Takafumi Mashiko

Developmentally Regulated RNA-binding Protein 1 (Drb1)/RNA-binding Motif Protein 45 (RBM45), a Nuclear-Cytoplasmic Trafficking Protein, Forms TAR DNA-binding Protein 43 (TDP-43)-mediated Cytoplasmic Aggregates.

Cytoplasmic protein aggregates are one of the pathological hallmarks of neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Several RNA-binding proteins have been identified as components of inclusion bodies. Developmentally regulated RNA-binding protein 1 (Drb1)/RNA-binding motif protein 45 is an RNA-binding protein that was recently described as a component in ALS- and FTLD-related inclusion bodies. However, the molecular mechanism underlying cytoplasmic Drb1 aggregation remains unclear. Here, using an in vitro cellular model, we demonstrated that Drb1 co-localizes with cytoplasmic aggregates mediated by TAR DNA-binding protein 43, a major component of ALS and FTLD-related inclusion bodies. We also defined the domains involved in the subcellular localization of Drb1 to clarify the role of Drb1 in the formation of cytoplasmic aggregates in ALS and FTLD. Drb1 predominantly localized in the nucleus via a classical nuclear localization signal in its carboxyl terminus and is a shuttling protein between the nucleus and cytoplasm. Furthermore, we identify a double leucine motif serving as a nuclear export signal. The Drb1 mutant, presenting mutations in both nuclear localization signal and nuclear export signal, is prone to aggregate in the cytoplasm. The mutant Drb1-induced cytoplasmic aggregates not only recruit TAR DNA-binding protein 43 but also decrease the mitochondrial membrane potential. Taken together, these results indicate that perturbation of Drb1 nuclear-cytoplasmic trafficking induces toxic cytoplasmic aggregates, suggesting that mislocalization of Drb1 is involved in the cause of cytotoxicity in neuronal cells.

A case of Marfan syndrome with ischemic stroke due to middle cerebral artery dissection

Marfan syndrome is known to cause aneurysm and dissection of the aorta and cerebral artery. Although there are many reports of dissection of the aorta, there are few of intracranial artery dissection. We report a 32‐year‐old man with Marfan syndrome. He was presented to our hospital with sudden left hemiparesis and dysarthria. The initial diffusion‐weighted image revealed high‐intensity lesions in the right corona radiata. Magnetic resonance angiography revealed the disruption of the blood flow signal in the proximal M1 portion of the right middle cerebral artery. The clinical course of acute occlusion and gradual recanalization was confirmed, and we diagnosed the dissection of the right middle cerebral artery. Anticoagulant therapy was started, and the neurological symptoms disappeared about 1 week after the onset. In Marfan syndrome, dissection of the intracranial cerebral artery is rare, so further investigation is required.

Peripheral type facial palsy caused by pontine lacunar infarction

Cases of central nervous system (CNS) disorders manifesting peripheral type facial palsy are rare. We report a 70‐year‐old man with a small infarct of the pontine tegmentum who presented with acute‐onset peripheral facial palsy. In the case of infarction in this area, combined symptoms of peripheral facial palsy and abducens nerve palsy are often found, but peripheral facial palsy may occur as the only symptom as in our present case. In the differential diagnosis of peripheral facial nerve palsy, we should also consider the possibility of stroke such as pontine tegmentum infarction.

Vertical Gaze Palsy Caused by Selective Unilateral Rostral Midbrain Infarction

ABSTRACT Vertical gaze palsy is rarely a neurological symptom, although it has been observed in some cases. Here, we report the case of a patient presenting with complete upward and downward gaze palsy. In this case, a small lesion in the left rostral midbrain was observed on diffusion-weighted magnetic resonance (MR) images, and the lesion was considered to cause the ocular symptom. We consider that vertical gaze palsy is an important clue to an accurate topical diagnosis of a brain lesion.

Successful Tissue Plasminogen Activator for a Patient with Stroke After Stanford Type A Aortic Dissection Treatment

Some stroke patients with the acute aortic dissection receiving thrombolysis treatment resulted in fatalities. Thus, the concurrent acute aortic dissection is the contraindication for the intravenous recombinant tissue-type plasminogen activator. However, the safety and the effectiveness of the intravenous recombinant tissue-type plasminogen activator therapy are not known in patients with stroke some days after acute aortic dissection treatment. Here, we first report a case of a man with a cardioembolism due to the nonvalvular atrial fibrillation, who received the intravenous recombinant tissue-type plasminogen activator therapy 117 days after the traumatic Stanford type A acute aortic dissection operation. Without the intravenous recombinant tissue-type plasminogen activator therapy, the prognosis was expected to be miserable. However, the outcome was good with no complication owing to the intravenous recombinant tissue-type plasminogen activator therapy. Our case suggests the effectiveness and the safety of the intravenous recombinant tissue-type plasminogen activator therapy to the ischemic stroke some days after acute aortic dissection treatment.

Tissue Plasminogen Activator to Treat a Stroke after Foam Sclerotherapy in a Woman with a Patent Foramen Ovale

Although foam sclerotherapy to varicose veins is now a popular treatment because of its high efficacy and safety, some neurologic complications have recently been reported. Presently, the effectiveness and safety of intravenous recombinant tissue-type plasminogen activator therapy to stroke following foam sclerotherapy remain unclear. Here, we report the case of a 68-year-old woman whose ischemic symptoms following foam sclerotherapy were treated by intravenous recombinant tissue-type plasminogen activator. After she was admitted, the venous thrombosis in her right soleus vein and a patent foramen ovale causing the right-to-left shunt were revealed. Thus, we diagnosed the ischemic symptoms were due to paradoxical embolism following foam sclerotherapy. After intravenous recombinant tissue-type plasminogen activator therapy, there was no complication and the outcome was good. Our case suggests the effectiveness and the safety of intravenous recombinant tissue-type plasminogen activator therapy to paradoxical embolism following foam sclerotherapy.