Intravenous thrombolysis for patients with reverse magnetic resonance angiography and diffusion-weighted imaging mismatch: SAMURAI and NCVC rt-PA Registries.

BACKGROUND AND PURPOSE: The characteristics of reverse magnetic resonance angiography and diffusion-weighted imaging (MRA-DWI) mismatch (RMM), defined as a large DWI lesion in the absence of major artery occlusion (MAO), remain unknown, especially in patients treated with intravenous recombinant tissue plasminogen activator (rt-PA). METHODS: Patients with stroke in the middle cerebral artery territory were included. Early ischaemic changes (EIC) were assessed with the Alberta Stroke Program Early CT Score on DWI (DWI-ASPECTS). All patients were divided into four groups based on the presence of MAO and a DWI-ASPECTS cut-off value of <7. RMM was defined as DWI-ASPECTS <7 without MAO. Clinical characteristics, symptomatic intracerebral hemorrhage (sICH) and favorable functional outcome (modified Rankin Scale score 0-2) at 90 days were compared amongst the four groups. RESULTS: Of the 486 patients enrolled (167 women, median age 74 years, median initial National Institutes of Health Stroke Scale score 13), reverse MRA-DWI mismatch was observed in 24 (5%). Of the clinical characteristics, cardioembolism was the only factor that was independently associated with RMM [odds ratio (OR) 5.49, 95% confidence interval (CI) 1.25-24.1]. Multivariable analyses revealed that patients with RMM more commonly had sICH than those with DWI-ASPECTS ≥ 7 irrespective of the presence (OR 5.44, 95% CI 1.13-26.1) or absence (13.1, 2.07-83.3) of MAO, and they had a more favorable functional outcome than those with DWI-ASPECTS < 7 plus MAO (7.45, 2.39-23.2). CONCLUSION: RMM was observed in 5% of patients treated with rt-PA and associated with cardioembolism. Patients with RMM may benefit from thrombolysis compared with those with EIC with MAO, although increment in the rate of sICH is a concern.

Run-up to participation in ATACH II in Japan.

Intracerebral hemorrhage (ICH) is a major cause of morbidity and mortality in Japan. Seventeen Japanese institutions are participating in the Antihypertensive Treatment for Acute Cerebral Hemorrhage (ATACH) II Trial (ClinicalTrials.gov no. NCT01176565; UMIN 000006526). This phase III trial is designed to determine the therapeutic benefit of early intensive systolic blood pressure (BP) lowering for acute hypertension in ICH patients. This report explains the long run-up to reach the start of patient registration in ATACH II in Japan, including our preliminary study, a nationwide survey on antihypertensive treatment for acute ICH patients, a multicenter study for hyperacute BP lowering (the SAMURAI-ICH study), revision of the official Japanese label for intravenous nicardipine, and construction of the infrastructure for the trial.

Pretreatment ASPECTS on DWI predicts 3-month outcome following rt-PA: SAMURAI rt-PA Registry.

OBJECTIVE: To evaluate whether the pretreatment Alberta Stroke Programme Early CT Score (ASPECTS) assessed using diffusion-weighted imaging (DWI) predicts stroke outcomes at 3 months following IV recombinant tissue-type plasminogen activator (rt-PA) therapy. METHODS: Stroke patients treated with rt-PA (0.6 mg/kg alteplase) in 10 stroke centers in Japan were retrospectively studied. ASPECTS was assessed on DWI just prior to rt-PA injection. The primary outcome was a modified Rankin Scale (mRS) score of 0-2 at 3 months. Secondary outcomes included death at 3 months and symptomatic intracerebral hemorrhage (sICH) within 36 hours. RESULTS: For the 477 patients (316 men, 71 +/- 11 years old) enrolled, the median NIH Stroke Scale score was 13 (interquartile range 7-18.5), the median ASPECTS on DWI was 8 (7-10), and sICH was identified in 15 patients (3.1%). At 3 months, 245 (51.4%) had an mRS score of 0-2, and 29 (6.1%) had died. Patients with an mRS score of 0-2 had higher median ASPECTS (9; interquartile range 8-10) than other patients (8; 6-9, p < 0.001). Using receiver operating characteristic curves, the optimal cutoff ASPECTS to predict an mRS score of 0-2 was > or =7. On multivariate regression analysis, ASPECTS > or =7 was related to an mRS score of 0-2 (odds ratio 1.85; 95% confidence interval 1.07-3.24), ASPECTS < or =4 was related to death (3.61; 1.23-9.91), and ASPECTS < or =5 was related to sICH (4.74; 1.54-13.64). CONCLUSION: ASPECTS on DWI was independently predictive of functional and vital outcomes at 3 months, as well as sICH within 36 hours, following rt-PA therapy for stroke patients.

A Newly Developed 3 cm Marker Balloon Microcatheter.

SUMMARY: No balloon microcatheter with a 3 cm marker has been developed to date.We developed a new balloon microcatheter with a double marker. This balloon microcatheter, with an outer diameter of 2.8 F, has a balloon on the most distal portion with a maximum inflation diameter of 4 mm and two markers, one is on the tip and the other is 3 cm proximal to the tip. This balloon microcatheter would make interventional procedures, especially for parent artery occlusion, simple to perform and safer.

Long-term effect of intravenous immunoglobulin on anti-MuSK antibody-positive myasthenia gravis.

Anti-muscle-specific receptor tyrosine kinase (MuSK) antibody-positive myasthenia gravis (MG) patients show various responses to conventional immunosuppressive treatment and some patients are resistant to these therapies. We report a 50-year-old Japanese man with anti-MuSK antibody-positive MG, who showed no or poor response to various therapies, including plasmapheresis, corticosteroid, and tacrolimus. The patient was then treated with intravenous immunoglobulin (IVIG), and showed a good response that persisted over 20 months. The outcome of this case suggests that IVIG treatment may be an effective therapeutic option for anti-MuSK antibody-positive MG, with a potentially long-term effect.

Periprocedural monitoring with regional cerebral oxygen saturation in carotid artery stenting.

SUMMARY: Hemodynamic instability during and after carotid artery stenting (CAS) may reduce cerebral blood flow (CBF), leading to cerebral ischemia. To investigate changes in CBF in the periprocedural period, we continuously recorded the regional cerebral oxygen saturation (rSO2) using near-infrared spectroscopy. In 46 consecutive patients with carotid artery stenosis, rSO2 was continuously recorded during and after CAS. In addition, the patients underwent SPECT to evaluate a change in CBF on the next day after CAS. Introprocedural bradycardia (heart rate < 50 bpm) occurred in 21 patients (46%) including one transient cardiac arrest. Intraprocedural hypotension (systolic blood pressure < 80 mmHg) occurred in 18 patients (39%), and 16 of them showed prolonged hypotension. The rSO2 in patients with bradycardia/hypotension during CAS was significantly less than that in patients without them (p < 0.01). Moreover, the SPECT on the next day after CAS demonstrated that the ipsilateral CBF in patients with bradycardia/hypotension during CAS significantly more than that in patients without them (p < 0.05). Intraprocedural hemodynamic instability resulted in a significant decrease in rSO2, leading to a possible severe cerebral ischemia. In addition, intraprocedural bradycardia/hypotension might be related with postprodedural hyperperfusion, causing the morbidity and mortality after CAS.

"Tail sign" associated with microembolic signals.

BACKGROUND AND PURPOSE: Transcranial Doppler ultrasound (TCD) can detect circulating microembolic signals (MES). We focused our attention on tail signs (TS), a signal associated with MES that appeared as a small reversal signal after MES on the high time resolution spectral display. We examined MES and artifacts in an animal study to determine whether TS were specific changes associated with MES and investigated the characteristics of TS in both animal and clinical studies. METHODS: In an animal study, adult pigs with venoarterial extracorporeal membrane oxygenation and minimal anticoagulation therapy were used as a model for cerebral embolism. After performing TCD monitoring with a multigated approach, we did an offline analysis to investigate several parameters concerning MES and TS. We also examined TS in patients in a clinical study. RESULTS: From a total of 362 MES investigated in the animal study, 72.9% were followed by TS. We could not find any TS associated with artifacts. The time delay between TS and MES was negatively correlated with the velocity of MES. MES almost always appeared first in the proximal channel, whereas TS conversely appeared first in the distal channel. In the clinical study, we were also able to observe TS associated with MES. CONCLUSIONS: TS may represent emboli passing down a branch vessel or twisted downstream vessel. TS are specific for MES and can be used as another criterion for MES identification.

[Cerebral embolism due to left atrial ball thrombus without mitral stenosis--usefulness of the transesophageal echocardiography for the diagnosis].

We reported two cases of cerebral embolism associated with atrial fibrillation. Left atrial ball thrombus without mitral stenosis was diagnosed by the transesophageal echocardiography, followed by successful removal. Left atrial ball thrombus has a risk for lethal complications, and a high incidence of systemic embolism even during anticoagulation therapy. An immediate surgical treatment is needed. The transthoracic echocardiography is not useful in diagnosis for left atrial ball thrombus. It is important to examine left atrial ball thrombus by the transesophageal echocardiography in patients with cerebral embolism associated with atrial fibrillation.

Familial limb-girdle myasthenia with tubular aggregates.

Two sisters developed slowly progressive limb-girdle weakness in their childhood. The weakness responded to acetylcholinesterase inhibitors. Repetitive nerve stimulation showed decremental responses and single-fiber electromyography demonstrated increased jitter and blocking. Needle electromyography revealed myopathic changes. Antiacetylcholine receptor antibodies were negative. Histologic examinations demonstrated myopathy with tubular aggregates in the muscle fibers while the neuromuscular junctions appeared normal. They were diagnosed with familial limb-girdle myasthenia. This is the first report of this syndrome with morphologic studies of neuromuscular junctions.

[A case of myasthenia gravis associated with long-term phenytoin therapy].

A 22-year-old woman had been suffering from blepharoptosis and fatigabilities of both shoulders for a year. She had been administered phenytoin since age 4 to prevent febrile convulsion. On admission, she had bilateral blepharoptosis with left one being more severely affected. Her pupils and eye movement were normal. Other cranial nerve functions were normal. Her both deltoid muscles were mildly weak. A repetitive stimulation study revealed a 35% decline of the evoked responses recorded from either the orbicularis oculi or the abductor pollicis brevi muscle. Antibody activity for acetylcholine receptor was higher than normal range. Her blepharoptosis transiently disappeared after an intravenous administration of 5mg of edrophonium. She was diagnosed as having myasthenia gravis. Her myasthenic signs had continued one month after phenytoin withdrawal, then an extended thymectomy was done. The thymus was histologically hypertrophic. Although a direct blocking at a neuromuscular junction by phenytoin has been reported in animal experiments, our case is not likely to be affected by this effect. Since a large population of young epileptic patients needs a long-term phenytoin therapy, detailed investigation is necessary to elucidate how frequently they manifest myasthenia gravis.

[Fornix transection stimulates locus coeruleus neurons transplanted in the rat hippocampus to increase noradrenaline].

Fetal noradrenergic neurons from the brain stem locus coeruleus region were transplanted, as a cell suspension, into the hippocampus of rats. Adult male rats were subjected to removal of the superior cervical ganglia and were used as recipients. In the fornix transection (FT) group, rats were sacrificed before fornix transection, or received fornix transection and were sacrificed 3, 5 or 7 weeks after fornix transection. In the transplantation (TP)-FT group, rats received transplants 3 weeks before fornix transection and were sacrificed 3, 5 or 7 weeks after fornix transection. In the FT-TP group rats received transplants a week after fornix transection and were sacrificed 7 weeks after fornix transection. At sacrifice, the noradrenaline (NA) concentration in the hippocampus was measured. The differences in the NA concentration between the FT group and either the TP-FT group or the FT-TP group were statistically significant 7 weeks after fornix transection, respectively. Results suggested that the fornix transection stimulates transplanted neurons to increase NA. This stimulation depended not on the time after transplantation but on the time after fornix transection.

[Acute deterioration of myasthenia gravis in association with tuberculous mediastinal lymphadenitis, simulating recurrence of thymoma. A case report].

We reported a unique case of myasthenia gravis in association with tuberculous mediastinal lymphadenitis. A 56-year-old man suffering from generalized myasthenia gravis underwent thymothymectomy followed by good clinical recovery for 2 years. Thereafter, the patient complained of acute onset of ptosis, diplopia, dysphagia and limb weakness with elevated titers of serum anti-acetylcholine receptor antibody. CT scans of the chest showed a mediastinal lymphadenopathy and the Thallium-201 SPECT revealed an abnormal mediastinal accumulation, suggesting recurrence of thymoma in the mediastinal lymphonode. Histologically, the re-operated mediastinal tumor was of tuberculous lymphadenitis. This patient gives us a caution that we must guard against errors in differentiation between thymoma and tuberculous mediastinal lymphadenitis, particularly when myasthenic patients with mediastinal tumors are expected to receive the corticosteroids therapy. (120 words).