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Repulsive guidance molecule-a (RGMa) is a glycosylphosphatidylinositol-linked glycoprotein which has multiple functions including axon growth inhibition and immune regulation. However, its role in the pathophysiology of neuromyelitis optica (NMO) is poorly understood. Perivascular astrocytopathy, which is induced by the leakage of aquaporin-4 (AQP4)-specific IgG into the central nervous system parenchyma, is a key feature of NMO pathology. We investigated the RGMa involvement in the pathology of NMO astrocytopathy, and tested a therapeutic potential of humanized anti-RGMa monoclonal antibody (RGMa-mAb).Using a clinically relevant NMO rat model, we evaluated the therapeutic effect of a RGMa-mAb by behavioral testing, immunohistochemistry, and gene expression assay. We further performed in vitro experiments to address the RGMa-signaling in macrophages.In both NMO rats and an NMO-autopsied sample, RGMa was expressed by the spared neurons and astrocytes, whereas its receptor neogenin was expressed by infiltrating macrophages. AQP4-IgG-induced astrocytopathy and clinical exacerbation in NMO rats were ameliorated by RGMa-mAb treatment. RGMa-mAb treatment significantly suppressed neutrophil infiltration, and decreased the expression of neutrophil chemoattractants. Interestingly, neogenin-expressing macrophages accumulated in the lesion expressed CXCL2, a strong neutrophil chemoattractant, and further analysis revealed that RGMa directly regulated CXCL2 expression in macrophages. Finally, we found that our NMO rats developed neuropathic pain, and RGMa-mAb treatment effectively ameliorated the severity of neuropathic pain.RGMa signaling in infiltrated macrophages is a critical driver of neutrophil-related astrocytopathy in NMO lesions, and RGMa-mAb may provide an efficient therapeutic strategy for NMO-associated neuropathic pain and motor deficits in patients with NMO. ANN NEUROL 2022;91:532-547.

Spinocerebellar ataxia (SCA) is a genetically heterogeneous disease characterized by cerebellar ataxia. Many causative genes have been identified to date, the most common etiology being the abnormal expansion of repeat sequences, and the mutation of ion channel genes also play an important role in the development of SCA. Some of them encode calcium and potassium channels. However, due to limited reports about potassium genes in SCA, we screened 192 Japanese individuals with dominantly inherited SCA who had no abnormal repeat expansions of causative genes for potassium channel mutations (KCNC3 for SCA13 and KCND3 for SCA19/SCA22) by target sequencing. As a result, two variants were identified from two patients: c.1973G>A, p.R658Q and c.1018G>A, p.V340M for KCNC3, and no pathogenic variant was identified for KCND3. The newly identified p.V340M exists in the extracellular domain, and p.R658Q exists in the intracellular domain on the C-terminal side, although most of the reported KCNC3 mutations are present at the transmembrane site. Adult-onset and slowly progressive cerebellar ataxia are the main clinical features of SCA13 and SCA19 caused by potassium channel mutations, which was similar in our cases. SCA13 caused by KCNC3 mutations may present with deep sensory loss and cognitive impairment in addition to cerebellar ataxia. In this study, mild deep sensory loss was observed in one case. SCA caused by potassium channel gene mutations is extremely rare, and more cases should be accumulated in the future to elucidate its pathogenesis due to channel dysfunction.

Previous studies that have investigated the potential of in vivo abnormal α-synuclein deposits as a pathological biomarker for PD included few participants and reported different diagnostic accuracies. Here, we aimed to confirm the diagnostic value of in vivo α-synuclein deposits in PD through a systematic review and meta-analysis, with special emphasis on determining the tissue most suitable for examination and assessing whether anti-native α-synuclein or anti-phosphorylated α-synuclein antibodies should be used. Databases were searched on December 30, 2018. We finally included 41 case-control studies that examined in vivo tissue samples using anti-native α-synuclein or anti-phosphorylated α-synuclein antibody in PD patients and controls. Using a univariate random-effects model, pooled sensitivity and specificity (95% confidence interval) of anti-native α-synuclein antibody were 0.54 (0.49-0.60) and 0.72 (0.68-0.76) for the gastrointestinal tract and 0.76 (0.60-0.89) and 0.60 (0.43-0.74) for the skin. Pooled sensitivity and specificity (95% confidence interval) of anti-phosphorylated α-synuclein antibody were 0.43 (0.37-0.48) and 0.82 (0.78-0.86) for the gastrointestinal tract, 0.76 (0.69-0.82) and 1.00 (0.98-1.00) for the skin, 0.42 (0.26-0.59) and 0.94 (0.84-0.99) for the minor salivary glands, and 0.66 (0.51-0.79) and 0.96 (0.86-1.00) for the submandibular glands. Although ubiquitous heterogeneity between the included studies should be noted when interpreting our results, our analyses demonstrated the following: (1) in vivo α-synuclein immunoreactivity has the potential as a pathological biomarker for PD; (2) anti-phosphorylated α-synuclein antibody consistently has higher specificity than anti-native α-synuclein antibody; and (3) skin biopsy examination using anti-phosphorylated α-synuclein antibody has the best diagnostic accuracy, although feasibility remains an important issue. © 2019 International Parkinson and Movement Disorder Society.

This case report describes involuntary trembling of the tongue accompanied by throat discomfort and affected voice quality in a patient with a history of hypertension and ventricular extrasystole.

Background and Purpose: High blood pressure increases bleeding risk during treatment with antithrombotic medication. The association between blood pressure levels and the risk of recurrent stroke during long-term secondary stroke prevention with thienopyridines (particularly prasugrel) has not been well studied. Methods: This was a post hoc analysis of the randomized, double-blind, multicenter PRASTRO-I trial (Comparison of Prasugrel and Clopidogrel in Japanese Patients With Ischemic Stroke-I). Patients with noncardioembolic stroke were randomly assigned (1:1) to receive prasugrel 3.75 mg/day or clopidogrel 75 mg/day for 96 to 104 weeks. Risks of any ischemic or hemorrhagic stroke, combined ischemic events, and combined bleeding events were determined based on the mean level and visit-to-visit variability, including successive variation, of systolic blood pressure (SBP) throughout the observational period. These risks were also compared between quartiles of mean SBP level and successive variation of SBP. Results: A total of 3747 patients (age 62.1±8.5 years, 797 women), with a median average SBP level during the observational period of 132.5 mm Hg, were studied. All the risks of any stroke (146 events; hazard ratio, 1.318 [95% CI, 1.094–1.583] per 10-mm Hg increase), ischemic stroke (133 events, 1.219 [1.010–1.466]), hemorrhagic stroke (13 events, 3.247 [1.660–6.296]), ischemic events (142 events, 1.219 [1.020–1.466]), and bleeding events (47 events, 1.629 [1.172–2.261]) correlated with increasing mean SBP overall. Similarly, an increased risk of these events correlated with increasing successive variation of SBP (hazard ratio, 3.078 [95% CI, 2.220–4.225] per 10-mm Hg increase; 3.051 [2.179–4.262]; 3.276 [1.172–9.092]; 2.865 [2.042–4.011]; 2.764 [1.524–5.016], respectively). Event rates did not differ between the clopidogrel and prasugrel groups within each quartile of SBP or successive variation of SBP. Conclusions: Both high mean SBP level and high visit-to-visit variability in SBP were significantly associated with the risk of recurrent stroke during long-term medication with either prasugrel or clopidogrel after stroke. Control of hypertension would be important regardless of the type of antiplatelet drugs. Registration: URL: https://www.clinicaltrials.jp ; Unique identifier: JapicCTI-111582.

Nocturnal hypertension (NH) is a symptom of cardiovascular dysautonomia in multiple system atrophy (MSA); however, care and medication are often insufficient. We herein report a patient with MSA who showed posterior reversible encephalopathy syndrome (PRES) caused by hypertension during sleep. He presented clinically with total blindness; T2-weighted magnetic resonance imaging showed high signal intensities in the bilateral subcortical occipital-temporal lobes. His PRES was completely reversed by blood pressure control. NH may contribute to the development of PRES. The appropriate assessment and management of hemodynamic changes in MSA, including NH, is necessary to prevent severe complications such as PRES.

A 49-year-old woman was admitted to our hospital with recurrent episodes of paresthesia attacks evolving in 5 to 15 minutes from the left hand to the left leg through the left trunk. Neurological examination revealed cortical sensory disturbance in her left hand. Although contrast-enhanced T1-weighted MRI findings were unremarkable, contrast-enhanced fluid-attenuated inversion recovery (FLAIR) MRI revealed abnormal leptomeningeal enhancement over the sulcus of the parietal lobe, including the sulcus around the postcentral gyrus. Because we assumed the cause of the recurrent sensory attack to be meningeal inflammation around the primary somatosensory cortex, we treated this patient by increasing the dose of prednisolone. The increase in prednisolone dose completely resolved the symptom, as well as the abnormal leptomeningeal enhancement on contrast-enhanced FLAIR MRI. In patients with suspected meningeal inflammation, contrast-enhanced FLAIR MRI, which is reported to be more sensitive than contrast-enhanced T1-weighted MRI in detecting subtle abnormal leptomeningeal enhancement, should be the modality of choice.

Spinocerebellar ataxia (SCA) is a genetically heterogeneous disease characterized by cerebellar ataxia. Many causative genes have been identified to date, the most common etiology being the abnormal expansion of repeat sequences, and the mutation of ion channel genes also play an important role in the development of SCA. Some of them encode calcium and potassium channels. However, due to limited reports about potassium genes in SCA, we screened 192 Japanese individuals with dominantly inherited SCA who had no abnormal repeat expansions of causative genes for potassium channel mutations (KCNC3 for SCA13 and KCND3 for SCA19/SCA22) by target sequencing. As a result, two variants were identified from two patients: c.1973GA, p.R658Q and c.1018GA, p.V340M for KCNC3, and no pathogenic variant was identified for KCND3. The newly identified p.V340M exists in the extracellular domain, and p.R658Q exists in the intracellular domain on the C-terminal side, although most of the reported KCNC3 mutations are present at the transmembrane site. Adult-onset and slowly progressive cerebellar ataxia are the main clinical features of SCA13 and SCA19 caused by potassium channel mutations, which was similar in our cases. SCA13 caused by KCNC3 mutations may present with deep sensory loss and cognitive impairment in addition to cerebellar ataxia. In this study, mild deep sensory loss was observed in one case. SCA caused by potassium channel gene mutations is extremely rare, and more cases should be accumulated in the future to elucidate its pathogenesis due to channel dysfunction.

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease presenting with various manifestations including dementia, weakness, transient impaired consciousness, encephalitis-like episodes and also epileptic seizures. However, the nature of epileptic seizures, focal or generalized onset, remains unclear. A man at age 76 was admitted to a local hospital due to febrile impaired consciousness lasting several days. During the hospital stay, a generalized convulsion occurred, and afterward he remained obtunded. He was transferred to our hospital for further treatment. One additional seizure occurred while on an ambulance to our hospital and two additional seizures shortly after the arrival, which indicated convulsive status epilepticus (SE). The ictal EEG showed low amplitude fast activity arising from the left centro-parietal area with an evolutionary pattern. The clinical concomitant was the contralateral versive seizure evolving to a bilateral convulsion. Inter-ictal epileptiform abnormalities seen on the tracings taken on later days consisted of brief potentially ictal rhythmic discharges (B(I)RDs) and frequent sharp waves recorded from both frontal areas. These findings along with the ictal discharges would indicate a multifocal epileptic disorder in this patient. Diffusion weighted images (DWIs) of this patient showed hyperintensity signals in the cortico-medullary junctions in the bilateral frontal and the left parietal regions. Skin biopsy revealed characteristic intranuclear inclusions, and hence the diagnosis of NIID was made. The regions of epileptic foci on EEG corresponded well to the hyperintensity areas in DWIs, which suggests the cerebral cortices near the DWI hyperintensity could be more hyperactive than other regions. This case report suggests that some of the prolonged impaired consciousness and the encephalitis-like episodes in NIID could be related to epileptic seizures and even non-convulsive SE or a post-ictal twilight state after an unwitnessed convulsion. This issue should be further studied for the appropriate treatment of episodic encephalopathy and epileptic seizures in NIID.

Focal nerve enlargements at sites of conduction blocks can be visualized sonographically in patients with multifocal acquired demyelinating sensory and motor neuropathy (MADSAM). However, little is known about association between nerve morphological changes and treatment responses. Here we present a 73-year-old female MADSAM patient whose sonographical multifocal nerve enlargements normalized following a good treatment response. She was admitted to our department with progressive asymmetrical muscle weakness and sensory disturbances for 6 months. Ultrasonography revealed multifocal nerve enlargements at sites of electrophysiological demyelination. Intravenous immunoglobulin improved her symptoms and electrophysiological abnormalities. Six months later, ultrasonography revealed normalization of multifocal nerve enlargements. Contrary to our observations, one previous report described a MADSAM patient with persistent nerve enlargements at the sites of resolved conduction blocks. In this earlier patient, however, the time from onset to remission was approximately 30 months. Morphological changes of nerve enlargements in MADSAM may vary with treatment response.

Objectives Studies of longitudinally extensive spinal cord lesions (LESCLs) in neuromyelitis optica (NMO) have focused on gray matter, where the relevant antigen, aquaporin-4 (AQP4), is abundant. Because spinal white matter pathology in NMO is not well characterized, we aimed to clarify spinal white matter pathology of LESCLs in NMO. Methods We analyzed 50 spinal cord lesions from eleven autopsied NMO/NMO spectrum disorder (NMOSD) cases. We also evaluated LESCLs with three or fewer spinal cord attacks by 3-tesla MRI in 15 AQP4 antibody-positive NMO/NMOSD patients and in 15 AQP4 antibody-negative multiple sclerosis (MS) patients. Results Pathological analysis revealed seven cases of AQP4 loss and four predominantly demyelinating cases. Forty-four lesions from AQP4 loss cases involved significantly more frequently posterior columns (PC) and lateral columns (LC) than anterior columns (AC) (59.1%, 63.6%, and 34.1%, respectively). The posterior horn (PH), central portion (CP), and anterior horn (AH) were similarly affected (38.6%, 36.4% and 31.8%, respectively). Isolated perivascular inflammatory lesions with selective loss of astrocyte endfoot proteins, AQP4 and connexin 43, were present only in white matter and were more frequent in PC and LC than in AC (22.7%, 29.5% and 2.3%, Pcorr = 0.020, and Pcorr = 0.004, respectively). MRI indicated LESCLs more frequently affected PC and LC than AC in anti-AQP4 antibody-seropositive NMO/NMOSD (86.7%, 60.0% and 20.0%, Pcorr = 0.005, and Pcorr = 0.043, respectively) and AQP4 antibody-seronegative MS patients (86.7%, 73.3% and 33.3%, Pcorr = 0.063, and Pcorr = 0.043, respectively). PH, CP and AH were involved in 93.3%, 86.7% and 73.3% of seropositive patients, respectively, and in 53.3%, 60.0% and 40.0% of seronegative patients, respectively. Conclusions NMO frequently and extensively affects spinal white matter in addition to central gray matter, especially in PC and LC, where isolated perivascular lesions with astrocyte endfoot protein loss may emerge. Spinal white matter involvement may also appear in early NMO, similar to cerebral white matter lesions.

Background: Therapeutic strategies to prevent degeneration of dopaminergic neurons in Parkinson’s disease have not been developed to date. Although previous non-clinical and clinical studies have shown that selegiline and zonisamide can protect dopamine neurons, their protective action has been clinically evaluated in few studies. In this study, we will compare levodopa/decarboxylase inhibitor (DCI) alone with the combination of levodopa/DCI and selegiline or zonisamide to investigate whether degeneration of dopaminergic neurons could be prevented by the combination therapy in patients with early Parkinson’s disease. Methods: This multicenter, open-label, randomized controlled study will enroll 180 patients. Sixty patients will be randomly assigned to receive levodopa/DCI alone, 60 patients will be assigned to receive levodopa/DCI and selegiline, and 60 patients will be assigned to receive levodopa/DCI and zonisamide, and followed-up for 1 year. The primary endpoint is the percent change of specific binding ratio (SBR; Southampton’s method) of 123Iodine-labelled N-(3-fluoropropyl) -2β-carbomethoxy-3β-(4-iodophenyl) nortropane ([123I]FP-CIT) single-photon emission computed tomography (SPECT) (dopamine transporter SPECT, DAT-SPECT) from baseline to the end of one-year follow-up. The secondary endpoints are the percent change of Unified Parkinson’s Disease Rating Scale (Part II and Part III) scores and Parkinson's Disease Questionnaire -39 scores from baseline to post-treatment. Discussion: This multicenter, randomized controlled study will evaluate the disease-modifying effect of selegiline and zonisamide on degeneration of nigrostriatal dopaminergic neurons in patients with Parkinson’s disease based on the percent change of SBR of DAT-SPECT (primary endpoint). If our study findings suggest that selegiline or zonisamide has a disease-modifying effect from the clinical aspect, the long-term efficacy should be evaluated in a larger-scale phase III study. T Trial Registration: University hospital medical information network (UMIN): UMIN000022533. Registered 30 May 2016, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000025960

Neuromyelitis optica, a rare neuroinflammatory demyelinating disease of the CNS, is characterized by the presence of specific pathogenic autoantibodies directed against the astrocytic water channel aquaporin 4 (AQP4) and is now considered as an astrocytopathy associated either with complement-dependent astrocyte death or with astrocyte dysfunction. However, the link between astrocyte dysfunction and demyelination remains unclear. We propose glial intercellular communication, supported by connexin hemichannels and gap junctions, to be involved in demyelination process in neuromyelitis optica. Using mature myelinated cultures, we demonstrate that a treatment of 1 h to 48 h with immunoglobulins purified from patients with neuromyelitis optica (NMO-IgG) is responsible for a complement independent demyelination, compared to healthy donors’ immunoglobulins (P

A 69-year-old female with an old infarct of the left parietotemporal lobe was admitted for the evaluation of suspected painful seizures accompanying ictal paresis. The painful seizure and ictal paresis involved her right extremities without convulsions, although intermittent tremulous movements were noted on the right upper extremity. She also showed right hemianopia during the seizure. Ictal scalp EEG demonstrated lateralized rhythmic sharply contoured delta activity intermingled with a large amount of spikes, sharp waves, and fast activity mainly on the posterior half of the left hemisphere. Ictal MRI showed restricted diffusion in the postcentral gyrus and dilatation of distal branches of the left middle cerebral artery (MCA). 99mTc-ECD SPECT revealed hyperperfusion on the left parietal cortex. Treatment with antiepileptic drugs successfully prevented seizure recurrence, then she was discharged home. On the follow-up SPECT after 1 month, the abnormal hyperperfusion disappeared. MRI demonstrated resolution of the restricted diffusion and the MCA dilatation. Taken together with the EEG abnormality and the transient abnormalities in SPECT and MRI, we concluded that her seizures were epileptic and that her painful seizures likely arise from the left primary somatosensory cortex. The mechanism of ictal paresis would be attributed to some disturbed functional architecture in the left primary motor cortex leading to loss of normal motor function through epileptic interference by ictal discharges. The same mechanism in the visual cortex could be assumed for her ictal hemianopia. Painful seizure and ictal paresis each is rarely encountered, even more so the combination thereof. These ictal manifestations might be difficult to differentiate from transient ischemic attack or postictal paresis, and thus EEG is essential to diagnose this treatable condition.

A 45-year-old male was admitted with an acute-onset visual field defect. Goldmann perimetry revealed an incongruent, incomplete right homonymous hemianopia. The left eye showed a wedge-shaped, horizontal right hemianopia, whereas the right eye showed constriction of the right visual hemifield. MRI showed acute infarction localized to the left lateral geniculate body (LGB). LGB has a dual blood supply: from the anterior choroidal artery and from the lateral posterior choroidal artery (LPChA). The LPChA territory of LGB receives projection from the retinal area around the macula and horizontal meridian. Therefore, an LPChA territory infarction of LGB can cause a wedge-shaped, horizontal visual field defect. The visual field defect in our patient would be caused by an LPChA territory infarction of LGB. Our patient showed an incongruent homonymous hemianopia. LGB has six laminae, with the ipsilateral retinal fibers terminating in layers two, three, and five and the crossed fibers terminating in layers one, four, and six. The laminar structure provides the anatomical basis for the incongruous visual field defects in a case of partial lesion of LGB. Based on the present data, we believe that an ischemic lesion localized to LGB should be considered in patients presenting with incongruous, incomplete homonymous hemianopia.

A 35-year-old man was admitted due to somnolence and progressive sensory-motor polyneuropathy, followed by severe visual impairment in both eyes after direct skin exposure to an acrylamide monomer solution. The results of an ophthalmological examination including central critical flicker fusion frequency and the decreased amplitude of action potentials observed in the visual evoked potential studies suggested that acrylamide intoxication resulted in neuronal degeneration in the optic pathways. Additional attention should be directed to the potential effect of acrylamide on the human visual system.

A 65-year-old woman with long-standing rheumatoid arthritis (RA) experienced a recurrent tingling sensation in her left arm followed by aphasia and a tingling sensation in her right arm. A subsequent imaging study showed bilateral subdural fluid accumulation and we initially diagnosed her with a transient ischaemic attack and chronic subdural haematoma (CSDH). The cerebral spinal fluid study revealed an inflammatory response without any indications of infection or malignant tumours. After a meningeal biopsy, we redefined the diagnosis to rheumatoid meningitis (RM), and the patient showed remarkable improvement with prednisolone administration. RM should be considered as an alternative diagnosis when examining central nervous system diseases in patients with RA, as RM presents a highly variable clinical picture with image findings similar to those of CSDH.

We report a case of lymphocytic primary angiitis of the central nervous system (PACNS) with a characteristic gadolinium-enhancement pattern on magnetic resonance imaging (MRI). A 48-year-old, right-handed man presented with a 3-month history of tremor and progressing dementia. Neurologic examination revealed cognitive decline with anterograde amnesia and postural tremor of the fingers. Except for the positive result of serum antinuclear antibody, intense investigations for infectious, rheumatic and neoplastic diseases were negative. Analysis of cerebrospinal fluid showed mild pleocytosis (14 cells/μl). Brain MRI revealed diffuse hyperintense areas in the deep cerebral white matter on T2-weighted images. Gadolinium-enhanced T1-weighted images demonstrated fan-shaped multiple linear enhancements converging to the body of the lateral ventricles. Brain biopsy showed intense infiltration of small lymphocytes without atypia or granuloma mainly within the vessel walls and perivascular spaces. The diagnosis of lymphocytic PACNS was made. Administration of corticosteroid markedly improved the tremor and cognitive dysfunction. MRI after the treatment showed resolution of the abnormal fan-shaped linear enhancement. He returned to his previous occupation. PACNS should be included in the differential diagnosis for fan-shaped linear enhancement converging to the lateral ventricles on MRI in patients with unexplained progressing dementia.

A 53-year-old woman was admitted to the department of neurology in Tenri Hospital because of progressive thoracic myelitis a month after she had eaten uncooked bovine liver. A previous episode of right optic neuritis and a positive test for serum anti-aquaporin-4 antibodies indicated a diagnosis of neuromyelitis optica spectrum disorders. Although the patient initially recovered with the reduction of anti-aquaporin-4 antibodies during treatment with intravenous methylprednisolone infusion and plasma exchange, her neurological symptoms deteriorated soon after the completion of plasma exchange. Western blotting analysis detected anti-Toxocara canis antibodies in the serum; thus, the patient underwent oral albendazole treatment. This resulted in the alleviation of her symptoms. We therefore consider that rigorous investigation should be encouraged to detect rare pathogens including parasites in cases of treatment-resistant neuromyelitis optica spectrum disorders.

An 85-year-old man with type 2 diabetes mellitus presented to our emergency department with sudden right limb weakness and dysarthria 90 min after onset. He was alert when examined and had a blood pressure of 163/89 mm Hg. Although right hemiplegia with facial weakness and dysarthria were noted, sensations to pinpricks were intact. MRI showed a hyperintense lesion in the posterior limb of the left internal capsule (IC), with decreased apparent diffusion coefficient values on diffusion-weighted imaging (DWI), suggesting acute ischaemic stroke (AIS) (figure 1). In the coronal …

Neuromyelitis optica (NMO) and associated NMO spectrum disorders (NMOSDs) are neuroinflammatory diseases that frequently result in severe neurological disabilities. The aim of this study was to explore additional treatment options for NMO/NMOSD patients who are seropositive for anti-aquaporin 4 (AQP4) antibodies. We retrospectively evaluated the efficacy of immunosuppressants for NMO/NMOSDs by reviewing the clinical records of 52 patients confirmed as seropositive for anti-AQP4 antibodies. Of the 52 patients, 26 (23 women, three men) had received at least one kind of immunosuppressant other than corticosteroids. After eliminating ineligible cases, we evaluated the following 24 treatments in 22 patients (20 women, two men) that used azathioprine (AZA) (n = 9), cyclophosphamide (n = 1), cyclosporine A (CyA) (n = 9), tacrolimus (n = 2), methotrexate (n = 1), and mizoribine (n = 2). Both AZA and CyA treatments allowed us to decrease the median dose of the coadministered prednisone without affecting the expanded disability severity scale scores. In patients with relapsing-remitting courses, the annual relapse rate decreased from 1.7 (1.2-2.7) to 0.47 (0.36-0.59) after AZA treatments (n = 6, P = 0.028), and also showed a significant decrease from 2.7 (1.8-4.3) to 0.38 (0-0.97) after CyA treatment (n = 8, P = 0.012). These results indicate that CyA as well as AZA may help stabilize the disease activity in NMO/NMOSD patients seropositive for anti-AQP4 antibodies. This is the first case series study demonstrating the efficacy of CyA for the treatment of NMO/NMOSDs.

We studied the incidence and clinical characteristics of pseudogout complicating stroke and the clinical characteristics of pseudogout occurring after stroke. Ten of 181 patients with stroke developed pseudogout. Compared with the patients of other disease, the incidence of pseudogout in the stroke patients was significantly high. Age at onset was 75 to 90, with a mean of 82. The time interval from stroke to onset of pseudogout ranged from 3 to 31 days, with a median of 5.5 days. The most common initial symptom was fever (90%), whereas subjective arthralgia was not highly frequent (50%). The affected joints were the knee in 6, wrist in 5, shoulder in 2, elbow in 2, atlantoaxial (crowned dens syndrom) in 2 and ankle in the remaining one. All patients developed pseudogout either on the paretic side or on atlantoaxial joint when their condition required extended bed-rest or limited their mobility. All the patients had elevated CRP levels (mean CRP 12.0 mg/dl). Our findings suggest that this underrecognized disease should be noted as one of the complications after stroke.

An 87-year-old man taking antihypertensive medications, including 10 mg enalapril, daily visited our hospital complaining of motor aphasia, dysarthria, and right hemiparesis. Magnetic resonance imaging revealed an ischemic lesion in the left frontal lobe including the insular cortex and severe stenosis of the left middle cerebral artery. After he received intravenous alteplase infusion, he developed orolingual angioedema followed by transient bradycardia with subsequent hypotension, resulting in the deterioration of his neurological signs and expansion of the ischemic lesion. Orolingual angioedema after intravenous alteplase infusion may follow cardiovascular instability and disease progression in stroke patients.

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a hereditary small artery disease which is phenotypically similar to Binswanger’s disease (BD), a nonhereditary form of small artery disease. Recent studies have indicated that lesions in the temporopolar, medial frontopolar areas and external capsule are frequently seen in Caucasian patients with CADASIL. However, it remains unclear whether magnetic resonance (MR) imaging findings are helpful in diagnosing small artery disease outside countries with Caucasian populations, since CADASIL is rare despite the high prevalence of small artery disease in Japan. We examined 58 patients with small artery disease, all of whom were devoid of major vessel occlusion or severe stenosis. These patients included 7 patients from 3 families with CADASIL, 27 nondemented patients with extensive leukoaraiosis (LA) and 24 patients with BD. On T2-weighted MR images, hyperintensities in the temporopolar areas were observed in all 7 patients with CADASIL, whereas these lesions were observed in only 1 subject from each of the nondemented LA and BD groups. Hyperintensities in the medial frontopolar areas were seen in 4 of the 7 patients with CADASIL (57%) and in 14 of the 24 patients with BD (58%), and were more frequent than in the nondemented LA group (4 of the 27 patients; 15%). In contrast, hyperintensities in the external capsule were frequently observed in all groups. Therefore, temporopolar lesions can also serve as diagnostic markers for CADASIL in non-Caucasian patients.