Serum anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder presenting as acute eosinophilic encephalomyelitis

金沢大学附属病院神経内科We report the case of a 57-year-old man with neuromyelitis optica spectrum disorder (NMOSD) presenting as acute eosinophilic encephalomyelitis. Magnetic resonance imaging revealed central nervous system lesions typical of NMOSD and anti-aquaporin-4 antibodies in the serum were identified; however, eosinophilia was evident in the cerebrospinal fluid (CSF) at the early stage of the disease. The number of eosinophils in the CSF decreased subsequently. Although activation of eosinophils is known to be an important factor in the development of NMOSD lesions, prominent eosinophilia in the CSF at the early stage of the disease has never been reported in patients with NMOSD. © 2017 Elsevier Ltd.Embargo Period 12 month

lmmunohistochemical and in situ hybridization studies of choline acetyltransferase in large motor neurons of the human spinal cord

The localization of choline acetyltransferase (ChAT) protein and mRNA was investigated in large motor neurons of the lumbar spinal cord of 10 autopsied individuals without neurological diseases, by immunohistochemistry and in situ hybridization. In the immunohistochemistry using 20 serial tissue sections with a total thickness of 80 pm, about 58-85% (average 67%) of the large motor neurons (30 pm and more in somal minimal diameter) in the ventral horn were stained with the anti-human ChAT antibody. In the positive neurons, most immunoreactive products were observed focally in the perikarya. Occasionally, the perikarya of some neurons were stained diffusely. In situ hybridization with a single 4 pm-thick tissue section showed that almost all large motor neurons had positive signals (93-loo%, average 98%), which were distributed diffusely in the perikarya. The positivity rate in the in situ hybridization was higher than that in the immunohistochemistry for all 10 cases. These results indicate that ChAT mRNA is transcribed in almost all large motor neurons in the ventral horn of the human spinal cord, but ChAT protein cannot always be detected in the cytoplasm by immunohistochemistry

lmmunohistochemical and in situ hybridization studies of choline acetyltransferase in large motor neurons of the human spinal cord

The localization of choline acetyltransferase (ChAT) protein and mRNA was investigated in large motor neurons of the lumbar spinal cord of 10 autopsied individuals without neurological diseases, by immunohistochemistry and in situ hybridization. In the immunohistochemistry using 20 serial tissue sections with a total thickness of 80 pm, about 58-85% (average 67%) of the large motor neurons (30 pm and more in somal minimal diameter) in the ventral horn were stained with the anti-human ChAT antibody. In the positive neurons, most immunoreactive products were observed focally in the perikarya. Occasionally, the perikarya of some neurons were stained diffusely. In situ hybridization with a single 4 pm-thick tissue section showed that almost all large motor neurons had positive signals (93-loo%, average 98%), which were distributed diffusely in the perikarya. The positivity rate in the in situ hybridization was higher than that in the immunohistochemistry for all 10 cases. These results indicate that ChAT mRNA is transcribed in almost all large motor neurons in the ventral horn of the human spinal cord, but ChAT protein cannot always be detected in the cytoplasm by immunohistochemistry

Clinicopathological study of involvement of granulocyte colony stimulating factor and granulocyte-macrophage colony stimulating factor in non-lymphohematopoietic malignant tumors accompanied by leukocytosis

Involvement of granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) in nonlymphohematopoietic malignant tumors accompanied by leukocytosis was clinicopathologically investigated. Among 1,778 autopsy cases in the last 20 years, 485 lesions of 439 cases with non-lymphohematopoietic malignant tumors accompanied by leukocytosis with a white blood cell count of 10,000/mm3 or greater during the course were immunohistologically examined for GCSF and GM-CSF. Three (0.7%) and two cases (0.5%) were G-CSF- and GM-CSF-positive, respectively. GMCSF mRNA was confirmed by using non-fixed cryopreserved tumor tissues in one case positive for GM-CSF. G-CSF-positive cases were large cell carcinoma of the lung, adenocarcinoma of the colon, and adenocarcinoma of the stomach, and GM-CSF-positive cases were spindle cell carcinoma of the lung and malignant thymoma. In the case with stomach carcinoma, the primary lesion showing moderately differentiated adenocarcinoma was negative, but the lung metastatic lesion showing less differentiated adenocarcinoma was G-CSF-positive. The survival period was six months or less in four out of five positive cases. The highest white blood cell count in five CSFpositive cases was markedly elevated: 29,400- 103,500/mm3 (mean: 59,700/mm3). In four cases, excluding one case which may have been markedly affected by chemotherapy, the bone marrow showed hyperplasia, and the number of the granulocyte series cells significantly increased. There were three cases (0.7%) negative for both G-CSF and GM-CSF, although they showed marked leukocytosis (60,000/mm3 or higher) which were higher than the mean count of CSFpositive cases and was not observed in autopsy cases with non-tumorous diseases. Other stimulating factors may be involved in the development of leukocytosis in such cases

Intravenous Administration of Self-complementary AAV9 Enables Transgene Delivery to Adult Motor Neurons

Therapeutic gene delivery to the whole spinal cord is a major challenge for the treatment of motor neuron (MN) diseases. Systemic administration of viral gene vectors would provide an optimal means for the long-term delivery of therapeutic molecules from blood to the spinal cord but this approach is hindered by the presence of the blood–brain barrier (BBB). Here, we describe the first successful study of MN transduction in adult animals following intravenous (i.v.) delivery of self-complementary (sc) AAV9 vectors (up to 28% in mice). Intravenous MN transduction was achieved in adults without pharmacological disruption of the BBB and transgene expression lasted at least 5 months. Importantly, this finding was successfully translated to large animals, with the demonstration of an efficient systemic scAAV9 gene delivery to the neonate and adult cat spinal cord. This new and noninvasive procedure raises the hope of whole spinal cord correction of MN diseases and may lead to the development of new gene therapy protocols in patients