Multicenter Prospective Analysis of Stroke Patients Taking Oral Anticoagulants: The PASTA Registry - Study Design and Characteristics.

OBJECTIVES: The management of atrial fibrillation and deep venous thrombosis has evolved with the development of direct oral anticoagulants (DOAC), and oral anticoagulant (OAC) might influence the development or clinical course in both ischemic and hemorrhagic stroke. However, detailed data on the differences between the effects of the prior prescription of warfarin and DOAC on the clinical characteristics, neuroradiologic findings, and outcome of stroke are limited. DESIGN: The prospective analysis of stroke patients taking anticoagulants (PASTA) registry study is an observational, multicenter, prospective registry of stroke (ischemic stroke, transient ischemic attack, and intracerebral hemorrhage) patients receiving OAC in Japan. This study is designed to collect data on clinical background characteristics, drug adherence, drug dosage, neurological severity at admission and discharge, infarct or hematoma size, acute therapy including recanalization therapy or reverse drug therapy, and timing of OAC re-initiation. Patient enrollment started in April 2016 and the target patient number is 1000 patients. CONCLUSIONS: The PASTA prospective registry should identify the status of stroke patients taking OAC in the current clinical practice in Japan.

Emergent Large Vessel Occlusion Screen Is an Ideal Prehospital Scale to Avoid Missing Endovascular Therapy in Acute Stroke.

Background and Purpose- The strong evidence of endovascular therapy in acute ischemic stroke patients with large vessel occlusion (LVO) is revealed. Such patients are required to direct transport to the hospital capable of endovascular therapy. There are several prehospital scales available for paramedics to predict LVO. However, they are time consuming, and several of them include factors caused by other types than LVO. Therefore, we need a fast, simple, and reliable prehospital scale for LVO. Methods- We developed a new prehospital stroke scale, emergent large vessel occlusion (ELVO) screen, for paramedics to predict LVO. The study was prospectively performed by multistroke centers. When paramedics referred to stroke center to accept suspected stroke patients, we obtain the following information over the telephone. ELVO screen was designed focusing on cortical symptoms: 1 observation; presence of eye deviation and 2 questions; paramedics show glasses, what is this? and paramedics show 4 fingers, how many fingers are there? If the presence of eye deviation or ≥1 of the 2 items were incorrect, ELVO screen was identified as positive. We evaluated between results of ELVO screen and presence of LVO on magnetic resonance angiography at hospital arrival. Results- A total of 413 patients (age, 74±13 years; men, 234 [57%]) were enrolled. Diagnosis was ischemic stroke, 271 (66%); brain hemorrhage 73 (18%); subarachnoid hemorrhage, 7 (2%); and not stroke, 62 (15%). One hundred fourteen patients had LVO (internal carotid artery, 33 [29%]; M1, 52 [46%]; M2, 21 [18%]; basilar artery, 5 [4%]; P1, 3 [3%]). Sensitively, specificity, positive predictive value, negative predictive value, and accuracy for ELVO screen to predict LVO were 85%, 72%, 54%, 93% and 76%, respectively. Among 233 patients with negative ELVO screen, only 17 (7%) had LVO, which indicated to be an ideal scale to avoid missing endovascular therapy. Conclusions- The ELVO screen is a simple, fast, and reliable prehospital scale for paramedics to identify stroke patients with LVO for whom endovascular therapy is an effective treatment.

Brainstem infarction with wall-eyed bilateral internuclear ophthalmoplegia syndrome and vertical one-and-a-half syndrome.

We describe a rare case in which both wall-eyed bilateral internuclear ophthalmoplegia syndrome and vertical one-and-a-half syndrome were observed in a 68-year-old man with acute ischemic stroke. Concurrent horizontal and vertical gaze palsies are rare because the corresponding gaze centers are anatomically separated. The complicated gaze palsies observed in this patient might have resulted from long, vertical lesions affecting oculomotor pathways for both sides of the brain stem.

Prior direct oral anticoagulant dosage and outcomes in patients with acute ischemic stroke and non-valvular atrial fibrillation: A sub-analysis of PASTA registry study.

BACKGROUND AND PURPOSE: Prescribing under-dose direct oral anticoagulants (DOACs) for non-valvular atrial fibrillation (NVAF) is alerted to increase cardiovascular events or death. However, the association between dose selection of DOACs and the clinical course remains unclear. This study aimed to propose a novel criterion for selecting the DOAC dose and investigate clinical characteristics of ischemic stroke (IS) under this criterion. METHODS: We assessed the pooled prospective multicenter registry data of stroke patients taking anticoagulant agents, including IS patients with NVAF and prior DOAC usage. The recommended dose according to the reduction criteria of each DOAC and the selected dose were identified for each patient, and patients were categorized into four groups: no alternative low-dose, selecting low-dose appropriately with all DOACs applicable for reduction criteria; selected low-dose, selecting low-dose appropriately or inappropriately despite at least one DOAC inapplicable for reduction criteria; selected standard-dose, appropriate standard-dose use; and absolute over-dose, inappropriate standard-dose regardless of criteria. We investigated the effects of dose selection of DOACs on short-term poor functional outcomes. RESULTS: 322 patients were included in the analysis. The prevalence of no alternative low-dose, selected low-dose, selected standard-dose, and absolute over-dose was 74 (23%), 144 (45%), 89 (27%), and 15 (5%), respectively. Multivariable analysis found that the selected low-dose group showed significantly poorer functional outcomes than the selected standard-dose group only in patients without renal dysfunction (OR, 2.60; 95% CI, 1.17-6.00; P = 0.0186). CONCLUSIONS: Selecting a low dose DOAC might be associated with poor functional outcomes in patients without renal dysfunction.

Characteristics of Ischemic Versus Hemorrhagic Stroke in Patients Receiving Oral Anticoagulants: Results of the PASTA Study.

Objective Limited data exist regarding the comparative detailed clinical characteristics of patients with ischemic stroke (IS)/transient ischemic attack (TIA) and intracerebral hemorrhage (ICH) receiving oral anticoagulants (OACs). Methods The prospective analysis of stroke patients taking oral anticoagulants (PASTA) registry, a multicenter registry of 1,043 stroke patients receiving OACs [vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulant (NOACs)] across 25 medical institutions throughout Japan, was used. Univariate and multivariable analyses were used to analyze differences in clinical characteristics between IS/TIA and ICH patients with atrial fibrillation (AF) who were registered in the PASTA registry. Results There was no significant differences in cardiovascular risk factors, such as hypertension, diabetes mellitus, dyslipidemia, smoking, or alcohol consumption (all p>0.05), between IS/TIA and ICH among both NOAC and VKA users. Cerebral microbleeds (CMBs) [odds ratio (OR), 4.77; p<0.0001] were independently associated with ICH, and high brain natriuretic peptide/N-terminal pro B-type natriuretic peptide levels (OR, 1.89; p=0.0390) were independently associated with IS/TIA among NOAC users. A history of ICH (OR, 13.59; p=0.0279) and the high prothrombin time-international normalized ratio (PT-INR) (OR, 1.17; p<0.0001) were independently associated with ICH, and a history of IS/TIA (OR, 3.37; 95% CI, 1.34-8.49; p=0.0101) and high D-dimer levels (OR, 2.47; 95% CI, 1.05-5.82; p=0.0377) were independently associated with IS/TIA among VKA users. Conclusion The presence of CMBs, a history of stroke, natriuretic peptide and D-dimer levels, and PT-INR may be useful for risk stratification of either IS/TIA or ICH development in patients with AF receiving OACs.

Risk factors, etiology, and outcome of ischemic stroke in young adults: A Japanese multicenter prospective study.

PURPOSE: This study aimed to evaluate the risk factors, etiology, and outcomes of ischemic stroke (IS) in Japanese young adults. METHODS: This was a prospective multicenter study. We enrolled patients aged 16 to 55 years with IS within seven days of the onset of symptoms. We assessed the demographic data, risk factors, stroke etiology, and outcome at discharge. The clinical characteristics were compared between sexes and among age groups. RESULTS: We prospectively enrolled 519 patients (median age, 48 years: 139 females). The mean National Institute of Health Stroke Scale score was 3.6 ± 0.2. The most common risk factors were hypertension (HT) (55%), dyslipidemia (DL) (47%), and current smoking (42%). Body mass index, incidence of current smoking, and heavy alcohol consumption were higher in males. The prevalence of current smoking, HT, DL, and diabetes mellitus increased with aging. The most common etiologic subgroup of IS was small vessel disease (145/510, 28%). Intracranial arterial dissection (IAD) was the most common among the other determined causes (56/115, 49%). The outcome at discharge was relatively good (mRS 0-1, 71.7%); however, poor outcome (mRS ≥ 4) was observed at an incidence of 9.5%. CONCLUSIONS: Most young adults with IS had modifiable risk factors, of which prevalence increased with age. This emphasizes lifestyle improvement to prevent IS in the young population. Furthermore, we indicated that the incidence rate of IAD was high among the other determined causes.

Nicotinic acid treatment for Paralepistopsis acromelalga intoxication: assessment using magnetic resonance imaging.

CONTEXT: Paralepistopsis acromelalga, formerly known as Clitocybe acromelalga, is a rare poisonous mushroom. The mycotoxins in this mushroom cause symptoms resembling those of erythromelalgia; however, its pathogenesis remains unclear. In this report, a patient who received nicotinic acid treatment for P. acromelalga poisoning and radiological evaluation for erythromelalgia has been presented. Case detail: A 59-year-old woman was hospitalized for redness, swelling, and burning pain in her extremities that rendered difficulty in walking, and a diagnosis of P. acromelalga poisoning was made by detailed interview and mushroom identification. She was treated with intravenous nicotinic acid for 17 days followed by oral nicotinic acid amide for 2 months. She exhibited rapid symptomatic improvement and walked independently after 11 days of initial treatment. Initial MRI of her feet revealed toe-dominated subcutaneous thickening. After nicotinic acid treatment, those radiological findings improved dramatically. DISCUSSION: The subcutaneous thickening evident on MRI indicated P. acromelalga poisoning-induced erythromelalgia involved subcutaneous inflammatory edema. The typical duration of edema without treatment is more than a month. The improvement on MRI after nicotinic acid treatment indicated that the adequate vasodilation induced by nicotinic acid contributed to resolution of the symptoms. Nicotinic acid was associated with the improvement of the edematous changes caused by the P. acromelalga intoxication.

[Ophthalmoplegia without severe painful eyelid swelling in acute dacryoadenitis: a case report].

Here, we present a case of right eyelid drooping in a 79-year-old man. Neurological examination revealed ptosis of the right eye without severe painful eyelid swelling and redness. An ocular motility examination of the right eye revealed upward limitation and downward overshoot. The results of routine blood examinations were within normal limits, and no autoantibodies were detected. Orbital magnetic resonance images revealed mild right eyelid swelling and lacrimal gland enlargement, indicating orbital inflammation. The ocular discharge was positive for Staphylococcus hominis by culture and the patient was diagnosed as having acute dacryoadenitis. Treatment with topical and systemic administration of antibiotics rapidly improved symptoms. Ocular infection is not usually suspected in the absence of local severe painful swelling and redness, and painless acute dacryoadenitis presenting as ophthalmoplegia and ptosis may be misdiagnosed. Orbital inflammation may rapidly progress to orbital cellulitis with treatment delay, which may also lead to aggravation of ophthalmic prognosis. Therefore, neurologists should be aware of the possibility of acute dacryoadenitis occurring without the local severe inflammatory findings mimicking neurological diseases, and acute dacryoadenitis should be considered in patients with ophthalmoplegia even in the absence of severe painful eyelid swelling and redness.

[A rare case of the lumbar ectopic kidney in Japanese adult].

In this paper, about the left lumber ectopic kidney of a 87-years-old Japanese woman, we observed the size of her kidney, the form of her renal hilum, and the form of her calicopelvic system. In addition, we measured the index of cortex and medulla (C/M), and examined the difference between the lumber ectopic and the normal kidney. There was no significant difference in the size (length, width, thickness, weight), without the external form was the distorted oval of lumber ectopic kidney. The renal hilum was divided into the upper and lower parts by the septum consisted of the parenchyma of kidney. In the calicopelvic system of the left lumber ectopic kidney, an obstructive distension due to the oppression by branch of the renal vein was observed in the superior minor renal calices. It seemed that it was Fraley's syndrome. From the viewpoint of C/M in the lumber ectopic kidney, it was suggested that there was no difference in the renal function, because the C/M was within a normal range.

Putaminal changes before the onset of clinical symptoms in diabetic hemichorea-hemiballism.

An 81-year-old woman with poorly controlled diabetes mellitus was hospitalized due to hemichorea-hemiballism. A radiological examination revealed typical putaminal changes of diabetic hemichorea-hemiballism (DHC-HB). Interestingly, brain computed tomography, performed before symptom onset, disclosed a hyperdense lesion in the left basal ganglia, indicating persistent basal ganglia impairment, even before the onset of symptoms, under sustained hyperglycemia. Additionally, an increase in the cerebrospinal fluid level of homovanillic acid was related to the symptom appearance of DHC-HB. Pronounced potential basal ganglia impairment under hyperglycemia and central dopaminergic hyperactivity was important for the development of DHC-HB in this patient.

Hypoglycemia-induced spontaneous unilateral jerking movement in bilateral internal capsule posterior limb abnormalities.

We report an 89-year-old woman who developed consciousness disturbance associated with marked hypoglycemia, and showed involuntary movements manifested as spontaneous quick-jerking flexion followed by slow relaxation, in the right leg. Diffusion-weighted imaging revealed bilateral hyperintensities in the posterior limbs of the internal capsule (P-IC). She was treated with intravenous glucose supplementation, and her symptoms dramatically improved. The P-IC lesions are common abnormalities on MRI in hypoglycemia, and may cause paralysis. However involuntary movements associated with the lesions are rarely observed. The spontaneous jerking movements observed in this patient might result from transient impairment of the pyramidal tract associated with hypoglycemia.

[Acute oropharyngeal palsy with localized sensory impairment resembling symptom distribution of acute pharyngeal-cervical-brachial variant in a patient with Guillain-Barré syndrome].

We present the case of a 40-year-old woman who experienced dysarthria and, numbness in her upper extremities and posterior region of her neck. Upon admission to our hospital, neurological examination revealed rhinolalia aperta and an incomplete palatoplegia; however, muscle strength in the neck and limbs was satisfactorily preserved, tendon reflexes were normal, and pathological reflexes were not observed. Cerebrospinal fluid and electrophysiological test results were also normal. On day 3 of hospitalization, a slight backflow of fluid into the nasal cavity was observed upon deglutition, and vibration perception was also impaired in the bilateral arms. Her serum tested positive for immunoglobulin G antibodies against such gangliosides as GT1a, GQ1b, GT1b, and GD1a. Despite normal tendon reflexes, she was diagnosed with a subtype of Guillain-Barré syndrome (GBS), and was treated with intravenous immunoglobulin therapy. Subsequently, her symptoms improved. Due to the combination of oropharyngeal palsy and sensory impairment, it was more likely the GBS subtype in this patient was acute oropharyngeal palsy (AOP) rather than pharyngeal-cervical-brachial (PCB) variant; though interestingly, the patient's sensory disturbance was limited to the posterior neck and upper extremities, which resembles the distribution of motor symptoms in PCB variant. The present case was a rare and important phenotype, demonstrating diversities of GBS variants. We also believe that GBS subtypes may represent a continuum of pathological conditions and not just one static condition. However, further studies involving serological characteristics of anti-ganglioside antibodies and clinical features for GBS are needed to clarify this possibility.

Optic neuritis following aseptic meningitis associated with modified measles: a case report.

In this study, we report the case of a 35-year-old woman with modified measles complicated by aseptic meningitis and subsequent optic neuritis. Although her initial manifestations were only flu-like symptoms without any Koplik's spots or skin rashes, virological testing confirmed an acute measles infection. Subsequently, right optic neuritis appeared after aseptic meningitis and was completely resolved following steroid pulse therapy. In general, modified measles is believed to be associated with mild symptoms and few neurological complications; however, our present observations demonstrated that modified measles can cause rapid neurological complications.

Posterior reversible encephalopathy syndrome due to hypercalcemia associated with parathyroid hormone-related peptide: a case report and review of the literature.

We herein report the case of a 58-year-old man with advanced esophageal carcinoma who developed posterior reversible encephalopathy syndrome (PRES). He initially presented with a severe consciousness disturbance. A subsequent examination revealed hypercalcemia and an elevated serum parathyroid hormone-related peptide (PTHrP) level. Magnetic resonance imaging performed on admission and 24 days later showed reversible widespread white matter abnormalities, which confirmed a diagnosis of PRES. The patient's clinical and radiological manifestations improved upon normalization of the serum calcium level. To the best of our knowledge, this is the first report describing hypercalcemia-induced PRES occurring in association with elevated PTHrP.

Therapeutic response to pramipexole in a patient with multiple system atrophy with predominant parkinsonism: positron emission tomography and pharmacokinetic assessments.

Multiple system atrophy with predominant parkinsonism (MSA-P) usually shows poor responsiveness to dopaminergic medications. We herein describe a patient with MSA-P who exhibited a good response to pramipexole but not to an ordinary dose of L-dopa. Positron emission tomography (PET) displayed severely impaired presynaptic dopaminergic availability and relatively preserved postsynaptic D2 receptor binding capacity. The pharmacokinetic analyses demonstrated relatively low bioavailability for L-dopa and adequate plasma levels of pramipexole, even at baseline, on a stable daily dose. The PET features and pharmacokinetic differences between L-dopa and pramipexole indicate the presence of unique therapeutic responses to dopaminergic medications in the patient.