Circular walking is useful for assessing the risk of falls in early progressive supranuclear palsy.

BACKGROUND: Progressive supranuclear palsy (PSP) is characterized by early onset postural instability and frequent falls. Circular walking necessitates dynamic postural control, which is impaired in patients with PSP. We aimed to explore gait parameters associated with the risk of falls in patients with PSP, focusing on circular walking. METHODS: Sixteen drug-naïve patients with PSP, 22 drug-naïve patients with Parkinson's disease (PD), and 23 healthy controls were enrolled. Stride lengths/velocities and their coefficients of variation (CV) during straight and circular walking (walking around a circle of 1-m diameter) were measured under single-task and cognitive dual-task conditions. Correlation analysis was performed between gait parameters and postural instability and gait difficulty (PIGD) motor subscores, representing the risk of falls. RESULTS: Patients with PSP had significantly higher CVs of stride lengths/velocities during circular walking than those during straight walking, and the extent of exacerbation of CVs in patients with PSP was larger than that in patients with PD under single-task conditions. Stride lengths/velocities and their CVs were significantly correlated with PIGD motor subscores in patients with PSP only during single-task circular walking. In addition, patients with PSP showed progressive decrements of stride lengths/velocities over steps only during single-task circular walking. CONCLUSIONS: Worse gait parameters during circular walking are associated with an increased risk of falls in patients with PSP. Circular walking is a challenging task to demand the compromised motor functions of patients with PSP, unmasking impaired postural control and manifesting sequence effect. Assessing circular walking is useful for evaluating the risk of falls in patients with early PSP.

Is there a spinal tap responder in progressive supranuclear palsy? The first prospective study.

OBJECTIVE: Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disease, and sometimes shows idiopathic normal pressure hydrocephalus (iNPH)-like presentations. We aimed to evaluate spinal tap responsiveness in patients with PSP, including the effect of sham spinal tap. METHODS: Eleven patients with PSP, ten with probable/definite iNPH, and eight control patients were prospectively enrolled. All participants underwent sham spinal tap and spinal tap procedures. Gait was evaluated using wearable inertial sensors. We defined "tap responders" as individuals with a 10% or more improvement from baseline in any of the gait parameters (timed up-and-go test total time, stride length, and velocity during straight walking under single-task and cognitive dual-task conditions). We compared the ratio of responders in patients with PSP to patients with iNPH and controls. RESULTS: The ratio of tap responders and the ratio of sham tap responders in patients with PSP were significantly higher than those in control patients, and not different from those in patients with iNPH. PSP patients with iNPH-like MRI features tended to respond to the spinal tap compared to those without such imaging features. Notably, one patient with PSP, who responded to the spinal tap beyond the effect of sham spinal tap, was treated by the shunt operation. CONCLUSION: This is the first prospective study to demonstrate tap and shunt responsiveness in patients with PSP while highlighting the placebo effects of the spinal tap in patients with PSP or iNPH. Our findings suggest that some PSP patients have impaired cerebrospinal fluid circulation, contributing to a distinct component of the clinical spectrum.

Long-term levodopa ameliorates sequence effect in simple, but not complex walking in early Parkinson's disease patients.

BACKGROUND: The sequence effect (SE) is characterized by the progressive decrement of movements and is often observed in Parkinson's disease (PD) patients. While acute effect of levodopa does not ameliorate the SE, the effect of long-term levodopa treatment for the SE remains unknown. OBJECTIVE: We aimed to elucidate the SEs during various gait conditions and their response to long-term levodopa treatment in drug-naïve PD patients. METHODS: Nineteen drug-naïve PD patients and 21 healthy controls were enrolled. Gait parameters were measured via wearable inertial sensors in the following conditions:1) straight walking, 2) circular walking: walking a circle of 1 m diameter in a clock-wise direction for 3 laps, 3) straight or circular walking under cognitive-motor dual-task (serial 7s subtractions). PD patients were evaluated at baseline, within 1 h after intravenous administration of levodopa, and after one, three, and six months treatment with levodopa. The SE was measured by a linear regression slope by plotting consecutive stride lengths over steps. Patients were also separately analyzed depending on laterality of symptoms. RESULTS: Long-term levodopa treatment ameliorated the SE only during single-task straight walking. The SE during circular walking was exacerbated after long-term levodopa treatment for right-side dominant patients. During dual-task straight walking, the SE at baseline was greater in right-side dominant PD patients. CONCLUSIONS: The SE only during single-task straight walking can be ameliorated by long-term levodopa treatment. However, the SE may be exaggerated by cognitive motor interference or by asymmetrical stride length with/without long-term levodopa treatment, depending on the laterality of symptoms.

Correlation of callosal angle at the splenium with gait and cognition in normal pressure hydrocephalus.

OBJECTIVE: Idiopathic normal pressure hydrocephalus (iNPH) is characterized by ventricular enlargement that deforms the corpus callosum, making the callosal angle (CA) small. The authors aimed to evaluate the clinical usefulness of the CA in different planes in iNPH. METHODS: Forty patients with iNPH were included in the study. As a control group, 241 patients with other neurological diseases and 50 healthy controls were included. The subjects had been seen at the authors' institutions from 2010 to 2020. The Timed Up and Go (TUG) test total time and Mini-Mental State Examination (MMSE) total score were evaluated. CAs were measured in the axial plane at the splenium and genu and in the coronal plane at the anterior commissure and posterior commissure by using 3-dimensional T1-weighted MR images. As other hydrocephalus parameters, the Evans index, frontal-occipital horn ratio, and third ventricular width were also measured in patients with iNPH. Associations between each CA or hydrocephalus parameter and clinical parameters were evaluated. The classification efficacy of each CA in differentiating between iNPH and other neurological diseases and healthy controls was evaluated. RESULTS: The CA at the splenium, but no other hydrocephalus parameters, was correlated with TUG total time or MMSE total score in patients with iNPH. Receiver operating characteristic analysis showed that a CA of 71.1° at the splenium has 90.0% sensitivity and 89.0% specificity in discriminating iNPH from other neurological diseases and healthy controls. Probabilistic tractography analysis showed that neuronal fibers via the splenium connect the superior parietal lobules, temporal lobes, and occipital lobes. CONCLUSIONS: The study results suggest that interhemispheric disconnections at the splenium are, at least in part, responsible for gait and cognitive disturbance in iNPH. The CA at the splenium is a unique morphological feature that correlates with gait and cognition in iNPH, and it is useful for discriminating iNPH from other neurological diseases and healthy controls.

Turning and multitask gait unmask gait disturbance in mild-to-moderate multiple sclerosis: Underlying specific cortical thinning and connecting fibers damage.

Multiple sclerosis (MS) causes gait and cognitive impairments that are partially normalized by compensatory mechanisms. We aimed to identify the gait tasks that unmask gait disturbance and the underlying neural correlates in MS. We included 25 patients with MS (Expanded Disability Status Scale score: median 2.0, interquartile range 1.0-2.5) and 19 healthy controls. Fast-paced gait examinations with inertial measurement units were conducted, including straight or circular walking with or without cognitive/motor tasks, and the timed up and go test (TUG). Receiver operating characteristic curve analysis was performed to distinguish both groups by the gait parameters. The correlation between gait parameters and cortical thickness or fractional anisotropy values was examined by using three-dimensional T1-weighted imaging and diffusion tensor imaging, respectively (corrected p < .05). Total TUG duration (>6.0 s, sensitivity 88.0%, specificity 84.2%) and stride velocity during cognitive dual-task circular walking (<1.12 m/s, 84.0%, 84.2%) had the highest discriminative power of the two groups. Deterioration of these gait parameters was correlated with thinner cortical thickness in regional areas, including the left precuneus and left temporoparietal junction, overlapped with parts of the default mode network, ventral attention network, and frontoparietal network. Total TUG duration was negatively correlated with fractional anisotropy values in the deep cerebral white matter areas. Turning and multitask gait may be optimal to unveil partially compensated gait disturbance in patients with mild-to-moderate MS through dynamic balance control and multitask processing, based on the structural damage in functional networks.

Striatal Dopamine Denervation Impairs Gait Automaticity in Drug-Naïve Parkinson's Disease Patients.

BACKGROUND: Gait automaticity, which is impaired in patients with Parkinson's disease (PD), can be quantified by gait variability analysis. Among the 3 regions of the striatum (sensorimotor, executive, and limbic), the sensorimotor region may play a crucial role in motor automaticity in healthy individuals. However, neural correlates of impaired gait automaticity are poorly investigated in PD. OBJECTIVE: We aimed to examine the relationship between gait automaticity and striatal dopaminergic depletion in drug-naïve PD patients. METHODS: A total of 21 drug-naïve PD patients and 12 healthy controls were enrolled. Gait parameters were measured via wearable inertial sensors under fast-paced gait or cognitive dual-task conditions, and their respective coefficient of variation (CV) and dual-task cost were calculated. The extent of striatal dopaminergic depletion was evaluated by dopamine transporter (DAT) imaging with single-photon emission computed tomography using N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-[123 I]iodophenyl)nortropane. Correlation between DAT uptake and gait variables was analyzed using the region-of-interest analysis for the 3 right or left striatal regions and voxel-based analysis. RESULTS: PD had higher mean bilateral CV and dual-task cost of stride length than healthy controls. The mean bilateral CV of stride length was negatively correlated with DAT uptake in the bilateral executive regions of the striatum. Voxel-based analysis revealed a negative correlation between the mean bilateral CV of stride length and DAT uptake in the anteromedial striatum. CONCLUSIONS: Dopaminergic denervation in the anteromedial striatum, a part of the executive region, is associated with impaired gait automaticity in drug-naïve PD patients. This region may compensate for the posterior sensorimotor striatum, maintaining gait automaticity. © 2020 International Parkinson and Movement Disorder Society.

[Relationship between dynamic CT angiography-based collateral flow evaluation and outcome of patients with stroke induced by acute basilar artery occlusion].

OBJECTIVE: To evaluate the collateral flow in patients with ischemic stroke due to acute basilar artery occlusion by dynamic CT angiography and to predict the outcome after reperfusion therapy. METHODS: Forty-five patients with stroke due to acute basilar artery occlusion undergoing reperfusion treatment in the Second Affiliated Hospital of Zhejiang University School of Medicine during January 2012 and August 2016 were retrospectively reviewed. Univariate and binary logistic regression model were used to identify the independent predictors of patient's outcome, and the receiver operating characteristic (ROC) curve was used to determine the optimal threshold of the posterior circulation collateral score (PC-CS) in predicting the prognosis of the patients. RESULTS: Binary logistic regression analysis indicated that the baseline National Institutes of Health Stroke Scale (NIHSS) score (OR=0.886, 95% CI:0.802-0.979, P<0.05) and PC-CS (OR=1.962, 95%CI:1.026-3.752, P<0.05) were independent predictors of patient's outcome, and PC-CS 4.5 was the optimal threshold (AUC:0.837, sensitivity of 68.2%, specificity of 87.0%). CONCLUSIONS: Dynamic CT angiography based on CT perfusion imaging can be used to evaluate collaterals in posterior circulation, and to predict clinical outcome after reperfusion therapy in patients with acute basilar artery occlusion.

Significant elevation of serum caspase-3 levels in patients with intracerebral hemorrhage.

BACKGROUND: Caspase-3 is a potential marker of apoptosis. We investigated whether serum caspase-3 concentrations were increased and its association with severity and prognosis after intracerebral hemorrhage (ICH). METHODS: This prospective clinical study recruited 112 ICH patients and 112 healthy individuals. Serum was assayed for caspase-3 using enzyme-linked immunosorbent assay. Stroke severity was quantified by National Institute of Health Stroke Scale (NIHSS) and hematoma volume. Six-month outcome was measured by modified Rankin Scale. Analyses were performed using univariate and multivariate analyses. RESULTS: Patients had significantly higher serum caspase-3 concentrations than controls. Capase-3 concentrations correlated with NIHSS score and hematoma volume. Serum caspase-3 emerged as an independent predictor for 6-month mortality and bad prognosis (modified Rankin scale score>2). Based on receiver operating characteristic curve, caspase-3 concentrations showed similar prognostic value when compared with NIHSS score and hematoma volume. CONCLUSION: Serum caspase-3 concentrations are increased in ICH patients as well as correlate with clinical severity and prognosis.

The Prognostic Value of a Four-Dimensional CT Angiography-Based Collateral Grading Scale for Reperfusion Therapy in Acute Ischemic Stroke Patients.

OBJECTIVE: Leptomeningeal collaterals, which affects tissue fate, are still challenging to assess. Four-dimensional CT angiography (4D CTA) originated from CT perfusion (CTP) provides the possibility of non-invasive and time-resolved assessment of leptomeningeal collateral flow. We sought to develop a comprehensive rating system to integrate the speed and extent of collateral flow on 4D CTA, and investigate its prognostic value for reperfusion therapy in acute ischemic stroke (AIS) patients. METHODS: We retrospectively studied 80 patients with M1 ± internal carotid artery (ICA) occlusion who had baseline CTP before intravenous thrombolysis. The velocity and extent of collaterals were evaluated by regional leptomeningeal collateral score on peak phase (rLMC-P) and temporally fused intensity projections (tMIP) (rLMC-M) on 4D CTA, respectively. The cutoffs of rLMC-P and rLMC-M score for predicting good outcome (mRS score ≤ 2) were integrated to develop the collateral grading scale (CGS) (rating from 0-2). RESULTS: The CGS score was correlated with 3-months mRS score (non-recanalizers: ρ = -0.495, p = 0.01; recanalizers: ρ = -0.671, p < 0.001). Patients with intermediate or good collaterals (CGS score of 1 and 2) who recanalized were more likely to have good outcome than those without recanalization (p = 0.038, p = 0.018), while there was no significant difference in outcome in patients with poor collaterals (CGS score of 0) stratified by recanalization (p = 0.227). CONCLUSIONS: Identification of collaterals based on CGS may help to select good responders to reperfusion therapy in patients with large artery occlusion.

Association between Leukoaraiosis and Poor Outcome is not due to Reperfusion Inefficiency after Intravenous Thrombolysis.

Leukoaraiosis (LA) is associated with structural and functional cerebrovascular impairment, which may compromise the capacity of ischemic tissue to maximize reperfusion after intravenous thrombolysis (IVT). We aimed to determine whether severe LA is correlated with reperfusion inefficiency, which contributes to infarct growth and poor functional outcome. We analyzed data from our consecutive acute ischemic stroke (AIS) patients who had acquired baseline and 24-h follow-up diffusion- and perfusion-weighted imaging. Reperfusion was defined as reduction of ≥70 % of hypoperfusion lesion at 24 h from baseline. Severe LA was defined as Fazekas score 2 or 3 on FLAIR images. We investigated the relationship between severity of LA and reperfusion status. Multivariate statistical analysis was carried out for modeling the independent predictors of reperfusion, infarct growth, and functional outcome. Finally, 79 patients were included, among them 30 (37.97 %) had severe LA. Reperfusion was observed in 41 (51.89 %) patients, the proportion of reperfusion was very similar in patients with and without severe LA (53.33 vs 51.02 %, p = 1.000). Large artery occlusion was the only independent unfavorable predictor for reperfusion (OR = 0.202, 95 % confidence interval, 0.060-0.673; p = 0.014). Multiple linear regression analysis revealed that severe LA was independently associated with infarct growth (standardized coefficients = 0.191, p = 0.040). Severe LA was also an independent predictor of poor outcome (mRS ≥ 3) (OR = 4.004, 95 % confidence interval, 1.267-12.656, p = 0.018) after adjusting for reperfusion and baseline severity of stroke. Severe LA was associated with infarct growth and poor outcome independent of reperfusion status, which may expand the notion that LA contributes the intrinsic vulnerability of brain tissue to acute ischemic insults. The burden of LA may not serve as an imaging indicator of reperfusion inefficiency after IVT for AIS patients.

Defining Core and Penumbra in Ischemic Stroke: A Voxel- and Volume-Based Analysis of Whole Brain CT Perfusion.

Whole brain computed tomography perfusion (CTP) has the potential to select eligible patients for reperfusion therapy. We aimed to find the optimal thresholds on baseline CTP for ischemic core and penumbra in acute ischemic stroke. We reviewed patients with acute ischemic stroke in the anterior circulation, who underwent baseline whole brain CTP, followed by intravenous thrombolysis and perfusion imaging at 24 hours. Patients were divided into those with major reperfusion (to define the ischemic core) and minimal reperfusion (to define the extent of penumbra). Receiver operating characteristic (ROC) analysis and volumetric consistency analysis were performed separately to determine the optimal threshold by Youden's Index and mean magnitude of volume difference, respectively. From a series of 103 patients, 22 patients with minimal-reperfusion and 47 with major reperfusion were included. Analysis revealed delay time ≥ 3 s most accurately defined penumbra (AUC = 0.813; 95% CI, 0.812-0.814, mean magnitude of volume difference = 29.1 ml). The optimal threshold for ischemic core was rCBF ≤ 30% within delay time ≥ 3 s (AUC = 0.758; 95% CI, 0.757-0.760, mean magnitude of volume difference = 10.8 ml). In conclusion, delay time ≥ 3 s and rCBF ≤ 30% within delay time ≥ 3 s are the optimal thresholds for penumbra and core, respectively. These results may allow the application of the mismatch on CTP to reperfusion therapy.

Thrombus Length Estimation on Delayed Gadolinium-Enhanced T1.

BACKGROUND AND PURPOSE: Previous studies revealed a close relationship between thrombus length and recanalization rate after intravenous thrombolysis (IVT). As a novel approach, we prospectively adjusted the order of sequence acquisition to obtain delayed gadolinium-enhanced T1 (dGE-T1) and thereby assess thrombus length on dGE-T1 to evaluate its predictive value for recanalization after IVT. METHODS: We reviewed prospectively collected clinical and imaging data from acute ischemic stroke patients with middle cerebral artery occlusion who underwent multimodal magnetic resonance imaging before and 24 hours after IVT. Perfusion-weighted imaging was performed followed by conventional T1. We measured thrombus length on dGE-T1 and examined its association with middle cerebral artery recanalization. RESULTS: Of the included 74 patients, the median age was 66 years and 28 (37.8%) were women. Thrombus length was 8.18±4.56 mm on dGE-T1, which was an acceptable predictor for no recanalization (odds ratio, 1.196; 95% confidence interval, 1.015-1.409; P=0.033), with a receiver-operator characteristic of 0.732 (95% confidence interval, 0.619-0.845; P=0.001). The optimal cut-off point was identified at 6.77 mm, which yielded a sensitivity of 77.8%, a specificity of 57.9%, and an odds ratio of 4.81 (95% confidence interval, 1.742-13.292; P=0.002). Moreover, no one achieved recanalization after IVT when length of thrombus exceeded 14 mm on dGE-T1. CONCLUSIONS: The dGE-T1, obtained by simply adjusting scanning order in multimodal magnetic resonance imaging protocol, is a useful tool for thrombus length estimation and middle cerebral artery recanalization prediction after IVT.

Lower serum calcium level is associated with hemorrhagic transformation after thrombolysis.

BACKGROUND AND PURPOSE: We aim to investigate whether lower admission serum calcium levels are associated with hemorrhagic transformation (HT) after intravenous thrombolysis (IVT). METHODS: A total of 362 patients treated with IVT was divided into 4 quartiles based on admission serum calcium levels (Q1[<2.16], Q2[2.16, 2.23], Q3[2.24, 2.31], and Q4[>2.31] mmol/L). HT was classified as hemorrhagic infarction and parenchymal hemorrhage. Logistic regression was applied to assess the association between serum calcium levels and the incidence of HT. RESULTS: Compared with Q4, HT was more common in Q1 (odds ratio, 2.580; 95% CI, [1.258-5.292]; P=0.010), Q2 (odds ratio, 2.382; 95% CI, [1.163-4.877]; P=0.018), and Q3 (odds ratio, 2.293; 95% CI, [1.133-4.637]; P=0.021). Hemorrhagic infarction was more common in Q1 (P=0.037), and Q2 (P=0.018), compared with Q4, and parenchymal hemorrhage was more common in Q1 (P=0.029) than Q4. CONCLUSIONS: Lower admission serum calcium level is independently associated with HT after IVT, and this hypothesis needs larger confirmatory trials.

[Relationship between early blood pressure variability and reperfusion in acute ischemic stroke patients with intravenous thrombolysis].

OBJECTIVE: To investigate the impacts of blood pressure (BP) variability on reperfusion and long-term outcome in patients with acute ischemic stroke after intravenous thrombolysis (IVT). METHODS: The clinical data of 188 patients with acute ischemic stroke receiving IVT in Department of Neurology, the Second Affiliated Hospital, Zhejiang University School of Medicine from June 2009 to September 2014, including hour-to-hour BP measurements, clinical manifestations, laboratory tests and radiologic findings were retrospectively analyzed. The mean 24-h BP values, and BP variability profiles, including standard deviation (sd), average squared difference between successive measurements (sv), average squared difference between rise and drop successive measurements (sv-rise and sv-drop) were calculated. Reperfusion, defined as >50% reduction in Tmax >6 s perfusion lesion volume from baseline to follow-up scans, and clinical neurological outcome based on modified Rankin scale (mRS) at 3 months after onset were also analyzed. The favorable outcome was defined as mRS 0-1 and unfavorable outcome as mRS 2-6. The binary logistic-regression model was performed to determine the independent risk factors of reperfusion and favorable outcome, respectively. RESULTS: Among 188 patients, 114 (60.6%) achieved reperfusion. During the 0-to-24 h blood pressure course, only systolic blood pressure (SBP) variability parameters were negatively correlated with reperfusion (sv: OR=0.421, 95% CI:0.187-0.950, P=0.037; sv-rise: OR=0.311, 95% CI:0.137-0.704, P=0.005) and long-term clinical outcomes (sv: OR=6.381, 95% CI:2.132-19.096, P=0.001; sv-rise: OR=5.615, 95% CI:2.152-14.654, P<0.001; sv-drop: OR=3.009, 95% CI:1.263-7.169, P=0.013). CONCLUSION: SBP variability during the first 24 hours after IVT is negatively associated with cerebral reperfusion and unfavorable neurological outcome in patients with acute ischemic stroke receiving IVT.

[Thrombus length evaluated by CT perfusion imaging and its value in prediction of recanalization after intravenous thrombolysis therapy].

OBJECTIVE: To evaluate the thrombus length on CT perfusion imaging and to assess its predictive value for recanalization and clinical outcome after intravenous thrombolysis therapy (IVT). METHODS: Fifty-six consecutive acute ischemic stroke patients with proximal middle cerebral artery (M1 segment) occlusion underwent CT perfusion imaging examination before IVT between June 2009 and May 2015. The onset-to needle time was (214.3 ± 82.0) min, and the pretreatment NIHSS score of patients was 13 (IQR 8-17). The thrombus length was determined as the distance between the proximal and distal thrombus end delineated on dynamic angiography, which was reconstructed from CT perfusion source images. Recanalization was evaluated according to Arterial Occlusive Lesion (AOL) scale, and functional outcome was based on modified Rankin scale (mRS) 3 months after IVT. Logistic regression model was used to investigate the relationship between thrombus length and recanalization, and the optimal cut-off points were determined by receiver operating characteristic curve (ROC). RESULTS: Among 56 patients, 42 (75%) achieved recanalization 24 h after IVT with mean thrombus length of (9.0 ± 4.7) mm; and 14 (25%) patients remained occlusion with mean thrombus length of (10.0 ± 5.4) mm. Logistic regression analysis demonstrated that thrombus length was an independent predictor for both recanalization (OR=0.869; 95% CI:0.764-0.987; P=0.031) and unfavorable outcome (OR=1.180;95% CI:1.023-1.362; P=0.023). Thrombus length of 11.3 mm was identified as the optimal cut-off value for recanalization (AUC=0.697, sensitivity 71.4%, specificity 76.2%), while thrombus length of 9.9 mm was the optimal cut-off value for unfavorable functional outcome (AUC=0.689, sensitivity 64.7%, specificity 71.4%). CONCLUSION: The thrombus length evaluated on CT perfusion imaging is an effective predictor for recanalization and unfavorable outcome after IVT in acute ischemic stroke patients with middle cerebral artery occlusion.