be aware of the diverse and heterogenous clinical presentations of autoimmune encephalitis. We aim to emphasize the importance of ruling out autoimmune encephalitis in patients presenting with acute or subacute parkinsonism. This case additionally reinforces that negative antibody tests do not exclude the diagnosis of AE.

Association of blood pressure parameters post mechanical thrombectomy in anemic versus non-anemic patients and clinical outcomes.

INTRODUCTION: Higher blood pressure (BP) is considered to be detrimental in patients who undergo mechanical thrombectomy (MT), however, the impact of BP post-MT based on comorbidities like anemia has not been well studied. We aim to determine the association of 24-h post-MT BP parameters with clinical outcomes depending on their anemia status. METHODS: We conducted a retrospective chart review of patients who underwent MT at a comprehensive stroke center from 1/2015 to 12/2020. Patients were dichotomized into anemic and non-anemic groups based on the World Health Organization's definition of anemia [hemoglobin < 12.0 g/dL in women and < 13.0 g/dL in men]. We performed a multivariable analysis with binary logistic regression with the 24-h post-MT BP parameters as predictors. The outcomes were functional dependence (3-month mRS 3-6), mortality, and an early neurological improvement. RESULTS: 220 patients met the inclusion criteria. 158 (71.82 %) patients had functional dependence at 3-months. In the multivariable analysis, the parameters of a higher mean SBP (132.9 ± 11.94 vs.126.52 ± 13.3; OR, 1.05; 95 % CI, 1.02-1.09; P 0.011), a higher mean MAP (93.35 ± 8.44 vs.89.69 ± 10.03; OR,1.06; 95 % CI, 1.01-1.11; P 0.029) and a higher maximum MAP (115.26 ± 11.73 vs.109.37 ± 12.51; OR,1.05; 95 % CI, 1.01-1.08; P 0.023)were significantly associated with functional dependence in non-anemic patients, while a lower mean DBP (65.53 ± 9.73 vs. 71.94 ± 10.16; OR, 0.92; 95 % CI, 0.86-0.98; P 0.007), lower mean MAP (85.7 ± 8.65 vs. 91.38 ± 10; OR, 0.93; 95 % CI, 0.86-0.99; P 0.02), a lower minimum DBP (49.27 ± 10.51 vs. 55.1 ± 11.23; OR, 0.93; 95 % CI, 0.88-0.99; P 0.019), a lower minimum MAP (68.96 ± 9.54 vs. 74.73 ± 10.47; OR, 0.93; 95 % CI, 0.87-0.99; P 0.023) were significantly associated with mortality in patients with anemia, and a lower minimum DBP (54.75 ± 10.42 vs. 59.69 ± 8.87; OR, 0.95; 95 % CI, 0.91-0.99; P 0.012) and a lower minimum MAP (71.92 ± 14.7 vs.75.67 ± 14.17; OR, 0.97; 95 % CI, 0.94-0.99; P 0.047) were significantly associated with an early neurological improvement in non-anemic patients. For patients with anemia, there was no association between 24-hour BP Parameters post-MT and functional dependence and early neurological improvement, and between 24-hour BP Parameters post-MT and mortality in non-anemic patients. CONCLUSION: In our study, higher BP parameters were associated with worse outcomes in patients without anemia, however, this effect was not found in patients with anemia. Certain lower BP parameters were associated with higher 3-month mortality in anemic patients; however, this effect was not found in non-anemic patients. Higher BP post-MT can potentially promote perfusion and thus is not associated with worse outcomes in anemic patients post-MT, whereas in non-anemic patients it may potentially lead to reperfusion injury While our study is limited because of size and its retrospective nature, the findings suggest that an individualized approach to tailor the target BP post-MT to a patient's risk factor profile and associated co-morbid conditions to achieve optimization of medical care post-MT and associated co-morbid conditions to achieve optimization of medical care post-MT.

Neuro-ophthalmic complications of varicella-zoster virus.

PURPOSE OF REVIEW: This review broadly describes recent neuro-ophthalmic manifestations of varicella-zoster virus (VZV) reported in literature. RECENT FINDINGS: Despite varicella vaccination, the incidence of herpes zoster continues to rise, potentially leading to devastating consequences when ocular complications occur.A small but growing literature documents cases of retinal disease because of varicella reactivation after SARS-CoV-2 vaccination, ischemic optic neuropathy occurring during herpes zoster ophthalmicus, VZV-induced orbital apex syndrome, and immune-mediated ocular complications in patients with prior neuro-ophthalmic manifestations of VZV. SUMMARY: It is important for clinicians to keep abreast of the diverse neuro-ophthalmic manifestations of VZV as early diagnosis and treatment often lead to better visual outcomes.

Association of pre-mechanical thrombectomy collateral scores with functional outcomes in the early versus extended window for thrombectomy.

Introduction: Cerebral collateral circulation refers to the anastomoses that reroute the blood flow to the ischemic penumbra in the event of a large vessel occlusion (LVO). We aim to determine the utility of pre-mechanical-thrombectomy (MT) collateral scores in the early (<6 h from onset) versus extended (6-24 h from onset) window for MT with respect to a 3-month functional outcome, 3-month mortality, and early neurological improvement. Methods: We performed a retrospective chart review of patients who underwent MT for an anterior circulation LVO at a comprehensive stroke center from 7/2014 to 12/2020. A board-certified neuroradiologist, who was blinded to the clinical outcomes, used the collateral grading scales of Miteff (ordinal), Maas (ordinal), and modified-Tan (dichotomous) to designate collateral scores on the pre-MT CT Angiogram. The patients were divided into early (<6 h from onset) versus extended (6-24 h from onset) window groups depending on their timing of presentation to the emergency department. A regression analysis was performed, controlling for the baseline parameters, with the pre-MT collateral grading scores as predictors. The outcome measures were a good functional outcome (3-month mRS 0-2), mortality, and early neurological improvement. Results: A total of 220 patients met the inclusion criteria. In the overall cohort, the pre-MT scale of Maas was associated with a good functional outcome (OR, 0.58; 95% CI, 0.34-0.99; P 0.047) and mortality (OR, 0.55; 95% CI, 0.31-0.97; P 0.036). For the 162 patients who presented in the early window for MT, all of three pre-MT scales of Maas (OR, 0.39; 95% CI, 0.2-0.77; P 0.006), Miteff (OR, 0.43; 95% CI, 0.19-0.97; P 0.042) and modified-Tan (OR, 5.62; 95% CI, 1.16-27.37; P 0.033) were associated with a good functional outcome, whereas the Maas (OR, 0.48; 95% CI, 0.26-0.9; P 0.021) and the Miteff scale (OR, 0.4; 95% CI, 0.22-0.74; P 0.003) were associated with mortality. For the 58 patients who presented in the extended window for MT, none of the collateral grades were associated with functional outcome, mortality, or early neurological improvement. Conclusions: Our study demonstrates that while several collateral grades are helpful to predict outcomes in patients presenting in the early window, none of the pre-MT collateral scores were associated with outcomes in patients who presented in the extended window for MT. Thus, the current strategy of using perfusion imaging for the selection of patients for MT in the extended window should continue.

Interplay between anemia parameters and collateral status in patients who undergo mechanical thrombectomy.

INTRODUCTION: Anemia is associated with higher morbidity and mortality, but its association with acute ischemic stroke (AIS) is not well established. We aim to determine the association of five-day anemia parameters with clinical outcomes in patients with an AIS, depending on their pre-mechanical thrombectomy (MT) collateral status. METHODS: We performed a retrospective chart review of patients who underwent MT at a comprehensive stroke center from 7/2014 to 12/2020. The patients were divided into good and poor collateral groups depending on their pre-MT collateral status. A blinded board-certified neuroradiologist used collateral grading scale of Maas ≥ 3 to designate good collaterals on the pre-MT CT Angiogram. A binary logistic regression analysis was performed, controlling for the baseline parameters, with the five-day anemia parameters as predictors. The outcomes were functional independence (mRS 0-2), mortality, and early neurological improvement. RESULTS: A total of 220 met the inclusion criteria. 94 (42.72 %) patients had good collaterals, while 126 (57.27 %) patients had poor collaterals. In the multivariable analysis, for patients with good collaterals, the higher values of five-day mean Hb (12.41 ± 1.87 vs 11.32 ± 1.95; OR, 0.72; 95 % CI, 0.54-0.95; P 0.018), five-day mean HCT (37.43 ± 5.1 vs 34.35 ± 5.5; OR, 0.89; 95 % CI, 0.81-0.98; P 0.018) and lower values of the difference between peak and trough values of Hb (1.75 ± 1.15 vs 2.41 ± 1.35; OR, 1.71; 95 % CI, 1.07-2.74; P 0.025) were associated with functional independence. For patients with poor collaterals, there was no association between five-day mean Hb, mean HCT parameters with functional independence, lower mortality, and early neurological improvement. CONCLUSION: Our study was suggestive of an association between higher mean values of Hb and HCT over a five-day period and good clinical outcomes in patients with good collaterals who undergo MT for an anterior circulation LVO. This association was not found in the poor collateral group.

Association of 24-hour blood pressure parameters post-thrombectomy with functional outcomes according to collateral status.

INTRODUCTION: Elevation of blood pressure (BP) after mechanical thrombectomy (MT) can theoretically restore perfusion to the ischemic brain tissue, but it comes at a risk of causing reperfusion injury. We aim to determine the association of 24-h post-MT BP parameters with clinical outcomes depending on the pre-MT collateral status. METHODS: We performed a retrospective chart review of patients who underwent MT at a comprehensive stroke center from 7/2014 to 12/2020. The patients were divided into good versus poor collateral groups depending on their collateral status. A board-certified neuroradiologist, who was blinded to the clinical outcomes, used collateral grading score of Miteff ≥3 to designate good collaterals on the pre-MT CT Angiogram. A binary logistic regression analysis was performed, controlling for baseline parameters, with the 24-h post-MT BP parameters as predictors. The outcomes were functional dependence [3-month mRS (3-6)] and mortality. RESULTS: A total of 220 met the inclusion criteria. In the multivariable analysis, for patients with poor collaterals, the parameters of higher mean SBP (131.7 ± 12.7 vs. 122.3 ± 14.2; OR, 1.06; 95% CI, 1.01-1.11; P 0.022), higher mean MAP (91.2 ± 8.2 vs. 86.1 ± 6.3; OR, 1.13; 95% CI, 1.03-1.23; P 0.015) and a higher maximum SBP (156.3 ± 13.7 vs. 145.3 ± 19.1; OR, 1.05; 95% CI, 1.01-1.1; P 0.019) were significantly associated with functional dependence at 3-months. For patients with good collaterals, the parameters of lower 24-h mean DBP (69.1 ± 11.1 vs. 73.8 ± 11 95% CI, OR, 0.96; 95% CI, 0.92-1; P 0.025) was significantly associated with higher mortality at 3-months. CONCLUSION: Our study demonstrates that there is a significant difference with respect to certain 24-h post-MT BP parameters in patients on clinical outcomes depending on their collateral status. In our study, some higher BP parameters were associated with worse outcomes in patients with a poor collateral profile, however, this effect was not replicated in patients with a good collateral profile.

Association of anemia with functional outcomes in patients with mechanical thrombectomy.

INTRODUCTION: Anemia at presentation is associated with worse outcomes in patients with acute ischemic stroke (AIS). We aim to investigate the association of anemia parameters with functional dependence and mortality in patients who undergo mechanical thrombectomy (MT). METHODS: We performed a retrospective chart review of patients who underwent MT for an anterior circulation large vessel occlusion at a comprehensive stroke center from 1/2015-6/2020. Anemia was considered as a dichotomous categorical variable with a cutoff point of hemoglobin (Hb) < 12.0 g/dL in women and < 13.0 g/dL in men, as per the definition of the World Health Organization. Mean values of Hb and hematocrit (HCT) were obtained over the first five days of admission. Hemoglobin and HCT variability were measured using standard deviation (SD), and coefficient variability (CV) over the first five days of admission. Values of variance and difference (the difference between peak and trough of Hemoglobin or HCT) were also recorded. Multivariate logistic regression analyses were performed, including the predictor variables which were contributing significantly to the model (P < 0.05) in the univariate analysis, with 30-day functional dependence (mRS 3-6) (primary outcome) and 30-day mortality (secondary outcome) as the dependent variables. RESULTS: 188 patients met our inclusion criteria. Anemia on presentation, lower mean and minimum values of five-day Hb and HCT, and higher variability in five-day Hb and HCT parameters were associated with higher 3-month mortality. Men with lower mean and minimum values of five-day Hb and HCT had a significantly higher likelihood of functional dependence at 3-months. This finding was not replicated amongst women in our cohort. CONCLUSION: Our study demonstrated higher 3-mortality in patients with anemia and Hb variability. Our study also demonstrated a higher likelihood of functional dependence in patients amongst men with anemia.