White matter edematous change with moderate vascular lesions in pretreated acute stage of leukoencephalopathy with cerebral amyloid angiopathy.

A 79-year-old man presented with subacute onset of dementia. Brain magnetic resonance imaging revealed leukoencephalopathy in the posterior lobes with presence of microbleeds. Although clinical manifestation suggested a diagnosis of leukoencephalopathy associated with cerebral amyloid angiopathy (CAA), the patient died of sudden rupture of an aneurysm of the thoracic aorta two months after the onset of dementia. Autopsy revealed pathological features of advanced-stage Alzheimer's disease. Immunohistochemistry for amyloid-ß revealed CAA mainly affecting arteries but not capillaries. Klüver-Barrera staining revealed white matter edema predominantly in the occipital lobes without ischemic changes. Perivascular cuffing was found to be sparse, but there was no evidence of angiitis. Pathological findings suggest that leukoencephalopathy was caused by the disruption of the blood-brain barrier rather than ischemia. Because the present patient died before immunotherapy, his neuropathological findings could reflect the pathomechanism of the acute stage of leukoencephalopathy with CAA.

[A case of oculomotor disorder and urinary retention due to a lower midbrain lesion].

We report an 86-year-old woman who suffered sudden onset of diplopia while cooking. The patient presented with binocular diplopia, bilateral adduction weakness, convergence disorder and bilateral abduction nystagmus. Although brain MRI on admission detected no abnormality, a repeat MRI examination on the following day demonstrated a focal hyperintense lesion in the tegmentum of the midbrain on diffusion-weighted images. At 36 hours after admission, lower abdominal distension became apparent, and about 1 liter of urine was drained via a urethral catheter. Bladder filling sensation was not present, and we considered that the midbrain lesion had been responsible for the oculomotor disorder and urinary retention. As cerebral infarction was the most likely pathology of this lesion, an antiplatelet agent was administered. At two months after onset, the eye movement disorder was resolved and there was no diplopia. Bladder voiding also resumed at normal intervals. We considered that the bilateral medial longitudinal fasciculi and subgroups of the oculomotor nucleus, which contain motor neurons supplying the medial rectus muscle, had been responsible for the oculomotor disorder. The urinary retention was thought to have been caused by a lesion in the periaqueductal gray, which is one structure controlling micturition. This was a rare case of urinary retention due to a small midbrain infarction.

Bilateral oculomotor nerve palsy in a case of anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) has a wide disease spectrum and sometimes shows abnormal eye movement with brainstem manifestations. However, bilateral oculomotor nerve palsy with a midbrain lesion has never been reported in a patient with NMOSD. We describe a 61-year-old woman with progressive ptosis and diplopia. She displayed bilateral oculomotor nerve palsy and hypersomnia. Brain MRI demonstrated abnormal signal intensities in the midbrain and around the third ventricle and hypothalamus with a mild contrast enhancement. A cerebrospinal fluid study indicated elevated protein and pleocytosis. Because serum anti-aquaporin-4 IgG antibody was positive, the patient was diagnosed with neuromyelitis optica spectrum disorder with aquaporin-4 IgG. We report for the first time bilateral oculomotor nerve palsy as an initial manifestation in a patient with aquaporin-4 positive NMOSD.

Pretreatment Blood Pressure is a Simple Predictor of Hemorrhagic Infarction after Intravenous Recombinant Tissue Plasminogen Activator (rt-PA) Therapy.

BACKGROUND: Hemorrhagic infarction (HI) is among the most severe complications that can occur following the administration of intravenous recombinant tissue plasminogen activator (rt-PA). In the present study, we aimed to determine the optimal cut-off points of blood pressure (BP) for HI after rt-PA treatment, and to compare our findings with those for other prediction models. METHODS: We analyzed data from 109 consecutive patients with stroke treated at our hospital between 2009 and 2016. HI was confirmed via computed tomography or magnetic resonance imaging. Patients were classified into a symptomatic HI group, an asymptomatic HI group, and a non-HI group. BP was measured on admission and before rt-PA treatment. Glucose Race Age Sex Pressure Stroke Severity (GRASPS) and Totaled Health Risks in Vascular Events (THRIVE) scores were also calculated. Receiver operating characteristic (ROC) analysis was used to determine factors associated with symptomatic and asymptomatic HI. RESULTS: Among the 109 total patients, 25 patients developed symptomatic HI, while 22 patients developed asymptomatic HI. ROC analysis for predicting symptomatic and asymptomatic HI revealed that the area under the curve for pretreatment systolic BP (SBP) was .88 (95% confidence interval[CI]: .83-.94), while those for GRASPS and THRIVE scores were .75 (95% CI: .66-.85) and .69 (95% CI: .59-.79), respectively. We identified an optimal cut-off point of 160 mm Hg (sensitivity: 82.3%; specificity: 76.6%; diagnostic accuracy: 80.0%; positive predictive value: 76.6%; negative predictive value: 82.5%). CONCLUSIONS: Pre-treatment SBP may be a simple predictor of symptomatic and asymptomatic HI in patients with stroke undergoing rt-PA treatment.

[An autopsy case after endovascular thrombectomy for cardioembolic stroke due to nonbacterial thrombotic endocarditis].

A 73-year-old women visited emergency department because of sudden right hemiplegia. She had a history of duodenum papilla cancer terminal stage and multiple liver metastasis. On admission, diffusion weighted images revealed high intensity area at left middle cerebral artery territory. In addition, 3D-TOF MRA depicted proximal part of the left internal carotid artery. We performed endovascular thrombectomy because low platelet count met contraindication of intravenous recombinant tissue plasminogen activator therapy. Although we could get partial recanalization of middle cerebral artery occlusion after thrombectomy, the patient eventually died due to multiple organ failure. Autopsy findings showed white thrombus on mitral valve and also left middle cerebral artery occluded by similar white thrombus without infective findings. The patient was finally diagnosed with nonbacterial thrombotic endocarditis due to white thrombus on the mitral valve. We should select appropriate mechanical thrombectomy devices with a case of cerebral infarction due to nonbacterial thrombotic endocarditis because its thrombus is often white thrombus and would be hard.

Leukoencephalopathy with a case of heterozygous POLG mutation mimicking mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).

Diseases due to mutations of polymerase γ (POLG) usually present with progressive external ophthalmoplegia. However, a few studies have been reported on POLG1 mutations with the mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)-like phenotype. All cases with POLG1 mutations mimicking MNGIE have never shown leukoencephalopathy on brain magnetic resonance imaging (MRI) or demyelinating polyneuropathy. We present a 26-year-old male with gait disturbance, recurrent bowel obstruction, peripheral neuropathy, ophthalmoplegia or ptosis, which represented MNGIE phenotype. Though he displayed demyelinating peripheral neuropathy or leukoencephalopathy on brain MRI, genetic analysis revealed heterozygous mutation in POLG1 gene. We report for the first time two newly characteristics in our patient with heterozygous POLG1 mutations with the MNGIE-like phenotype: leukoencephalopathy and demyelinating polyneuropathy.

High-Density Lipoprotein Subclasses and Mild Cognitive Impairment: Study of Outcome and aPolipoproteins in Dementia (STOP-Dementia)1.

BACKGROUND: High-density lipoprotein (HDL) containing apolipoprotein A-I is associated with the pathogenesis of Alzheimer's disease (AD). HDL particle size is modified in the presence of pathological conditions, while the significance of the HDL particle size remains controversial. OBJECTIVE: The aim of this study was to investigate the HDL lipoprotein subclasses in mild cognitive impairment (MCI) and AD. METHODS: This cross-sectional study included 20 AD patients, 17 MCI patients, and 17 age-matched controls without cognitive impairment, selected from the database of the Study of Outcome and aPolipoproteins in Dementia (STOP-Dementia) registry. The diagnoses of AD and MCI were performed by expert neurologists according to the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition criteria. Serum HDL subclasses were measured by electrophoretic separation of lipoproteins using the Lipoprint System. The neutrophil-lymphocyte ratio (NLR), a marker of inflammation, was calculated by dividing the neutrophil count by the lymphocyte count. RESULTS: Small-sized HDL particle levels in the MCI group were significantly higher than in the control group, although there was no difference in serum HDL-cholesterol levels between MCI and control groups. NLR in the MCI group was higher than in the control group, but this difference was non-significant (p = 0.09). There was no difference in HDL subclasses or NLR between the AD and control groups. CONCLUSION: These findings suggest that HDL subclasses might be associated with the development of MCI.

Early use of donepezil against psychosis and cognitive decline in Parkinson's disease: a randomised controlled trial for 2 years.

OBJECTIVES: Brain acetylcholine is decreased even in patients with cognitively preserved Parkinson's disease (PD). We investigated whether early and long-term use of donepezil prevents psychosis in non-demented PD patients. METHODS: A double-blinded, placebo-controlled trial was conducted. A total of 145 non-demented PD patients were randomly assigned to receive 5 mg/day donepezil (n=72) or placebo (n=73) for 96 weeks. Medications for PD were not restricted, but antipsychotic drugs were not permitted throughout the study. The primary outcome measure was survival time to psychosis that was predefined by Parkinson's Psychosis Questionnaire (PPQ) B score ≥2 or C score ≥2. Secondary outcome measures included psychosis developing within 48 weeks, total PPQ score, Mini-Mental State Examination (MMSE), Wechsler Memory Scale (WMS) and subgroup analysis by apolipoprotein ε4 genotyping. RESULTS: Kaplan-Meier curves for psychosis development were very similar between the two groups, and the Cox proportional hazard model revealed an adjusted HR of 0.87 (95%CI 0.48 to 1.60). The changes in MMSE and WMS-1 (auditory memory) were significantly better with donepezil than in placebo. In the subgroup analysis, donepezil provided an HR of 0.31 (0.11-0.86) against psychosis in 48 weeks for apolipoprotein ε4 non-carriers. CONCLUSIONS: Although donepezil provided beneficial effects on PPQ, MMSE and auditory WMS score changes in 2 years, it had no prophylactic effect on development of psychosis in PD. Apolipoprotein ε4 may suppress the antipsychotic effect of donepezil. TRIAL REGISTRATION NUMBER: UMIN000005403.

Predictors of Cardioembolic Stroke in Japanese Patients with Atrial Fibrillation in the Fushimi AF Registry.

BACKGROUND: Large-scale clinical trials have analyzed risk factors for any ischemic stroke in patients with atrial fibrillation (AF). However, the risk factors for cardioembolic stroke (CES), specifically, have not been reported. To clarify the risk factors for CES and clinically significant cardioembolic infarction, we examined the incidence of CES and larger infarct volume (IV) (> 30 mL) CES, employing the Fushimi AF Registry, a community-based prospective cohort of AF patients in the Fushimi ward, Kyoto, Japan. METHODS: A total of 4,182 Fushimi AF patients were enrolled from March 2011 to December 2014. The risk factors for CES were evaluated using multivariate analysis. RESULTS: Of 4,182 patients enrolled, 3,749 patients were observed for ≥1 year. During the follow-up period (mean duration, 979 ± 7.7 days), 91/3,749 patients experienced a CES (2.43%). Significant risk factors associated with CES were older age (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.01-1.72; p = 0.046), low body weight (OR, 1.30; 95% CI, 1.03-1.65; p = 0.033), sustained AF (OR, 1.67; 95% CI, 1.05-2.71; p = 0.034), and previous stroke or transient ischemic attack (TIA) (OR, 1.94; 95% CI, 1.22-3.06; p = 0.004). Predictors of a large IV were chronic kidney disease (CKD) (OR, 2.08; 95% CI, 1.09-4.05; p = 0.027) and previous stroke/TIA (OR, 2.27; 95% CI, 1.19-4.24; p = 0.011). CONCLUSIONS: In this population-based cohort of Japanese patients with AF, in addition to previous stroke/TIA and older age, sustained AF and low body weight emerged as risk factors for CES, as opposed to any stroke, which may have a different risk profile. Patients with CKD or previous stroke/TIA who developed cardioembolic infarction exhibited more advanced severity. There is a need for direct oral anticoagulants that can be used safely in patients with comorbid AF and CKD.

[A case of chronic inflammatory demyelinating polyradiculoneuropathy, showing radicular pain due to tuberous hypertrophy of the spinal roots and plexuses after 20 years interval without relapsing sensorimotor symptoms].

A 40-year-old man visited our department because of chest and back pain. He had a history of diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) 20 years ago. He received immunosuppressive therapy and had no relapses after that. On Admission, MRI showed tuberous hypertrophy of the spinal roots, intercostal nerves, and brachial and lumbar plexuses. The genetic analysis showed no mutations in any of Charcot-Marie-Tooth related genes. He was finally diagnosed with CIDP and administration of high dose intravenous methylprednisolone relieved his chest and back pain within a few days. We present a rare case of CIDP in which showed marked enlarged spinal roots in long clinical course and have a relapse with radicular pain without sensorimotor symptoms.

A case of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated hypertrophic pachymeningitis presenting with multiple cranial nerve palsies and diabetes insipidus.

A 61-year-old woman developed hearing difficulties and became thirsty after experiencing cold symptoms. A neurological examination revealed a loss of odor sensation, facial palsy, dysphasia, and dysarthria. Vocal cord palsy was observed during pharyngoscopy. Brain magnetic resonance imaging (MRI) showed a thickened pituitary stalk and swelling of the pituitary gland, but no high signal intensity regions were seen in the posterior portion of the pituitary gland. Gadolinium-enhanced MRI demonstrated a thickened dura mater over the anterior cranial fossa. A biopsy specimen of the thickened dura mater showed fibrosis, granulomatous inflammation, and necrotic foci. Blood tests detected myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA). The patient's urine osmolarity was low even though she exhibited hypernatremia. We diagnosed her with hypertrophic pachymeningitis associated with MPO-ANCA and diabetes insipidus. The patient received two courses of 5-day high-dose intravenous methylprednisolone (1.0 g/day), and was subsequently administered oral prednisolone, which gradually relieved her symptoms. However, the patient's symptoms recurred despite the high-dose prednisolone treatment. It was difficult to control the patient's symptoms in this case with oral prednisolone monotherapy, but combined treatment with cyclosporine resulted in sustained remission. It is considered that patients with MPO-ANCA-positive hypertrophic pachymeningitis require combination therapy with prednisolone and immunosuppressive agents at an early stage.

Incidence and predictors of ischemic stroke during hospitalization for congestive heart failure.

Heart failure (HF) increases the risk of ischemic stroke. Data regarding the incidence and predictors of ischemic stroke during hospitalization for HF are limited. The study population of this retrospective cohort study consisted of patients with congestive HF, consecutively admitted to our center from October 2010 to April 2014. We excluded patients complicated with acute myocardial infarction, infective endocarditis, and takotsubo cardiomyopathy. We also excluded those with dialysis or mechanical circulatory support. We investigated the incidence of ischemic stroke during hospitalization for HF. Thereafter, we divided the patients without oral anticoagulants at admission into two groups: patients with ischemic stroke and those without it, and explored the predictors of ischemic stroke. A total of 558 patients (287 without atrial fibrillation (AF), 271 with AF) were enrolled. The mean age was 76.8 ± 12.3 years, and 244 patients (44 %) were female. The mean left-ventricular ejection fraction was 47.4 %. Oral anticoagulants were prescribed in 147 patients (8 without AF, 139 with AF). During hospitalization (median length 18 days), symptomatic ischemic stroke (excluding catheter-related) occurred in 15 patients (2.7 % of the total, 8 without AF, 7 with AF). Predictors significantly associated with increased risk of ischemic stroke in patients without oral anticoagulants were as follows; short-term increases in blood urea nitrogen after admission (at day 3; odds ratio (per 1 md/dl): 1.06, 95 % confidence interval (CI) 1.01-1.11, p = 0.02, and at day 7; odds ratio: 1.03, 95 % CI 1.00-1.07, p = 0.03, respectively), and previous stroke (odds ratio; 3.33, 95 % CI 1.01-11.00, p = 0.04). The incidence of ischemic stroke during hospitalization for HF was high, even in patients without AF. Previous stroke and short-term increases in blood urea nitrogen was significantly associated with the incidence of ischemic stroke.

[At-home music therapy intervention using video phone (Skype) for elderly people with dementia].

There are various nonpharmacological therapies available for elderly people with dementia, and these can improve quality of life and the behavioral and psychological symptoms of dementia (BPSD) that appear throughout the progression of the disease. Since a substantial number of effects have been reported for music therapy, we focused on this nonpharmacological intervention. Generally, musical therapy is provided collectively in facilities. However, the music used in this context may not consider the preferences and music abilities of each person. Therefore, in this study we created made-to-order music CDs that accounted for each participant's musical preferences and abilities. Utilizing the CDs, we conducted an intervention study of music therapy using a video phone (Skype) that elderly people with dementia can use at home. An advantage of conducting music therapy for individuals with dementia using a video phone is that those who have difficulty going to the hospital or participating in dementia-related therapy groups can participate in therapy in a familiar place. The results of this intervention showed that participants demonstrated signs of improvement as measured by the smile degree(Smile scan)and Behavior Pathology in Alzheimer's Disease (BEHAVE-AD) scale.

A novel GATA3 nonsense mutation in a newly diagnosed adult patient of hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome.

OBJECTIVE: Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is an autosomal dominant disorder caused by a GATA3 gene mutation. Here we report a novel mutation of GATA3 in a patient diagnosed with HDR syndrome at the age of 58 with extensive intracranial calcification. METHODS: A 58-year-old Japanese man showed severe hypocalcemia and marked calcification in the basal ganglia, cerebellum, deep white matter, and gray-white junction on computed tomography (CT). The serum intact parathyroid hormone level was relatively low against low serum calcium concentration. The patient had been diagnosed with bilateral sensorineural deafness in childhood and had a family history of hearing disorders. Imaging studies revealed no renal anomalies. The patient was diagnosed with HDR syndrome, and genetic testing was performed. RESULTS: Genetic analysis of GATA3 showed a novel nonsense mutation at codon 198 (S198X) in exon 3. The S198X mutation leads to a loss of two zinc finger deoxyribonucleic acid (DNA) binding domains and is considered to be responsible for HDR syndrome. CONCLUSION: We identified a novel nonsense mutation of GATA3 in an adult patient with HDR syndrome who showed extensive intracranial calcification.

[Pseudogout as a complication of stroke].

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.

[A case of autoimmune autonomic neuropathy with marked orthostatic hypotension, decreased salivation, constipation, and Adie pupil].

We report a 68-year-old man with subacute autonomic failure who developed orthostatic hypotension, decreased salivation, constipation, and Adie pupil. There was no evidence of central neurodegeneration, sensory and motor dysfunction. Head-up tilt test showed marked orthostatic hypotension without tachycardia. The patient had a low plasma noradrenaline concentration while supine and a poor noradrenaline response to head-up. Adie pupil responded to 0.125% pilocarpine, establishing denervation hypersensitivity of the parasympathetic nerve. Blood pressure, However, did not show a remarkable response to 0.05-0.2gamma noradrenaline, demonstrating the absence of denervation hypersensitivity of the sympathetic nerve. In contrast to patients with pure autonomic failure, the patient showed normal uptake of I-123-MIBG in the myocardium, indicating intact postganglionic sympathetic innervation. Serologic testing demonstrated circulating antibody to the ganglionic acetylcholine receptor (AchR). Because of subacute clinical course, autonomic symptoms and presence of anti-ganglionic AchR antibody, autoimmune autonomic neuropathy was diagnosed.

[Histopathological features of biopsied peroneus brevis muscle in patients with peripheral neuropathies].

We examined the peroneus brevis (PB) muscles obtained with the sural nerves from 12 consecutively biopsied patients who were clinically and electrophysiologically ascertained to have peripheral neuropathies. Histopathological examinations revealed fiber type grouping in all of the 12 PB muscles and group atrophy associated with hypertrophic fibers in 6. These neuropathic changes were ascribable to denervation and reinnervation, being compatible with the neuropathies. Further, internal nuclei were noted in all PB muscles, and fiber splittings in 10. These myopathic changes tended to be more pronounced in the PB muscles having severe neuropathic changes and regarded as the alteration secondary to the preceding neuropathic changes. Degenerated muscle fibers, consisting of phagocytosis, basophilia and whorled fibers, were sparsely found in 8 PB muscles, while rare necrotic fibers were seen in 2. Type 1 fiber predominance was present in 7 PB muscles, in 4 of which the ratio of type 1 fiber was more than 67%. Overall, the neuropathic changes were milder in the PB muscles of CIDP patients and more marked in those showing definite axonal degeneration in the sural nerve. The severity of the neuropathic changes in the PB muscles, however, did not necessarily correlate with the strength of the leg muscles, prognoses of the diseases or the results of the nerve conduction study in the peroneal nerve. The PB muscle is liable to be affected by trauma or aging, which may modify the histopathological features of the biopsied PB muscle and therefore make the relationship between the clinical findings and the alteration of this muscle seems obscured. The available data of PB muscle have been sparse, particularly in the normal individuals, and we should be cautious in interpretation of the results of PB muscle biopsy.