關於Stephen Spring Protocol

Some interesting material from Stephen Spring

Backup from here
http://archive.is/m4yUq
==========================================
Thanks to Angelea for bringing this to my attention.

Many of you have probably read this, but I wanted to post it for newbies or people with questions about Spring's treatment. It's from a long thread on the MDUK (Meniere's Disease United Kingdom) forum about a year ago. There's a lot of dissension from certain forum members, as there is on our forum--people calling him a charlatan, etc. But keep an open mind and forget that.

I extracted Stephen's comments, which are pretty detailed, and put them into a bulleted list below.

If you want to read the whole thread, I included the link:

Stephen Spring, Meniere’s researcher, Sydney Australia
Comments from thread on the Meniere’s Disease United Kingdom web forum
The entire thread can be accessed at http://www.mduk.org/index.php?topic=4341.0

• I was once the VP of the Meniere’s Research Fund at Sydney Uni and former sufferer.

I spent 7 years researching the medical literature. In essence, I connected the dots of thousands of research studies to conclude what I have written to you above. MD is an infection with particular characteristics including immune dysfunction. This causes cytokine controlled inflammation cascades that will render the endolymphatic sac inoperable and thus causes the hydrops causing MD symptoms. This mechanism has been, in part, proven recently at Sydney Uni.

My protocol simply addresses the immune dysfunction and the infection and restores normal function. If you are in Sydney, you can get tested at the Sydney Cochlea Implant Centre.

• Md is an infection of the malt, the mucosa associated lymphatic system. The malt is a bit like an immune system within an overall, serum or blood immune system. Malt covers the throat, sinuses, gut, nose, tonsils, vagina etc with a continual mucus blanket, reacting to and washing away, sweeping away, sneezing away, snotting away etc nasty viruses and bugs. One aspect of a very complex chain is that the malt presents fragments of bugs to the serum immune that does a whole bunch of stuff to use that information so specialised immune cells called T cells learn about that particular bug out of millions we live with. This is the basis of vaccination or delayed immune response. If the bug strikes again, the immune system memory kicks in and cells for that bug rapidly multiply and outpace the infection.

The endolymphatic sac controls fluid pressure and volume of one inner ear compartment that connects the cochlea for hearing and semi circular canals for balance and the utricle for acceleration and deacceleartion. The endolymphatic sac is also the immune defence organ of the ear. It is the interface between blood immune system and the malt. To keep it very simple here, the sac stuffs up in md, it can no longer process infection, the fluid swells the compartment. This is hydrops. Unknown reasons for Hydrops is md but pagets, aied, cholesteoma, syphilis, trauma, otitis etc can all cause hydrops, transient or permanent.

Thus, you need to correct the serum immune system which corrects the malt which corrects the hydrops and remove the infection. Up to a point, the sac will repair itself and so symptoms go away. My tinnitus is not complete silence, but close to it for example.

This is all confirmed with tests as everyone has a slightly differing immune profile. A vaccine and antinfectives are used. Chronic infections take a long time to resolve, at least 36-48 weeks.

• The idea of pathogens exploiting weakness in one part of the human immune system is hardly new, AIDS victims don’t die of AIDS. They die because they cannot fight multiple infections. Cystic fibrosis gene defect won’t kill you if you don’t get infections. MD is mainly an acquired immune defect.

• MD is idiopathic hydrops. This is really when, the treating doctor does not know or cannot work out what it is that caused the Hydrops. It does not mean that no one knows or never will. That’s the start point.

Hydrops is a dynamic concept. The endolymphatic sac is a dynamic organ. The entire inner ear is a stable organ with parameters governing fluid control such as volume but it is also dynamic enough so that when under stress conditions, the endolymphatic sac can work and the hearing and balance still functions. Hydrops can be measured and when the hydrops is present and there are symptoms, there are different signals to when there it is not.

Many things can “cause” hydrops, it can be transient or it can eventually become so severe that the inner ear will no longer function. Hydrops for some people is a minor nuisance, for others it’s a permanent and chronic misery.

If the doctor does not go through the known things that can cause hydrops, or does not test for hydrops, or is lazy or other reasons, the patient is left wondering. In other words there are many variables that can contribute to a diagnoses of MD (“You have hydrops I think, but I don’t know what causes it or how to treat it madam and because its idiopathic in my eyes, you have Meniere’s Disease.") This includes the doctor’s attitude, experience and many other factors. It also implies a correct diagnose because the person might have what is termed autoimmune inner ear disease, cholesteoma, sac tumor and others which can cause hydrops too and are treated differently depending on the doctor’s point of view.

Some hydrops is so mild and transient that the patient thinks they can control it with diet. Some doctors and even support groups say salt retains fluid in the inner ear but in reality there is very little evidence for this, but if that gives the person some degree of control (even though it is unlikely to long term, there is nothing wrong thinking it will) it does no harm and gets the patient out the office.

Some people take larger and larger amounts of antihistamines to help themselves and some people simply walk up the treatment ladder to get worse and worse and have surgery.

My work has investigated the immunological basis for hydrops that can arise after a number of common events that lead to it. This is simply another way of looking at hydrops initiation and is something that many doctors do not know how to do. I provide the tools so that doctors and patient can work on the problem together. As is understandable, some doctors will not help and one or two can be hostile, others will help and others are keen to learn more and for some doctors it is waaay above them because its not the specialty. As is also understandable, some people with MD react the same way.

My protocol will not, for instance remove hydrops that is being "fed" with an undetected neuroma. It will not reverse destructive surgery. It will not resurrect hearing when a congenital (unformed sac or valve of Bast for example) or genetic problem (IPEX syndrome or immunoglobulin or complement fixation defect) but it does explain in many cases why someone can be normal one week and chronically ill the next. It is simply another reason to define more finely the nature of hydrops so that its not idiopathic and can be treated correctly and the person not left wondering. MD is idiopathic hydrops. This is really when, the treating doctor does not know or cannot work out what it is that caused the Hydrops. It does not mean that no one knows or never will. That’s the start point.

• As explained above, many foreign-to-the-body proteins (mycoplasama, bacteria, viruses, L-Form cysts etc called antigens) can create hydrops. Hydrops creates the symptoms doctors called MD.

As explained above, the infection is in the MALT. The MALT is a connected to, but distinct part of the immune system. It relies on its antigenic information from the blood and lymphatic system.

Hydrops is a problem of the endolymphatic sac. That organ is defender of the inner ear. When antigens get into the inner ear, it reacts to communicate with the MALT and lymph (that’s why its endoLYMPHATIC) so release antibodies and summons T cells etc and produce inflammation so that the infection can be cleared (see above). It does this with cell to cell communication of messenger proteins and some are called cytokines.

Hydrops is caused by antigens, but which ones? There are thousands of types and thousands of antiifectives. Identification has proved impossible in the living. The difficulty is that the inner ear is TOTALLY INACCESSIBLE AND VERY, VERY SENSITIVE.

Let’s say a female goes to the MALT doctor and says I have a dull ache in my pelvis and my vagina itches and is discharging. The doctor can order imagery of the sore region to detect inflammation, can swab the vaginal wall to send the swab off to culture (to incubate any infection in a broth at a lab and thus identify the infection if there is one) and isolate the part of the MALT that is the problem. The doctor could, after narrowing down the region, use a speculum and knife on a probe to cut a tiny piece of tissue, say at the entrance of the fallopian tube. Then too send if off to be cultured. Out of the hundreds of antibiotics on the market, one can be chosen if it is say, for example, a bacterial infection. No point taking a blood sample because the infection is not in the blood clinically and may be in levels undetectable.

Contrast that to inner ear inflammation/hydrops. If the doctor opens the inner ear in any way, it loses its fluid and goes deaf. No doctor will do that. So they look at the eardrum. If they see no signs of infection, they say you don’t have one. They will not take a swab of anything as you cannot get close to it easily, even via the Eustachian tube, nor do they see any reason to. No point in taking a blood sample, there is no blood borne infection. “Sorry, its idiopathic.”

However, MD (because the endolyphatic sac is the INTERFACE ORGAN FROM THE MALT TO THE BLOOD/LYMPH) leaves a particular basic immunological footprint in blood draw (also in mucus, but that's another story altogether). The blood tests identify that footprint. From the same way an archeologist can tell from a footprint roughly, and sometimes very accurately what species gave rise to it, the same can be said with some types of antigens that can manifest in a cytokine profile from blood tests. In combination with a viral panel and full blood count, it is possible to identify certain infectious elements that can be addressed.

As noted above, none of that means that finding viral particles in inner ears of dead MD'rs prove MD is caused by a virus and antivirals will fix it. As everyone who tries antivirals eventually finds out.

關於國小數學

大叔碎碎念 關於國小數學

最近不知道為什麼常常想到一個老話題，事情是這樣的，一個媽媽在某社團分享了一張圖片是關於他小學的孩子在學校考卷上答了一個問題，明明答的方式正確，但被老師打叉。這個問題印象中是這樣：

"小明跟發哥的雜貨店買了5顆光碟機IC，一顆IC價錢是2塊錢，請問小明花了多少錢？"

結果小孩的答案是 5 X 2 = 10 元  (然後上面被畫了一個大紅叉)
然後老師的答案是 2 X 5 = 10 元

OK，我想你應該猜的到底下的留言應該是幹聲連連，說什麼老師莫名其妙什麼的，然後就有老師出來解釋說：這是在建立孩子解讀題目以及乘數/被乘數的觀念，要告訴孩子 "單位量×單位數＝總量"
所以
2 X 5 =10元 代表你用2塊之單價買了5顆IC

但我想，難道我們的數學教育不能引導孩子解釋成 "買了5顆2塊錢的IC"嗎？我的意思是說，為什麼一定要遵守"單位量×單位數＝總量"這個沒有科學概念的說明式，如果硬要照這樣教，那麼比較妥善的說明式是
5[顆] X 2 [元/每顆] = 10 元
2 [元/每顆] X 5[顆] = 10 元
兩者都對

也就是要求直接把單位寫上來，這樣一來純量交換率不會被破壞，也同時讓孩子知道單位的重要性，更重要的是當孩子學到除法與分式的時候他會知道[顆]是可以跟著算式一起被相消的，學校該教的是這樣的真理，不會因為時間的過去才發現今是昨非，更不需要在那邊咬文嚼字然後沒事找事做

純量的乘法有交換性，我相信每個數學老師都有大學數學系或是相關學歷，難道這些老師在說服自己接受"單位量×單位數＝總量"這個說明式的時候，心裡沒有痛苦的矛盾感嗎？難道這種教育方式不是間接的告訴孩子：即使是真理 也可以今是昨非，而且現在又不是在教孩子向量或是張量，有必要讓孩子的數學表達跟生活經驗充滿了矛盾嗎？當你用這種尺度去作為數學教育的度量衡，那麼你期待教出來的孩子要怎麼用正確的數學態度去解釋所有的生活行為？

OK這只是一個問題，其他不少留言才更讓我傻眼了，有家長說:"數學這麼計較幹嘛啦，我以前數學很爛，現在還不是月入X萬，而且離開學校以後根本就用不到數學，數學又不能拿來賺錢，現在手機這麼發達拿出來按一下就知道答案了啦，學什麼數學"。這種"數學無用論"留言讓我覺得很心裡很憂鬱

我憂鬱的並不是 "對啊數學真的沒有用 我還花這麼多時間學 ，根本浪費時間"，而是憂鬱: 在台灣，基礎學問的重要性被忽視與踐踏的程度，事實上這些忽視與踐踏的人都是曾經在學校學過這些學科然後靠著這些分數畢業拿到文憑的人，為什麼這些人會這麼輕視數學？

首先 台灣的教育並沒有好好的區分 "算術 與 數學"，讓很多人在畢業若干年後只記得"算術"，而根本忘記數學，很多人會說"學算術就夠用了啊，學什麼一元二次方程式, 二元一次方程式啊？會這些真的用不到又不能賺錢啊"

其實生活在現代，數學真真實實的存在你生活裡的每一處
你每天乘坐的各種交通工具如果沒有數學，你每天出門根本都是在自殺；你每天用的GPS如果沒有數學，不會看地圖的你根本永遠到不了目的地；隨便把一根USB裝置插上電腦這過程有數學；你家會有電也是數學；引擎內燃機有數學；潮潮最愛的唉鳳溝溝肉裏面是滿到多出來的數學。

不要再告訴你的孩子學數學不能賺錢了，會這樣想的人你一定永遠都想不到用數學賺錢的人到底從你身上賺了多少錢

#小弟數學沒有很好不要噹我啦

Stephen Spring Protocol 進度報告 (持續更新中)

Stephen Spring Protocol 進度報告 2017/07/02 - update to 2017/07/26

之前我的梅尼爾氏症(MD)病況已經在下列這篇文章的前言中有敘述到
https://allenmeniere.blogspot.tw/2017/01/43441810-reviewent-currently-there-is.html
簡單來說我的MD發作程度已經讓我沒辦法工作賺錢，現在已經留停在家休養，家裡經濟也呈現斷炊的狀態，為了拯救全家的命運，後來努力在網路上找尋國外資訊，輾轉得知關於Stephen Spring這個人的資訊(也看到了一些關於他的爭議)，他有一個網站，有興趣可以點進去看看。總之，在死馬當活馬醫的狀況下，後來我決定跟他合作看看。

因為必須要跟Stephen Spring簽一張NDA才能正式進行SSP treatment，所以我不能在部落格上寫出SSP進行的細節，這篇文主要只是紀錄我在開始與進行SSP過程中的一些大事紀時間點與病情變化。

2017/01/01, 決定開始用email跟Stephen諮詢他對MD研究的看法,主要是我提問關於與他合作的模式, 付費方式, 需要做什麼樣的檢查才能確認我是他的target, 以及SSP treatment的副作用, 這個過程差不多花了兩個禮拜，在這之前眩暈的發作頻率大約是一周2~3次

2017/01/13, 我根據在網路上蒐集到的資訊判斷思考後，決定告知SS我要嘗試SSP並且開始進行一連串的檢查(想當然爾健保不給付, 前前後後跑醫院和醫檢所大約花了一萬五)

2017/02/14, SS認為我的狀況屬於他的防守範圍，答應會寄MeniVac給我，這期間我已經開始使用抗HSV病毒藥物Valtrex進一個半月了(依照國外研究建議的劑量)，但沒什麼進展，眩暈發作頻率仍然是一週兩到三次

2017/04/10, 收到第1批MeniVac, 這段期間仍然持續吃Valtrex，但眩暈一樣一週兩到三次

2017/04/12, 開始第1次服用MeniVac

2017/05/08, 服用大約1個月(用量約2罐)，眩暈一樣一週兩到三次，有時候似乎變嚴重了，嚴重到每天1次，因為手上只剩下1罐，所以下訂單請SS再寄一批給我

2017/05/24, 第1批買的3罐已經用完了，但遲遲不見新的一批寄來, 此時眩暈大約減緩到一周一次 (似乎是有好轉的預兆？)，發作的強度似乎有降低，天旋地轉的程度似乎沒有之前嚴重了, 此時因為反正MeniVac沒得吃，所以我把之前買了沒用的左旋離胺酸+B12來搭配Valtrex一起用

2017/05/30, 端午節連假回高雄，回程在高鐵上發作，一路吐回家，此時眩暈大約一周一次

2017/06/10, 眩暈發作，與上次眩暈發作大約10天了，似乎眩暈發作間隔又拉長了，且眩暈強度又再降低，服用Diazepam與Meclizine後不至於到吐的程度，但這次發作完，左耳的低頻一直處於聽不到的狀態，低頻耳鳴也持續嗡嗡作響

2017/06/13, 終於第2批MeniVac寄來了，左旋離胺酸+B12仍然沒有中斷，持續搭著服用

2017/07/02, 一直到做紀錄的今天，這接近三周的時間都沒有眩暈發作，且低頻聽力與低頻耳鳴用一種非常緩慢的速度在緩解，漸漸的低頻耳鳴不見了，低頻聽力也慢慢聽的到了，剩下高頻的eeeee耳鳴，但還在可以接受的範圍，這應該是從去年發病以來，維持不發作的時間最長的一次，希望可以保持下去

=====================2017/07/26 update

2017/07/07 話真的不能說太早，07/02開始發燒，07/07我就也被傳染到也開始發燒，燒了四天以後看醫生說是流感，直接投克流感，這四天過程中又開始覺得耳悶 低頻聽不到了，

2017/07/15 眩暈又發作，之後又開始維持三四天一次的頻率到 07/26 ，不過暈的程度沒有之前嚴重，有時候三四個小時就過了，也不至於天旋地轉

2017/07/19 開始去大林慈濟看李醫師，當天就打了有名的慢點滴 (類固醇 + Diazepam + 心率調節藥物當作自律神經調節用) 口服藥物則是領了flunarizine  + 舒安得(輕微的BZD藥物) ，感覺這個口服藥的組合跟楊怡和醫師開的 flunarizine  + fludiazepam(中度的BZD藥物) 作用差不多，希望可以跟李醫師溝通不要打類固醇，因為類固醇有免疫抑制的作用，擔心會跟SSP起衝突。

Immulox與梅尼爾氏症的關聯

Immulox與梅尼爾氏症的關聯

從網路上可以找到梅尼爾的免疫治療 與 Immulox之間的有趣關聯

相關連結

http://baike.baidu.com/item/%E5%AF%8C%E8%84%AF%E6%B0%A8%E9%85%B8%E5%A4%9A%E8%82%BD

http://www.bio2u.us.com/%E7%B4%A0%E6%9D%90%E4%BB%8B%E7%B4%B9/item/aps-biogroup-immulox-%E7%9B%8A%E6%95%8F%E8%82%BD.html

http://www.choicesunlimited.ca/when-t1-t2-are-out-of-balance/

https://www.kingnet.com.tw/knNew/news/single-article.html?newId=7990

還是有點懶，細節之後有空再補上好了 @@

*首先兩者都是從牛乳製品中製造而來 (Immulox是從初乳的過慮製程而來)

*再者Immulox中的PRPs (富脯氨酸多肽)也同樣具備有特定的Th1/Th2平衡效果,

" In particular PRP are thought to modulate thymus function, specifically the T helper 1 / T helper 2 (Th1 / Th2) balance. "

from

http://calostart.com/app/docs/ALZHEIMER/CALOSTART-ALZHEIMER/CaloStart%20-%20THE%20EFFECT%20OF%20A%20COLOSTRUM%20EXTRACT%20OF%20PROLINE%20RICH%20POLYPEPTIDES.pdf

這跟某個梅尼爾氏症的免疫治療其假設為需要改變 T1/T2 balance的精神很類似

過敏與梅尼爾的關係?

Is Allergy Related to Meniere’s Disease?

原文：  https://www.researchgate.net/publication/223136937_Is_Allergy_Related_to_Meniere's_Disease

過敏與梅尼爾氏病的關係之前有跟大家分享國外許多研究對梅尼爾氏病的不同面向，有自體免疫, 過敏, 病毒, 壓力, 等等, 這篇論文則是review過敏這個因素，其中提到幾個重點跟大家分享

*在一個大型的研究中，從734個MD病人當中survey，發現過敏在MD病人中的盛行率約為41%

*有過敏性鼻炎的人，可能會有氣喘,鼻瘜肉,中耳炎,或慢性鼻竇炎。而有氣喘與過敏性鼻炎的人則會有較高的食物過敏盛行率。在2000年的一份研究中指出在MD病人中，小麥是最常見的食物過敏原68%。麥膠蛋白被認為是造成小麥過敏的人們對"IgE誘導產生的過敏"(第1型過敏)最主要的原因

*Derebery等人認為有三種過敏機制可能造成梅尼爾症狀，第1種是IgE誘導的過敏反應在內淋巴囊造成局部發炎, 第2種是免疫複合物在內耳淋巴囊附近的微血管堆積造成局部發炎，有研究顯示MD病人的循環免疫複合物的檢驗結果比控制組高了21~96%, 第3種是病毒侵入造成內淋巴囊的輕微發炎反應

*Derebery等人建議病人使用過敏免疫治療(allergen immunotherapy)並且/或是移除過敏源，在113個接受治療的病人中，所有人都回報症狀有所改善

摘錄一些重點如下


• In a large study, Derebery and Berliner investigated the prevalence of allergy in MD. In a survey of 734 patients with MD, concurrent allergic disease was found in 41 %.

在一個大型的研究中，從734個MD病人當中survey，發現過敏在MD病人中的盛行率約為41%

•  Likewise, in allergy-susceptible patients, an allergic response can evoke responses in distal sites.

在疑似過敏的患者身上，過敏反應可能會觸發末梢的反應

• This likely occurs via an integration of neurological, immunologic, and allergic responses involved in inflammation.

這可能會經由神經性,免疫性, 與有發炎之過敏反應的結合而發生

• People with ARmay have asthma, nasal polyposis, otitis media, or chronicrhinosinusitis [36]. People with asthma and AR have a higherprevalence of food allergies, the estimated prevalence ofwhich in America is 3.5 % to 6 % 

有過敏性鼻炎的人，可能會有氣喘,鼻瘜肉,中耳炎,或慢性鼻竇炎。而有氣喘與過敏性鼻炎的人則會有較高的食物過敏盛行率

• Derebery and Berliner [18] in 2000 reported wheat as the most common food allergen found in patients with MD(68.2 %).

2000年的一份研究中指出在MD病人中，小麥是最常見的過敏原68%

• Gliadin is considered the major cause of IgE-mediated hypersensitivity in people with wheat allergy.

麥膠蛋白被認為是造成小麥過敏的人們對"IgE誘導產生的過敏"(第1型過敏)最主要的原因

• Allergic reactions are considered to be one of the many causes of migraines. Numerous studies have reported an association between migraines and allergies. They found that the incidences of both allergy and migraine were significantly higher in the Meniere’s group and that the incidence of allergy in the MD migraine group was significantly higher than that in the group with MD alone.
• 
  
• Derebery and Berliner [21] outlined three proposed mechanisms by which allergy can produce MD symptoms.
• 
  
• The first mechanism, the endolymphatic sac, could be atarget organ of the allergic reaction. The antigen enters the endolymphatic sac andcauses an IgE-mediated degranulation of mast cells. Thisproduces a local inflammatory response that impairs theendolymphatic sac’s filtering function, and a buildup oftoxic metabolic products results, interfering with hair cell function. Histamine and other vasoactive mediators releasedin an allergic response elsewhere may also exert an effecton the well-vascularized fenestrated blood vessels of the endolymphatic sac, thereby affecting reabsorption. 
• 
  
• The second mechanism proposed is deposition of circu-lating immune complexes (CICs). These CICs are depositedand accumulate in the fenestrated blood vessels of the en-dolymphatic sac and stria vascularis. This results in inflam-mation and an increased permeability of the leaky capillariesthat surround the endolymphatic sac. The inflammationinterferes with the capability of the endolymphatic sac’shomeostasis function. Several studies demonstrated an in-crease in circulating immune complexes: 21 % to 96 % ofpatients with MD compared with controls 
• 
  
• The third mechanism is the viral antigen–allergic inter-action. This mechanism suggests that a viral insult canantigenically stimulate Waldeyer’s ring, with T-cell homingto the endolymphatic sac, causing a low-grade inflammatoryresponse. This impairs absorption of the endolymphatic sacbut does not produce symptoms. Then, later in life, anunknown trigger in the system stimulates excessive fluidproduction. Then, later in life, anunknown trigger in the system stimulates excessive fluidproduction.  Derebery and Berliner [21] referenced howviruses are capable of exacerbating allergic symptoms by avariety of means, including causing histamine release,thought to be mediated by interferon. They can also damageepithelial surfaces, enhancing antigen entry and increasingresponsiveness of target organs to histamine. Derebery[22••]noted heat shock protein 70 (HSP70), an antibodyfrequently seen increased in both MD and autoimmuneinner ear disease, is often upregulated in viral infections. They concluded that patients with clinically “certain” MD do not have a significantly raised incidence of HSP70 antibodies.
• 
  
• Derebery [19] (2000): 113 patients accepted treatment;all 113 reported improvementof symptoms after treatmentof allergy
• In Derebery’s clinicalexperience, patients who have both MD and allergybenefit from immunotherapy and/or dietary avoidanceof reactive food allergens. The symptoms of MD aregenerally better controlled, with fewer vertigo attacksand more stable hearing
• 
  
• The association of allergy andMD is well-documented. At the present time, it is generallyaccepted that the cause of MD is likely to be multifactorial,consisting of an underlying genetic predisposition, com-bined with an extrinsic insult. Allergy may well be involvedin the final common inflammatory pathway in a selectsubpopulation of patients with MD 
• 有點懶，之後再繼續讀這篇論文

關於第一二三型過敏反應的解釋 可參照這裡
https://smallcollation.blogspot.tw/2013/10/hypersensitivity.html#gsc.tab=0
"1.第Ⅰ型過敏反應－IgE誘導發生的過敏反應
造成第I型過敏反應的機制為：當過敏原第一次進入人體在與特定B細胞上的抗體結合後，會引起特定IgE的大量製造，分泌出的IgE與過敏原結合後，會附著在肥大細胞(Mast cell)表面的Fcε受體。當相同的過敏原再度入侵人體，過敏原和肥大細胞表面上的IgE結合，會誘發肥大細胞釋出發炎物質，如組織胺、介白素、細胞激素，造成紅腫發癢等症狀"

"3.第Ⅲ型過敏反應－免疫複合體(immune complex)引發的過敏反應
...複合物如果沒有被清除，且在腎、血管壁、心臟瓣膜等處沉積，進而引發過度的免疫反應，如吞噬細胞企圖吞噬複合物，但複合物太大無法吞噬，於是釋放出酵素，導致發炎並造成該部位的傷害...複合物沉積的位置可以是全身性或局部性...造成的原因有可能是病患自己產生自體抗體與自體抗原形成免疫複合體而引發，如全身紅斑性狼瘡(systemic lupus erythematosus) 、類風濕關節炎的患者；或者是持續性感染，其抗原的量雖然不多，但一直存在，使得免疫複合物持續產生，並堆積在各個器官，如麻瘋病、瘧疾、B型肝炎"

前庭神經炎 最新的治療方法

前庭神經炎 最新的治療方法

耳科主治醫師 廖文輝

原文出處

前庭神經炎又稱流行性眩暈症，此病好發於氣候轉換的季節如晚秋、初春時節，臨床上為第二常見的末稍性前庭障礙疾患，僅次於最常見的良性陣發位置性眩暈；後者發病後，其前庭功能一般可完全恢復至正常，但前庭神經炎的預後很不同，本病症眩暈發作後，其前庭功能恢復情況並不樂觀，僅有少數患者可完全恢復至先前正常的前庭（溫差測試）功能，即使經過一年後，仍有半數的患者其前庭功能未能恢復至發病前正常的情形；甚至多數的患者會有殘存非典型的眩暈症狀及身體姿勢不平衡的後遺症；同時本病眩暈發作的期間會較其他眩暈
症長，短則數小時甚至到數天之久；部分病患也會有再復發的眩暈發作情況，可能持續有數個月之久，此種殘留的暈眩發作情形和身體姿勢不平衡的後遺症，時常造成病患夜夜無法安眠，隨時擔心有眩暈不定時的發作，如此心靈受到的煎熬與痛苦，除非真正有過此種可怕經
歷的患者，是無法用筆墨形容的！前庭神經炎對於病患的影響如同惡魔的靈魂附身般痛苦，這種情形是患者真正難以忍受的情況。前庭神經炎的臨床典型症狀為急性、持續性、旋轉式的眩暈發作，身體姿勢常無法保持平衡，有自發性眼振出現，會有噁心甚至嘔吐的情
形。臨床上診斷前庭神經炎的標準是依眩暈發作的病史和前庭功能檢查的異常為依據，必需先排除其他中樞性與周邊性前庭疾患，並且要符合以下四個診斷條件：1.急性、持續性的眩暈發作，發作後無法立即恢復到發作前的前庭功能狀況。2.不伴隨有聽力損失的情形。3.患
側的前庭功能檢查溫差測試有明顯的低下。4.為急性單側末稍性前庭的病變。眩暈發作是前庭神經炎最主要的症狀，許多中樞性與末稍性前庭的疾患也有類似的症狀，因此需要仔細做鑑別診斷，所以許多眩暈患者常需要耳鼻喉科與神經內科兩科的共同會診，才能做出正確診
斷。前庭神經炎常是選擇性侵犯前庭神經的上半支（影響到水平和前側三半規管及橢圓囊），而下半支（影響到後側三半規管及橢圓囊）的部位一般不會侵犯到。前庭神經炎真正的病因目前仍不明，以病毒感染的病因較為醫界所接受。因為許多患者發病前皆有病毒感染的一些症狀；例如上呼吸道感染，至於真正病因仍是眾說紛紜，此病症常好發於氣候轉變的時候，如初春、晚秋的季節，也正是流行性感冒盛行的季節，治療的目標是使用抗病毒藥物來阻斷其發炎的情況，期能有效地改善前庭神經炎患者發病後前庭功能恢復的情形。

臨床上對於前庭神經炎有三種基本標準治療的原則：第一種為使用抗眩暈藥物，以控制其急性眩暈發作和嘔吐的症狀，但是眩暈發作時常常無法口服給予，多數採用靜脈或肌肉注射，以減輕急性期發作的症狀，主要的目的是幫助患者度過眩暈發作的急性期，待依患者本身的
免疫功能逐漸地恢復，當患者已產生中樞性代償的現象，即不會有嚴重的眩暈感覺，但如果其前庭功能有嚴重受損的情形，仍會有不定時姿勢不平衡的後遺症。第二種為給予靜脈注射點滴補充體液，以控制患者急性暈眩發作及嘔吐所導致的脫水症狀。第三種為眩暈復健運動
治療，至於眩暈復健運動治療的情形，儘早進行眩暈復健運動，其前庭功能恢復的情形會較好，而病患的眩暈症狀和身體姿勢不平衡的改善情況也會較明顯。

目前針對於此病症的治療方法，除了以上傳統標準抗眩暈藥物治療方法外，本科於 2005 年開始嘗試使用抗病毒藥物來治療，其治療劑量為每天兩次，每次兩顆（Valtrex 500mg），治療期約為 10-14 天（此為日本北海道七戶醫師依其治療約三千位病患的實際臨床經驗調整後的
建議劑量），本人使用的臨床經驗為：急性發作期仍是以類固醇（Decadron）為首選（要排除糖尿病、胃潰瘍、高血壓等患者），因其效果較為快速，而此抗病毒藥物的療效，約於 7-10 天後才會明顯的看到效果，但是對於復發性前庭神經炎或不明原因的眩暈症，此抗病
毒藥物的療效卻相當不錯，尤其對於反覆性前庭病變的病患，因其慢性且長期的眩暈症狀，故療效常要 10-14 天才會明顯看到效果，希望各位要耐心等待。也不知是否是病患已經用盡所有抗眩暈藥物，腦部循環改善劑、止嘔吐藥等？或而且此藥物的價錢較高（健保不給
付），目前病患們反映其療效是很滿意！因此特別於順風耳這裡告知各位前輩及先進們，以提供另一種前庭神經炎治療方法。

VIRAL THEORY FOR MENIERE’S DISEASE

VIRAL THEORY FOR MENIERE’S DISEASE
很有趣的一篇文章 原文網址是:

http://www.whirledfoundation.org/wp-content/uploads/2015/10/0212_Viral-Theory-For-Menieres-Disease.pdf
裡面提到了一些內容關於傳統認定的眩暈發生機制與病毒致病的可能性，我摘錄一些重點如下

• 最早認為梅尼爾氏症的致病機制為血管痙攣收縮，因此有了betahistine這種藥物的治療，用意為擴張血管，也因為這個中心思想，醫生多囑咐病人少食用咖啡因與避免尼古丁，但這個觀念現在多半已經被捨棄
• 有研究指出過分的攝取鹽分會引發眩暈，但因為沒辦法進行有效的雙盲試驗去證明，不過一些傳聞的確指出鹽攝取量是一個重要的因素
• 1960年提出的薄膜破裂理論，是過去50年最受歡迎的理論，其主張為過多的內淋巴液造成薄膜破裂而造成鉀離子對前庭神經產生中毒，過多的淋巴液堆積是由於淋巴液無法流進內淋巴囊，此理論認為內淋巴液會持續的流入內淋巴囊，因此如果發生阻塞則會造成淋巴液堆積進而壓迫薄膜破裂，這個概念引導出了內淋巴囊引流手術，藉由於內淋巴囊置入小管或是矽膠片去吸收淋巴液，這個手術觀念目前已經被大幅捨去，有研究顯示內淋巴囊並不是被動的吸入淋巴液，而是一種類似海綿組織的構造，且只有在它分泌醣蛋白並且重新吸收時才會引入內淋巴液，也有研究顯示內淋巴液不會持續的流入內淋巴囊，而是只有在內淋巴液體積突然增加時才會產生流動，甚至還有研究指出眩暈發作期間患者的耳蝸功能並沒有喪失
• 新的研究提出眩暈的產生是因為淋巴液突然變多以後，拉扯或是壓垮了半規管皺摺內的前庭毛細胞
• 一位研究人員提出的排水理論假設前庭部的橢圓囊裡的內淋巴液會突然增加是因為在縱向排水期間從內耳耳蝸來的內淋巴液逆流而產生
• 這個排水理論提出一開始淋巴液會增加的原因為內耳內部的發炎反應，一旦多餘的淋巴液產生，淋巴液輕微的波動就會造成發作，經過一連串的發作後，多餘的體積減少，則會進入一段緩解期，等到下一次的發炎狀況產生就又會產生一連串的發作
• 由皰疹病毒造成初始發炎反應的說法十分令人信服，病毒在發作後會進入休眠期潛藏在內耳神經附近，等待下一次的活躍又會產生發炎反應，進而產生過多淋巴液造成一連串的發作

VIRAL THEORY FOR MENIERE’S DISEASE

By Professor William Gibson AM M.D., F.R.A.C.S. F.R.C.S.
Professor of Otolaryngology, University of Sydney

Meniere’s disease was first described by Prosper Ménière in 1861. His idea that vertigo was caused by an inner ear disorder was not accepted by the scientific community who supported the concept that vertigo was a brain disorder.

Ménière accurately described the condition but his original paper was not published because of the adverse scientific opinions. Fortunately several of his subsequent papers were published. Prosper Ménière died in 1862 after contracting pneumonia. It was ten years later that Ménière’s ideas became accepted so he never received any acknowledgement during his lifetime.

Meniere’s disease causes four major symptoms; attacks of vertigo which tend to occur in clusters, a fluctuating and usually progressive hearing loss in the affected ear, tinnitus and a sensation of aural fullness. Other symptoms such as tiredness, ‘brain fog’, and poor memory are less commonly mentioned.

It is estimated that approximately 50,000 people in Australia suffer from Meniere’s disease. Meniere’s disease tends to occur initially in mid adult life with a median age of 50 years. The attacks of vertigo tend to occur in clusters lasting a few months followed by variable periods of remission. Eventually the attacks of vertigo peter out when the hearing becomes poor, which is known as ‘burn out’ or stage 3 of the condition.

The attacks of vertigo cause great distress. The sensation of spinning can last for several hours associated with nausea and vomiting. The attacks are unpredictable and often the bread winner cannot continue work or a parent is unable to cope with the family. Often the sufferer hopes for ‘burn out’ even though they become very deaf in the affected ear and may continue to be plagued by tinnitus. Discovering the cause of the attacks of vertigo must be the first step towards finding the cure for this terribly disabling condition.

Discovering the cause of the attacks of vertigo

The initial concept was that the vertigo was due to vascular spasms within the inner ear. In the period after WW2, this belief led to the use of medications which dilate the blood vessels such as nicotinic acid and an operation called cervical sympathectomy [1]. To avoid the skin of the face reddening, Betahistine (Serc®) was developed and this still remains a popular treatment. The concept that constriction of the blood vessels in the inner ear caused the attacks was the reason why doctors told their patients to avoid coffee, caffeine drinks and nicotine. As Meniere’s disease occurs in a younger age group than vascular disease and there is no increased prevalence of Meniere’s disease amongst people with vascular problems, the concept that Meniere’s is due to vascular spasm has been mostly abandoned.

In the 1930’s, Swedish doctors noticed that many people noticed that salty foods could precipitate attacks of vertigo [2]. In the 1950’s two English researchers (Harrison and Naftalin) gave Meniere’s disease sufferers salt loads and demonstrated that vertigo attacks occurred when increased salt was excreted in the urine [3]. It is not possible to do a proper ‘double blinded trial’ of salt but the anecdotal evidence does suggest that salt loading is a significant factor.

In 1960, Schucknect at Boston showed small ruptures had occurred in the membranes in the inner ear which had healed up but left some tell-tale scarring. He proposed a rupture theory [4]. This theory suggested that an increase in the inner ear fluid called endolymph bulged the membrane causing ruptures which allowed potassium from the endolymph to poison the balance nerve endings leaving the ear. This caused a temporary loss of function resulting in vertigo until the rupture was closed off and the ionic balance restored. This theory has been favoured for the past 50 years.

The cause of the increased endolymph volume was attributed to a failure of the flow of endolymph to the endolymphatic sac. It was thought that there was a constant ‘longitudinal’ flow of endolymph toward the sac, and if a blockage occurred there was a build up of endolymph in the inner ear until the membranes ruptured. This led to the concept of endolymphatic shunt surgery, where a tube or sialastic sheeting was placed in the endolymphatic sac to facilitate its ability to absorb the fluid. This concept has now been largely discounted. Swedish workers have shown that the endolymphatic sac
is a sponge like structure and not a sac which passively accepts endolymph [5]. Endolymph is only attracted into the sac when it secretes and reabsorbs glycoproteins. Salt and his co-workers have demonstrated that there is no constant flow of endolymph to the endolymphatic sac but longitudinal flow only occurs when there is a sudden increase in endolymph volume [6]. Furthermore, audiological studies and electrophysiological studies undertaken by the author and others have shown no loss of cochlear function during the attacks of vertigo [7]. In a controversial study the author has shown that removal of the endolymphatic sac rather than shunt surgery provides a better outcome as it hastens the ‘burn out’ stage of MD [8].

The search is now on to find the real cause of the attacks of vertigo. The Meniere’s Research Laboratory has been established in Sydney under the care of Dr Daniel Brown. Here work has been undertaken to increase the volume of endolymph in the inner ear while observing the changes in the firing of the vestibular and cochlear nerves. Studies suggest that sudden changes in endolymph volume cause a stretching or collapse of the vestibular hair cells within the cristae of the semicircular canals. The author proposed a ‘drainage theory’ which postulates that the increased volume of endolymph inside the utricle (vestibular portion) is due to reflux of endolymph from the cochlear part of the inner ear during periods of longitudinal drainage [9]. Further studies are presently occurring.

Gibson’s drainage theory proposes that there is an initial increase in endolymph volume due to an inflammatory reaction inside the inner ear. Once this extra volume of fluid is present minor fluctuations in the level of excess endolymph could be the trigger for each attack: for example, after ingestion of salt or when stress causes a hormone (vasopressin) to be released. After a series of attacks the excess volume decreases and a period of remission from attacks occurs until another inflammatory event occurs causing another cluster of attacks.

What causes the initial increase in endolymph volume and the recurrent attacks of vertigo?

Many researchers consider that Meniere’s Disease is multifactorial and there are many different causes which lead to the situation which results in Meniere’s disease.

It is known that the bony vestibular duct which contains the membranous duct leading to the endolymphatic sac is narrow in Meniere’s disease sufferers although it is also narrow in some people who do not suffer with Meniere’s disease. Furthermore, there is a genetic abnormality associated with Meniere’s disease.

Possible causes include congenital disorders such as viral illness during the pregnancy including rubella (German measles) and toxoplasmosis. Diseases of the bone surrounding the ear such as otosclerosis or Padgets disease, tumours of the endolymphatic sac or vestibular nerve, allergies especially to food substances, various infections caused by syphilis, yaws or viruses, autoimmune problems and failure of the immunodefence mechanism.

If the cause of the increased endolymph is due to an inflammatory reaction inside the inner ear, then steroids should limit this inflammation. There has been a vogue towards using oral or intratympanic steroids to stop clusters of attacks of vertigo. The validity of this approach has yet to be clearly shown although clinical evidence does seem to suggest it is an effective treatment.

Is a virus the most common cause of Meniere’s disease?

Over fifty years ago Lempert and his co-workers suggested that Meniere’s disease was caused in the majority of ears by a herpes virus [10]. The herpes family of viruses consist of at least 8 members including HSV1 (causes cold sores), HSV2 (causes genital herpes), VCV (causes chicken pox and shingles), EBV (causes glandular fever) and CMV (causes birth defects).

The herpes virus has been found in autopsy specimens obtained from Meniere’s disease sufferers in both the endolymphatic sac and in the ganglion of the vestibular and cochlear nerves. However ears from non Meniere’s disease sufferers often also contain the virus.

The idea of a herpes virus causing the initial inflammatory response in the inner ear is compelling. For example, herpes simplex virus causes cold sores which erupt on the lip and then the virus lies latent or hides in the nerve for a while and then can erupt again causing more cold sores. It is postulated that a similar virus causes an initial inflammatory response in the ear and results in inflammation which causes excess endolymphatic fluid (endolymphatic hydrops). As the virus lies latent within the ear, it can erupt again causing another cluster of attacks.

Unfortunately there is no medical treatment which can kill the virus when it goes into its latent state. Anti-virals may be effective in stopping eruptions of the virus but would have to be taken continually.

The need for research into a viral cause

The first step in the research will be to find out which Meniere’s disease sufferers have a viral cause for their condition. A prolonged, double blind trial needs to be undertaken to determine if antiviral drugs can prevent clusters of attacks occurring. A double blind trial means that a placebo which looks exactly like the antiviral agent is used in some subjects and the actual antiviral medication is used in others. Neither the doctor nor the patient will know which is being used. If a subject has
another cluster of attacks, the secret is revealed and if that person is on the placebo, they will be offered the active medication.

Why do some ears have the virus present but do not develop Meniere’s disease?

While the virus lies latent (hidden) within the inner ear structures, the function of the ear is unaffected. When the virus erupts it causes the inflammatory response resulting in the production of excess endolymph. If the ear can mount an adequate defence mechanism, the virus can be destroyed before it causes an excessive inflammatory reaction. Some ears can mount this defence mechanism, whereas ears affected by Meniere’s disease cannot.

The immune system clears viruses and other pathogens from the body using special cells called lymphocytes. Lymphocytes are developed in the bone marrow (B lymphocytes) and in the thymus (T lymphocytes or T cells). Viruses are cleared by a specific lymphocyte known as Th1 and the ear needs lots of these Th1 lymphocytes to prevent the virus from causing the inflammatory reaction.
T cells are made specifically for certain tasks. T cells develop from immature T cells in the thymus and these can differentiate into specific types with highly specialised tasks. Some may develop into T1 cells and these can be measured with a blood test using a special marker called CD8+. Other immature T cells develop into Th2 cells which communicate with B lymphocytes (which produce anti-bodies to combat bacterial infections and parasites). Th2 cells have a CD4+ marker. Furthermore, other T cells are produced that limit the immune system so the body does not attack its own tissues, a process known as autoimmunity.
Perhaps if a person with Meniere’s disease has insufficient or inefficient specialised immune cells, they may be unable to prevent the virus erupting and causing inflammation in the inner ear. This may be the reason why some ears which contain the virus do not suffer from Meniere’s disease.
Stephen Spring, himself a Meniere’s disease sufferer, has discovered a possible means of altering the T1/T2 balance which may provide long term relief and we hope to be able to properly evaluate his ideas at the University, but such is the fickle nature of Meniere’s disease that isolated cures cannot be taken as definite proof of efficacy.

Our hopes for the future
It is our aim at the University of Sydney to be able to explain the mechanism which causes Meniere’s and to find an eventual cure. We feel that some definite strides towards this goal have already been made. We are desperately keen to be able to complete the tasks and hope that there will be sufficient funding to make this possible. The Meniere’s Research Fund under the superb leadership of Bruce Kirkpatrick has been the lifeline and we urge all Meniere’s disease sufferers and their families to continue to support this cause.

We need to recruit Meniere’s disease sufferers who are willing to become part of our research programme. Specifically we need sufferers who are experiencing clusters of attacks of vertigo so that we can discover if antiviral medication can be effective.
If a reader wishes to help us, please contact me (Professor Gibson at 02 9844 6801).

References
1. Passe ERG, Seymour JS (1948) Meniere’s syndrome: successful treatment by surgery on the sympathetic. Brit Med J, 2,
812-816
2. Furstenberg AC, Lashmet FH, Lathrop F (1934) Ann ORL, 43, 1035-1046
3. Harrison MS, Naftalin L (1968) Meniere’s disease: Mechanism and management, Springfield: Charles C Thomas
4. Schuknecht H. Correlation of pathology with symptoms of Meniere’s disease. Otolaryngol Clin N Amer 1968; 1:433-438
5. Bagger-Sjöbäck, Friberg U, Rask-Andersen H: The human endolymphatic sac: an ultrastructural study. Arch Otoalryngol Head Neck Surg 112: 398-409 1986
6. Salt AN: Fluid homeostasis in the inner ear. In Harris JP (ed) Meniere’s Disease. The Hague, Kugler Publications 93-101 1999
7. McNeil C, Cohen M, Gibson WPR (2009) Changes in audiometric thresholds before, during and after attacks of vertigo associated with Meniere’s syndrome Acta Otolaryngol. 129, 1404-1409.
8. Gibson WPR (2005) The effect of removal of the extra-osseous portion of the endolymphatic sac in ears affected by Meniere’s disease. In ‘Meniere’s Disease & Inner ear homeostasis disorders’ Ed Lim DJ. Pages 239-240. House Ear Institute publication, Los Angeles (ISBN 0-9776204-0-9)
9. Gibson WPR (2010) Hypothetical mechanism for vertigo in Meniere’s Disease. Otolaryngol Clin N Am 43: 1019-1027
10. Lempert J, Wolff D, Rambo JHT, Wever EG, Lawrence M. (1952) New theory for the correlation of the pathology and the symptomatology of Meniere’s disease; a research study of the vestibular endolymphatic labyrinth. Anna ORL.61,717–746