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To investigate the effect of alteplase, either combined with stent-retriever thrombectomy or a direct aspiration first pass technique (ADAPT), in patients with large-vessel occlusion stroke. This was a retrospective post hoc analysis of data from The Direct Mechanical Thrombectomy in Acute LVO Stroke (SKIP) study. Patients were divided into two groups according to the first-line thrombectomy technique: stent-retriever and ADAPT. Each group was further divided into two subgroups, namely MT and MT + alteplase. The procedural outcomes, such as first pass effect (FPE) ratio and number of passes, were evaluated. The clinical outcomes included mRS score at 3 months. A total of 180 patients were included (116 in the stent-retriever group and 64 in the ADAPT group). No interaction was detected between the first-line technique and alteplase administration. In the stent-retriever group, after adjusting for factors associated with FPE, the adjusted odds ratio (95% confidence interval) of FPE of the MT + alteplase subgroup versus the MT subgroup was 3.57 (1.5–8.48) and in the ADAPT group it was 1.35 (0.37–4.91). With alteplase, the number of passes decreased with adjusted odds ratios of 0.59 (0.37–0.93) in the stent-retriever group but not in the ADAPT group. In both first-line technique groups, clinical outcomes did not differ between subgroups. In the SKIP study, alteplase administration was associated with increased FPE when combined with stent-retriever thrombectomy, but not with ADAPT. We found no differences in the clinical outcomes.

Rationale Bridging therapy with endovascular therapy (EVT) and intravenous thrombolysis (IVT) has been reported to improve outcomes for acute stroke patients with large-vessel occlusion in the anterior circulation. While the IVT may increase the reperfusion rate, the risk of hemorrhagic complications increases. Whether EVT without IVT (direct EVT) is equally effective as bridging therapy in acute stroke remains unclear. Aim This randomized study of endovascular therapy with versus without intravenous tissue plasminogen activator for acute stroke with ICA and M1 occlusion aims to clarify the efficacy and safety of direct EVT compared with bridging therapy. Methods and design This is an investigator-initiated, multicenter, prospective, randomized, open-treatment, blinded-endpoint clinical trial. The target patient number is 200, comprising 100 patients receiving direct EVT and 100 receiving bridging therapy. Study outcome The primary efficacy endpoint is a modified Rankin Scale score of 0–2 at 90 days. Safety outcome measures are any intracranial hemorrhage at 24 h. Discussion This trial may help determine whether direct EVT should be recommended as a routine clinical strategy for ischemic stroke patients within 4.5 h from onset. Direct EVT would then become the choice of therapy in stroke centers with endovascular facilities. Trial registration UMIN000021488.

The epidemiology of patients with traumatic brain injury (TBI) has changed dramatically over recent decades as a result of rapid advances in aging societies. We assessed the influence of age on outcomes of patients with TBI and sought to identify prognostic factors for in-hospital mortality of TBI among elderly patients.Using a nationwide database, we analyzed data from 5651 patients with TBI. Univariate analysis was conducted to compare patient demographics, neurologic status on admission, radiologic findings, systemic complication rates, length of hospital stay, in-hospital mortality, and home discharge rates between elderly and nonelderly groups. Multivariable analysis was conducted to determine prognostic factors for in-hospital mortality among elderly patients.Overall in-hospital mortality was significantly higher in elderly patients (12.8% vs. 19.3%; P0.001). In-hospital mortality of elderly patients with mild TBI increased significantly at7 days after admission, whereas that of elderly patients with moderate or severe TBI was significantly higher immediately after admission. Age (odds ratio [OR], 1.62; P = 0.024), male sex (OR, 1.30; P = 0.004), Japan Coma Scale score on admission (OR, 5.95, P0.001), and incidence of acute subdural hematoma (OR, 1.89; P0.001) were associated with in-hospital mortality in elderly patients with TBI.Elderly patients with TBI showed significantly higher in-hospital mortality. Delayed increases in in-hospital mortality were observed among elderly patients with mild TBI. Level of consciousness on admission was the strongest predictor of in-hospital mortality among elderly patients.

Supplemental Material for The randomized study of endovascular therapy with versus without intravenous tissue plasminogen activator in acute stroke with ICA and M1 occlusion (SKIP study) by Kentaro Suzuki, Kazumi Kimura, Masataka Takeuchi, Masafumi Morimoto, Ryuzaburo Kanazawa, Yuki Kamiya, Keigo Shigeta, Norihiro Ishii, Yohei Takayama, Yorio Koguchi, Tomoji Takigawa, Mikito Hayakawa, Takahiro Ota, Seiji Okubo, Hiromichi Naito, Kazunori Akaji, Noriyuki Kato, Masato Inoue, Teruyuki Hirano, Kazunori Miki, Toshihiro Ueda, Yasuyuki Iguchi, Shigeru Fujimoto, Toshiaki Otsuka and Yuji Matsumaru in International Journal of Stroke

Importance Whether intravenous thrombolysis is needed in combination with mechanical thrombectomy in patients with acute large vessel occlusion stroke is unclear. Objective To examine whether mechanical thrombectomy alone is noninferior to combined intravenous thrombolysis plus mechanical thrombectomy for favorable poststroke outcome. Design, Setting, and Participants Investigator-initiated, multicenter, randomized, open-label, noninferiority clinical trial in 204 patients with acute ischemic stroke due to large vessel occlusion enrolled at 23 hospital networks in Japan from January 1, 2017, to July 31, 2019, with final follow-up on October 31, 2019. Interventions Patients were randomly assigned to mechanical thrombectomy alone (n = 101) or combined intravenous thrombolysis (alteplase at a 0.6-mg/kg dose) plus mechanical thrombectomy (n = 103). Main Outcomes and Measures The primary efficacy end point was a favorable outcome defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 2 at 90 days, with a noninferiority margin odds ratio of 0.74, assessed using a 1-sided significance threshold of .025 (97.5% CI). There were 7 prespecified secondary efficacy end points, including mortality by day 90. There were 4 prespecified safety end points, including any intracerebral hemorrhage and symptomatic intracerebral hemorrhage within 36 hours. Results Among 204 patients (median age, 74 years; 62.7% men; median National Institutes of Health Stroke Scale score, 18), all patients completed the trial. Favorable outcome occurred in 60 patients (59.4%) in the mechanical thrombectomy alone group and 59 patients (57.3%) in the combined intravenous thrombolysis plus mechanical thrombectomy group, with no significant between-group difference (difference, 2.1% [1-sided 97.5% CI, −11.4% to ∞]; odds ratio, 1.09 [1-sided 97.5% CI, 0.63 to ∞];P = .18 for noninferiority). Among the 7 secondary efficacy end points and 4 safety end points, 10 were not significantly different, including mortality at 90 days (8 [7.9%] vs 9 [8.7%]; difference, –0.8% [95% CI, –9.5% to 7.8%]; odds ratio, 0.90 [95% CI, 0.33 to 2.43];P > .99). Any intracerebral hemorrhage was observed less frequently in the mechanical thrombectomy alone group than in the combined group (34 [33.7%] vs 52 [50.5%]; difference, –16.8% [95% CI, –32.1% to –1.6%]; odds ratio, 0.50 [95% CI, 0.28 to 0.88];P = .02). Symptomatic intracerebral hemorrhage was not significantly different between groups (6 [5.9%] vs 8 [7.7%]; difference, –1.8% [95% CI, –9.7% to 6.1%]; odds ratio, 0.75 [95% CI, 0.25 to 2.24];P = .78). Conclusions and Relevance Among patients with acute large vessel occlusion stroke, mechanical thrombectomy alone, compared with combined intravenous thrombolysis plus mechanical thrombectomy, failed to demonstrate noninferiority regarding favorable functional outcome. However, the wide confidence intervals around the effect estimate also did not allow a conclusion of inferiority. Trial Registration umin.ac.jp/ctr Identifier:UMIN000021488

We studied 33 patients with thromboembolic stroke in carotid territory treated with superselective intra-arterial fibrinolysis with aspecial attention to collateral flows and residual cerebral blood flow (CBF). Patients were divided into four subgroups by the location of thromboembolus. Group M2 with occlusion at M2 or more distal portion of the middle cerbral artery (MCA) contained 13 patients. Group MI-D with occlusion at distal M1 portion of MCA, without ischemia of perforators' area of MCA, comprised 9 patients. Group M1-P with occlusion at proximal M1, with ischemia of perforators' area, consisted of 8 patients. Group IC with occlusion at the intracranial internal carotid artery contained 4 patients. Collateral flows and residual CBF were evaluated by angiography, dynamic CT and SPECT.100% of patients in Group M2 and 78% of Group MI-D had favorable outcome. However, 57% in Group M1-P and 50% in GroupIC were unfavorable, especially 43% in the former and 25% in the latter died because of hemorrhagic transformation. The evaluations of angiography, dynamic CT and SPECT showed poor collateral flows and residual CBF in all unfavorable patients.We conclude that locations of thromboembolus, collateral flows and residual CBF, as well as the time from onset, are very important factors in indication for acute fibrinolytic therapy in thromboembolic stroke in carotid territory.

Objective: To describe an unusual symptom characterized by an inability to stand still despite the ability to walk in eight patients with paraparesis due to peripheral neuropathy. Design: Case series during the past 18 years. Setting: Referral center. Patients: Six patients with acute or subacute polyneuropathies recovering from flaccid paralysis of the lower limbs and two patients with chronic progressive polyneuropathy for more than 10 years were studied. Weakness around the ankle joints was profound, while muscle strength around the hip joints was well recovered or preserved. Main Outcome Measures: Standing and walking were recorded and reviewed on videotape or motion pictures. Spectral content of postural sway was analyzed in three recent cases. Results: The symptom was transient in acute or subacute cases and was continual in chronic cases. The patients were compelled to take a series of steps forward and backward while standing until they initiated locomotion. They swayed rapidly around the hip joints before stepping. The anteroposterior component of postural sway in three patients had frequency peaks around 1 Hz. Conclusion: We have termed this symptom astasiawithout abasia, orstilts phenomenon, in which maintenance of the body mass depends on a moving base of support. Both an abnormal pattern of postural movements and defective somatosensory feedback for postural stabilization may be responsible for the symptom.

We measured the concentration of neural thread protein (NTP) in cerebrospinal fluid (CSF) by an automatized microparticle enzyme immunoassay from 11 progressive supranuclear palsy (PSP) patients and 11 Parkinson's disease (PD) patients and 7 patients with cervical spondylosis as controls. The mean levels did not differ significantly among the groups. In the PSP group, however, the levels correlated significantly with the severity of motor symptoms, signs and functional disability but not with dementia, while the opposite was true in the PD group. The elevated levels in PSP cases may reflect an increase with progression of the disease in such pathological structures as neurofibrillary tangles or neuropil threads, while in PD such levels may indicate associated Alzheimer-type pathology.

We presented a report on four cases of juvenile parkinsonism with a marked diurnal fluctuation of symptoms and dystonia. Among parkinsonian signs, rigidity fluctuated the most and increasing rigidity by passive or active movements or emotional stress was observed. When we analyzed patients previously reported, in addition to our own new patients, apart from the diurnal fluctuation and predominant occurrence in females, many similarities to Yokochi's third group of juvenile parkinsonism were found. In the previous reports, the patients with the marked fluctuation of parkinsonian symptoms have not always shown dystonia. The changes of symptoms in relation to menstruation and pregnancy were other characteristic features in our three female patients. Here we proposed that for the present, it is preferable to call this disorder "juvenile parkinsonism with a marked diurnal fluctuation."