Cardiovascular Autonomic Dysfunction in Mild and Advanced Parkinson's Disease.

OBJECTIVE: The purpose of the present study was to investigate cardiovascular autonomic dysfunction in patients with Parkinson's disease (PD) with mild to severe stages of motor symptoms and to compare cardiovascular autonomic dysfunction between drug-naïve and dopaminergic drug-treated groups. METHODS: This study included 188 PD patients and 25 age-matched healthy controls who underwent head-up tilt-testing, 24-h ambulatory blood pressure (BP) monitoring and 24-h Holter monitoring. Autonomic function test results were evaluated among groups categorized by motor symptom severities (mild vs. moderate vs. severe) and treatment (drug-naïve or dopaminergic drug treatment). RESULTS: Orthostatic hypotension and supine hypertension were more frequent in patients with PD than in healthy controls. The frequencies of orthostatic hypotension, supine hypertension, nocturnal hypertension and non-dipping were not different among groups. Additionally, no significant differences were detected in supine BP, orthostatic BP change, nighttime BP, nocturnal BP dipping, or heart rate variabilities among groups. CONCLUSIONS: Cardiovascular autonomic dysfunction is not confined to moderate to severe PD patients, and starts early in the course of the disease in a high proportion of PD patients. In addition, dopaminergic drug treatments do not affect cardiovascular autonomic function.

Supra-additive neuroprotection by renexin, a mixed compound of ginkgo biloba extract and cilostazol, against apoptotic white matter changes in rat after chronic cerebral hypoperfusion.

BACKGROUND AND PURPOSE: White-matter (WM) lesions are known to potentiate cognitive impairment in poststroke patients. The present study was designed to assess whether Ginkgo biloba extract (GB) and cilostazol, which were evaluated alone and in a combination formula (Renexin), can attenuate the WM lesions and cognitive decline caused by chronic hypoperfusion in the rat. METHODS: ANIMALS WERE DIVIDED INTO FIVE TREATMENT GROUPS: cilostazol (25 mg/kg/day), GB (20 mg/kg/day), Renexin (25 mg/kg/day cilostazol + 20 mg/kg/day GB), vehicle, and sham. The animals received the treatments orally 1 day after bilateral common carotid artery occlusion [two-vessel occlusion (2VO); except for the sham group, which underwent the surgery but the arteries were not occluded], and then the same dose every day for 21 days thereafter. Prior to sacrificing the rats, repetitive eight-arm radial maze testing was performed to examine their cognitive abilities. After drug administration and cognitive testing, brain tissues were isolated for Klüver-Barrera and terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick end-labeling (TUNEL) staining, immunohistochemical assessment of glial fibrillary acidic protein (GFAP) and CD11b (OX-42), and to assay free-radical scavenging activity. RESULTS: We found that the significant WM lesions induced by 2VO was ameliorated significantly by treatment with cilostazol, GB, and Renexin, in association with increased TUNEL-positive cells. In addition, chronic cerebral hypoperfusion caused a large increase in the degree of GFAP and OX-42 immunoreactivity and free-radical activity in the optic tract. These abnormalities were significantly reversed by the three drugs, but most prominently by Renexin, suggesting a markedly enhanced or supra-additive effect of cilostazol and GB when administered together. CONCLUSIONS: Significant attenuation of cytoarchitectural damage and apoptotic cell death was found with GB and cilostazol, but a markedly enhanced effect was seen for treatment with their combination in the WM of rat brains after bilateral occlusion of the common carotid arteries. We suggest that combination therapy with GB and cilostazol provides enhanced neuroprotective effects and induces subsequent cognitive improvement in patients with chronic ischemic conditions.

Central pontine and extrapontine myelinolysis that developed during alcohol withdrawal, without hyponatremia, in a chronic alcoholic.

Central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) are osmotic demyelination syndrome. A 45-year-old man with a history of alcoholism visited the ER with dysarthria and dysphagia for 2 days. These symptoms occurred 3 days after he had stopped drinking alcohol. The neurological symptoms progressed to anarthria, pseudobulbar palsy and gait disturbance. During admission, the electrolyte studies were within the normal range. Diffusion-weighted images revealed high signal intensities in the pons, thalamus and basal ganglia. Apparent diffusion coefficient image showed low signal intensities in the pontine lesion, but isosignal intensities in the extrapontine lesion. The symptoms gradually improved after 1 month with only conservative treatment. The 1 month-follow-up MRI showed significant reduction of the previous extrapontine lesions. These findings suggest that cytotoxic edema is central to the pathogenesis of CPM, but vasogenic edema plays an important role in the pathogenesis of EPM occurring during alcohol withdrawal.

Differential expression of activating transcription factor-2 and c-Jun in the immature and adult rat hippocampus following lithium-pilocarpine induced status epilepticus.

PURPOSE: Lithium-pilocarpine induced status epilepticus (LPSE) causes selective and age-dependent neuronal death, although the mechanism of maturation-related injury has not yet been clarified. The activating transcription factor-2 (ATF-2) protein is essential for the normal development of mammalian brain and is activated by c-Jun N-terminal kinase (JNK). It induces the expression of the c-jun gene and modulates the function of the c-Jun protein, a mediator of neuronal death and survival. Therefore, we investigated the expression of c-Jun and ATF-2 protein in the immature and adult rat hippocampus to understand their roles in LPSE-induced neuronal death. MATERIALS AND METHODS: Lithium chloride was administrated to P10 and adult rats followed by pilocarpine. Neuronal injury was assessed by silver and cresyl violet staining, performed 72 hours after status epilepticus. For evaluation of the expression of ATF-2 and c-Jun by immunohistochemical method and Western blot, animals were sacrificed at 0, 4, 24, and 72 hours after the initiation of seizure. RESULTS: Neuronal injury and expression of c-Jun were maturation-dependently increased by LPSE, whereas ATF-2 immunoreactivity decreased in the mature brain. Since both c-Jun and ATF-2 are activated by JNK, and targets and competitors in the same signal transduction cascade, we could speculate that ATF-2 may compete with c-Jun for JNK phosphorylation. CONCLUSION: The results suggested a neuroprotective role of ATF-2 in this maturation-related evolution of neuronal cell death from status epilepticus.

Serotonin transporter protein polymorphism and harm avoidance personality in migraine without aura.

OBJECTIVE: To investigate polymorphisms in the serotonin transporter protein gene and harm avoidance personality dimension in patients with migraine without aura (MWOA). BACKGROUND: The serotonin transporter protein is a key modulator of serotonergic synaptic neurotransmission. Two polymorphic regions of the gene for serotonin transporter protein have been found, and are associated with variations in the functional activity of serotonin caused by differing transcriptional efficiency. The harm avoidance (HA) personality trait may also be heritable and associated with altered serotonergic neurotransmitter activity. DESIGN: We amplified the polymorphism in the promoter of serotonin transporter protein (5-HTTLPR) and the variable number of tandem repeats polymorphism within intron 2 (VNTR) using the polymerase chain reaction and performed genotype polymorphism analyses in 97 patients with MWOA and 100 healthy controls. We investigated serotonin-related personality traits by evaluating the HA personality dimension using a tridimensional questionnaire. RESULTS: The genotype frequencies and allele distributions of 5-HTTLPR did not differ between patients with MWOA and controls. The VNTR genotype STin2.12/STin2.12 was significantly more common in patients with MWOA (90%) than in controls (77%; P= .017). Patients with MWOA also had HA scores (21.9 +/- 6.4) significantly higher than those of controls (16.3 +/- 6.1; P < .001). CONCLUSIONS: Serotonergic activity might be involved in the development of MWOA and VNTR of serotonin transporter gene might be one of the genetically contributing factors.

Periodic limb movement during sleep developed after pontine lesion.

We describe 2 patients who suffered a pontine infarction and subsequently developed periodic leg movement (PLM). The temporal relationship between a stroke and subsequent PLM, as well as the absence of sleep-related disorders in patients' histories, favors the argument of a cause-and-effect relationship, with the observed association providing evidence for an anatomic substrate for PLM.

Perioperative stroke in the brain and spinal cord following an induced hypotension.

A 49-year-old woman presented with stupor and paraplegia following an induced hypotension. The temporal relationship to the induced hypotension and the absence of a clear embolic source on diagnostic tests support a causal association between the hypotensive episode and the ischemic infarct. However, despite the association, a cause-and-effect relationship could not be automatically inferred.

Decreased striatal dopamine transporter binding in a patient with extrapontine myelinolysis.

We describe the case of a 61-year-old woman who developed extrapontine myelinolysis (EPM) with parkinsonism. Decreased striatal dopamine transporter binding assessed by [(123)I]N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane and single photon emission computed tomography ([(123)I]IPT) SPECT) were observed in the patient, suggesting that osmotic injury causes the demyelination of nigrostriatal dopaminergic neurons and that such injury may be involved in the pathogenesis of EPM with parkinsonism.

The apolipoprotein E epsilon4 haplotype is an important predictor for recurrence in ischemic cerebrovascular disease.

OBJECTIVE: To determine whether a specific apolipoprotein E (APOE) allele is a predictor for ischemic cerebrovascular disease (ICVD). BACKGROUND: The role of APOE in atherosclerosis has been a focus of intensive research. The APOE epsilon4 allele is overrepresented in Alzheimer's disease, atherosclerosis, ischemic heart disease, and ICVD. Also, epsilon4 carriers have higher cholesterol levels than non-epsilon4 carriers. METHODS: We performed a prospective, longitudinal study on patients who have ICVD. The patients were recruited from St. Mary Hospital, Korea, and investigated for ICVD through interviews and by reviewing their medical records and neuroimaging studies. APOE genotypes were determined for each patient. RESULTS: 20 of the 91 enrolled patients had recurrent ICVD, yielding a 3-year cumulative recurrence rate of 22%. Carriers of the epsilon4 allele had a 3-year recurrence rate of 53%, as compared with only 16% for patients who had the APOE non-epsilon4 allele (the risk ratio was 4.11; the 95% CI was 1.49-11.32; P<0.01). CONCLUSIONS: Our results make possible the identification of patients with ICVD who are at high risk for recurrence by assessing their APOE genotype. Also, this data might be clinically useful in methods for assessing potential strategies for prevention.