Research Career Development

1. Research Career Development 外科部 神經外科 李明陽 醫師

2. 住院醫師時期 • Join intracerebral hemorrhage, canine & sheep cervical spine studies

3. 感謝張冠諒老師及李宜堅主任的指導

4. Results

5. 主治醫師時期 • 國立中醫藥研究所 • University of Massachusetts, Worcester • Harvard Medical School, Brigham & Women’s Hospital

7. 國立中醫藥研究所 蕭永基 老師

8. Neuronal Culture

9. University of Massachusetts, Worcester Lawrence J. Hayward • Hyperkalemic Periodic Paralysis: a Muscle Ion Channel Disorder

16. Methods in Neuroscience • Cell Attached Clamp Technique • Whole Cell Patch Clamp Technique

20. UMass Medical School Professor Wins Nobel Prize Dr. Craig Mello and colleague Dr. Andrew Fire of Stanford honored for 1998 discovery of RNAi WORCESTER, Mass.-The Nobel Assembly at Karolinska Institutet today awarded The Nobel Prize in Physiology or Medicine for 2006 to the University of Massachusetts Medical School'sCraig C. Mello, PhD, and his colleague Andrew Fire, PhD, of Stanford University, for their discoveries related to RNA interference. In 1998, Drs. Mello and Fire, then of the Carnegie Institution of Washington, published research findings in Nature that demonstrated that a particular form of ribonucleic acid or RNA-the cellular material responsible for the transmission of genetic information-can silence targeted genes. This RNAi process offers astounding potential for understanding and manipulating the cellular basis of human disease, and RNAi is now the state-of-the-art method by which scientists can "knock out" the expression of specific genes to thus define the biological functions of those genes. Just as important has been the finding that RNAi is a normal process of genetic regulation that takes place during development, opening a new window on developmental gene regulation.

21. Harvard Medical SchoolBrigham &Women’s Hospital Peter M. Black Rona S. Carroll

23. 良師益友

24. Normal Pressure Hydrocephalus (NPH) • First described in 1965 by Hakim and Adams • Clinical triad of symptoms: - gait disturbance - dementia - incontinence • Image: communicating hydrocephalus • Potentially reversible by shunting: symptoms < 2 yrs J Neurol Sci 2:307–327, 1965

25. Etiology of NPH • Idiopathic: ~ 8.7%, elderly > 60 y/o, worse response to shunting (30–50%) • Secondary: younger age, better response to shunting (50–70%) - head injury, trauma - subarachnoid hemorrhage - meningitis - previous neurosurgery

26. Prevalence of INPH • Roughly 7,000,000 cases of dementia, of which 350,000 are most likely due to NPH • approximately 11,500 have been treated, leaving a large number of patients who have a potentially treatable cause of dementia, but have not been treated • NPH is the only potentially treatable cause of dementia

27. Clinical Triad • Gait disturbance: short-stepped, magnet, broad based gait • Dementia: Attention, psychomotor speed, verbal fluency, executive function and memory impairment • Urinary impairment: frequency and urgency, Urodynamic testing demonstrates bladder hyperactivity

30. Japanese Guideline for Management of INPH • Masatsune Ishikawa, Etsuro Mori et. al., Neurol Med Chir Suppl (Tokyo) 48, 2008 • Diagnostic levels: possible, probable and definite • CSF tap test as an important diagnostic test • Programmable valves recommended used in the shunt operation

31. Neurol Med Chir Suppl (Tokyo) 48, 2008

32. Treatment • Medication: No definitive evidence exists that medication can successfully treat INPH. • Surgery: Shunting the CSF remains the main treatment modality.

33. Treatment • NPH is the only common form of dementia that is reversible • Drug therapy is ineffective • Programmable shunt technology more effective to NPH, non-invasive adjustment optimize the outcome • Early intervention yields improved outcomes