癲癇藥物對自律神經的影響

The Impact of different antiepileptic agents on the Autonomic Nervous System in Patients with epilepsy

林勳章(Hsun-Chang Lin)

指導教授 ： 徐崇堯

共同指導教授 ： 賴秋蓮(Chiou Lian Lai)

高雄醫學大學/醫學院/醫學研究所碩士班/碩士(2016年)

摘要

癲癇病人非預期猝死在癲癇病人身上是一個死亡重要的因素，不過他實際的發生機轉我們不是太清楚。在過去研究中我們發現他和抽搐性癲癇的發作史、近三個月抽搐性癲癇發作次數、carbamazepine的使用、Lamotrigine的使用和夜間發作的癲癇(nocturnal seizure)相關。
過去我們探討心臟疾病的病人猝死會使用心律變異分析，心律變異分析是個可以反映生理心臟調控的工具，包含交感和副交感對心臟調控的總和。我們假設癲癇病人猝死和自律神經調控改變相關，我們用心律變異分析去分析癲癇病人非預期猝死上述的這些危險因子。
我們的研究是回溯型的研究，從門診找出癲癇有使用藥物的病人，排除糖尿病、慢性腎臟病洗腎病人、心律不整的病人、甲狀腺功能亢進、帕金森氏症、癌症病人、使用乙型拮抗劑、鈣離子阻斷劑的病人，因為這些都會影響心律變異分析結果。我們收集的是使用單一抗癲癇藥物的病人，以避免不同藥物在同一個病人身上造成的影響，同一種抗癲癇藥物必須是穩定在這個病人身上使用超過一個月以上。我們蒐集他腦波裡面的心電圖紀錄，把品質良好的心電圖紀錄切成五分鐘片段，再去做心律變異分析。
分析結果發現心律變異分析在年紀越大和generalized tonic clonic seizure類型的病人身上會降低，性別在女性會有降低的趨勢，不同藥物和近一個月內有癲癇發作的病人在心律變異分析是沒有統計上的差別意義。我們再做多變相分析去看不同因素彼此的影響，發現心律變異分析在年紀越大、女性和generalized tonic clonic seizure類型的病人身上會降低。
上述的這些心律變異分析改變會改變自律神經功能，可能會增加猝死的機率，在抗癲癇藥物就沒有發現這樣的改變，所以也許Carbamazepine和Lamotrigine增加癲癇猝死的機轉還有其他的可能。我們研究需要更大的樣本，也許我們可以收集更多病人在不同類型的癲癇做好的分析。

關鍵字

癲癇藥物 ； 自律神經

並列摘要

SUDEP is an important cause of death in the patients with epilepsy. The clear mechanism of sudden death is not clear. In the previous study, we found there were associated factors of SUDEP including history of general tonic-clonic seizure, the frequency of seizure in the recent 3 months, the use of Carbamazepine and Lamotrigine, and nocturnal seizure.
In previous study, we investigated sudden death with HRV (heart rate variability) in patients with heart disease. HRV is a reliable reflection of the many physiological factors modulating the normal rhythm of the heart including sympathetic and parasympathetic function. We hypothesized that SUDEP is related to autonomic change in the patients with epilepsy. We plan to investigate the risk factos of SUDEP with HRV and and try to reveal if there is association of autonomic change with them.
We do a retrospective study and collect the epilepsy patients followed in our out patient department. We excluded patients with diabetes mellitus, renal failure, alcoholism, cardiac arrthymia, hyperthyroidism, parkinsonism, patients with malignancy, the use of beta blocker and calcium channel blocker, because they may influence the result the heart rate variability. We included the epilepsy patients with monotherapy to eliminate confounding effect of different antiepileptic agents in the same patient. The antiepileptic agents should be in stable dose in the patient for over one month. We collected their EKG recording in their EEG study. The well-qualified and 5 minutes segmented EKG recording was analyzed with the parameters of heart rate variability.
In the results of HRV, the parameters declined with age, and the patients with the general tonic clonic seizure. There was a trend in the female with lower HRV. There was no stastic association with HRV and different antiepileptic agents, and either in the patient with recent seizure in one month. We did multiple linear regression to analyze the confounding effect. The result revealed that the HRV declined with old age, female and patients with general tonic clonic seizure.
In our study, we have the clonclusion that the heart rate variability was decreased in old age, female gender and patients with general tonic clonic seizure. This may predicte a declined autonomic function and may be related to increasing risk of sudden death. We cannot find the association of HRV change with different antiepileptic medication. So the increased risk of sudden death in Carbamazepine and Lamotrigine mayresult from other mechanism but rather than autonomic change. The limitation of our study is case number. We expect that we can include more patients to clearify the the impact of the seizure type on the autonomic function.

並列關鍵字

antiepileptic agents ； autonomic Nervous System

參考文獻

參考文獻

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