Cortical and Internal Watershed Infarcts Might Be Key Signs for Predicting Neurological Deterioration in Patients with Internal Carotid Artery Occlusion with Mild Symptoms.

BACKGROUND: Treatment for acute ischemic stroke due to large vessel occlusion (LVO) with mild symptoms is under discussion. Although most patients have good outcomes, some patients deteriorate and have unfavorable results. Imaging findings that predict the prognosis of LVO with mild symptoms are needed to identify patients who require treatment. In this study, we focused on watershed infarctions (WSIs), because this clinical phenomenon quite sensitively reflects changes in cerebral blood flow. The purpose of this study was to assess positive rates of WSI on MRI findings in patients with internal carotid artery (ICA) occlusion, and compare WSI-positive rates between patients divided according to their clinical course. METHODS: We retrospectively collected data of 1,531 patients who presented with acute ischemic stroke between June 2006 and July 2019. Among them, we chose symptomatic ICA occlusion patients with a past history of atrial fibrillation who were treated conservatively. We divided these patients into two groups, those with maintenance or improvement in their NIHSS score after hospitalization, and those whose NIHSS score worsened. We compared WSI-positive rates between these two groups. RESULTS: Thirty-seven of the 1,531 patients were included in this study. Of them, total NIHSS score was maintained or improved in 8 patients (group A), 3 of whom (37.5%) had internal watershed infarctions (IWIs). In group B, consisting of patients whose NIHSS score worsened by >2 at 7 days from symptom onset, 24 (82.8%) had IWIs. Group A thus had statistically lower IWI positivity rates than group B (p = 0.02). Three patients (37.5%) in group A had cortical watershed infarctions (CWIs), while 27 patients in group B (93.1%) had CWIs. Group A thus had a significantly lower CWI positivity rate than group B (p = 0.002). CONCLUSION: In patients with mildly symptomatic ICA occlusion, CWIs and IWIs might be key signs for predicting neurological deterioration after hospitalization.

Chronic subdural hematoma in a patient with congenital afibrinogenemia successfully treated with fibrinogen replacement.

A 37-year-old woman with congenital afibrinogenemia presented with chronic subdural hematoma (CSDH) manifesting as severe headache, nausea, and somnolence after a minor head trauma. Brain computed tomography scans showed a right subdural hematoma associated with midline shift. Laboratory studies showed prolongation of prothrombin time, activated partial thromboplastin time, and undetectably low level of fibrinogen. Until the present episode, she had received plasma-derived fibrinogen concentrate around menstruation and pregnancy. She had also suffered from spinal cord infarction due to vertebral artery occlusion. Burr-hole evacuation and drainage of CSDH was successfully performed using fibrinogen concentrate. The development of CSDH with afibrinogenemia is very rare. Although the past repeated administrations of fibrinogen concentrate were suspected to generate CSDH, paradoxical thrombotic complications caused by upregulation of prothrombin activation, thrombin generation, and growth factors released from platelets might be related to the development of CSDH with congenital afibrinogenemia.

Dynamic changes of striatal dopamine D2 receptor binding at later stages after unilateral lesions of the medial forebrain bundle in Parkinsonian rat models.

Our previous study regarding the changes of D(2) receptor in nigrostriatal dopamine system at an early stage (4 weeks after lesion) indicated a different functional activity of striatal D(2) receptor between two different rat parkinsonian models, lesioning with 6-hydroxydopamine in the striatum and in the medial forebrain bundle (MFB). In the present study, we further examined binding of D(2) receptor as well as pre-synaptic dopamine transporter (DAT) at later stages (6 months after lesion) both in the striatal and MFB lesion models. The D(2) receptor binding in MFB model at 6 months after lesion was significantly lower than that at 4 weeks after lesion, albeit it was still higher than the normal side. The D(2) receptor binding in striatal model was decreased to the same extent at both 4 weeks and 6 months after lesion. DAT binding decreased at 6 months after lesion, more profound in MFB model, and the degree of reduction was not different from that at 4 weeks after lesion. These findings indicated different dynamic processes of the D(2) receptor and DAT during a longer time observation in the striatal and MFB lesion models. The dynamic changes of D(2) receptor activity after lesion should be considered when selecting 6-hydroxydopamine-induced rat parkinsonian models.

The different performance among motor tasks during the increasing current intensity of deep brain stimulation of the subthalamic nucleus in rats with different degrees of the unilateral striatal lesion.

Of all the parameters in the deep brain stimulation (DBS) of the subthalamic nucleus (STN) in the Parkinson disease (PD) animal models, the selection of the stimulation current intensity is alterable and argumentative to affect the stimulation charge or charge density. In order to observe the different performances among several motor tasks during the STN-DBS in rats, we observed the behavioral performance during the stimulation with 0, 100, 150 and 200microA currents. We found that the DBS efficacy reached the climax during the 200microA stimulation at the methamphetamine-induced rotational behavioral test, however at the stepping test and rotarod test, the critical current were 150microA to reach the best improvements. Such findings suggest that the stimulation parameters to reach the climax efficacy among the different symptoms are different during the STN-DBS experiments in rats. The appropriate stimulation parameters should be selected by the symptoms separately according to the aim of each study.

Different striatal D2-like receptor function in an early stage after unilateral striatal lesion and medial forebrain bundle lesion in rats.

Unilateral striatal lesion and complete medial forebrain bundle (MFB) lesion by 6-hydroxydopamine in rats have been widely used as Parkinson disease (PD) models. However, the difference of pre- and post-synaptic dopamine (DA) system in these two models are not well concerned. In order to investigate the pathophysiologic difference between the MFB lesion rats and striatal lesion rats, we studied the variation of pre-synaptic DA transporter and post-synaptic D(2)-like receptor in nigrostriatal DA system using binding assay, behavioral test and a small animal PET. Our data showed that there was a same tendency of the striatal DA transporter decrease both in MFB lesion rats and striatal lesion rats 4 weeks after lesion, however, it showed increase (up-regulation) of D(2)-like receptor in the MFB lesion rats, whereas showed decrease (down-regulation) in the striatal lesion rat. This finding strongly indicated the different dynamic pathophysiologic process between the MFB lesion model and striatal lesion model. MFB lesion model mimics an early stage of PD, whereas striatal lesion model mimics Parkinson syndrome, such as vascular Parkinson syndrome. Such difference should be taken into account in the selection of these model systems.

Improvements in motor behavioral tests during deep brain stimulation of the subthalamic nucleus in rats with different degrees of unilateral parkinsonism.

Deep brain stimulation (DBS) improves motor performance in Parkinson's disease (PD) patients. To evaluate the effects of subthalamic nucleus (STN)-DBS on impaired motor behavior, we studied improvements in motor performance after delivery of unilateral stimulation to the STN in rats with mild and severe lesions of the nigrostriatal dopamine system caused by injecting 6-hydroxydopamine into the striatum. The rats were trained and performed motor behavioral tests including rotational behavior test, stepping test, and rotarod test before and after receiving DBS. We demonstrated that stimulation at a current strength of 200 microA, which stopped most of the D-amphetamine-induced rotational behaviors in these two groups, improved movement impairments in both the mild and severe groups and that the improvements in the mild group were significantly better than those in the severe group. More experimental and clinical studies are needed to evaluate the efficiency of STN-DBS for different stages of PD.

Relationship of stimulation site location within the subthalamic nucleus region to clinical effects on parkinsonian symptoms.

OBJECTIVE: To determine the relationship of the stimulation site in the subthalamic region to the clinical effects on parkinsonian symptoms, the monopolar stimulation of 4 electrode contacts and the resulting effects on parkinsonian symptoms were evaluated. METHODS: Seventeen consecutive patients (3 males and 14 females) were enrolled in the study. The patients were evaluated while in a nonmedicated state, and 10-20 min after switching on the pulse generator the effects of stimulation were assessed using separate-subset Unified Parkinson's Disease Rating Scale scores. RESULTS: The relationship between the site stimulated and the percent improvement was analyzed using polynomial regression. Rigidity (p = 0.0004, R2 = 0.15), akinesia (p = 0.02, R2 = 0.07) and total score (p = 0.009, R2 = 0.089) well fit to second-order polynomial regression and showed the greatest improvement after stimulation at 0-1 mm below the horizontal anterior-posterior commissure (AC-PC) plane. Tremor (p = 0.24, R2 = 0.18) and gait (p = 0.36, R2 = 0.001) had a weak relation to the site stimulated, but stimulation at the sites 0-1 mm below the AC-PC plane also produced greater improvement than stimulation at more ventral or dorsal sites. The percent improvement of the posture (p = 0.92, R2 = 0.002) had no relation to the site stimulated. The dorsal border of the subthalamic nucleus was located 0.6 +/- 1.2 mm (n = 27) below the AC-PC plane and the most effective electrode contact 1.2 +/- 1.3 mm (n = 27) below it. CONCLUSIONS: Stimulation around the dorsal border of the subthalamic nucleus, close to the AC-PC plane, produces greater improvement of parkinsonian symptoms than stimulation at more ventral or dorsal sites.

The stepping test and its learning process in different degrees of unilateral striatal lesions by 6-hydroxydopamine in rats.

Four different levels of the nigrostriatal dopamine system lesions were produced by injections of 6-hydroxydopamine at one-, two-, three-, or four-sites in the striatum and drug-induced rotational movement and stepping test were performed to evaluate behavioral impairments in the rat model of Parkinson's disease. A dose-dependent progressive loss of tyrosine hydroxylase-positive cells in the substance nigra pars compacta was observed in rats with striatal lesion from one- to four-sites. Though the differences in the rotational behavior and stepping test between the lesioned and control rats were highly significant, there were no differences in those behaviors among four groups of lesioned rats. During observation of these behavioral tests, the authors found that the times of trials required for acquisition of the stepping test on the first day of training, which reflected learning acuity, increased in a dose-dependent manner in the lesioned rats as compared with the controls. On the contrary, the times of trials on the next day and in the next week, which reflected retention of the acquired memories, were not different among the groups. In conclusion, the rotational movement and stepping test were not sensitive enough to distinguish severity of the striatal lesions, and learning acuity, but not retention of memories, was disturbed by the striatal lesions.

Methylenetetrahydrofolate reductase gene polymorphisms in patients with cerebral hemorrhage.

Elevated plasma total homocysteine (HCY) level is a risk factor for coronary heart disease and ischemic stroke. We investigated relationships between polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, and plasma levels of HCY and folate in patients of Mongolian races who suffered from cerebral ischemia (CI, n = 42) or cerebral hemorrhage (CH, n = 20) and in the 24 age-matched controls. The incidences of both homozygous and heterozygous MTHFR gene mutations in CI (26 and 43%) and in CH (25 and 60%) were significantly higher than those in the controls (8 and 25%). Homozygous MTHFR gene mutation was associated with reduced plasma folate levels, but not with increased plasma HCY levels. Among the subjects with homozygous MTHFR gene mutation, plasma folate levels in CH was significantly lower than those in CI and controls. MTHFR gene mutation in CH was found to be as common as that in CI and was associated with reduced plasma folate levels in the both. In homozygous MTHFR gene mutation, the plasma folate level was profoundly reduced in CH as compared with CI and controls, suggesting that subjects with low plasma folate levels have a predisposition to intracerebral bleeding.

Differences in diffusion-weighted and T2-weighted magnetic resonance imaging findings in the acute and chronic stages of ischemic cerebrovascular disease--two case reports.

A 71-year-old man presented with sudden onset of vertigo and a 77-year-old man suffered consciousness disturbance. Diffusion-weighted magnetic resonance (MR) imaging on admission showed hyperintense areas in the left cerebellar hemisphere in the first patient and in the brainstem in the second patient. Both patients were treated with argatroban and edaravone, and the neurological deficits markedly improved one month after admission. T2-weighted MR imaging one month after the onset showed much smaller hyperintense areas compared with the findings on admission in both patients. These results indicate that findings of hyperintense areas by diffusion-weighted MR imaging in the acute stage of ischemic cerebrovascular disease indicate not only the ischemic core but also parts of the reversible incomplete ischemic lesion and suggest that intensive treatment in the acute stage might reverse ischemic brain damage in some patients.