Mitral Valve Replacement for Enlarged Libman-Sacks Endocarditis in a Patient with Persistent Primary Antiphospholipid Syndrome and Recurrent Stroke: A Case Report.

BACKGROUND Anticardiolipin antibodies in patients with Libman-Sacks endocarditis (LS) are indicative of comorbid antiphospholipid syndrome (APS) and can result in cerebral infarctions. We describe a case of LS and primary APS with recurrent cerebral infarctions despite anticoagulation treatment. The patient underwent surgery for enlarged LS vegetation with high titers of antiphospholipid antibodies. CASE REPORT A 41-year-old Japanese man was admitted to hospital for small cerebral infarction recurrence in a left parietal lesion. At age 35, the patient had suffered multiple cerebral infarctions. He was found to have high serum titers of all 3 antiphospholipid antibodies. Transesophageal echocardiography (TEE) findings were normal. Differential diagnosis ruled out other autoimmune diseases and a clinical diagnosis of primary APS was made. Warfarin anticoagulation was started. When cerebral infarction recurred 6 years after the first episode, serum titers of antiphospholipid antibodies remained high, and TEE showed a 7×8 mm area of mitral vegetation. A TEE results from his first admission revealed a 5×6 mm area of mitral vegetation, which was believed to be related to the current vegetation. As anticoagulation produced no improvement, the mitral valve was replaced with a mechanical valve. Examination of the excised vegetation found it to be consistent with LS. The patient made good progress within 3 years after surgery. CONCLUSIONS LS size can increase despite anticoagulation in cases with high titers of all 3 antiphospholipid antibodies and cerebral infarction. Such patients require ongoing TEE follow-up and surgical treatment should be considered.

Serum Alkaline Phosphatase in Cryptogenic Stroke Cases with Active Cancer.

Objective We assessed the relationship between the levels of serum alkaline phosphatase, which is often increased with biliary obstruction and bone metastasis, and active cancer in patients with cryptogenic stroke. Methods Serum alkaline phosphatase levels in patients with cryptogenic stroke sampled upon admission were measured using the Japan Society of Clinical Chemistry method used in Japan. Active cancer was defined as a new diagnosis, treatment, progression, or recurrence within six months before admission or metastatic cancer. Multivariate logistic regression analyses were performed to explore the relationship between serum alkaline phosphatase and active cancer in these patients. Results Among the 249 patients classified as having cryptogenic stroke, 64 had active cancer. Patients with cryptogenic stroke with active cancer had significantly higher serum alkaline phosphatase levels (486±497 vs. 259±88.2 U/L; p<0.001) than those without cancer. Multivariate logistic analysis revealed that serum alkaline phosphatase levels ≥286 U/L were associated with cryptogenic stroke with active cancer [odds ratio (OR), 2.669, 95% confidence interval (CI), 1.291-5.517; p=0.008] independent of age ≤70 years old (OR, 3.303, 95% CI, 1.569-6.994; p=0.002), male sex (OR, 0.806, 95% CI, 0.380-1.710; p=0.573), and serum D-dimer levels ≥2.6 µg/mL (OR, 18.78, 95% CI, 8.130-43.40; p<0.001). Conclusion In patients with cryptogenic stroke, high serum alkaline phosphatase levels may be related to active cancer.

Electroencephalographic findings after convulsive seizures due to cerebral arterial air embolism secondary to lung cancer: a case report.

BACKGROUND: Cerebral arterial air embolism is often associated with an invasive iatrogenic etiology and a high rate of convulsive seizures. There are only a few descriptions of electroencephalogram findings in convulsive seizures due to cerebral arterial air embolism of noniatrogenic etiology. Herein, we describe the case of a patient with lung cancer and convulsive seizures with abnormalities detected on electroencephalogram caused by cerebral arterial air embolism of noniatrogenic etiology. CASE PRESENTATION: A 55-year-old Japanese man underwent radiotherapy and chemotherapy for cancer in the hilum of the left lung that was diagnosed after hemoptysis. One year after the diagnosis, he developed fever and chest pain that required hospitalization. At admission, he was in shock, and chest computed tomography revealed invasion of the left atrium and left main bronchus by the hilar cancer. Chest and abdominal computed tomography revealed small low-density areas within the tumor and around the intestinal membrane, which were interpreted as the presence of air due to invasion of the lung cancer. He was diagnosed with septic shock due to necrotic infection secondary to cancer invasion into the left atrium. The following day, he complained of difficulty in speaking and weakness in the left side of his body. A head computed tomography scan revealed multiple small low-density areas in the right cortex and bilateral subcortex, which were interpreted as air emboli. On day 3, he experienced generalized tonic-clonic seizures for approximately 1 minute, followed by myoclonus-like convulsions in the left lower limb and a right-sided gaze. The electroencephalogram findings after the convulsive seizures revealed partial epilepsy-like waves with intermittent spikes in the bilateral cerebral hemispheres and a diffuse slow wave in the left frontal lobe. He recovered from sepsis without recurrence of convulsive seizures; however, he died of hemoptysis on day 50 after discharge. CONCLUSIONS: Electroencephalogram findings of focal spike activities and diffuse slow waves were detected in early seizures due to cerebral arterial air embolism of noniatrogenic etiology associated with lung cancer. Additional case descriptions are warranted to establish patterns in electroencephalogram findings specific to cerebral arterial air embolism.

Gene Expression Profiles of Human Cerebral Organoids Identify PPAR Pathway and PKM2 as Key Markers for Oxygen-Glucose Deprivation and Reoxygenation.

Ischemic stroke is one of the most common neurological diseases. However, the impact of ischemic stroke on human cerebral tissue remains largely unknown due to a lack of ischemic human brain samples. In this study, we applied cerebral organoids derived from human induced pluripotent stem cells to evaluate the effect of oxygen-glucose deprivation/reoxygenation (OGD/R). Pathway analysis showed the relationships between vitamin digestion and absorption, fat digestion and absorption, peroxisome proliferator-activated receptor (PPAR) signaling pathway, and complement and coagulation cascades. Combinational verification with transcriptome and gene expression analysis of different cell types revealed fatty acids-related PPAR signaling pathway and pyruvate kinase isoform M2 (PKM2) as key markers of neuronal cells in response to OGD/R. These findings suggest that, although there remain some limitations to be improved, our ischemic stroke model using human cerebral organoids would be a potentially useful tool when combined with other conventional two-dimensional (2D) mono-culture systems.

[Elevation of cerebrospinal fluid anti-cyclic citrullinated peptides antibody index is useful for rheumatoid meningitis preceding neurological symptoms without arthritis: a case report].

We report a 62-year-old female with rheumatoid meningitis. She presented with mental disorder, loss of consciousness, generalized seizures, and cognitive impairment. Brain MRI demonstrated high intensity lesions and abnormal enhancement along the left frontal and parietal sulci. Her serum and cerebrospinal fluid were positive for anti-cyclic citrullinated peptides (CCP) antibody, and the antibody index of cerebrospinal fluid anti-CCP antibody increased, which led us to suspect rheumatoid meningitis. Her symptoms improved immediately by methylpredonisolone pulse therapy and anti-CCP antibody turned negative in cerebrospinal fluid. However, she revealed arthritis with the reduction of betamethasone and was diagnosed as rheumatoid arthritis. We suggest that the elevation of antibody index of cerebrospinal fluid anti-CCP antibody is useful in the diagnosis of rheumatoid meningitis preceding neurological symptoms without arthritis, and anti-CCP antibody in cerebrospinal fluid may be helpful as the evaluation of the treatment.

Low Serum Eicosapentaenoic Acid Levels in Cryptogenic Stroke with Active Cancer.

BACKGROUND AND PURPOSE: The increased prevalence of cancer has led to it being considered an important factor in the cause of cryptogenic stroke. In recent years, polyunsaturated fatty acids, particularly omega-3 polyunsaturated fatty acids, have been shown to prevent cancer development and progression. This study aimed to clarify the characteristics of serum polyunsaturated fatty acids in cryptogenic stroke with active cancer. METHODS: The serum levels polyunsaturated fatty acid fractions (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA; dihomo-gamma-linolenic acid, DHLA; and arachidonic acid, AA) in cases of cryptogenic stroke, sampled within 5 days after admission, were measured. Active cancer was defined as a new diagnosis, treatment, progression or recurrence within 6 months before admission, or metastatic cancer. Multivariate logistic regression analyses were performed to explore the relationship between serum polyunsaturated fatty acids and cryptogenic stroke with active cancer. RESULTS: Among 123 cases classified as cryptogenic stroke, 27 had active cancer. The serum EPA levels (1.26 ± 0.72 versus 1.89 ± 1.27 umol/l; P = 0.02) were significantly lower in cryptogenic stroke with active cancer, whereas the serum DHA, DHLA and AA levels did not significantly differ. Multivariate logistic analysis revealed that the serum EPA levels were associated with cryptogenic stroke with active cancer independently of age and serum D-dimer levels (odds ratio, 0.974; 95% confidence interval, 0.949-0.999; P = 0.04). CONCLUSIONS: In our study, low serum EPA levels were associated with cryptogenic stroke with active cancer. This suggests that low serum EPA levels may have some involvement in the pathogenesis of cryptogenic stroke with active cancer.

Intracranial varicella zoster virus infection may elicit an unusual hyperkinetic volitional tremor.

Central nervous system manifestations of varicella zoster virus (VZV) infection are uncommon, and associated involuntary movement is rare. Herein, we describe a patient with VZV induced encephalopathy who presented with an unusual hyperkinetic volitional tremor.

Increased Signal in the Superior Cerebellar Peduncle of Patients with Progressive Supranuclear Palsy.

OBJECTIVE: The provisional diagnosis of progressive supranuclear palsy (PSP) depends on a combination of typical clinical features and specific MRI findings, such as atrophy of the tegmentum in the midbrain. Atrophy of the superior cerebellar peduncle (SCP) distinguishes PSP from other types of parkinsonism. Histological factors affect the conventional fluid-attenuated inversion recovery (FLAIR) signals, such as the extent of neuronal loss and gliosis. METHODS: We investigated patients with PSP to verify the percentage of patients with various PSP phenotypes presenting a high signal intensity in the SCP. Three interviewers, who were not informed about the clinical data, visually inspected the presence or absence of a high signal intensity in the SCP on the FLAIR images. We measured the pixel value in the SCP of each patient. Clinical characteristics were evaluated using the Mann-Whitney test, followed by the χ2 test. RESULTS: Ten of the 51 patients with PSP showed a high signal intensity in the SCP on FLAIR MRI. Higher pixel values were observed within the SCP of patients with a high signal intensity in the SCP than in patients without a high signal intensity (p < 0.001). The sensitivity and specificity of the high signal intensity in the SCP of patients with PSP was 19.6% and 100%, respectively. This finding was more frequently observed in patients with PSP with Richardson's syndrome (PSP-RS) (25.7%) than other phenotypes (6.2%). CONCLUSION: The high signal intensity in the SCP on FLAIR MRI might be an effective diagnostic tool for PSP-RS.

Rivastigmine Improves Appetite by Increasing the Plasma Acyl/Des-Acyl Ghrelin Ratio and Cortisol in Alzheimer Disease.

BACKGROUND: Weight loss accelerates cognitive decline and increases mortality in patients with dementia. While acetylcholinesterase (AChE) inhibitors are known to cause appetite loss, we sometimes encounter patients in whom switching from donepezil (AChE inhibitor) to rivastigmine (AChE and butyrylcholinesterase [BuChE] inhibitor) improves appetite. Since BuChE inactivates ghrelin, a potent orexigenic hormone, we speculated that rivastigmine improves appetite by inhibiting BuChE-mediated ghrelin inactivation. METHODS: The subjects were patients with mild to moderate Alzheimer disease treated with either rivastigmine patch (n = 11) or donepezil (n = 11) for 6 months. Before and after treatment, we evaluated appetite (0, decreased; 1, slightly decreased; 2, normal; 3, slightly increased; 4, increased), cognitive function, and blood biochemical variables, including various hormones. RESULTS: Rivastigmine treatment significantly improved appetite (from 1.6 ± 0.5 to 2.6 ± 0.7), whereas donepezil treatment did not (from 2.0 ± 0.0 to 1.8 ± 0.4). Simultaneously, rivastigmine, but not donepezil, significantly decreased the serum cholinesterase activity (from 304.3 ± 60.5 to 246.8 ± 78.5 IU/L) and increased the cortisol level (from 11.86 ± 3.12 to 14.61 ± 3.29 µg/dL) and the acyl/des-acyl ghrelin ratio (from 4.03 ± 2.96 to 5.28 ± 2.72). The levels of leptin, insulin, total ghrel-in, and cognitive function were not significantly affected by either treatment. CONCLUSIONS: Our results suggest that compared with donepezil, rivastigmine has the advantage of improving appetite by increasing the acyl/des-acyl ghrelin ratio and cortisol level, thereby preventing weight loss.

Step Numbers and Hoehn-Yahr Stage after Six Years.

BACKGROUND: Freezing of gait (FOG) has been linked to increased numbers of steps taken while walking. We tested the hypothesis that an increased number of steps associated with FOG might predict the exacerbation of the severity of Parkinson's disease (PD). METHODS: We prospectively studied 26 patients. Clinical assessments were performed and balance was evaluated in 30 patients with Hoehn-Yahr stage III PD 6 years previously. Gait parameters were analyzed with the use of an originally designed, suddenly narrowed path. PD-related independent variables, balance investigation-related variables, and gait-independent-related variables were analyzed by multiple logistic regression analysis. RESULTS: The Hoehn-Yahr stage increased in 14 patients and was unchanged in 12 patients. The 36-item Short-Form Health Survey score (OR 1.079, p = 0.041, 95% CI 1.003-1.161) and the number of steps on the suddenly narrow path (OR 1.605, p = 0.047, 95% CI 1.006-2.56) were related to an increase in the Hoehn-Yahr stage. The number of steps was significantly higher on the suddenly narrowed path (11.3 ± 3.6) than on a straightly narrowed path (10.1 ± 3.2) at the time of final follow-up in the 26 patients (p < 0.001). CONCLUSIONS: An increased number of steps associated with FOG, which was elicited by the suddenly narrowed path, might be one predictor of an upgrade of stage in patients with Hoehn-Yahr stage III PD.

Characteristic MRI Findings of upper Limb Muscle Involvement in Myotonic Dystrophy Type 1.

The objective of our study was to evaluate the relation between muscle MRI findings and upper limb weakness with grip myotonia in patients with myotonic dystrophy type 1 (DM1). Seventeen patients with DM1 were evaluated by manual muscle strength testing and muscle MRI of the upper limbs. Many DM1 patients presenting with decreased grasping power frequently showed high intensity signals in the flexor digitorum profundus (FDP) muscles on T1-weighted imaging. Patients presenting with upper limb weakness frequently also showed high intensity signals in the flexor pollicis longus, abductor pollicis longus, and extensor pollicis muscles. Disturbances of the distal muscles of the upper limbs were predominant in all DM1 patients. Some DM1 patients with a prolonged disease duration showed involvement of not only distal muscles but also proximal muscles in the upper limbs. Muscle involvement of the upper limbs on MRI strongly correlated positively with the disease duration or the numbers of CTG repeats. To our knowledge, this is the first study to provide a detailed description of the distribution and severity of affected muscles of the upper limbs on MRI in patients with DM1. We conclude that muscle MRI findings are very useful for identifying affected muscles and predicting the risk of muscle weakness in the upper limbs of DM1 patients.

Comparison of brain 3.0-T with 1.5-T MRI in patients with multiple sclerosis: a 6-month follow-up study.

OBJECTIVES: The 2010 revisions to the McDonald criteria for the diagnosis of multiple sclerosis (MS) were recently published. One objective of the revision was to simplify the MRI criteria. The MRI criteria do not specify magnetic field strength. We studied whether there was any difference in diagnosis between brain 3.0-T and 1.5-T MRI according to the 2010 revisions of the McDonald criteria. PATIENTS AND METHODS: We prospectively studied brain 3.0-T and 1.5-T MRI in 22 patients with MS. 1.5-T MRI was performed 24h after 3.0-T MRI, and the scanning protocol included contiguous axial sections of T2-weighted images (T2WI), T1WI, and enhanced T1WI. These two different MRI and neurological assessments were scheduled to be repeated 3 and 6 months after study entry. RESULTS: The regions where MS lesions were better visualized on 3.0-T MRI tended to be in deep white matter on T2WI. Dissemination of lesions in space and time was similar for 3.0-T and 1.5-T MRI. CONCLUSION: Our study found no difference between brain 3.0-T and 1.5-T MRI. There was no apparent impact of brain 3.0-T MRI on the diagnosis of MS according to the 2010 version of the MRI criteria.

Cerebellar dentate nucleus in progressive supranuclear palsy.

OBJECTIVES: Some patients with progressive supranuclear palsy (PSP) present with cerebellar dysfunction. Severe degeneration of the cerebellar dentate nucleus (CDN) was evident in these patients. We evaluated signal intensity on MRI in the CDN of PSP patients with or without cerebellar ataxia. PATIENTS AND METHODS: We reviewed the clinical histories and brain MRI studies of 28 patients with clinically probable PSP. Three disease control groups were studied: a group of 28 sex- and age-matched patients with Parkinson's disease (PD), a group of 15 patients with multiple system atrophy with predominant parkinsonian features (MSA-P), and 15 control subjects. Turbo spin-echo sequences for T2-weighted images were used using a 1.5T magnetic resonance imager. RESULTS: Eight patients with PSP (28%) and one patient with MSA-P (6%) had heterogeneous regions in the CDN. This finding was not evident in the patients with PD or controls. Three out of four PSP patients with cerebellar ataxia had heterogeneous regions in the CDN and other one patient with cerebellar ataxia as the initial and principal symptoms had no heterogeneous regions in the CDN. CONCLUSION: Heterogeneous regions in the CDN on MRI do not always reflect cerebellar ataxia in PSP patients, and this finding might be an additional marker to support a probable diagnosis of PSP.

Bihemispheric subcortical infarcts in the middle cerebral artery territory.

BACKGROUND AND PURPOSE: Previous studies have suggested embolic mechanisms for bihemispheric subcortical infarcts involving the anterior and posterior circulation. However, the mechanism of bihemispheric subcortical infarcts in middle cerebral artery (MCA) territories remains uncertain. We describe a patient with acute bihemispheric subcortical infarcts in restricted MCA territories suggesting an embolic mechanism. CASE DESCRIPTION: A 62-year-old woman with a history of hypertension and hyperlipidemia suddenly presented with left hemiplegia. Diffusion-weighted and T(2)-weighted magnetic resolution imaging of the brain showed multiple subcortical high intensity in the MCA territories. There were no acute infarctions in the cerebrum, brain stem, or cerebellum, including cortical lesions. The patient had no carotid, internal carotid artery, or MCA disease. CONCLUSION: Bihemispheric subcortical infarcts in the MCA territory are likely to have a proximal embolic source and such infarcts could be associated with multiple subcortical infarcts due to small vessel disease.

Risk of falling in Parkinson's disease at the Hoehn-Yahr stage III.

BACKGROUND: It is difficult to predict the risk of falling, especially in patients with good motor ability, and the mechanisms underlying the relation between gait patterns and falling in Parkinson's disease (PD) remain unclear. We investigated factors related to falling, including walking speed and time, in patients with Hoehn-Yahr stage III PD. METHODS: We performed clinical assessments and evaluated balance in 30 patients with PD. Information on falling was obtained from questionnaires and personal interviews. Gait patterns were analyzed with the use of an originally designed, suddenly narrowed path. RESULTS: Gait velocity was slower in fallers than in non-fallers (p = 0.047). Unified Parkinson's Disease Rating Scale part II (UPDRS part II) score, fear of falling, and gait velocity were significantly related to falling on analysis with a single logistic model. When a multiple logistic model was used, the UPDRS part II score was significantly related to falling (OR: 1.48, p = 0.037, 95% CI: 1.02-2.16). CONCLUSIONS: Patients with Hoehn-Yahr stage III PD showed slow gait velocity attributed to fear of falling before arrival at a narrowed entrance or while walking on a narrowed path. The UPDRS part II score is significantly related to the risk of future falls.

Infarction limited to both middle cerebellar peduncles.

BACKGROUND: The middle cerebellar peduncle (MCP) is supplied mainly by the anterior inferior cerebellar artery and partly by the superior cerebellar artery. The bilateral MCP infarctions in previous patients were attributed to alternations of two vessels, such as the unilateral vertebral artery and basilar artery or both vertebral arteries. METHODS: We describe a case of bilateral acute infarction of the MCP and the stroke was apparently caused by occlusion of only one vertebral artery. RESULTS: A 63-year-old man presented with vertigo and auditory distortion, accompanied by difficulty in speaking and walking. Neurological examinations revealed bilateral horizontal nystagmus, scanning speech, and ataxia of the trunk and all four limbs. Brain MRI showed high signal intensity in the both MCPs on diffusion-weighted and T2-weighted images. Enhanced computed tomographic angiography showed fusiform dilatation at the V4 level of the right vertebral artery; a false lumen was evident in the dilatation. Right vertebral angiography showed occlusion from the C1 level to the foramen magnum. Left vertebral angiography revealed a hypoplastic vertebral artery with a maximum diameter of 2.5 mm. CONCLUSIONS: Alternations of the vertebral artery should be considered as a possible cause of MCP infarction, particularly when such anomalies are suggested.