Background: Human oscillator is observed in and outside the nervous system. Cardiac rhythm is gen... more Background: Human oscillator is observed in and outside the nervous system. Cardiac rhythm is generated by heart itself but can be modulated by brain. Using the technique of transcranial magnetic stimulation (TMS) and resetting index, we studied if single-pulse TMS could reset the cardiac rhythm and help differentiate oscillator of neurogenic or non-neurogenic origin. Methods: In addition to the study of 4 patients with essential tremor, cardiac rhythm was studied in 6 normal subjects. The magnetic intensity was initiated from motor threshold of hand muscle, and then with an increment of 10% up to the maximal output of magnetic stimulator. We used the resetting index (RI) to quantify the influence of the TMS. Results: The resetting phenomenon was observed in essential tremor (RI = 0.92) but not in cardiac rhythm (RI = 0.02). Conclusions: Single-pulse TMS is able to reset the rhythm of essential tremor but not heart beat. The pacing mechanism is different between essential tremor and heart beat. The cardiac rhythm is regulated and modulated chiefly by heart itself. Essential tremor should not share the same mechanism with heart beat.
In 1998 some patients with hyperglycemia-related hemichorea-hemiballism have been reported with a... more In 1998 some patients with hyperglycemia-related hemichorea-hemiballism have been reported with a hyperintense putamen on T1-weighted MR images, presumably resulting from petechial hemorrhage. I questioned this explanation from my experience because (1) the areas of hyperintense lesions and their time evolutions did not match with those of the high density lesions on CT, (2) these hyperintense lesions persisted for years, and (3) the hyperintense lesions extended inferiorly to the midbrain. Therefore, a biopsy was performed in one patient and disclosed a fragment of gliotic brain tissue with abundant gemistocytes, which I proposed was sufficient to explain the shortening of T1 relaxation time. In addition, because two of our patients were associated with cortical infarcts and without hyperglycemia, I have suggested that cerebral ischemia might be a more important cause. In 1999 Fujioka et al reproduced the MR finding in animals 7 days after 15-minute occlusion of the middle cerebral artery. Therefore, both studies have suggested that the MRI finding resulted from a progressive pathological reaction in an incomplete infarction. In 2003 Fujioka et al further reported that the hyperintensity on T1-weighted MR images after mild ischemia may involve a paramagnetic effect resulting from tissue manganese accumulation in reactive astrocytes.
Journal of The Chinese Medical Association, Dec 1, 1996
Polyneuropathy associated with acute myelocytic leukemia is rare. We report a woman aged 34 years... more Polyneuropathy associated with acute myelocytic leukemia is rare. We report a woman aged 34 years with acute monoblastic leukemia and polyneuropathy in hematology remission. The clinical, electrophysiological and pathological findings revealed acute symmetrical sensorimotor axonal polyneuropathy that differs from previous reports of three cases.
ing MR imaging. This report illustrates the unique MR imaging appearances of gadolinium leakage i... more ing MR imaging. This report illustrates the unique MR imaging appearances of gadolinium leakage into the subarachnoid space after development of an SAH.
Human neuroblastoma SK‐N‐SH‐SY5Y (SY5Y) and rat pheochromocytoma PC12 cells are model cell lines ... more Human neuroblastoma SK‐N‐SH‐SY5Y (SY5Y) and rat pheochromocytoma PC12 cells are model cell lines used in the study of nerve growth factor (NGF) effect. The effects of NGF are initiated by binding to cell surface receptors (NGFR). The amino acid sequence for NGFR has been deduced based on the identification of a single gene for NGFR. However, there are two kinds of NGF binding activities and several reported molecular weights of NGFR. We report here on the demonstration of NGFR‐like proteins from PC12 and SY5Y cells by sequential lectin chromatography, reverse‐phase HPLC, and SDS‐PAGE analysis of immunoprecipitates obtained with NGFR‐specific monoclonal antibodies. For both human and rodent NGFR, there was a tendency for the higher molecular‐ weight species of NGFR‐like proteins to be eluted in more hydrophobic fractions. Also, the expression of different species of NGFR could be modified by treatment with retinoic acid (RA). These results are consistent with the hypothesis that the different molecular species of NGFR may result from the generation of a truncated form of NGFR, the presence of sugar residues on the NGFR protein, dimer formation between NGFR, or the association of NGFR with a receptor‐ associated protein.
OBJECTIVE To report a case in which significant hypotension occurred after initiation of tizanidi... more OBJECTIVE To report a case in which significant hypotension occurred after initiation of tizanidine in a patient using the antihypertensive agent lisinopril. CASE SUMMARY A 48-year-old woman was admitted due to cerebral hemorrhage at the midbrain and pons, with extension to the fourth ventricle. Consciousness disturbance (Glasgow coma scale 4) with a decerebrate posture improved 5 days after stroke onset. As the BP was fairly high, antihypertensive agents, including lisinopril, were initiated. Three weeks later, the decerebrate rigidity and high BP remained, and tizanidine was initiated to see whether the decrease in muscle tone could facilitate hypertension control and motor recovery. However, the BP dropped dramatically within 2 hours after the first dose of tizanidine. The tizanidine and all of the antihypertensive medications were withdrawn. Tizanidine was used again after her BP had stabilized, but did not produce similar problems. DISCUSSION A similar event was reported in 2000. The reaction in our patient appeared after tizanidine initiation and improved after both lisinopril and tizanidine were discontinued. According to the Naranjo probability scale, this was classified as a possible drug interaction. This kind of reaction is seldom mentioned as occurring during co-administration with tizanidine. With its characteristics, tizanidine has the potential to compromise hemodynamic stability during concomitant angiotensin-converting enzyme inhibitor use. CONCLUSIONS Based upon the literature review, the hypotension in this patient was possibly due to the interaction between tizanidine and lisinopril.
Journal of Neurology, Neurosurgery & Psychiatry, 1986
Two young men had similar nonobstructive idiopathic pachymeningitis cervicalis hypertrophica, cau... more Two young men had similar nonobstructive idiopathic pachymeningitis cervicalis hypertrophica, causing chronic (13 and 11 years respectively) C8-Tl radiculomyelopathy proved by surgical and pathological findings. The preoperative Queckenstedt tests and myelography showed no evidence of CSF obstruction. These unusual findings contrast with previous reports which all described complete or at least partial, block. The findings on metrizamide computed tomogram have not been described before. In the two patients it revealed diffuse cord atrophy from C7 to T2 and hemiatrophy with lateral beaking from C4 to C7. The patients benefited from multiple transverse durotomies. The main pathogenesis of the cord atrophy was the compromizing of feeding radicular arteries rather than direct compression.
Journal of Stroke and Cerebrovascular Diseases, 2017
Background: We investigated the impact of serum cholesterol levels on 30-day mortality after isch... more Background: We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients. Methods: From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013. Results: Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum
Many expensive treatments have been developed for Parkinson's disease (PD), and a good cost-u... more Many expensive treatments have been developed for Parkinson's disease (PD), and a good cost-utility analysis is required. Quality-adjusted life-years (QALY) allows comparison of the cost-utility of different medical conditions. If a treatment strategy gives a patient an extra but unhealthy year, the QALY he obtained will be less than one. When a therapeutic strategy is more effective, but causes higher costs, it is mandatory to calculate the incremental cost-effectiveness ratio (ICER). In keeping with guidance from the UK National Institute for Health and Clinical Excellence (NICE), a therapy that deliver QALYs of £20,000 or less are likely to be approved. The threshold used by NICE for the maximum it is prepared to pay for a QALY, which lies between £20,000 and £30,000, will be reviewed case by case. Subthalamic deep brain stimulation (STN-DBS) is an effective therapy, which can improve the quality of life in PD patients immediately, but has not been approved by the Bureau of N...
Objective: HER2, a receptor tyrosine kinase, was originally identified based on its role in cance... more Objective: HER2, a receptor tyrosine kinase, was originally identified based on its role in cancer research. The protein has subsequently received attention for its role in nerve injury and neurodevelopment. We investigated the polymorphic association of HER2 variants at amino acid residues 655 and 1170 with Parkinson's disease (PD), a neurodegenerative disorder. Design and methods: Polymerase chain reaction (PCR) was used to amplify DNA samples from PD patients and control subjects. The resulting PCR fragments, which spanned HER2 residues 655 and 1170, were analyzed by restriction fragment length polymorphism and/or direct nucleotide sequencing. Results: The genetic distribution at residue 655 in PD patients did not differ from that in controls. However, homozygosity for genes encoding Pro at residue 1170 (Pro/Pro) occurred at a significantly lower rate among PD subjects. In other words, Ala-allele carries higher frequency in PD, especially among female PD subjects. Conclusion: Different signals or potency of the kinase activities resulting from the Ala1170Pro allele of HER2 may be associated with vulnerability to stress on dopaminergic neurons in PD.
The beneficial effects of subthalamic nucleus deep brain stimulation (STN-DBS) on motor symptoms ... more The beneficial effects of subthalamic nucleus deep brain stimulation (STN-DBS) on motor symptoms and quality of life in Parkinson's disease (PD) are well known, but little is known of the effects on autonomic function. Diffusion of current during stimulation of the STN may simultaneously involve the motor and nonmotor, limbic and associative areas of the STN. The aims of this study were to examine whether STN stimulation affects functions of the autonomic nervous system and, if so, to correlate the effects with the active contacts of electrodes in the STN. Eight PD patients with good motor control and quality of sleep after STN-DBS surgery were recruited. All patients had two days of recordings with portable polysomnography (PSG) (first night with stimulation ''on'' and second night ''off''). From the PSG data, the first sleep cycle of each recording night was defined. Heart rate variability (HRV) was analyzed between the same uninterrupted periods of the two sleep nights. In addition, the optimal electrode positions were defined from postoperative MRI studies, and the coordinates of active contacts were confirmed. HRV spectral analysis showed that only low-frequency (LF)/high-frequency (HF) power was significantly activated in the stimulation ''on'' groups (P = 0.011). There was a significant negative correlation between power change of LF/HF and electrode position lateral to the midcommissural point (q = 0.857, P = 0.007) These results demonstrate that STN-DBS can enhance sympathetic regulation; the autonomic response may be due to electrical signals being distributed to limbic components of the STN or descending sympathetic pathways in the zona incerta.
Tremor-induced electrocardiographic artifacts could be misdiagnosed as ventricular tachycardia (V... more Tremor-induced electrocardiographic artifacts could be misdiagnosed as ventricular tachycardia (VT). However, there has been no electrocardiographic algorithm effectively differentiating pseudo-VT. In this study, we used 3 electrocardiographic ''signs'': ''Sinus'' sign, ''Spike'' sign, and ''Notch'' sign, and created an electrocardiographic algorithm. The algorithm was prospectively tested in 98 electrocardiographs (37 tremor-induced pseudo-VT and 61 true VT) Thirty-six out of 37 (97.3%) tremor-induced pseudo-VTs could be accurately diagnosed. In conclusion, this is the first study to systemically analyze the tremor-induced pseudo-VT. Our new electrocardiographic algorithm provides a useful tool for a rapid and accurate diagnosis.
Background: Human oscillator is observed in and outside the nervous system. Cardiac rhythm is gen... more Background: Human oscillator is observed in and outside the nervous system. Cardiac rhythm is generated by heart itself but can be modulated by brain. Using the technique of transcranial magnetic stimulation (TMS) and resetting index, we studied if single-pulse TMS could reset the cardiac rhythm and help differentiate oscillator of neurogenic or non-neurogenic origin. Methods: In addition to the study of 4 patients with essential tremor, cardiac rhythm was studied in 6 normal subjects. The magnetic intensity was initiated from motor threshold of hand muscle, and then with an increment of 10% up to the maximal output of magnetic stimulator. We used the resetting index (RI) to quantify the influence of the TMS. Results: The resetting phenomenon was observed in essential tremor (RI = 0.92) but not in cardiac rhythm (RI = 0.02). Conclusions: Single-pulse TMS is able to reset the rhythm of essential tremor but not heart beat. The pacing mechanism is different between essential tremor and heart beat. The cardiac rhythm is regulated and modulated chiefly by heart itself. Essential tremor should not share the same mechanism with heart beat.
In 1998 some patients with hyperglycemia-related hemichorea-hemiballism have been reported with a... more In 1998 some patients with hyperglycemia-related hemichorea-hemiballism have been reported with a hyperintense putamen on T1-weighted MR images, presumably resulting from petechial hemorrhage. I questioned this explanation from my experience because (1) the areas of hyperintense lesions and their time evolutions did not match with those of the high density lesions on CT, (2) these hyperintense lesions persisted for years, and (3) the hyperintense lesions extended inferiorly to the midbrain. Therefore, a biopsy was performed in one patient and disclosed a fragment of gliotic brain tissue with abundant gemistocytes, which I proposed was sufficient to explain the shortening of T1 relaxation time. In addition, because two of our patients were associated with cortical infarcts and without hyperglycemia, I have suggested that cerebral ischemia might be a more important cause. In 1999 Fujioka et al reproduced the MR finding in animals 7 days after 15-minute occlusion of the middle cerebral artery. Therefore, both studies have suggested that the MRI finding resulted from a progressive pathological reaction in an incomplete infarction. In 2003 Fujioka et al further reported that the hyperintensity on T1-weighted MR images after mild ischemia may involve a paramagnetic effect resulting from tissue manganese accumulation in reactive astrocytes.
Journal of The Chinese Medical Association, Dec 1, 1996
Polyneuropathy associated with acute myelocytic leukemia is rare. We report a woman aged 34 years... more Polyneuropathy associated with acute myelocytic leukemia is rare. We report a woman aged 34 years with acute monoblastic leukemia and polyneuropathy in hematology remission. The clinical, electrophysiological and pathological findings revealed acute symmetrical sensorimotor axonal polyneuropathy that differs from previous reports of three cases.
ing MR imaging. This report illustrates the unique MR imaging appearances of gadolinium leakage i... more ing MR imaging. This report illustrates the unique MR imaging appearances of gadolinium leakage into the subarachnoid space after development of an SAH.
Human neuroblastoma SK‐N‐SH‐SY5Y (SY5Y) and rat pheochromocytoma PC12 cells are model cell lines ... more Human neuroblastoma SK‐N‐SH‐SY5Y (SY5Y) and rat pheochromocytoma PC12 cells are model cell lines used in the study of nerve growth factor (NGF) effect. The effects of NGF are initiated by binding to cell surface receptors (NGFR). The amino acid sequence for NGFR has been deduced based on the identification of a single gene for NGFR. However, there are two kinds of NGF binding activities and several reported molecular weights of NGFR. We report here on the demonstration of NGFR‐like proteins from PC12 and SY5Y cells by sequential lectin chromatography, reverse‐phase HPLC, and SDS‐PAGE analysis of immunoprecipitates obtained with NGFR‐specific monoclonal antibodies. For both human and rodent NGFR, there was a tendency for the higher molecular‐ weight species of NGFR‐like proteins to be eluted in more hydrophobic fractions. Also, the expression of different species of NGFR could be modified by treatment with retinoic acid (RA). These results are consistent with the hypothesis that the different molecular species of NGFR may result from the generation of a truncated form of NGFR, the presence of sugar residues on the NGFR protein, dimer formation between NGFR, or the association of NGFR with a receptor‐ associated protein.
OBJECTIVE To report a case in which significant hypotension occurred after initiation of tizanidi... more OBJECTIVE To report a case in which significant hypotension occurred after initiation of tizanidine in a patient using the antihypertensive agent lisinopril. CASE SUMMARY A 48-year-old woman was admitted due to cerebral hemorrhage at the midbrain and pons, with extension to the fourth ventricle. Consciousness disturbance (Glasgow coma scale 4) with a decerebrate posture improved 5 days after stroke onset. As the BP was fairly high, antihypertensive agents, including lisinopril, were initiated. Three weeks later, the decerebrate rigidity and high BP remained, and tizanidine was initiated to see whether the decrease in muscle tone could facilitate hypertension control and motor recovery. However, the BP dropped dramatically within 2 hours after the first dose of tizanidine. The tizanidine and all of the antihypertensive medications were withdrawn. Tizanidine was used again after her BP had stabilized, but did not produce similar problems. DISCUSSION A similar event was reported in 2000. The reaction in our patient appeared after tizanidine initiation and improved after both lisinopril and tizanidine were discontinued. According to the Naranjo probability scale, this was classified as a possible drug interaction. This kind of reaction is seldom mentioned as occurring during co-administration with tizanidine. With its characteristics, tizanidine has the potential to compromise hemodynamic stability during concomitant angiotensin-converting enzyme inhibitor use. CONCLUSIONS Based upon the literature review, the hypotension in this patient was possibly due to the interaction between tizanidine and lisinopril.
Journal of Neurology, Neurosurgery & Psychiatry, 1986
Two young men had similar nonobstructive idiopathic pachymeningitis cervicalis hypertrophica, cau... more Two young men had similar nonobstructive idiopathic pachymeningitis cervicalis hypertrophica, causing chronic (13 and 11 years respectively) C8-Tl radiculomyelopathy proved by surgical and pathological findings. The preoperative Queckenstedt tests and myelography showed no evidence of CSF obstruction. These unusual findings contrast with previous reports which all described complete or at least partial, block. The findings on metrizamide computed tomogram have not been described before. In the two patients it revealed diffuse cord atrophy from C7 to T2 and hemiatrophy with lateral beaking from C4 to C7. The patients benefited from multiple transverse durotomies. The main pathogenesis of the cord atrophy was the compromizing of feeding radicular arteries rather than direct compression.
Journal of Stroke and Cerebrovascular Diseases, 2017
Background: We investigated the impact of serum cholesterol levels on 30-day mortality after isch... more Background: We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients. Methods: From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013. Results: Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum
Many expensive treatments have been developed for Parkinson's disease (PD), and a good cost-u... more Many expensive treatments have been developed for Parkinson's disease (PD), and a good cost-utility analysis is required. Quality-adjusted life-years (QALY) allows comparison of the cost-utility of different medical conditions. If a treatment strategy gives a patient an extra but unhealthy year, the QALY he obtained will be less than one. When a therapeutic strategy is more effective, but causes higher costs, it is mandatory to calculate the incremental cost-effectiveness ratio (ICER). In keeping with guidance from the UK National Institute for Health and Clinical Excellence (NICE), a therapy that deliver QALYs of £20,000 or less are likely to be approved. The threshold used by NICE for the maximum it is prepared to pay for a QALY, which lies between £20,000 and £30,000, will be reviewed case by case. Subthalamic deep brain stimulation (STN-DBS) is an effective therapy, which can improve the quality of life in PD patients immediately, but has not been approved by the Bureau of N...
Objective: HER2, a receptor tyrosine kinase, was originally identified based on its role in cance... more Objective: HER2, a receptor tyrosine kinase, was originally identified based on its role in cancer research. The protein has subsequently received attention for its role in nerve injury and neurodevelopment. We investigated the polymorphic association of HER2 variants at amino acid residues 655 and 1170 with Parkinson's disease (PD), a neurodegenerative disorder. Design and methods: Polymerase chain reaction (PCR) was used to amplify DNA samples from PD patients and control subjects. The resulting PCR fragments, which spanned HER2 residues 655 and 1170, were analyzed by restriction fragment length polymorphism and/or direct nucleotide sequencing. Results: The genetic distribution at residue 655 in PD patients did not differ from that in controls. However, homozygosity for genes encoding Pro at residue 1170 (Pro/Pro) occurred at a significantly lower rate among PD subjects. In other words, Ala-allele carries higher frequency in PD, especially among female PD subjects. Conclusion: Different signals or potency of the kinase activities resulting from the Ala1170Pro allele of HER2 may be associated with vulnerability to stress on dopaminergic neurons in PD.
The beneficial effects of subthalamic nucleus deep brain stimulation (STN-DBS) on motor symptoms ... more The beneficial effects of subthalamic nucleus deep brain stimulation (STN-DBS) on motor symptoms and quality of life in Parkinson's disease (PD) are well known, but little is known of the effects on autonomic function. Diffusion of current during stimulation of the STN may simultaneously involve the motor and nonmotor, limbic and associative areas of the STN. The aims of this study were to examine whether STN stimulation affects functions of the autonomic nervous system and, if so, to correlate the effects with the active contacts of electrodes in the STN. Eight PD patients with good motor control and quality of sleep after STN-DBS surgery were recruited. All patients had two days of recordings with portable polysomnography (PSG) (first night with stimulation ''on'' and second night ''off''). From the PSG data, the first sleep cycle of each recording night was defined. Heart rate variability (HRV) was analyzed between the same uninterrupted periods of the two sleep nights. In addition, the optimal electrode positions were defined from postoperative MRI studies, and the coordinates of active contacts were confirmed. HRV spectral analysis showed that only low-frequency (LF)/high-frequency (HF) power was significantly activated in the stimulation ''on'' groups (P = 0.011). There was a significant negative correlation between power change of LF/HF and electrode position lateral to the midcommissural point (q = 0.857, P = 0.007) These results demonstrate that STN-DBS can enhance sympathetic regulation; the autonomic response may be due to electrical signals being distributed to limbic components of the STN or descending sympathetic pathways in the zona incerta.
Tremor-induced electrocardiographic artifacts could be misdiagnosed as ventricular tachycardia (V... more Tremor-induced electrocardiographic artifacts could be misdiagnosed as ventricular tachycardia (VT). However, there has been no electrocardiographic algorithm effectively differentiating pseudo-VT. In this study, we used 3 electrocardiographic ''signs'': ''Sinus'' sign, ''Spike'' sign, and ''Notch'' sign, and created an electrocardiographic algorithm. The algorithm was prospectively tested in 98 electrocardiographs (37 tremor-induced pseudo-VT and 61 true VT) Thirty-six out of 37 (97.3%) tremor-induced pseudo-VTs could be accurately diagnosed. In conclusion, this is the first study to systemically analyze the tremor-induced pseudo-VT. Our new electrocardiographic algorithm provides a useful tool for a rapid and accurate diagnosis.
Uploads
Papers by Din-E Shan