BACKGROUND AND PURPOSE: The detection of alpha-synuclein in the body fluids of patients with synucleinopathy has yielded promising but inconclusive results, in part because of conformational changes of alpha-synuclein in response to environmental conditions. The aim of this study was to determine the feasibility of using alpha-synuclein as a biological marker for Parkinson's disease (PD). METHODS: Twenty-three drug-naive patients with PD (age 62.4+/-12.7 years, mean+/-SD; 11 males) and 29 age- and sex-matched neurologic control subjects (age 60.1+/-16.2 years; 16 males) were recruited. The levels of oligomeric and total alpha-synuclein in the cerebrospinal fluid (CSF) and plasma were measured using two simultaneous enzyme-linked immunosorbent assays. RESULTS: The level of alpha-synuclein oligomer in the CSF of PD patients was significantly higher in PD patients than in neurological controls, but other findings (plasma alpha-synuclein oligomer and total alpha-synuclein in CSF and plasma) did not differ significantly between the two groups. When the control subjects were divided into a symptomatic control group (11 patients who complained of parkinsonian symptoms and were diagnosed with hydrocephalus and drug-induced or vascular parkinsonism) and a neurologic control group (10 normal subjects and 8 patients with diabetic ophthalmoplegia), the level of alpha-synuclein oligomer in the CSF was still significantly higher in PD patients than in both of the control subgroups. CONCLUSIONS: These findings provide further evidence for a pathogenic role of the alpha-synuclein oligomer and suggest that CSF levels of alpha-synuclein oligomer can be a reliable marker for PD.
alpha-Synuclein ; Biomarkers ; Body Fluids ; Enzyme-Linked Immunosorbent Assay ; Humans ; Hydrocephalus ; Parkinson Disease ; Plasma

BACKGROUND AND PURPOSE: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited microangiopathy caused by mutations in the Notch3 gene. Although previous studies have shown an association between lacunar infarction and cognitive impairment, the relationship between MRI parameters and cognition remains unclear. In this study we investigated the influence of MRI parameters on cognitive impairment in CADASIL. METHODS: We applied a prospective protocol to 40 patients. MRI analysis included the normalized volume of white-matter hyperintensities (nWMHs), number of lacunes, and number of cerebral microbleeds. Cognition was assessed with the aid of psychometric tests [Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognition (ADAS-cog), Trail-Making Test, and Stroop interference (Stroop IF)]. RESULTS: A multivariate regression analysis revealed that the total number of lacunes influenced the performance in the MMSE, ADAS-cog, and Stroop IF, while nWMHs had a strong univariate association with ADAS-cog and Stroop IF scores. However, this association disappeared in the multivariate analysis. CONCLUSIONS: These findings demonstrate that the number of lacunes is the main predictive factor of cognitive impairment in CADASIL.
Alzheimer Disease ; CADASIL ; Cognition ; Humans ; Leukoencephalopathies ; Prospective Studies ; Psychometrics ; Stroke, Lacunar

BACKGROUND AND PURPOSE: Remnant lipoproteins (RLPs) are products of partially catabolized chylomicrons and very-low-density lipoprotein, from which some triglycerides have been removed. These particles are smaller and denser than the parent particles and are believed to be strongly atherogenic. We explored the association between RLP cholesterol (RLP-C) and ischemic stroke, including stroke subtypes. METHODS: A cohort of 142 ischemic stroke patients (90 men and 52 women; age, 65.2+/-12.8 years, mean+/-SD) was enrolled; all had acute infarcts confirmed by diffusion-weighted MRI, and had fasting lipograms. A full stroke-related evaluation was conducted on each patient. An outpatient population of 88 subjects without a history of cerebrovascular or cardiovascular disease served as a control group. Serum RLP fractions were isolated using an immunoaffinity gel containing specific antiapolipoprotein (anti-apo)B-100 and anti-apoA-I antibodies. RLP-C values were considered to be high when they were in the highest quartile of all values in the study. RESULTS: High RLP-C values were more common in stroke patients than in control patients (31.0% vs. 14.8%, p=0.01), when 5.6 mg/dL (>75th percentile) was used as the cutoff value. Multivariable analyses indicated that RLP-C was a risk factor for stroke, with an odds ratio of 2.54 (p=0.045). The RLP-C level was higher in the large artery atherosclerosis subgroup (5.7+/-3.9 mg/dL) than in any other stroke subgroup (small vessel occlusion, 4.9+/-5.9 mg/dL; cardioembolism, 1.8+/-2.3 mg/dL; stroke of undetermined etiology, 3.1+/-2.9 mg/dL). CONCLUSIONS: We have found an association between high RLP-C levels and ischemic stroke, and in particular large artery atherosclerotic stroke.
Antibodies ; Arteries ; Atherosclerosis ; Cardiovascular Diseases ; Cholesterol ; Chylomicrons ; Cohort Studies ; Fasting ; Glycosaminoglycans ; Humans ; Lipoproteins ; Male ; Odds Ratio ; Outpatients ; Parents ; Risk Factors ; Stroke ; Triglycerides

BACKGROUND AND PURPOSE: Plasma D-dimer levels are elevated during the acute phase of cerebral infarction (CI). We investigated whether the D-dimer level on admission and other clinical characteristics could be used to predict the poor outcome of patients with acute CI. METHODS: The clinical characteristics and plasma D-dimer levels measured within 3 days of onset were compared according to outcome among patients with acute CI. RESULTS: In total, 359 consecutive patients (mean age, 71.8 years) were examined, of which 174 had a poor outcome [score on the modified Rankin scale (mRS) > or =3] at 30 days after hospitalization. The mean mRS score was higher and a poor outcome was observed more frequently among women than among men (p<0.001 for each). The proportions of women, cardioembolism, atrial fibrillation, advanced age (> or =75 years), prior history of CI or transient ischemic attack, and elevated D-dimer level (> or =1.0 microg/mL) were significantly higher among patients with a poor outcome than among those with a good outcome. A multivariate analysis showed that elevated D-dimer level [> or =1.0 microg/mL; odds ratio (OR), 2.45; 95% confidence interval (95% CI), 1.52-3.89; p<0.01], advanced age (OR, 1.93; 95% CI, 1.21-3.07; p<0.01), and female gender (OR, 1.75; 95% CI, 1.08-2.83; p=0.02) were independent predictors of a poor outcome. CONCLUSIONS: Certain clinical characteristics (gender and advanced age) and an elevated D-dimer level upon admission can be used to predict the outcome of patients with acute CI at 30 days after hospitalization.
Atrial Fibrillation ; Cerebral Infarction ; Female ; Fibrin Fibrinogen Degradation Products ; Hospitalization ; Humans ; Ischemic Attack, Transient ; Male ; Multivariate Analysis ; Odds Ratio ; Plasma ; Stroke

Vestibular rehabilitation therapy (VRT) is an exercise-based treatment program designed to promote vestibular adaptation and substitution. The goals of VRT are 1) to enhance gaze stability, 2) to enhance postural stability, 3) to improve vertigo, and 4) to improve activities of daily living. VRT facilitates vestibular recovery mechanisms: vestibular adaptation, substitution by the other eye-movement systems, substitution by vision, somatosensory cues, other postural strategies, and habituation. The key exercises for VRT are head-eye movements with various body postures and activities, and maintaining balance with a reduced support base with various orientations of the head and trunk, while performing various upper-extremity tasks, repeating the movements provoking vertigo, and exposing patients gradually to various sensory and motor environments. VRT is indicated for any stable but poorly compensated vestibular lesion, regardless of the patient's age, the cause, and symptom duration and intensity. Vestibular suppressants, visual and somatosensory deprivation, immobilization, old age, concurrent central lesions, and long recovery from symptoms, but there is no difference in the final outcome. As long as exercises are performed several times every day, even brief periods of exercise are sufficient to facilitate vestibular recovery. Here the authors review the mechanisms and the key exercises for each of the VRT goals.
Activities of Daily Living ; Cues ; Exercise ; Head ; Humans ; Immobilization ; Orientation ; Posture ; Vertigo ; Vision, Ocular

The prognosis of myasthenia gravis (MG) has improved dramatically due to advances in critical-care medicine and symptomatic treatments. Its immunopathogenesis is fundamentally a T-cell-dependent autoimmune process resulting from loss of tolerance toward self-antigens in the thymus. Thymectomy is based on this immunological background. For MG patients who are inadequately controlled with sufficient symptomatic treatment or fail to achieve remission after thymectomy, remission is usually achieved through the addition of other immunotherapies. These immunotherapies can be classified into two groups: rapid induction and long-term maintenance. Rapid induction therapy includes intravenous immunoglobulin (IVIg) and plasma exchange (PE). These produce improvement within a few days after initiation, and so are useful for acute exacerbation including myasthenic crisis or in the perioperative period. High-dose prednisone has been more universally preferred for remission induction, but it acts more slowly than IVIg and PE, commonly only after a delay of several weeks. Slow tapering of steroids after a high-dose pulse offers a method of maintaining the state of remission. However, because of significant side effects, other immunosuppressants (ISs) are frequently added as "steroid-sparing agents". The currently available ISs exert their immunosuppressive effects by three mechanisms: 1) blocking the synthesis of DNA and RNA, 2) inhibiting T-cell activation and 3) depleting the B-cell population. In addition, newer drugs including antisense molecule, tumor necrosis factor alpha receptor blocker and complement inhibitors are currently under investigation to confirm their effectiveness. Until now, the treatment of MG has been based primarily on experience rather than gold-standard evidence from randomized controlled trials. It is hoped that well-organized studies and newer experimental trials will lead to improved treatments.
Autoantigens ; B-Lymphocytes ; Complement System Proteins ; DNA ; Humans ; Immunoglobulins ; Immunoglobulins, Intravenous ; Immunosuppressive Agents ; Immunotherapy ; Myasthenia Gravis ; Perioperative Period ; Plasma Exchange ; Prednisone ; Prognosis ; Remission Induction ; RNA ; Steroids ; T-Lymphocytes ; Thymectomy ; Thymus Gland ; Tumor Necrosis Factor-alpha

Spontaneous primary medullary hemorrhage is a rare event. A 64-year-old man was admitted for sudden-onset vertigo and vomiting. His clinical features were similar to those of lateral medullary syndrome. The patient had no anticoagulant therapy, vascular malformation, or a caudal extension of a pontine hemorrhage. The patient had multiple hypertensive changes, including retinopathy, left ventricular hypertrophy on electrocardiography, multiple cerebral microbleeds, and small-vessel changes on MRI. T2*-weighted gradient echo MRI performed 3 months prior to admission and contrast-enhanced MRI showed no evidence of vascular malformation. We concluded that the patient had uncontrolled hypertension that may have lead to primary medullary hemorrhage.
Electrocardiography ; Hemorrhage* ; Humans ; Hypertension* ; Hypertrophy, Left Ventricular ; Lateral Medullary Syndrome ; Magnetic Resonance Imaging ; Middle Aged ; Vascular Malformations ; Vertigo ; Vomiting

Cortical laminar necrosis has been rarely observed in osmotic demyelination syndrome. We report a 32-year-old female patient who became comatose after the rapid correction of hyponatremia. There were high signal intensities in the pons and bilateral deep gray nuclei on T2-weighted MRI images, and linear hyperintensities along the cerebral cortices on T1-weighted images with a diffuse gyriform enhancement. MR spectroscopic findings showed a decrease of the N-acetyl aspartate peak and an increase in those of the lipid and lactate complex. The case demonstrates that a severe form of osmotic demyelination syndrome accompanying cortical laminar necrosis can result from the rapid correction of hyponatremia.
Adult ; Aspartic Acid ; Cerebral Cortex ; Coma ; Demyelinating Diseases* ; Female ; Humans ; Hyponatremia ; Lactic Acid ; Magnetic Resonance Imaging ; Necrosis* ; Pons

BACKGROUND AND PURPOSE: The closing-in phenomenon is the tendency to draw near or on the target when copying figures, which has been found mostly in patients with Alzheimer's disease (AD). We attempted to quantify the degree of closing-in and to compare it between patients with AD and vascular dementia (VaD). METHODS: The subjects (55 AD, 39 VaD and 38 normal controls) were asked to copy the figure of alternating square and triangle, starting at the designated point and continuing from left to right. The patients with AD and VaD did not differ in age, education, severity of dementia or Rey Complex Figure Test copy score. The proximity (Y-axis) of the subject's drawing to the target was plotted at intervals of 2 mm along the X-axis and the degree of closing-in was computed from the slope of the regression line. RESULTS: The AD and VaD patients showed a steeper slope than the controls. There was no significant difference, however, in the magnitude of closing-in of the AD and VaD patients. When closing-in was defined as a slope that was greater than the mean+2SD of the slope observed for the controls, 32.7% of the AD and 25.6% of the VaD patients showed closing-in. CONCLUSIONS: Our study, using a new method of measuring the degree of closing-in, suggests that this phenomenon is not specific to AD.
Alzheimer Disease* ; Dementia ; Dementia, Vascular* ; Education ; Humans

BACKGROUND AND PURPOSE: Blepharospasm (BSP) and apraxia of eyelid opening (AEO) have been reported as dystonia related with parkinsonism. However, systematic analysis of clinical characteristics of BSP and AEO in parkinsonism has been seldom reported. To investigate the clinical characteristics of BSP and AEO in parkinsonism and to find out the clinical significance to differentiate parkinsonism. METHODS: We enrolled 35 patients who had BSP with or without AEO out of 1113 patients with parkinsonism (913 IPD, idiopathic Parkinson's disease; 190 MSA, multiple system atrophy, 134 MSA-p, 56 MSA-c and 10 PSP, progressive supranuclear palsy). We subdivided MSA into MSA-p (predominantly parkinsonism) and MSA-c (predominantly cerebellar) according to the diagnostic criteria proposed by Quinn. We analyzed the clinical features of BSP and parkinsonism including onset age, onset interval to BSP, characteristics of BSP, presence of AEO, coexisted dystonias on the other body parts, severity of parkinsonism and relationship with levodopa treatment. RESULTS: BSP with or without AEO were more frequently observed in atypical parkinsonism (PSP, 70%; MSA-p, 11.2%; MSA-c, 8.9%) than in IPD (0.9%). Reflex BSP was observed only in atypical parkinsonism (4 MSA-p, 1 MSA-c and 2 PSP). BSP preceding parkinsonism (Pre-BSP) was observed mainly in atypical parkinsonism (2 MSA-p, 1 MSA-c, 1 PSP and 1 IPD). The presence of AEO was more frequent in atypical parkinsonism than in IPD, but isolated AEO was not detected. BSP related to levodopa ('off' symptom or 'peak-dose' effect) were observed only in IPD. CONCLUSIONS: Reflex BSP, Pre-BSP and the presence of AEO may be a unique feature of atypical parkinsonism. BSP related to levodopa might be representative of IPD. No differences were found in the clinical features of BSP between MSA-p and MSA-c.
Age of Onset ; Apraxias* ; Blepharospasm* ; Dystonia ; Eyelids* ; Human Body ; Humans ; Levodopa ; Multiple System Atrophy ; Parkinson Disease ; Parkinsonian Disorders* ; Reflex