Risk Factor Stratification for Intracranial Stenosis in Taiwanese Patients With Cervicocerebral Stenosis.

BACKGROUND: Intracranial stenosis (ICS) is a major determinant of ischemic stroke in Asians. We determined the clinical significance of different risk factors and the role of ICS in Taiwanese patients with varied distributions of cervicocerebral stenosis. METHODS AND RESULTS: Presence of extracranial carotid stenosis (ECS, ≥70%) and ICS (>50%) was examined in 13 539 patients using ultrasonography and magnetic resonance angiography, respectively. Seven hundred thirty-three patients with non-ECS/ICS (n=372), isolated ICS (n=112), isolated ECS (n=121), or combined ECS/ICS (CEIS, n=128) were selected. Prevalence of ischemic stroke in each group was compared, and risk factors for stenosis were determined. The area under the receiver operating characteristic curve for each risk factor was calculated. Prevalence of ischemic stroke was highest in patients with CEIS (odds ratio 15.86; P<0.001), followed in decreasing order by those with isolated ICS (odds ratio 7.16; P<0.001), isolated ECS (odds ratio 1.77; P=0.011), and non-ECS/ICS. Multivariate logistic regression analysis revealed that hypertension, coronary artery disease, and smoking were risk factors for isolated ECS; hypertension, diabetes mellitus, coronary artery disease, and smoking were risk factors for isolated ICS; and diabetes mellitus, coronary artery disease, and smoking were risk factors for CEIS. Smoking, diabetes mellitus, and coronary artery disease were the greatest contributors to CEIS, isolated ICS, and isolated ECS, respectively. CONCLUSIONS: CEIS was associated with higher odds of ischemic stroke compared with isolated ICS and isolated ECS. Smoking and diabetes mellitus, major determinants of CEIS and isolated ICS, should be targeted in therapeutic strategies to reduce the risk of ischemic stroke.

Interferon-alpha caused reversible parkinsonism.

Interferon has been used to treat chronic viral hepatitis and several malignancies. However, it may cause various neuropsychiatric adverse effects including parkinsonism. We report a rare case of interferon alpha-2a therapy-related parkinsonism in a 67-year-old man with metastatic papillary renal cell carcinoma and our experience of using Tc-99m-TRODAT-1 single photon emission computed tomography (SPECT) as a tool for evaluation of parkinsonism. Physicians should be alert to the possibility of interferon alpha-2a-related parkinsonism.

Post-insult valproate treatment potentially improved functional recovery in patients with acute middle cerebral artery infarction.

Animal stroke models suggest that valproate has multiple neuroprotective mechanisms against ischemic brain damage. This study investigated whether valproate improves functional recovery in patients with acute middle cerebral artery (MCA) infarction. This was an open-label controlled trial. Three to 24 hours after acute MCA infarction, patients were assigned to either the valproate group (n = 17) or the non-valproate group (n = 17). The valproate group received intravenous valproate (400 mg) at enrollment, and then every 12 hours for three days, followed by oral valproate (500 mg) every 12 hours for three months. Neurological function, laboratory data, and brain magnetic resonance imaging were examined at stroke onset, and at two-week and three-month follow-up. No significant differences were observed between the groups with regard to demographics or baseline characteristics. All patients were elderly, had a high pretreatment score on the NIH stroke scale (NIHSS), and slow stroke lesion growth with a final large infarct volume at two-week follow-up. At the three-month follow-up, functional outcome between pre- and post-treatment had improved significantly in the valproate group (NIHSS, p = 0.004; modified Rankin scale (mRS), p = 0.007; Barthel index (BI), p = 0.001). No such improvement was noted in the NIHSS or mRS for the non-valproate group, though mild improvement was seen on the BI (p = 0.022). This open-label trial is the first to demonstrate that valproate treatment markedly improves functional outcome in patients with acute MCA infarction.

Homocysteine induces cerebral endothelial cell death by activating the acid sphingomyelinase ceramide pathway.

Homocysteine (Hcy) levels may rise after a stroke, but the mechanism of Hcy-induced cerebral endothelial cell (CEC) dysfunction has not been explored. In this study we examined the role of the acid sphingomyelinase (Asm)-ceramide pathway in the molecular mechanism of Hcy-induced CEC dysfunction. Murine CECs were prepared from fresh mouse brains. CECs were treated with 50-500 µM Hcy and 30-100 µM C2-ceramide for 48 h. Sphingomyelinase assays were performed to determine Asm activity. Quantitative assessments of cell survival and death by the MTT reduction and LDH release were conducted. Treatment of murine CECs with Hcy and ceramide caused cell death in a dose-dependent manner as determined by LDH and MTT assays. 250 µM Hcy and 50 µM C2-ceramide caused 50% cell death. Hcy induced murine CEC death also occurred in a time-dependant manner with substantial cell death noted as early as 24h after Hcy exposure. C2-ceramide-induced murine CEC death occurred earlier than Hcy-induced cell death by about 18h. Hcy treatment increased Asm activity and intracellular ceramide accumulation. This study demonstrated that Hcy and C2-ceramide can cause murine CEC death. Hcy induces CEC death possibly by activating the Asm-ceramide pathway.

Cerebral venous sinus thrombosis as an initial manifestation of primary antiphospholipid syndrome.

Cerebral venous sinus thrombosis is a rare neurologic manifestation of antiphospholipid syndrome. We report a case of a 49-year-old woman who presented to the emergency department with recurrent episodes of transient clumsiness of the left upper extremity. The results of unenhanced brain computed tomography and electroencephalography were unremarkable. Serial neuroimages revealed superior sagittal sinus thrombosis. Thrombophilia screen disclosed positive lupus anticoagulant. In this case report, we aim to emphasize the significance of recognizing an unusual presentation of antiphospholipid syndrome.

Involvement of nigrostriatal pathway in Japanese encephalitis with movement disorders: evidence from 99mTc-TRODAT-1 and 123I-IBZM SPECT imagings.

PURPOSE: The purpose of this study was to evaluate molecular evidence of nigrostriatal pathway involvement in Japanese encephalitis (JE) survivors with movement complications. METHODS: Three JE patients were recruited. All had cranial magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) studies with (99m)Tc-TRODAT-1 and (123)I-IBZM. RESULTS: Cranial MRI revealed involvement of bilateral thalami, substantia nigra, and medial temporal lobes in all three patients, but only case 1 had additional bilateral basal ganglia involvement. The (99m)Tc-TRODAT-1 SPECT for presynaptic dopamine transporter imaging disclosed asymmetrical decreases in bilateral striatal uptake in all three patients. However, the (123)I-IBZM SPECT imaging for postsynaptic D2 dopamine receptors (D2Rs) revealed inconsistent abnormalities including asymmetrical bilateral decreases (case 1), unilateral decrease (case 2), and bilateral increases (case 3) in striatal uptakes. CONCLUSION: Data have suggested that presynaptic dopaminergic neurons in JE patients are more susceptible to JE virus than postsynaptic striatal neurons. The degree of movement impairment was more closely correlated to the degree of D2Rs disruption seen in (123)I-IBZM SPECT imaging.

A thrombophilic patient with a dural arteriovenous fistula presenting sensory aphasia and complicated with an acute pulmonary embolism.

BACKGROUND: Neuropsychiatric symptoms as the initial presentation of dural arteriovenous fistula (DAVF) are unusual. Anticoagulation therapy may be warranted for prevention of further thromboembolism if an underlying thrombophilia condition is diagnosed. CASE REPORT: We present a 70-year-old woman with sensory aphasia, who was diagnosed with a DAVF, Cognard type II a + b, by cerebral angiography. Her stroke-like syndrome resolved after transarterial embolization of the left occipital and middle meningeal arteries. Meanwhile, hypercoagulability was found because of hyperhomocysteinemia and the presence of a lupus anticoagulant. One month later, she suffered an acute pulmonary embolism and was started on anticoagulation therapy before stereotactic radiosurgery. CONCLUSION: Sensory aphasia may be the initial manifestation of a transverse-sigmoid sinus DAVF even if there are no symptoms such as headache or tinnitus. We postulate that early anticoagulation therapy is indicated for preventing thromboembolism in DAVF patients with thrombophilia because the possibility of intracranial bleeding has been reduced by embolization.

Glucose reduces the effect of water to promote orthostatic tolerance.

BACKGROUND: Recent studies have shown that ingestion of glucose water lowers blood pressure (BP) in patients with perturbed autonomic control and more modestly lowers BP in elderly normal subjects. Whether glucose water affects cardiovascular control during orthostatic stress in normal young healthy subjects is unknown. We hypothesized that glucose water ingestion will reduce orthostatic tolerance in young healthy volunteers. METHODS: In a randomized, controlled, within-subject study, 15 healthy male subjects (21-28 years of age) ingested water or 10% glucose water 5 min before tilt-table testing. We measured finger BP, brachial BP, heart rate, and peripheral vascular resistance. Orthostatic tolerance was measured as the time to presyncope during a 70 degrees head-up tilt, in which the head was tilted for 45 min or until presyncopal symptoms were observed. RESULTS: During the first 45 min of tilt, 8 of 15 subjects who ingested 10% glucose water experienced presyncope, but only 2 of 15 who ingested water (P = 0.029) experienced presyncope. Ingestion of 10% glucose water increased the heart rate significantly more than pure water during head-up tilt (P = 0.026). Ingestion of water increased the peripheral vascular resistance significantly >10% glucose water during the head-up tilt test (P = 0.013). CONCLUSIONS: Ingestion of 10% glucose water impairs head-up tilt tolerance relative to water ingestion. The contrasting effect of 10% glucose water vs. pure water on orthostatic tolerance is associated with increased heart rate and attenuation of the increase in peripheral vascular resistance in head-up tilt testing.

Inherited protein C deficiency with acute ischemic stroke in a young adult: a case report.

Hereditary protein C deficiency is inherited primarily as an autosomal dominant trait with incomplete penetrance. Arterial thrombosis, especially of the intracranial arteries, due to this deficiency is relatively rare. A 31-year-old man was admitted to our department because of sudden onset of neurological symptoms. Magnetic resonance imaging of the brain disclosed an acute ischemic infarction of the area supplied by the left middle cerebral artery. Protein C antigen was 40.7% (77-129%) and protein C activity was 46.3% (70-140%). No other possible associated causes of stroke were present. A survey of his relatives for protein C deficiency showed this deficiency in his mother, brother, sister and nephews. Protein C concentrations should be determined in cases of ischemic stroke in all young patients with no other major risk factors. Once protein C deficiency is detected, a search for protein C deficiency in the patient's relatives should be performed to prevent the occurrence of ischemic strokes.

Spontaneous early recanalization of an acute symptomatic critical stenosis of the extracranial internal carotid artery: a case report.

We present a 63-year-old female with critical stenosis of the extracranial portion of the internal carotid artery (ICA), diagnosed using color-coded Duplex ultrasonography (CCDU) and magnetic resonance imaging. Nine days later, the patient showed profound clinical improvement, at which time spontaneous recanalization of the previously highly stenosed ICA was seen in follow-up CCDU and magnetic resonance angiography (MRA) and confirmed by three-dimensional computed tomography angiography (CTA). The detection of recanalization is important in predicting the patient's prognosis and deciding a suboptimal secondary prophylaxis strategy of medical or surgical treatment. Therefore, we suggest performing imaging studies immediately in patients, especially potential surgical or stenting candidates showing great changes in neurological function, through examination with CCDU and confirmation with MRA or CTA, all safe and minimally invasive methods, to see whether recanalization has occurred.

Spinal myoclonus in subacute combined degeneration caused by nitrous oxide intoxication.

A 26-year-old patient developed ascending weakness and paresthesias. Megaloblastic anemia and mildly reduced serum vitamin B12 (B12) concentration were noted. Myoclonus-like muscular contractions appeared over four extremities and in the trunk. She admitted inhaling nitrous oxide (N2O) as a euphoriant repeatedly at party. Following parenteral B12 administration, her neurological deficit promptly resolved. This case demonstrated the abuse of N2OI is an important cause of subacute combined degeneration (SCD) of the spinal cord. To our knowledge, this is the first report of involuntary movements in a patient with N2O intoxication. Although the mechanism remains unknown, involuntary movements similar to myoclonus should be considered as one of the extraordinary neurological manifestations of N2O intoxication.

Status epilepticus associated with initiation of theophylline in an elderly patient with diabetic ketoacidosis.

An 80-year-old man with a history of Type 2 diabetes mellitus was hospitalized due to generalized convulsive status epilepticus. Initially, hyperglycemia and ketoacidosis were diagnosed, but his seizures were refractory to the medical treatment. Additionally, a high level of serum theophylline (29.1 mg/mL) was detected. Following detoxification of theophylline by oral activated charcoal, the patient regained consciousness and was free from seizures without antiepileptic drug treatment. Brain magnetic resonance imaging revealed subacute subdural hematomas at the bilateral occipital hemispheres. This case suggests that theophylline toxicity may be a predisposing factor for seizures in patients with a history of traumatic brain injury in spite of the presence of diabetic ketoacidosis that may have an anticonvulsant action.

Increased risk of cerebral hemorrhage in Chinese male heavy drinkers with mild liver disorder.

BACKGROUND: Epidemiological evidence suggests that heavy alcohol consumption increases the risk for either stroke or liver disease. The goal of this study was to determine whether heavy drinkers with mild liver disorder (MLD) are at risk of hemorrhagic stroke. METHODS: All of the 524 patients recruited were males with a first-ever acute stroke and were consecutively admitted to the Tri-Service General Hospital between January 2000 and December 2001. The risk factors, liver function, stroke subtypes, and hemostatic factors were assessed among 68 patients defined as heavy drinker stroke (HDS) and 456 patients as non-heavy drinker stroke (NHDS). RESULTS: HDS patients had a significantly higher incidence of hemorrhagic stroke than NHDS patients. HDS patients were also associated with significantly higher occurrence of cigarette smoking, hyperuricemia, liver dysfunction, and significantly lower platelet counts. HDS patients with MLD were more likely to have hemorrhagic stroke (76.5%) than HDS patients without MLD (33.3%) and NHDS patients with (40.3%) or without (26.7%) MLD. HDS patients with MLD also exhibited a significantly higher glutamic oxaloacetic transaminase/glutamic pyruvic transaminase ratio (2.0 +/- 1.2) and lower platelet number (185,000 +/- 85,000 per microl) when compared with HDS patients without MLD (1.4 +/- 0.5; 206,000 +/- 59,000 per microl) and NHDS patients with (1.1 +/- 1.0; 256,000 +/- 97,000 per microl) or without (1.4 +/- 0.7; 216,000 +/- 68,000 per microl) MLD. CONCLUSIONS: HDS patients with MLD are at higher risk for hemorrhagic stroke in part due to the changes in hemostatic factors, although other factors may also contribute to hemorrhagic stroke.

Resolution of intractable hiccups after near-infrared irradiation of relevant acupoints.

BACKGROUND: Intractable hiccups are occasionally encountered in the presence of stroke but are usually difficult to manage. METHODS: We describe two stroke patients with intractable hiccups that were refractory to pharmacological treatment but were well resolved by application to relevant acupoints with the modality linear polarized near-infrared ray equipment on PC 6 (Nei Guan), ST 36 (Zu San Li), and DU 9 (Chih Yang), which are the empirical acupoints aimed at regulating gastrointestinal mobility and function of the thoracic organ. RESULTS: The first patient who received the treatment for only one time came out with a dramatic termination of intractable hiccups 3 hours later and with no recurrence thereafter. We applied the same treatment on the second patient once a day for 8 consecutive days, which led to progressive amelioration of intractable hiccups. CONCLUSIONS: This is the first report about the complete resolution of intractable hiccups due to stroke using near-infrared irradiation to acupoints, rather than using conventional pharmacologic therapy, traditional acupuncture, or moxibustion. Consequently, these findings suggest that linear polarized near-infrared ray irradiation, with its noninvasive properties, might be an alternative treatment for intractable hiccups after stroke.

Potentiation of haloperidol neurotoxicity in acute hyperthyroidism: report of a case.

Haloperidol has been used extensively for the treatment of many psychiatric illnesses as well as for control of agitated patients. Side effects including anticholinergic, extrapyramidal, sedative side effects as well as neuroleptic malignant syndrome are not unusual. Many factors may contribute to these complications including withdrawal or toxicity, concomitant use of other medications or the underlying illness itself. We report a case without previous history of thyroid disorder sufferring acute manic episode. Haloperidol was prescribed to control psychotic symptoms. Symptoms and signs of extrapyramidal syndrome, catatonia and hyperthyroidism ensued. Prescription of anti-thyroid agents and discontinuation of haloperidol were essential in the successful treatment of this patient. It is hypothesized that underlying hyperthyroidism might have precipitated haloperidol neurotoxicity. Haloperidol might play a role in the exacerbation of hyperthyroidism.

Usefulness of brain 99mTc-TRODAT-1 SPET for the evaluation of Parkinson's disease.

Nigral dopaminergic projections to the striatum are targeted in Parkinson's disease (PD). The extent of the degeneration of the dopaminergic system in PD can be visualised by dopamine transporter imaging using single-photon emission tomography (SPET). In this study in 188 patients with PD, we analysed the image patterns and compared them with the clinical features in order to verify the usefulness of technetium-99m TRODAT-1 brain SPET in the evaluation of patients with PD. Two independent readers visually assessed SPET slices from three brain axes according to a "fine" visual scale; results were also grouped according to a "rough" visual scale. Results of both visual and semi-quantitative analyses were compared among patients with different stages of PD and healthy controls. There was good agreement between the readers in the interpretation of the image patterns [kappa statistic (kappa)=0.85 for the presence of PD; kappa=0.88 for the rough scale and 0.81 for the fine scale]. Good concordance was obtained when visual interpretation was used to evaluate the presence of PD (sensitivity = 98%, specificity = 86%, kappa = 0.85). Semi-quantitative analyses revealed significant negative correlations between both striatal and putaminal uptake and disease severity as assessed using the Hoehn and Yahr scale (rho = -0.89 and -0.93 respectively). An apparent decrease in striatal uptake in early PD, hardly discernible from the uptake level in advanced PD, was commonly found in visual analyses. The results suggest that both visual and semi-quantitative analyses of 99mTc-TRODAT-1 SPET images reflect neurodegeneration in PD, and that 99mTc-TRODAT-1 SPET represents an adequate means for evaluation of the status of patients with PD.

Crossover study of (99m)Tc-TRODAT-1 SPECT and (18)F-FDOPA PET in Parkinson's disease patients.

UNLABELLED: 99mTc-TRODAT-1 ([2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato(3-)-N2,N2',S2,S2']oxo-[1R-(exo-exo)]) is a potential agent for dopamine transporter (DAT) SPECT, whereas 6-(18)F-fluoro-L-dopa ((18)F-FDOPA) PET has been used for the quantitative assessment of presynaptic nigrostriatal dopaminergic function. The current study investigated the relationship between the 2 imaging modalities in evaluating patients with Parkinson's disease (PD). METHODS: Twenty patients in whom PD was diagnosed by generally accepted criteria were recruited. In addition to visual inspection, specific uptake ratios (SURs) of (99m)Tc-TRODAT-1 in the striatum and putamen were measured bilaterally. For PET, all patients received 100 mg of carbidopa 90 min before (18)F-FDOPA (300 MBq) injection. Images were acquired between 120 and 150 min after injection, using a whole-body PET scanner with settings identical to those for the SPECT studies. The SURs for PET were calculated similarly to those for SPECT. Individual SURs of the striatum or putamen from SPECT were correlated with the corresponding PET values using linear regression. RESULTS: A consistent image pattern between SPECT and PET was achieved by visual inspection except for 3 cases. In 1 case (a patient with Hoehn and Yahr Scale I PD), the SPECT images were more compatible with the patient's clinical findings whereas PET showed nearly normal uptake. In the other 2 cases (both patients with Hoehn and Yahr Scale II PD), PET correlated better with the clinical findings. The caudate and putamen nuclei were more discernable on PET. An acceptable correlation of SUR, however, was found between SPECT and PET in both the striatum and the putamen (P < 0.01 for both). CONCLUSION: The comparability of (99m)Tc-TRODAT-1 SPECT and (18)F-FDOPA PET suggests that (99m)Tc-TRODAT-1 SPECT may provide a reliable alternative to (18)F-FDOPA PET in the evaluation of clinical PD patients.

Depression and related factors in elderly patients with occlusion stroke.

The purpose of this study was to examine depression and the related factors in elderly stroke patients. Purposive sampling was used to recruit 106 participants from the outpatients department (OPD) of a teaching hospital in Taipei. The major findings of this study were: (1) Twenty-nine stroke survivors (27.4%) and eight stroke survivors (7.5%) were classified as having mild depression and moderate to severe depression, respectively. (2) There was no significant difference or correlation between the depression score and demographic characteristics, chronic illness condition, or disease characteristics. The depression scores in " worrying about nothing " were significantly lower than the depression scores in " worrying about disease " (t = -4.03, p =.03). (3) There was no significant correlation between the depression score and the Mini-Mental State Examination score, or the Barthel Index score. (4) Social support and depression were negatively correlated (r = -.306, p =.001). (5) Multiple regression analysis revealed that " worrying about disease, " " worrying about family, " and informational support from family, relatives and friends accounted for 22.1% of the variance in depression. The implications for clinical practice and further studies are suggested.