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Similaire à BPPV' de medikal tedavinin yeri ve D vitamini eksikliği ilişkisi
Similaire à BPPV' de medikal tedavinin yeri ve D vitamini eksikliği ilişkisi (20)
Plus de enisalpinguneri
Plus de enisalpinguneri (20)
BPPV' de medikal tedavinin yeri ve D vitamini eksikliği ilişkisi
- 2. BPPV’de medikal tedavi 4 grup Semont manevrası ±betahistin Brandt Daroff ± Betahistin Tx yanıtları : Epley kriterleri 100% Semont +Betahistin grubunda Semont ve Brandt Daroff +Betahistine Her ikisine tek başına manevralardan anlamlı ölçüde etkili Cavaliere M, Mottola G, Iemma M. Benign paroxysmal positional vertigo: a study of two manoeuvres with and without betahistine. Acta Otorhinolaryngol Ital. 2005 Apr;25(2):107-12
- 3. BPPV’de medikal tedavi Meta-analiz Betahistin vs plasebo ile 7 test Cupulo-canalolithiasis ve VBI olguları Tx yanıtları : iyileşmiş/iyileşmemiş Betahistin vs plasebo’nun faydası Maksimum etki 32-36 mg/g , 3-8 hafta Della Pepa C, Guidetti G, Eandi M. Betahistine in the treatment of vertiginous syndromes: a meta-analysis. Acta Otorhinolaryngol Ital. 2006 Aug;26(4):208-15
- 4. BPPV’de medikal tedavi Prospektif randomize, 2 grup Betahistin 24 mg/g, 1 ay Cawthorne-Cooksey egzersizi 6 kez/g, 4 hafta Tx yanıtları : VDI, VDIss, VDIHRQoL, VSS Ekzersiz betahistine göre daha iyi bir tedavi seçimi olarak bulundu Kulcu DG, Yanik B, Boynukalin S, Kurtais Y. Efficacy of a home-based exercise program on benign paroxysmal positional vertigo compared with betahistine. J Otolaryngol Head Neck Surg. 2008 Jun;37(3):373-9
- 5. BPPV’de medikal tedavi Betahistin 48 mg/g, QoL ve baş dönmesi semptomlarına etkisinin değerlendirilmesi 3 ay pazarlama sonrası gözetim 2037 olgu 13 ülke 4 kıta idiyopatik, BPPV, Meniere ve diğer Tx yanıtları: DHI, SF-36, HADS kesin sonuçlar yok Pérez-Garrigues H , Kuessner D, Benecke H. Patient baseline characteristics in an open-label multinational study of betahistine in recurrent peripheral vestibular vertigo: the OSVaLD study. Curr Med Res Opin. 2007 Nov;23(11):2753-61
- 6. BPPV’de medikal tedavi betahistine 48 mg/d in recurrent peripheral vestibular vertigo is associated with improvements in objective measures of health-related QoL and satisfactory tolerabilityBenecke H, Pérez-Garrigues H, Bin Sidek D, Uloziene I, D K, Sondag E, Theeuwes A; OSVaLD investigators. Effects of betahistine on patient-reported outcomes in routine practice in patients with vestibular vertigo and appraisal of tolerability: experience in the OSVaLD study. Int Tinnitus J. 2010;16(1):14-24
- 7. BPPV’de medikal tedavi Betahistin 48 mg/gün Tx yanıtları : DHI, SF-36, HADS Rusya ve Romanya’da rekürren periferal vestibülar vertigo hastalarının hayat kalitesinin iyileşmesi Betahistin ve piracetam, betahistine göre daha etkili olabilir
- 8. BPPV’de medikal tedavi Epley manevrası sonrasında betahistinin postural stabiliteye etkisinin belirlenmesi BPPV kesilme süresi: 60 gün Statik posturografi ile salınım hızı (+) DH testi sonrası 1 hf Epley sonrası 10/20 gün BPPV süresi < 60 gün olan hastaların betahistin ile 10 gün tedavi sonrasında postural stabilitelerinin normalleşmesi Stambolieva K, Angov G. Effect of treatment with betahistine dihydrochloride on the postural stability in patients with different duration of benign paroxysmal positional vertigo. Int Tinnitus J. 2010;16(1):32-6
- 9. BPPV’de medikal tedavi Prospektif randomize Epley manevrasına ek olarak betahistin 48 mg/g etkisi P-BPPV canalithiasis Tx yanıtları :DHI, VDADLS, EEV, VSS Betahistin+Epley, tek başına Epley veya Epley+plaseboya göre daha etkili Guneri EA, Kustutan O. The effects of betahistine in addition to epley maneuver in posterior canal benign paroxysmal positional vertigo. Otolaryngol Head Neck Surg. 2012 Jan;146(1):104-8.
- 10. BPPV’de medikal tedavi Prospektif randomize Epley manevrası ± 3 ilaç Betahistin mesilat, flunarizin, gingko Tx yanıtları:kür/ toplam efektif oran Grup 1’de tedavi sonuçları daha iyi 4 hafta: farklılık yok Zhang H, Geng M, Yan B, Lu X. Epley's manoeuvre versus Epley's manoeuvre plus labyrinthine sedative in the management of benign paroxysmal positional vertigo: prospective, randomised study. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2012 Aug;26(16):750-2.
- 11. BPPV’de medikal tedavi Grup 1: Epley/Lempert manevrası Grup 2: Betahistin mesilat Dozaj rejimi? MANEVRA UYGULANMAMASI? Tx yanıtları: kür,nüks, inatçı Manevra yapılan grupta düzelme zamanı daha kısa Otsuka K, Ogawa Y, Inagaki T, Shimizu S, Konomi U, Kondo T, Suzuki M. Relationship between clinical features and therapeutic approach for benign paroxysmal positional vertigo outcomes. J Laryngol Otol. 2013 Oct;127(10):962-7.
- 12. BPPV’de medikal tedavi Manevra sonrası rezidü semptomlarda dimenhydrinate 50 mg/gün etkisi Tx yanıtları :kür,nüks,inatçı Dimenhydrinate, plasebo ve tedavisiz grupla karşılaştırıldığında CRP sonrası rezidü semptomları azaltmaktadır DHI skorunda anlamlı düşüş yok Kim MB, Lee HS, Ban JH. Vestibular suppressants after canalith repositioning in benign paroxysmal positional vertigo. Laryngoscope. 2014 Oct;124(10):2400-3
- 13. BPPV’de medikal tedavi Epley vs Sham manevrası + Betahistin UYGUN MANEVRA UYGULANMAMASI? Tx yanıtları :DHI ve diğer ölçüler P-BPPV tedavisinde uygulanan etkisi gösterilmiş pozisyonel manevraların uygun pratisyen doktorlar tarafından yapılması Ballve Moreno JL, Carrillo Muñoz R, Villar Balboa I, Rando Matos Y, Arias Agudelo OL, Vasudeva A, Bigas Aguilera O, Almeda Ortega J, Capella Guillén A, Buitrago Olaya CJ, Monteverde Curto X, Rodero Perez E, Rubio Ripollès C, Sepulveda Palacios PC, Moreno Farres N, Hernández Sánchez AM, Martin Cantera C, Azagra Ledesma R. Effectiveness of the Epley's maneuver performed in primary care to treat posterior canal benign paroxysmal positional vertigo: study protocol for a randomized controlled trial. Trials. 2014 May 21;15:179.
- 14. BPPV’de medikal tedavi Acil servis hastalarında manevra vs medikal tedavi etkinliğinin karşılaştırılması Geleneksel terapiler (benzodiazepinler, antihistaminikler, antiemetikler, IV sıvılar) Randomize, konrollü Tx yanıtları:DHI ve diğer ölçütler Standart medikal tedaviler ve pozisyonel manevralar arasında semptomatik rahatlama, acil serviste kalış süresi ve hasta memnuniyeti açısından farklılık yok Sacco RR, Burmeister DB, Rupp VA, Greenberg MR. Management of benign paroxysmal positional vertigo: a randomized controlled trial. J Emerg Med. 2014 Apr;46(4):575-81
- 15. BPPV’de medikal tedavi Manevralar sonrasında rezidü baş dönmesine Danghong enjeksiyonun etkisinin değerlendirilmesi Servikal vertigo ve VBI iyileşmesinde geleneksel Çin tıbbı etkili Tx yanıtları :DHI ve diğer ölçütler Manevralar sonrası rezidü baş dönmesinin iyileşmesinde anlamlı Deng W, Yang C, Xiong M, Fu X, Lai H, Huang W4. Danhong enhances recovery from residual dizziness after successful repositioning treatment in patients with benign paroxysmal positional vertigo. Am J Otolaryngol. 2014 Nov-Dec;35(6):753-7
- 16. BPPV’de medikal tedavi Heterojen hasta populasyonu (vestibülar vertigo, BPPV altgrup) Düzgün olmayan sonuç ölçümleri Farklı tedavi doz rejimleri ve süreleri 1- pozisyonel manevralar: gerekli 2- rezidü semptomlara yönelik medikal tedavi: kalitenin iyileştirilmesine yönelik
- 18. Mevcut ilişki Vibert et al. Osteoporotik ratlarda Otoconia morfolojik değişimleri boyut dansite 2 mekanizma ile BPPV’yi indükleyebilir
- 19. Mevcut ilişki Vibert et al. bozulmuş biçimlenme otoconia’nın ilgisinin yetersizliği azalmış otoconia çözünmesi bozulmuş transdüksiyon
- 20. Mevcut ilişki Jeong SH et al. J Neurol 2013, Talaat HS et al Eur Arch Otorihinolaryngol 2014 Osteoporoz ,BPPV hastalarında daha yaygın vit D, BPPV ile ilgili vit D ,BPPV nüksetmesi ile ilişkili Ca+2 çözünmesi endolenfteki serbest Ca+2 artışı nedeniyle otoconia erimesini azaltabilir
- 21. Mevcut ilişki
- 23. BPPV’ye yatkınlık Kadın Kafa travması Meniere Vestibüler nörit Migren DM HT Tiroidit Hiperlipidemi İnme Osteoporoz İleri yaş Yaşla birlikte artış prevalansı 18 - 39 0.5% >60 3.4% Ömür boyu insidans: 10% at 80 Parham et al. Laryngoscope 2013
- 24. BPPV’de nüks 27 % Genellikle ilk 6 ay 40- 50% Başarılı tedaviyle 5 yıl kronik BPPV vakaları serum 25(OH)D düzeyi vit D takviyesinden sonra nüks yok Büki et al, Med Hypotheses 2013
- 25. OTOCONIA İmmatur : trigonal, iğsi ve çan şekilleri Matur : silindirik, 10–50 μm, sivri uçlu
- 26. OTOCONIA 1- ORGANIK merkezi çekirdek matriksi : Glikoproteins (Otoconin) 2- İNORGANIK periferik kalsit kristalleri : Ca+2 karbonat 3- DIŞ YÜZEY : fibröz bağlantı materyali (Otolin) Otoconia, membranöz/fibröz matriks ile gömülü Kinosilyuma proteinöz filamentler ile bağlı
- 27. OTOCONIN 90 Western blot Immunofluorescence
- 28. OTOCONIN 90- 95 Mice PLA2L in chromosome 15,encodes a 95-kDa glycoprotein: otoconin-95
- 29. OTOCONIA Yoğun kristal dış kabuk ve ağ örtüsü tarafından oluşturulan organik merkez çekirdek
- 30. OTOCONIA Merkez çekirdekten yayılan kısa filamentler dış kabuğun iç yüzeyinde dik olarak sonlanırlar
- 31. OTOCONIA Dış kabukta tabakalı yapılar dış yüze dik olarak yerleşmiştir Dış kabukta tabakalı yapılar dış yüze dik olarak yerleşmiştir
- 32. OTOCONIA ince yapısı 1- Dağınık filamentler 2- Küresel partiküller 3- Gözenekler 4- Radyal kanallar Lins U et al. J Structural Biol 2000
- 33. OTOCONIA Namlu-şekilli otoconia gevşek matriks filamenti içinde gömülü Filamentler lateral olarak bağlanmış yada otoconia yüzeyine bağlanır Otoconia çapraz bağlantılar ile diğerine bağlantılı
- 34. OTOCONIA Dağınık flamentlerin ve küresel partiküllerin otokonia yüzeyini kaplaması Filamentler otokonia yüzeyi kenarlarında uzun ve kıvrımlı olabilir
- 35. OTOCONIA Dış bağlantılı fibröz jelatin katmanların desteklenmesi Boşlukları sınırlandıran, çapraz bağlantılı, izotropik 3D ağ örğülü filamentler İnce filamentlerle çapraz bağlanmış boncuklu alt gruplar
- 37. OTOCONIA Mineral matriks yüzeyi gözenekleri açığa çıkarır İnce filamentler boncuklu filamentlerden laterale yayılır
- 38. OTOCONIA Yüzey filamentleri bağlantılı ince filamentleri gösterir Gözenekler ,yüzey filamentlerinin yanında yada altında görünürler
- 39. OTOCONIA ince yapısı Lins U et al. J Structural Biol 2000
- 41. OTOCONIA Otoconia oluşumu ? Otoconial membranda gömülme ? Embriyogenez ve devri başlangıç süresince tartışmalı Düşük Ca+2 endolenfiyle çevrili otoconia oluşumunun aktif süreçler tarafından sıkı kontrolü Mikroçevresel Ca+2 dengesi gereklidir normal otoconia oluşumu optimum mekanik duyu
- 42. OTOCONIA montajı Otoconia montajında gerekli 1- Kristallerin Peri-maküler tohumlanması Ca2+ sekestrasyonu by Oc90 recruiting otolin, osteopontin, fetuin, DSPP and/or calbindin 2- kristallerin merkezi maküler gelişimi Ca2+ ve HCO3 salınımı− tüysü hücrelerden Maküladan diğer otoconinlerin salgılanması Oc90, Ca2+, HCO3 salgılanması− ve karanlık hücrelerden diğer iyonlar
- 43. OTOCONIA montajı Montajlı otoconia kinosilyuma bağlantılıdır otolin, otogelin, tectorins ve otoancorin
- 44. OTOCONIA Otoconia montajında gerekli Uygun stoichiometry ve olay sırası Downregulasyon : anormal otoconia oluşumu (inorganik yada azaltılmış) Yaşa bağlı otokonia dejenerasyonu önlenmesi? 1- indükleyici protein yeniden ekspresyonu 2- iyonik homeostasis yeniden kurulması
- 45. OTOCONIA otoconin 90 gözenekler homeostasisi sağlamak Endolenf Ca+2 & (CO3− ) kritik seviyede tutulmalı Ca+2 kristal oluşumunda artmalı Fakat labirentin geri kalanı kurtarmak için düşük olmalı
- 47. OTOCONIA Kemik and otoconia biyomineralizasyonu 1- protein matriks organizasyonu 2- spesifik alanlarda matriks oluşumu 3- bir düzen içinde mineral kristalleri depozisyonu Biyomineralizasyon, osteoporozda işlevsiz Zhao X et al Dev Biol 2007; Xu et al Dev Dyn 2010; Yang H et al PLoS One 2011; Vibert et al Audiol Neurootol 2008
- 48. OTOCONIA Ca+2 kaynağı : tüylü hücreler Ca+2 kristallerinin büyümesini düzenleyen ağ oluşturan matriks proteinleri
- 49. OTOCONIA- Giriş uyaranı etkileyen faktörler 1. Bileşenler 2. Dansite 3. Kitle 4. Konum Tüylü hücrelerine uyarıcı girdi miktarını etkiler
- 51. Gene Symbol Aliases Function Consequences of Loss of Function Inner Ear Kidney Inner Ear Kidney Channels and ass proteins KCNJ10 Kir4.1 or Kir1.2 Formation of endocochlear potential Unknown Deafness Unknown KCNQ1/ KCNE1 KvLQT1/minK or ISK K+ secretion into endolymph; endolymph formation Maintain PT brush border membrane potential Deafness No (KCNQ1) or modest (KCNE1) urinary loss of Na+ and glucose KCNMA1/KCNMB1 BK channel, α1 and β1 K+ efflux from cochlear inner hair cells (Flow-dependent) K+secretion in CNT and CD Progressive hearing loss (only KCNMA1) Impaired (flow- dependent) renal K+ excretion CLCNKA Cl− channel Ka Recycling of Cl− in strial marginal cells and vestibular dark cells; endolymph formation Basolateral Cl−reabsorption in thin ascending limb Deafness when both CLCNKB and CLCNKA are defective Nephrogenic diabetes insipidus CLCNKB Cl− channel Kb Recycling of Cl− in strial marginal cells and vestibular dark cells; endolymph formation Basolateral Cl−reabsorption in thick ascending limb Deafness when both CLCNKB and CLCNKA are defective Bartter syndrome BSND Barttin Recycling of Cl− in strial marginal cells and vestibular dark cells; endolymph formation Basolateral Cl−reabsorption in thin and thick ascending limbs Deafness Bartter syndrome
- 52. Endolenfin Ca+2 hemostazı Tüysü hücre transdüksiyon kanalı: katyon kanalı ve Ca+2 transdüksiyonu baskılar ve endolenfatik Ca2+ olan hayvanlarda sağırlık ve vestibüer defisit oluşmakta
- 53. Endolenfin Ca+2 hemostazı Salgılama ve reabsorbsiyon mekanizmaları tarafından kontrolü Ca2+ reabsorbsiyonu Ca2+-geçirgen kanallar Ca2+ bağlayıcı proteinler Ca atılımı Ca2+-ATPaz yada Na+/Ca2+ dönüştürücü
- 54. Endolenfin Ca+2 hemostazı Calbindins Na+/Ca+2 exchangers Plasma membrane Ca+2 pumps
- 55. Ca+2 kanal transport sistemi 1- apikal giriş kanalları (TRPV5, TRPV6) 2- sitozolik Ca+2 bağlayıcı proteinler (calbindin-D9 K, calbindin-D28 K) 3- bazolateral Ca+2 taşıyıcılarının ekstrüzyonu (Na+ Ca+2 dönüştürücü, hücre zarı Ca+2 ATPaz) 1,25-OH2 vit D3- sistem upregülasyonunu sağlar
- 56. Vitamin D Vitamin D reseptörü vücutta mevcut Ca+2 ve P- metabolizması Hücre proliferasyonu ve diferansiasyonu İmmünomodülasyon nöromüsküler işlev yabani fareler : güçlü vestibüler VDR VDR olmadan Fareler : disfonksiyon
- 57. Vitamin D vit D etkileri Kemik dansitesi Kemik kalitesi kas performansı vit D ilavesi düşme ve yaşlılarda kırık risklerini azaltır
- 58. Vitamin D Vitamin D reseptörü vücutta mevcut Ca+2 ve P- metabolizması Hücre proliferasyonu ve diferansiasyonu İmmünomodülasyon nöromüsküler işlev yabani fareler : güçlü vestibüler VDR VDR olmadan Fareler : disfonksiyon
- 59. Vitamin D Serum 25(OH)D vit seviyesinin değerlendirilmesi <20 ng/ml: Eksiklik 21- 29 ng/mL : yetmezlik > 30 ng/mL : yeterli derecede (40-60 ng/mL tercihen) > 150 ng/mL : Zehirlenme
- 60. OSTEOPOROZ risk faktörleri Sigara içme Alkol Steroidler Kby Obezite
- 61. OSTEOPOROZ B(kemik) M(mineral) D(dansite) Omurga ve kalçanın dual x-ray absorpsiyometrisi (T-score)
- 62. Vit D eksikliği ve BPPV At 2003 Vibert et al. BPPV, osteoporoz ve osteopeni arasında bir bağlantı önerdi Vibert D, Kompis M, Hausler R. Benign paroxysmal positional vertigo in older women may be related to osteoporosis and osteopenia. Ann Otol Rhinol Laryngol 2003;112:885-9.
- 63. Vit D eksikliği ve BPPV Osteoporoz ( BMD) BPPV‘de yüksektir Vibert 75% İsviçre Parham 81% USA Jeong 68% Güney Kore Vibert et al Ann Otol Rhinol Laryngol 2003; Jang et al Otol Neurotol 2009 ; Mikulec et al J Laryngol Otol 2010; Yamanaka et al; Laryngoscope 2013; Jeong et al J Neurol 2013; Parham et al Laryngoscope 2013; Büki et al Med Hypotheses 2013
- 64. Ortalama 25-OH vitamin D düzeyi BPPV hastaları 14.4 ± 8.4 Kontrol 19.1 ± 6.8 25-OH vitamin D düzeyi <20 ng/ml BPPV hastaları 80% Kontrol 60% Jeong SH et al. J Neurol 2013
- 65. Vit D eksikliği ve BPPV >50 yaş kadınlar arasında Osteopeni 50% Osteoporoz 18% Düşük D düzeyi & osteoporoz BPPV nüksü Vit D takviyesi ile nükslerde azalma Nüksler artmış manevra sayısını gerektirir Vibert et al Ann Otol Rhinol Laryngol 2003; Jang et al Otol Neurotol 2009 ; Mikulec et al J Laryngol Otol 2010; Yamanaka et al; Laryngoscope 2013; Jeong et al J Neurol 2013; Parham et al Laryngoscope 2013; Büki et al Med Hypotheses 2013
- 66. Vit D eksikliği ve BPPV (-) BPPV ve tedavi edilmiş osteoporoz arasındaki ilişki BPPV ve kemik döngüsü belirteçleri arasındaki korelasyon P1NP düzeyi (oluşum belirteci) Vitamin D :negatif etki sNTX (rezorpsiyon belirteci):pozitif etki Parham et al. Laryngoscope 2013
- 68. En azından?
Notes de l'éditeur
- Dear colleagues
- The first report was published in 2005. The efficiency of treatment was evaluated using the ‘’Epley criteria’’. It was concluded that betahistine, in addition to Semont reposition maneuvre or Brandt Daroff exercises, increased the effectivenes of these treatments.
- An early metaanalysis included trials in which betahistine was compared with placebo. Those trials were composod of BPPV patients an VBI cases, treatment outcome was simply stated as improved or not improved, pointing towards a benefit of betahşstşne against placebo.
- A prospective randomised study, which used 4 different vertigo control scales as the tratment outcome evaluatin methods, concluded that physical theraphy, in the form of Cawthorne-Cooksey exercises 6 times/d for 4 wks, was more effective than Betahistine 24 mg/d for 1 mo.
- A large post marketing surveillance study involving more that 2000 patients, including BPPV patients, evaluated the effect of betahistine 48 mg/d on QoL and Dizziness symptoms; howvere no definite conclusions were drawn in this reort.
- A study, known as the Osvald study, included an enourmous number of investigators, evaluated the effects of betahistine on what is called ‘’vestibular vertigo’’. No definite conclusins can be drawn regarding BPPV treatment from this heterogenous grroup of patients.
- Consecutive Osvald studies from Russia and Romania, including patients with vestibular vertigo treated with Betahistine pointed out that medical treatment improves the quality of life of those patients.
- An interesting study revealed that Betahistine treatment , in addition to Epley’s maneuvre, effectively normalised the postural stability of patients with BPPV.
- Our prospective randomised and placebo controlled study included a homogenous group of BPPV cases, only posterior canal canalithiasis patients, in contrast to previous studies with a variety of BPPV and other vertigo patients. Treatment outcomes were measured with 4 different scales, and it was concluded that, Betahistine treatment in addiditon to Epley’s maneuvre was more effective than the maneuvre alone or combined with placebo with regard to improvement of symptoms in certain patients.
- A prospective randomised study evaluated the effects of 3 different drugs, Betahistine mesilate, flunarizine and gingko biloba, after Epley’s maneuvre. It was reported that, while a better response obtained in patients treated with Betahistine in addition to the maneuvre; there was no difference betweent the maneuvre alone or medically treeated groups at 1 month.
- A study, which I strongly criticise for not performing a respositioning maneuvre in one group of patients and leaving them alone with medical treatment; finally concluded that maneouvres lead to shorter resloyion times.
- Another study showed that dramamine reduced the residual syptoms after repositon maneuvres, however it was not effective in reducing DHI scores after treatment.
- Another study, which I strongly criticise again, utilised a Sham naeuvre instead of Epley maneuvre; and compared the results after these maneuvres alone or with Betahisteine treatment. I think that it is not ethical to perform a sham maneuver or not to perform any maneuver at all, for the sake of a scentific study in a disease like BPPV , which may lead to serious possible consequences like fall and injuries when not properly managed. This study, not surprisingly, pointed out to the effectiveness of repositioning maneuvers.
- A recent study, in which the ‘’standart medical care’’ was regarded as the conventional theraphy with benzozodiazepines, antihistamines, antiemetics and IV fluids; concluded that repositining maneuvres were not more effective than emergency department medications in BPPV patients. This study is in a strong conflict, not only with the daily practice, but also with the huge otology literature data, proving the great success of repositionign maneuvres for the tretment of PBBV.
- Lastly, traditional chinese medications were aslo shown to improve residual dizzness after maneuvres.
- Dear colleagues
- It was reported that the structure of otoconia changes significantly in osteoporotic rats; Their size is increased and their density is decreased These changes may induce BPPV by:
- 1- Decreased calcium fixation leading to a disturbed remodeling of the internal structure of the otoconia, as well as in their attachment on the otoconial membrane. 2- Increased concentration of free calcium in the endolymph might induce reduction in its capacity to dissolve the dislodged otoconia, in addition to affecting electromechanical transduction of the sensory epithelium.
- It was recently shown that osteoporosis is more common BPPV patients; Vit D defiiency is reltaed to BPPV and very low leves are associated eith recurrences.
- Vit D deficiency is very common, even in hot sunny countries. Scarf and burka wearing, and indoor living styles were thought to prevent the necessary ultrviolet exosure of the skin in those regions.
- Otseoporosis is more common in older patients; women are 7 times more affected.
- 1- year prevalence of new and recurrent BPPV attacks rises steeply with age: from 0.5% in 18 - 39 year olds to 3.4% in over 60 years of age. The lifetime incidence of BPPV reaches almost 10% by the age of 80
- There is a recurrence rate of BPPV 27 %, mostly in the first 6 month. Generally accepted recurrence rate of BPPV after successful treatment is 40–50% at 5 years Cases with chronically recurrent severe BPPV episodes are prone to multiple recurrences. In those patients serum 25(OH)D levels are low and BPPV was shown not to recur after supplementation with vitamin D
- Immature developing otoconia range in shapes and sizes with trigonal, spindle and dumbbell shapes. Mature otoconia are scylindrical in shape bodies with lengths of 10–50 μm and pointed ends.
- The otoconia are composed of inorganic calcium carbonate (calcite) crystals deposited onto a central core of organic central core matrix consisted of glycoproteins. The main inorganic component is a calcium carbonate (CaCO3). The organic component is usually a predominant glycoprotein plus low-abundant glycoproteins (minor otoconins), proteoglycans and glycosaminoglycans (GAGs). The core, periphery and the external surface of the crystals all have inter-connecting fibrous material with varied diameters and organization. These fibers are likely made up of the inner ear-specific collagen called otolin. They are the only mammalian hard tissue mineralized by calcium carbonate, whereas the other two systems, bone and teeth, consist of calcium phosphate. The core, periphery and external surface of the crystals have inter-connecting fibrous material with varied diameters and organization. Otoconia crystals are partially embedded in a membranous/fibrous matrix and are tethered by proteinaceous filaments to the kinocilium of the underlying hair cells.
- Western blot analysis of Otoconin 90 expression in mouse brain tissue extract (A) and SK-MEL-28 (B) and THP-1 (C) whole cell lysates. Immunofluorescence staining of methanol-fixed HeLa cells showing cytoplasmic and membrane localization.
- Expression of OTOCONIN at early embryonic stages; the growing endolymphatic duct (arrowhead) and the dorsal part of the otic vesicle are strongly labeled The gene PLA2L in chromosome 15, encodes a 95-kDa glycoprotein which s the major protein of the utricular and saccular otoconia and also SSCS and cochlea, thus was named otoconin-95.
- Panoramic view of an otoconium fractured in a plane parallel to its main axis, show an organic central core (CO) formed by a tight meshwork of filaments and a dense crystalline outer shell (OS). The transition between core and mineralized outer shell is abrupt and the interface between core and outer shell follows the basic contour of the otoconia, including their triplanar faceted ends. Occasionally the freeze-fracture knife shears the mineralized matrix, leaving knife marks on the surface (*)
- A closeup of the interface shows short filaments radiating in an orderly way from the core matrix (CO) ending perpendicularly on the inner surface of the outer shell.
- Laminar structures are disposed perpendicularly to the otoconial the external surface in outer shell mineral matrix. Globular glycoproteins particles are present on the fracture faces of the laminar composite crystalline matrix.
- Ultrastructure of the otoconia reval 4 different elements; namely
- Last figure: Three adjacent otoconia appear to be linked to one another by filament cross-links
- Meandering filaments (arrowheads) and globular particles (arrows) cover the surfaces of the otoconia The filaments can be long and bend over the edges of the otoconia surface; last figure: fine details of the filament’s “beaded” structure
- The layer consists of a cross-linked, isotropic three-dimensional meshwork of filaments that delimit small and large cavities. Higher magnification shows that the filaments have a beaded substructure (arrows) and are cross-linked by thinner filaments (arrowheads).
- Scanning electron micrograph of the utricular macula from the inner ear of a wild-type Mouse: The lower left area shows the layer of normal otoconia, In the upper right portion, the otoconia have been removed to reveal the supporting gelatinous matrix of the otoconial membrane.
- The exposed raw surface of the mineral matrix reveals pore-like openings. Inset: Thin filaments (arrowheads) radiate laterally from the beaded filaments
- Surface filaments shows interconnecting thinner filaments. The pore-like openings appear near or under the surface filaments. The mineralized outer shell of this otoconium shows several deep radial channels that connect the central core with the otoconium’s outer surface
- Diagram summarizing the organization of the filaments in the otoconial mass and gelatinous matrix. The supporting gelatinous matrix is in direct contact with the otoconial mass and consists of a cross-linked, isotropic three-dimensional network of filaments A loose filament network forms the inter-otoconial matrix (c) A network of meandering beaded filaments covers the surface of the otoconia (d) Internally, the otoconia contain a central core of densely organized filaments
- A number of proteins execute a variety of roles in otoconia development: Some are responsible for crystal seeding and growth and others for attachment to the specific site above the macular sensory epithelium of the utricle and the saccule.
- How otoconia are formed and subsequently embedded in the otoconial membrane remains still unclear: In mammals, this process is initiated during embryogenesis and turnover in otoconia has been debated after maturation. A number of proteins execute a variety of roles in otoconia development. Some are responsible for crystal seeding and growth and others for attachment to the specific site above the macular sensory epithelium of the utricle and the saccule. Despite the identification of numerous component and regulatory proteins involved in otoconia formation and numerous genes that underlie otoconia abnormality, to date, we have yet to learn what exactly these proteins/genes do in the process of otoconia formation Formation of otoconia surrounded by low-calcium endolymph is a tightly controlled active process It is still unclear how microenvironmental Ca2+ is balanced for normal otoconia formation and optimal mechanosensation in the gravity receptor organ Information is incomplete as to what guides this extracellular otoconial protein assembly to crystallize only above the macula but not the cupula or tectorial membrane
- A two-step model for otoconia assembly was reported as: 1- The first step is the peri-macular seeding of crystals near the transitional epithelium (TE) and the marginal zone (MZ) of the sensory epithelium. It involves the sequestration of Ca2+ by Oc90 (or OMP in fish) to form minute Oc90-CaCO3 seeds, which then recruit other minor proteins including otolin (or otolin-like protein), osteopontin, fetuin, DSPP (starmaker in fish) and/or calbindin Ca2+-protein refers to Ca2+ binding proteins (osteopontin, fetuin and possibly DSPP and/or calbindin). 2- The second stage involves the central macular growth of crystals, extrusion of Ca2+ and HCO3− from hair cells and secretion of other otoconins from the macula are critical for the central growth of otoconia. Oc90, Ca2+, HCO3− and other ions are also secreted by dark cells located in the “roof” of the utricle and they likely form minute Oc90-CaCO3 crystal seeds as well
- Assembled otoconia crystals are attached to the kinocilium by fibrous or adhesion proteins including otolin (or otolin-like protein), otogelin, tectorins, and otoancorin.
- Proper stoichiometry and a sequence of timed events are required for assembling the otoconia complex. Downregulation of a single protein can lead to anomalous (inorganic or much reduced) otoconia formation. In order to prevent age related otoconia degeneration; it might be logical to 1- induce protein re-expression and 2- re-establishment of ionic homeostasis of the endolymph
- The organic core is mainly (90%) composed of otoconin 90. It is directly in contact with the endolymph through pore-like openings located on the surface. These openings provide the homeostatic control of the chemical environment moving out of and into the core of otoconia. For normal otoconial function, Ca2+ and carbonate (CO3− ) in the endolymph should be kept at critical levels. Ca2+ level should be locally increased to initiate mineralization of the protein core. However, it is also important to maintain a low Ca2+ level to prohibit unnecessary mineralization of the rest of the labyrinth.
- Bone and otoconia biomineralization resembles to each other: 1- organization of the protein matrix is similar 2- matrix formation of at specific sites 3- deposition of mineral crystallites in an ordered manneris tightly regulated In animal experiments, it has been shown that biomineralization is dysfunctional in osteoporosis
- The source of calcium in the endolymph is thought to be the extrusion of Ca from the hair cells. Similiar to bone, matrix proteins form a network to regulate the growth of the Ca crystals.
- The components, density, mass and location of the crystals affect the amount of stimulus input to the hair cells. Fractured and loosened otoliths are shown
- Severeal genes are involved in the expression of ion channel and ion transporter systems of the inner ear: Compartments of the cochlea. Gene names of expressed ion channels and transporters are illustrated within the approximate position. A: cross section through the cochlear duct. B: inner hair cell (IHC). C: outer hair cell (OHC). D: stria vascularis. DC, Deiter's cells; CC, Claudius' cells; HC, Hensen's cells; OS, outer sulcus cells; SC, supporting cells; I–V, specialized fibrocyte types.
- Channels, transporters, and pumps expressed in both the inner ear and kidney.
- The transduction channel in hair cells is a Ca2+-permeable nonselective cation channel. Both elevated and reduced concentrations of Ca2+ have been shown to suppress transduction currents and microphonic potentials. Consistent with the importance of Ca2+ homeostasis in the endolymph are the observations that, mice and guinea pigs with reduced or elevated endolymphatic Ca2+ concentrations are deaf and have vestibular deficits.
- The endolymphatic Ca2+ concentration is controlled by secretory and reabsorptive mechanisms: Ca2+ reabsorption may occurs through paracellular and transcellular pathways. 1- Ca2+-permeable channels as Ca2+ uptake mechanisms, 2- Ca2+ binding proteins as Ca2+ buffers in the cytosol, and 3- Ca2+-ATPases or Na+/Ca2+ exchangers as Ca2+extrusion mechanisms
- Epithelial calcium channels (calbindins), Na/Ca exchangers and plasma membrane Ca pumps are involved in transepithelial absorption of Ca from the endolymph: These structures contribute to temporal and spatial modulation of endolymph Ca concentration endolymph to maintain the environment adequate for calcium homeostasis
- The critical Ca2+ balance is achieved by the epithelial Ca2+ channel transport system of the inner ear. This system includes: 1- apical entry channels (TRPV5 and TRPV6), 2- cytosolic Ca2+ buffering proteins (calbindin-D9 K and calbindin-D28 K), 3- basolateral Ca2+ extruding transporters (sodium–calcium exchangers and plasma membrane calcium ATPases) This epithelial Ca channel transport system is expressed as transcripts in the semicircular canal duct, cochlea and utricle Vitamin D (1,25-dihydroxy vitamin D3) upregulates the epithelial Ca2+ channel transport system through vitamin D receptors in the inner ear
- The serum level of vitamin D is influenced by various factors including nutritional status and exposure to sun. Through its receptors in every cell of the body, it has major roles in Calcium and phosphorus metabolism, Cell proliferation and differentiation , Immunomodulation and Neuromuscular function While the Wild mice with robust vestibular VDR has normal verstibular activites; Mice without VDR shows a clear vestibular ysfunction
- The classical effects of vitamin D are that on bone density, bone quality and muscle performance vitamin D supplementation reduces the risks of falls and fractures in elderly people due to the effect of vitamin D by improving neuromuscular function.
- vitamin D receptor is present in the cells throughout the body and is involved not only in the metabolism of calcium and phosphorus; but also in many important roles in cell proliferation and differentiation as well as immunomodulation. The functions of vitamin D are mediated through the nuclear VDR. The wild type mice have robust vitamin D receptor expression in the vestibular organs, however the mice without vestibular D receptor show vestibular dysfunction during evaluation of the balance function using the accelerating rotarod, tilting platform, rotating tube and the swim test,
- Kişideki vitamin D düzeyini değerlendirmek için yarı ömrü 2-3 hafta olan, hem vitamin D alımını hem de endojen yapımı gösteren 25(OH)D düzeyine bakılmalıdır. Biyolojik aktif form 1,25(OH)2D ideal ölçüm için uygun değildir, çünkü yarı ömrü 4-6 saat kadar kısa ve dolaşımdaki düzeyleri 25(OH)D’den 1000 kat daha düşüktür 25(OH)D düzeyi 20 ng/mL’den düşük ise D vitamini eksikliği, 21 ile 29 ng/mL arasında ise D vitamini yetersizliği, 30 ng/mL’den yüksek ise yeterli düzey (tercih edilen 40-60 ng/mL) ve 150 ng/mL’den yüksek ise D vitamini intoksikasyonu olarak kabul edilmektedir
- Predisposing factors for osteoporosis are smoking, alcohol consumption, steroids chronic renal failure,
- The diagnosis of osteoporosis is confirmed by BMD measurement made with dual x-ray absorptiometry of spine and hip.
- The prevalence of osteopenia/osteoporosis (decreased BMD) among BPPV is higher in both women and men with BPPV (Vibert 75% Switzerland; Parham 81% USA; Jeong 68% South Korea)
- The prevalence of osteopenia/osteoporosis (decreased BMD) among BPPV is higher in both women and men with BPPV
- Serum level of 25-hydroxyvitamin D was found to be significantly lower in patients with BPPV than the controls (14.4 versus 19.1 ng/ml). Also, patients with BPPV showed a significantly higher prevalence of decreased serum vitamin D below 20 ng/ml 80.0 vs. 60.1 % than the controls.
- Osteopenia may be as high as 50% and osteoporosis prevelance is 18% among women >50 years old. Low vitamin D levels are associated with recurrence of BPPV and the recurrences are relieved with vitamin D supplementation. Patients with osteoporosis have increased recurrence rate of BPPV and require increased number of repositioning maneuvers.
- A statistically significant negative association was observed between BPPV and “treated osteoporosis” in women aged 51 to 60 years and a trend in older women. Also (an indirect) correlation was reported to exists between the presence of BPPV and (disorders) levels of biochemical markers of bone turnover. P1NP is a marker of formation and NTx is a marker of resorption; and both are metabolites of type-I collagen (90% of organic bone matrix) BPPV patients had higher P1NP levels . Vit D had a negative influence and sNTX had a positive influence and on P1NP levels.
- A prospective randomised study is on the way since December 2013 to determine whether the supplementation of vitamin D and calcium prevents recurrences of benign paroxysmal positional vertigo in patients with vitamin D deficiency/insufficiency
- However, establishment of a causal link between BPPV and decreased vitamin requires animal experiments and after that, a clinical trial that looks for preventive effects of vitamin D supplementation on the recurrence rates in patients with BPPV and low serum vitamin D. As the link between two disorders appears to be strong, this fact may lead to a paradigm shift in the management of BPPV A proactive aprroach by 1- Not only treatment of the acute episode with canalith repositioning; but also 2- Prevention of recurrent episodes through management of associated disorder of bone turnover (routine D vit supplementtation) Such a proactive management may lead to a reduction in fall and fracture risk in the geriatric population; in patients without known history of osteoporosis, presentation with BPPV should serve as a harbinger of an undiagnosed disorder of bone turnover