Jiann-Chyun Lin

Vascular dementia of Binswanger's type: clinical, neuroradiological and99mTc-HMPAO SPET study

In 24 patients with vascular dementia of Binswangers type (VDBT) and 14 age-matched neurologically normal volunteers, we investigated the relationship between clinical features, white matter lesions (leucoaraiosis) and cerebral atrophy on computed tomography (CT) scan, and regional cerebral blood flow. All subjects underwent the Mini-Mental State Examination of Taiwan, version 1 (MMSE-T1), for assessing the severity of cognitive impairment. The patients were subdivided into two groups, one with mild to moderate (group I, MMSE-T1 scores: 11–24,n=ll), and the other with severe dementia (group II, MMSE-T1 scores: below 10,n=13). White matter degeneration was evaluated with densitometric methods. Loss of brain parenchyma was estimated with seven linear measurements (Evans ratio, third ventricle ratio, width of temporal horn tip, anterior-posterior length of temporal horn, anterior-posterior length of Sylvian fissure and width of frontal interhemispheric fissure) by CT scans. Regional cerebral blood flow was determined with technetium-99m hexamethylpropylene amine oxime (HMPAO) single-photon emission tomography (SPET). In neuroimaging studies, subcortical leuco-araiosis was localized at the frontal region in group I patients and scattered diffusely in group II patients.99mTc-HMPAO SPET analysis revealed reduction of regional cerebral blood flow in the frontal lobe in group I patients and widespread reduction of regional cerebral blood flow in group II patients. A correlation between frontal leuco-araiosis and perfusion defect of the frontal pole was demonstrated in group I patients, showing findings typical of subcortical dementia. There was no difference in frontal atrophic measurements between group I patients and controls. Ratios of volumes of lost brain parenchyma and leuco-araiosis were significantly higher in group II patients than in the age-matched controls, corresponding to a diffuse cerebral perfusion defect. These results suggest that patients with VDBT have early frontal lobe involvement with posterior progression. Patients with mild VDBT are more likely to show reduction of frontal cerebral blood flow and leuco-araiosis, while those with severe VDBT are more likely to have diffuse leuco-araiosis, cerebral hypoperfusion and brain atrophy.

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 nonheavy 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 µl) when compared with HDS patients without MLD (1.4 ± 0.5; 206,000 ± 59,000 per µl) and NHDS patients with (1.1 ± 1.0; 256,000 ± 97,000 per µl) or without (1.4 ± 0.7; 216,000 ± 68,000 per µl) 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.

Application of chromosome 4q35-qter marker (pFR-1) for DNA rearrangement of facioscapulohumeral muscular dystrophy patients in Taiwan

Facioscapulohumeral muscular dystrophy (FSHD) has been found to be linked to chromosome 4qter. A chromosome 4q35-ter marker, pFR-1 (subclone of the cosmid c51), has been recently isolated and used as a probe for mapping near, or within, the FSHD gene. To examine FSHD-associated DNA rearrangements in the Taiwan population, we used the pFR-1 probe to perform Southern blot analysis on 142 individuals, including 32 FSHD patients within 9 autosomal dominant families, five sporadic FSHD patients from 4 families (include one pair of twins), three sporadic scapuloperoneal syndrome (SPS) patients and two sporadic polymyositis patients with their unaffected parents, and 29 healthy controls. In 29 healthy individuals, 3 SPS and 2 polymyositis patients with their families, probe pFR-1 analysis revealed that all had polymorphic restriction fragments that were larger than 28 kb in length. All but 1 FSHD-affected individual had specific smaller EcoRI fragments (ranging in size from 10.5 to 27 kb). Two point linkage analysis between pFR-1 and the FSHD locus provided significant evidence for FSHD linkage (Z(max)=6.84). A similar smaller fragment was also present in 5 sporadic patients, while this smaller fragment could not be found in one of their parents. Identical EcoRI restriction fragment length polymorphism (RFLP) patterns linked to FSHD were shown in the monozygotic twins, even though they showed extreme variability in the expression of FSHD. We conclude that the pFR-1 probe is a tightly linked marker of FSHD and can be used to detect most DNA rearrangements associated with this disease in the Taiwan population. However, the same RFLP patterns may represent extreme variability in the expression of the FSHD gene.

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.

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.

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.

Compressive radial nerve palsy induced by military shooting training: clinical and electrophysiological study.

Ten recruited soldiers developed acute left wrist drop and numbness on the back of the thumb after a three hour military shooting training. Neurological examination disclosed decreased muscle power (0-2/5) of left wrist dorsiflexion, hypalgesia and hypaesthesia on the radial side of the left hand, and diminished brachioradialis reflex. Electrophysiological studies showed prolonged distal latency, reduced amplitude and slowness of left radial nerve motor conduction velocity between the axilla and elbow. Electromyography (EMG) revealed fibrillation potentials at rest, polyphasic motor unit and an incomplete interference pattern at volition over the extensor digitorum communis and brachioradialis. Nine patients recovered completely clinically and electrophysiologically between nine and 12 weeks after the onset of the palsy. Sensation recovered faster than the weakness. One patient failed to recover after three months, possibly because of the longer duration of nerve compression. Longer nerve compression time and sustained, decreased muscle power with signs of active denervation in EMG are indicators of poor prognosis.

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.

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.

Intrauterine Fetal Demise Followed by CVT in a Woman with SLE and Secondary APS

We recently encountered a rare case of systemic lupus erythematosus (SLE) with secondary antiphospholipid syndrome (APS) presenting with cerebral venous thrombosis (CVT). A 24-year-old woman with a history of recent fetal loss experienced an intractable headache, followed by right hemiparesis and hypoesthesia over her limbs with the exception of her left lower extremity. Head CT and MRI with magnetic resonance venography (MRV) demonstrated CVT. Early diagnosis and aggressive therapy of CVT are of prime importance for achieving a favorable outcome. We present this rare case to emphasize that CVT is often multifactorial. Further investigations and the clinical symptoms of the patient proved the diagnosis of SLE with secondary APS.