Severe aquaporin 4-IgG-positive neuromyelitis optica with disseminated herpes zoster in a pregnant woman successfully treated with intravenous immunoglobulin.

A 26-year-old, 17-week pregnant woman developed aquaporin-4-IgG-positive severe longitudinally extensive transverse myelitis during the course of disseminated herpes zoster and became quadriparetic. She was unresponsive to high-dose intravenous methylprednisolone but became able to walk without assistance after intravenous immunoglobulin. One and a half months later, left optic neuritis developed but her vision improved with intravenous immunoglobulin. The only sequela was left T5 girdle sensation, and she delivered a healthy baby. Intravenous immunoglobulin may be a rescue therapy in aquaporin-4-IgG-positive neuromyelitis optica attacks in pregnant women, especially those with severe infections.

[NMDA-GluR Subunit Antibody-Positive Encephalitis: A Clinical Analysis of Five Cases].

Five consecutive cases of anti-NMDA-receptor encephalitis that we encountered were marked by a rapidly fluctuating level of consciousness associated with psychotic and delirious mental states. Opisthotonus, catatonia, and rhythmic and non-rhythmic involuntary movements of the mouth and jaw were also characteristic features of these particular cases. Serious and potentially fatal problems included epilepsia partialis continua, partial and generalized seizures, and respiratory depression, resembling the symptoms of encephalitis lethargica. An epidemic of encephalitis lethargica, also known of Economo encephalitis, occurred around 1917. Magnetic resonance imaging revealed edema of the neocortex in two cases and electroencephalography showed polymorphic and monomorphic delta slowing in the acute stage, although electroencephalographic seizure activity were not apparent. Routine cerebrospinal fluid analyses revealed lymphocyte-dominant pleocytosis in three cases, but antibodies against the NMDA-GluR subunit, GluN2B N-terminal, were at a high level in the fluid. All patients recovered without apparent sequelae. Two patients found to have ovarian teratoma underwent surgery for tumor removal. Treatments included pulse intravenous methylprednisolone, high-dose immunoglobulin, and plasma exchange together with seizure control and respiratory support. However, rituximab and or cyclophosphamide pulse therapy should also be considered for intractable cases, as indicated by recent reports. (Received February 16, 2016; Accepted May 2, 2016; Published September 1, 2016).

Increased neuronal and astroglial aquaporin-1 immunoreactivity in rat striatum by chemical preconditioning with 3-nitropropionic acid.

Aquaporin-1 (AQP1) is a water channel expressed in the choroid plexus and participates in forming cerebrospinal fluid. Interestingly, reactive astrocytes also express AQP1 in the central nervous system under some pathological conditions. On the other hand, 3-nitropropionic acid (3NP) is a mitochondrial toxin that causes selective degeneration of striatum; however, its chemical preconditioning is neuroprotective against cerebral ischemia. We previously reported that mild 3NP application is accompanied with numerous reactive astrocytes in rat striatum devoid of typical necrotic lesions. Therefore, we studied whether AQP1 in the rat striatum could be upregulated with reactive astrocytosis using the 3NP model. Immunohistochemical or immunofluorescence analysis showed that reactive astrocytosis in the striatum, which upregulates glial fibrillary acidic protein and glutamine synthetase, was induced by mild doses of 3NP administration. Intriguingly, after 3NP treatment, AQP1 was intensely expressed not only by the subpopulation of astroglia but also by neurons. The AQP1 immunoreactivity became more intensified at the early-subtoxic stage (ES: 24-48h), but not as much in the delayed-subtoxic stage (DS: 96-120h). In contrast, AQP4 expression in the striatum was downregulated after 3NP treatment, in particular during the ES stage. AQP1 upregulation/AQP4 downregulation induced under subtoxic 3NP treatment may play a pivotal role in water homeostasis and cell viability in the striatum.

T2-weighted IDEAL fast spin echo imaging of the brachial plexus: comparison with STIR.

BACKGROUND: Short TI inversion-recovery (STIR) imaging is widely used, but its signal-to-noise-ratio (SNR) is relatively low. Iterative decomposition of water and fat with echo asymmetric and least-squares estimation (IDEAL) imaging has demonstrated promising results in several areas. PURPOSE: To compare T2-weighted fast spin-echo IDEAL (T2W IDEAL-FSE) with STIR to determine which sequence is superior to image the brachial plexus. MATERIAL AND METHODS: The brachial plexus was imaged in 18 patients and six volunteers. The patients' diseases comprised of: suspected chronic inflammatory demyelinating polyneuropathy (CIDP), brachial plexus palsy of unknown origin, and suspected amyotrophic lateral sclerosis. Frontal partial MIP images were acquired. Image quality was qualitatively and independently scored by two radiologists on a three-point grading scale for noise, visibility of the nerve roots, and overall image quality. Inter-observer agreement of the rating by two readers was assessed. The SNR and contrast-to-noise-ratio (CNR) were quantitatively calculated, and differences between T2W IDEAL-FSE and STIR were compared. RESULTS: Qualitatively, each score for T2W IDEAL-FSE was significantly higher (P < 0.01) than that for STIR. Quantitatively, both SNR and CNR for T2W IDEAL-FSE (45.3 ± 12.6 and 27.1 ± 12.1, respectively) were significantly higher (P < 0.001) than those for STIR (17.4 ± 6.1 and 8.2 ± 4.7, respectively). CONCLUSION: T2W IDEAL-FSE could be used to replace STIR for visualization of the brachial plexus.

Risk factors for left atrial thrombus from transesophageal echocardiography findings in ischemic stroke patients.

BACKGROUND: To identify the cause of cerebral embolism, we performed transesophageal echocardiography (TEE) in patients suspected of embolic brain infarction including transient ischemic attack (TIA). We analyzed TEE findings and investigated factors associated with left atrial thrombus (LAT) detected by TEE. METHODS: We enrolled 98 consecutive patients who underwent TEE and had acute brain infarction or TIA that was possibly due to embolism. We assessed age, sex, presence of atrial fibrillation (AF), days from admission to TEE and TEE findings, including the prevalence of LAT, spontaneous echo contrast (SEC), left atrial appendage (LAA) slow flow velocity, patent foramen ovale (PFO), atrial septal aneurysm and aortic plaque (ASA). RESULTS: LAT was detected with TEE in 20 patients (20%). The factors that were significantly associated with the presence of LAT were male sex (unadjusted odds ratio (OR), 3.94; 95% confidence interval (CI), 1.07-14.58; p=0.037), presence of AF (unadjusted OR, 9.58; 95% CI, 2.58-35.50; p< 0.001), SEC (unadjusted OR, 8.48; 95% CI, 2.57-28.00; p< 0.001) and LAA slow flow velocity (unadjusted OR, 5.18; 95% CI, 1.59-16.91; p=0.005). Multivariate logistic regression analysis revealed that male sex (adjusted OR, 5.30; 95% CI, 1.09-25.71; p=0.039), presence of AF (adjusted OR, 8.97; 95% CI, 1.10-73.20; p=0.041) and SEC (adjusted OR, 10.87; 95% CI, 1.001-118.0; p=0.049) were independently associated with LAT, but LAA slow flow velocity was not. CONCLUSION: SEC is an important risk factor associated with LAT in patients suspected of embolic brain infarction that is independent of AF.

Characteristics of aquaporin expression surrounding senile plaques and cerebral amyloid angiopathy in Alzheimer disease.

Senile plaques (SPs) containing amyloid ß peptide (Aß) 1-42 are the major species present in Alzheimer disease (AD), whereas Aß1-40 is the major constituent of arteriolar walls affected by cerebral amyloid angiopathy. The water channel proteins astrocytic aquaporin 1 (AQP1) and aquaporin 4 (AQP4) are known to be abnormally expressed in AD brains, but the expression of AQPs surrounding SPs and cerebral amyloid angiopathy has not been described in detail. Here, we investigated whether AQP expression is associated with each species of Aß deposited in human brains affected by either sporadic or familial AD. Immunohistochemical analysis demonstrated more numerous AQP1-positive reactive astrocytes in the AD cerebral cortex than in controls, located close to Aß42- or Aß40-positive SPs. In AD cases, however, AQP1-positive astrocytes were not often observed in Aß-rich areas, and there was a significant negative correlation between the levels of AQP1 and Aß42 assessed semiquantitatively. We also found that Aß plaque-like AQP4 was distributed in association with Aß42- or Aß40-positive SPs and that the degree of AQP4 expression around Aß40-positive vessels was variable. These findings suggest that a defined population of AQP1-positive reactive astrocytes may modify Aß deposition in the AD brain, whereas the Aß deposition process might alter astrocytic expression of AQP4.

[Case of primary central nervous system lymphoma after open head injury].

A 65-year-old man had suffered contusion of the left frontal lobe of the brain with a skull base fracture, pneumocephalus, and cerebrospinal fluid (CSF) leakage. He was treated with ceftriaxone 4 g/day for 14 days, but after 1 month he developed multiple cranial nerve palsies (bilateral III-X). CSF contained increased levels of protein (96 mg/dl) and mononuclear cells (72 cells/mm³), and low glucose levels (40 mg/dl, blood sugar 120 mg/dl), but no malignant cells were detected. Magnetic resonance imaging (MRI) disclosed swelling in multiple cranial nerves with Gd enhancement. Anti-biotic and antifungal therapy remitted the facial, glossopharyngeal, and vagus nerve palsies and reduced the Gd-enhancement lesion, as detected by MRI. However, the eyes were bilaterally dilated and medially fixed, and hearing impairments persisted. After 3 months, follow-up MRIs revealed the presence of Gd-enhanced small masses at the ventral pontine base, medulla, and cervicomedullary junctions despite a lack of change in neurological symptoms. Those lesions subsided favorably upon treatment with intravenous and oral corticosteroids. After 1 year and 9 months, Gd-enhanced small cystic masses appeared on the medulla and cerebellum. An open biopsy of the cerebellar tonsillar lesions revealed diffuse large B cell lymphoma. Although the development of primary central nervous system lymphoma after open head injury and infection has not been reported to date, central nervous system lymphomas may mimic diverse neurological diseases. Brain biopsy remains the only definitive diagnosis, and thus should be pursued if blood and CSF markers appear normal.

Aquaporin-4 expression in distal myopathy with rimmed vacuoles.

BACKGROUND: Distal myopathy with rimmed vacuoles/hereditary inclusion body myopathy is clinically characterized by the early involvement of distal leg muscles. The striking pathological features of the myopathy are muscle fibers with rimmed vacuoles. To date, the role of aquaporin-4 water channel in distal myopathy with rimmed vacuoles/hereditary inclusion body myopathy has not been studied. CASE PRESENTATION: Here, we studied the expression of aquaporin-4 in muscle fibers of a patient with distal myopathy with rimmed vacuoles/hereditary inclusion body myopathy. Immunohistochemical and immunofluorescence analyses showed that sarcolemmal aquaporin-4 immunoreactivity was reduced in many muscle fibers of the patient. However, the intensity of aquaporin-4 staining was markedly increased at rimmed vacuoles or its surrounding areas and in some muscle fibers. The fast-twitch type 2 fibers were predominantly involved with the strong aquaporin-4-positive rimmed vacuoles and TAR-DNA-binding protein-43 aggregations. Rimmed vacuoles with strong aquaporin-4 expression seen in the distal myopathy with rimmed vacuoles/hereditary inclusion body myopathy patient were not found in control muscles without evidence of neuromuscular disorders and the other disease-controls. CONCLUSIONS: Aquaporin-4 might be crucial in determining the survival or degeneration of fast-twitch type 2 fibers in distal myopathy with rimmed vacuoles/hereditary inclusion body myopathy.

Chemical preconditioning-induced reactive astrocytosis contributes to the reduction of post-ischemic edema through aquaporin-4 downregulation.

Aquaporins are a family of membrane proteins that promote the transmembrane diffusion of water. Aquaporin-4 (AQP4) is a predominant water channel protein in the brain and is concentrated in the end-feet of astrocytes. A critical question is what role astrocytic AQP4 plays in pathological conditions. Another matter to be elucidated is the relationship between morphological changes in astrocytes and AQP4 expression in such cases. We investigated the correlation between AQP4 expression and post-ischemic brain edema formation with astrocytic molecular markers after 3-nitropropionic acid (3NP) preconditioning. 3NP is a mitochondrial toxin, which can induce tolerance to ischemia at subtoxic levels. Rats were treated with 3NP at the tolerance-inducible and the non-tolerance-inducible stage (TS or NTS) before focal ischemia. The control group was injected with physiological saline. After ischemia, the hemispheric enlargement (HE) was volumetrically measured. Immunohistochemical and immunofluorescence analyses of AQP4, glial fibrillary acidic protein (GFAP), and glutamine synthetase (GS) were also conducted after the 3NP treatment and a vehicle was applied. HE was found to be significantly smaller in the TS group than in the vehicle group or the NTS group. The immunofluorescence analyses demonstrated that the AQP4 immunoreactivity in the cortex and striatum was significantly reduced in the TS group but not in the NTS group. In contrast, both GFAP expression and GS expression in the TS group were enhanced, with reactive astrocytosis. AQP4 downregulation in reactive astrocytosis may be one of the factors contributing to the role of 3NP preconditioning in attenuating post-ischemic edema.

Diabetic striatal disease: clinical presentation, neuroimaging, and pathology.

BACKGROUND: Unilateral movement disorders and contralateral neuroimaging abnormalities of the striatum have been sporadically reported as a rare syndrome associated with diabetes mellitus. Despite characteristic imaging findings and clinical manifestations, the mechanism underlying this syndrome is still unclear. METHODS: Six patients with this syndrome were studied clinically and subjected to MRI neuroimaging; one underwent biopsy of the striatum, and another underwent additional MR spectroscopy at 3.0T and FDG-PET. RESULTS: Neuroimaging findings were characterized by a T1-hyperintense unilateral lesion restricted to the striatum, contralateral to the symptomatic limbs. The biopsied striatum contained patchy necrotic tissue, severe thickening of all layers of arterioles, and marked narrowing of vessel lumens. Hyaline degeneration of the arteriolar walls, extravasation of erythrocytes, and prominent capillary proliferation were also notable, together with lymphocytic infiltration and macrophage invasion. In one patient, PET examination revealed decreased accumulation of FDG in the lesion. The MR spectrum for the diseased striatum revealed a decrease in the NAA/Cr ratio (1.35), normal Cho/Cr ratio (1.22), and a peak for myoinositol, while the spectrum on the contralateral site revealed a decrease in the NAA/Cr ratio (1.48), increase in Cho/Cr (1.32), but no peak for myoinositol. CONCLUSION: The constellation of signs and symptoms and neuroimaging characteristics in previous reports and the six additional cases described here with neuropathological data and findings of MR spectroscopy appears unique enough to be termed "diabetic striatopathy." This syndrome appears in poorly controlled diabetics due to obliterative vasculopathy with prominent vascular proliferation, vulnerability to which is restricted to the striatum.

Ischemic tolerance in chemical preconditioning: possible role of astrocytic glutamine synthetase buffering glutamate-mediated neurotoxicity.

Glutamine synthetase (GS), localized to astrocyte is a key enzyme in the glutamate-glutamine pathway in the brain. 3-Nitropropionic acid (3-NPA) is an irreversible inhibitor of succinate dehydrogenase in the tricarboxylic-acid cycle, and provides ischemic tolerance to the brain. So far, there have been no reports on the relationship of astrocytic GS and ischemic tolerance by chemical preconditioning. In order to test the hypothesis that astrocytes serve a pivotal role in 3-NPA-induced chemical preconditioning, we have investigated the temporal profile of GS expression in astrocyte parallel with those of glial fibrillary acidic protein and heat-shock protein 70 (HSP70). In our rat model of permanent focal ischemia, preconditioning with 3-NPA singnificantly reduced the subsequent neurological deficits and infarct volume within 24-72 hours after treatment. Immunohistochemically, protoplasmic astrocytes in the cortex and striatum were activated in terms of upregulation of GS and more abundant protoplasmic processes with 3-NPA preconditioning, however, HSP70 expression could not be induced. Thus, the activation of astrocytes and upregulation of GS play an important role in 3-NPA-induced preconditioning but HSP70 does not. In view of glutamate being imposed on the cerebral ischemic damage, the astrocytic GS may contribute to 3-NPA-induced ischemic tolerance.

Thymidine phosphorylase gene mutation is not a primary cause of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).

OBJECTIVE: The authors identified a patient with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), who completely fulfilled the clinical criteria with low thymidine phosphorylase (TP) activity. However, the same homozygotic S471L TP gene mutation was also found in her unaffected mother, but with normal TP activity. To elucidate the pathogenesis of MNGIE, we performed the analysis below. METHODS: We analyzed the TP gene mutation in the proband and 145 unrelated individuals by direct sequence and restriction fragment length polymorphism (RFLP). TP activity was determined by the spectrophotometric method for each TP S471L genotype. RESULTS: Among 145 normal persons, the S471L homozygote mutants were identified in 2.76% and their enzyme activity was normal. CONCLUSION: TP gene mutation is not a primary cause of MNGIE, but with a mitochondrial deletion mutation, a single nucleotide polymorphism (SNP) of the TP gene may be crucial in the pathogenesis of MNGIE.

[A case of ticlopidine-associated thrombotic thrombocytopenic purpura: special emphasis on diffusion weighted MRI].

A 69-year-old man of thrombotic thrombocytopenic purpura (TTP) associated with ticlopidine was reported. The patient initially complained of dysarthria and left hemiparesis one month after oral administration of ticlopidine. These motor symptoms were followed by gradual deline in level of consciousness. On admission, he was in apallic state with focal cerebral signs, accompanied by low-grade fever, and purpuric eruptions. Laboratory findings showed remarkable thrombocytopenia, hemolytic anemia, and renal dysfunction. The patient received diagnosis of TTP based on Moschcowitzs criteria. Prompt initiation of plasma exchange dramatically improved the patient's clinical symptoms. In this case, decreased activities of a disintegrin and metallo proteinase with thrombospondin type 1 motifs 13 (ADAMTS13) in plasma and anti-ADAMTS13 IgG antibodies were detected. Serial diffusion weighted MRI with six-day interval starting from the onset showed two interesting findings. First, appearance and disappearance of scattered high intensity areas were observed in the cerebellum, corpus callosum, cerebral white matter, and neocortex. Second, these lesions roughly corresponded to border-zone infarct in distribution. Cranial MRI findings of TTP in the literature could be classified into the following four groups: 1) multiple infarction caused by microthrombi; 2) infarction caused by occulusion of an intracranial main artery; 3) reversible edema involving the cerebral white matter; and 4) unremarkable finding without specific abnormality. This case could be classified into the group 1. Based on the diffusion weighted MRI findings of this case, a previous pathological report and recent elucidations of clinical conditions, it is hypothesized that TTP is a predisposition for resembling the border-zone infarction in group 1. The border-zone distribution of transient high intensity areas in diffusion weighted MRI in this case could be explained by either high resistant vascules zone or impaired clearance of emboli, taking an autopsy case report into consideration.

[Distigmine bromide induced Parkinsonism. A case report].

A 74-year-old man became unable to walk two days following the initiation of administration of oral distigmine bromide, 10 mg per day, for his constipation. Neurological examination revealed bradykinesia, rigidity and fine postural tremor without laterality. T2 weighted MRI showed mild front-temporal atrophy and multiple hyperintensities in both deep white matters. His symptoms fully improved one week after discontinuance of distigmine bromide. This is the first case report of distigmine bromide induced Parkinsonism.

[Evaluation of neurosonography for a case of brainstem transient ischemic attack (TIA) due to proximal subclavian artery stenosis, with favorable outcome after axillo-axillary bypass grafting].

We report an 82-year-old man with crescendo brainstem TIA and left upper-limb ischemia due to the left proximal subclavian artery stenosis. Angiography revealed that the left proximal subclavian artery was stenotic. The right vertebral artery was considered to be aplastic or occlusive. Neurosonography, especially the echo-Doppler study of the left vertebral artery, showed that the subclavian artery steal phenomenon did not occur. This study has enabled us to opt for axillo-axillary bypass. We preferred to avoid percutaneous transluminal angioplasty in order to avoid the risk of embolization. The patient received the axillo-axillary bypass operation. He has been free of TIAs and the left upper-limb ischemia since the surgery. We have evaluated his blood circulation fully, by comparing his state before and after the axillo-axillary bypass grafting.

The critical threshold of 3-nitropropionic acid-induced ischemic tolerance in the rat.

3-Nitropropionic acid (3-NPA) is a suicide inactivator of succinate dehydrogenase (SDH), commonly used as a pharmacological model of Huntington's disease in rodents. Several studies have shown that a single administration of 3-NPA given systemically provides subsequent ischemic tolerance. The present study has tested the hypothesis that 3-NPA is capable of inducing tolerance in a model of permanent focal cerebral ischemia and whether 3-NPA can be truly applicable as a tolerance-inducer to ischemia. Rats given 3-NPA intraperitoneally revealed that the mortality of 3-NPA of 15, 20, and 25 mg/kg groups was 20.5, 38.8, and 83.3%, respectively. All rats survived without behavioral sequelae at smaller doses. Three days after 3-NPA preconditioning, the rats showing no behavioral changes underwent the permanent middle cerebral artery occlusion. The groups treated with 10 and 15 mg/kg of 3-NPA showed significantly reduced neurological deficits and infarction volumes in comparison with the control group, whereas the groups treated with 5 and 20 mg/kg of 3-NPA revealed no tolerance effects. When the regional SDH activity (% of control) was photometrically semi-quantified, it was observed that the activity was reduced to 90.8, 76.1, 67.8, and 64.3% in the outer layers of the cerebral cortex, and to 79.4, 67.5, 63.2, and 62.9% in the striatum 1 h after 3-NPA application (5, 10, 15, 20 mg/kg), respectively. In conclusion, although the preconditioning with 3-NPA is clearly shown in the setting of permanent ischemia, the preconditioning with this mitochondrial toxin demonstrated a rather narrow safety margin (critical threshold).