Tissue plasminogen activator (t-PA) treatment is beneficial for patients with ischemic stroke within 4.5 h of stroke onset, because the risk of intracerebral hemorrhagic transformation (HT) increases with delayed t-PA treatment. The benefits of t-PA thrombolysis are heavily dependent on time to treatment. Development of vasoprotective drugs that attenuate HT after delayed t-PA treatment might improve the prognosis of stroke patients and extend the therapeutic time window of t-PA and endovascular thrombolysis. An angiogenic factor, vascular endothelial growth factor (VEGF), might be associated with the blood-brain barrier (BBB) disruption after focal cerebral ischemia. By using a rat thromboembolic model, delayed t-PA treatment at 4 h after ischemia promoted expression of VEGF in BBB, matrix metalloproteinase-9 (MMP-9) activation, degradation of BBB components, and HT. We demonstrated that HT was inhibited by intravenous administration of an anti-VEGF neutralizing antibody/VEGF receptor antagonist. In addition, for clinical application, reverse translation studies, a path from bedside to bench, are necessary.
Pericytes are mural cells embedded in the basal membrane surrounding endothelial cells in capillary and small vessels (from precapillary arterioles to postcapillary venules). They exist with a high coverage ratio to endothelial cells in the brain and play crucial roles in the formation and maintenance of the blood-brain barrier and the control of blood flow through a close interaction with endothelial cells. Thus, intactness of pericyte is absolutely needed for neuronal/brain functions. Ageing, life-style diseases, hypoperfusion/ischemia, drugs, and genetic factors can primarily cause pericyte dysfunctions, thereby leading to the development or progression of various brain disorders, including cerebrovascular diseases. Because pericytes also play an important role in tissue repair after brain injuries, they have received much attention as a therapeutic target even from the standpoint of functional recovery.
We analyzed the registration data of inpatients with facioscapulohumeral muscular dystrophy (FSHD) receiving care at 27 specialized institutions for muscular dystrophy in Japan from 1999 to 2013 using data from October 1 of each year. The number of inpatients of each year ranged from 63 to 72 (67.1 ± 3.3) throughout the study period. Those aged over 50 years gradually increased during the study period, while the oldest inpatient was 82.8 years old. Most could not walk. The rate of respirator dependency increased from 21.0% in 1999 to 71.0% in 2013, while the rate of patients receiving oral nutrition was 98.4% in 1999 and then reduced to 75.4% in 2013. There were 36 death cases reported in the database, including 15 patients with respiratory failure and 4 with heart failure. Our findings indicate that FSHD patients in a severe condition are impacted by respiratory and nutritional problems and their prognosis for survival is related to respiratory failure.
In order to clarify the changes in the medical management of patients with Duchenne muscular dystrophy after publication of a practical guideline, questionnaire surveys targeting Japanese certified neurologists and child neurologists before and four years after publication of the guideline were conducted. The practical guideline was evaluated by the majority of specialists as their preferred information source. After the guideline, a more aggressive trend was seen in steroid treatment, rehabilitation, regular assessment of spinal deformity, etc., and significant differences were observed in respiratory care and nutritional management. Although there were concerns that it would be hard to produce useful guidelines due to the lack of high-level evidence for a rare disease, guidelines including expert recommendations have proved to be an important tool for disseminating best practicable care. We are planning to revise the guideline based on the results of the analysis.
[Background] Supranuclear extraorbital muscle palsy is the core feature of progressive supranuclear palsy (PSP), and ordinarily presents as spontaneous vertical gaze constriction. However, higher visual function associated with visuospatial cognition in PSP patients was not previously considered. [Case presentation] We present a 72-year old right-handed man with PSP- Richardson syndrome (PSP-RS) and abnormal higher visual function. His symptoms began 2 years previously and included the use of small steps while walking, forgetfulness, and postural instability. Neurological examination revealed supranuclear vertical gaze limitation, akinesia, and lead-pipe rigidity without laterality. Neuro-ophthalmological examination showed abnormal ocular movement consistent with PSP, and no visual abnormality was observed. General cognitive functions, including attention and prominent visuospatial orientation and visual attention disturbances, were assessed using neuropsychological tests and concomitant spatial agraphia and impaired configuration using figure copying. Although he presented with mildly decreased and monotonous speech with palilalia, he showed no apparent aphasia, apraxia, visual object agnosia, or Bálint’s ‘optische Ataxie’ i.e. visual ataxia under fixation. Brain MRI revealed atrophy of the mesencephalic tegmentum, bilateral frontal lobe, and bilateral hippocampus. N-isopropyl-p-(iodine-123)-iodoamphetamine single photon emission computed tomography revealed decreased cerebral blood flow in the bilateral frontal lobe, lateral temporal lobe, and basal ganglia. Dopamine transporter single photon emission CT revealed uptake attenuation in the bilateral striatum. 123I-metaiodobenzyl-guanidine myocardium scintigraphy results were normal. [Discussion] The patient’s symptoms indicated classical PSP-RS accompanied with a combination of disturbances in spatial orientation and visual attention as noted by Holmes and Horrax and ‘ataxie optique’ by Garcin. Thus, as observed in this patient, many clinically diagnosed PSP patients with undiagnosed higher visual dysfunction, masked by limited eye movement may exist. These symptoms may further our understanding about posterior cortical atrophy and tauopathy including not only PSP but also corticobasal syndrome and Alzheimer disease.
A 20-year-old woman was hospitalized after experiencing headaches, high fever, and nausea for 1 week. She was conscious and had no abnormal neurological findings or neck stiffness. Examination of her cerebrospinal fluid showed a pronounced elevation of mononuclear cells. She was admitted to our hospital with the diagnosis of meningitis and had hypersomnia 3 days later. Brain MRI (FLAIR) demonstrated high-intensity lesions at the dorsal pons, and bilateral hypothalamus and spinal MRI demonstrated longitudinal T2 high-intensity lesions extending from C2 to C4 and from C6 to Th6. We suspected neuromyelitis optica spectrum disorder (NMOSD) and administered intravenous methylprednisolone after which her symptoms and MRI abnormalities improved immediately. Serum anti-aquaporin-4 antibody and anti-myelin oligodendrocyte glycoprotein antibody were negative. Thus, it is important to perform MRI imaging early in the onset of aseptic meningitis due to numerous case reports of patients diagnosed with neuromyelitis optica or NMOSD with initial meningitis-like symptoms.
A 33-year-old man presented with slowly progressive weakness in the lower extremities over 8 years. At the age of 16 years, the elevation of serum creatine kinase level was detected. Physical examination revealed scapular winging, exaggerated lumbar lordosis and tendoachilles contracture. Gowers sign was positive and proximal dominant limb weakness was noted. Hypertrophy was observed in the upper limbs such as the biceps brachii and forearm flexor muscles. Muscle biopsy showed distinct differences in size of muscle fibers and regenerating and necrotic muscle fibers. A histological study revealed decreased calpain3 expression. Gene analysis of CAPN3 revealed two known gene mutations, leading to a diagnosis of calpainopathy (limb girdle muscular dystrophy 2A; LGMD2A). We here report our patient to discuss findings of upper limb hypertrophy, which are frequently missed compared to the lower limb, but important clinical findings.
We present the case of a 74-year-old woman complaining of blurred vision in the left eye who was found to have a unilateral, continuous lesion of the optic nerve and nerve sheath accompanied by an intracranial mass next to the cavernous sinus and meninges. Surgical decompression of the left optic nerve in the optic canal and partial resection of the mass followed by prednisolone administration were successful. Immunohistochemical analysis disclosed abundant infiltration of IgG4-positive plasma cells at >10 cells/high power field. These findings indicated a new pattern of compressive optic neuropathy with confirmed IgG4 histopathological findings. Such an extensive lesion may produce visual disturbance.
A 45-year old man with untreated diabetes mellitus (HbA1c 11.0%) was admitted with headache and left limb weakness. Findings of diffusion-weighted and FLAIR MR images of the brain were unremarkable. However, cortical vein dilation and occlusion of the upper sagittal sinus were visualized on T2* and magnetic resonance venography images, respectively. Perfusion CT revealed increased mean transit-time in the right frontal lobe. Cerebral venous thrombosis was diagnosed and treated with intravenous heparin. The neurological symptoms disappeared on post onset day (POD) 8. Contrast CT on POD 13 revealed sagittal sinus recanalization and he was discharged 10 days later. Perfusion CT helped to identify cerebral venous thrombosis that might have been associated with untreated diabetes mellitus.