1. VENOUS INTERVENTIONS IN MENIERE’S DISEASE ALDO BRUNO MD GEPOS CLINIC
Telese T. (BN) ITALY

2. Disclosure Statement of Financial Interest
I, Aldo Bruno DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

3. Menière P.: Maladies de l’oreille interne offrant des symptomes de la congestion cerebral apoplectiforme Gaz Med de Paris. 1861;16:88.
…if a serious hypacusia happens, then the cause of the vertigo is in the Labyrinth
Prospero Menière, 1861
He also was the first to recognise that the function of equilibrium was in the inner ear 3

4. Committee on Hearing and Equilibrium guidelines for the diagnosis and therapy in Meniere’s disease AAO 1995
Meniere’s disease is a clinical disorder defined as the idiopathic syndrome of endolymphatic hydrops.
… endolymphatic hydrops can only be demonstrated with certainly by histopatholocic study of the temporal bones.
… The presence of endolymphatic hydrops can be inferred during life by the presence of the following as further defined below:
Recurrent, spontaneous episodic vertigo;
Hearing loss; aural fullness; tinnitus.
Either tinnitus or aural fullness (or both) must be present on the affected side to make diagnosis for reporting purpose under these guidelines

5. Journal of Vestibular Research,2015, 25, 1-7
The Classification Committee of the Bárány Society
The Japan Society for Equilibrium Research
The European Academy of Otology and Neurotology (EAONO)
The Equilibrium Committee of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS)
The KoreanBalance Society

6. Physiopatology of Meniere Disease
Genetic Predisposition
Autoimmunity
Inflammation
Blockage of the drainage/increase production of endolinfa
ADH System- Aquaporine
Canalopaty of membrane
Headache
Hydrops
Dizziness
Cellular Modification
ROS Deposit
Neuro e Citossicity
Modification of the idroionic omeostasis
Modification Endococlear Potential
Hypoacusis
Neurovegetaive Modification
Viral Infection
Diet deficiency
Trauma
Fullness
Tinnitus

7. Epidemiology Average age of onset : 30-40 years old
Rare in Childood (1-2%)
There are no significant gender differences

8. Incidences of Meniere’s Disease
The data available is often inconclusive hence not reliable
Cases of Meniere’s Disease
200/ (Giappone, 1997)
75/ ( Francia)
101/ (USA)
460/ (Svezia)
350/ (UK)
43/ (Finlandia, 2000)
100/ (Italy)

10. Currently there is no cure for
THERAPY
Currently there is no cure for
Meniere’s Disease.

11. Chronic Cerebro-Spinal Venous Insufficiency
CCSVI
Chronic Cerebro-Spinal Venous Insufficiency
Vascular syndrome characterized by stenosis of the internal jugular veins and / or azygos veins, with opening of collaterals and insufficient cerebrospinal venous drainage
Is it possible to hypothesize that CCSVI for congenital anatomical alteration or functional acquired alterations represents a predisposing factor for developing inner ear disorders like MD?
In 2006, Zamboni introduced the concept that chronic
impaired venous outflow of the central nervous system is
associated with multiple sclerosis (MS), coining the term of Chronic Cerebrospinal Venous Insufficiency (CCSVI). 11 11

12. Vascular Findings in MD
The stria vascularis plays an important role in the production and absorption of endolymph and consequently on the genesis of hydrops in MD.
In literature many studies have been published concerning the vascularization of the stria and the inner ear vascular conditions.

13. Vascular findings in MD
The stria vascularis are severely atrophic and degenerated in patients with MD. (Paparella et al., 2007) The number of vessels in the stria vascularis in ears with MD are smaller than in normal controls in all cochlear turns. (Paparella et al., 2009)

14. VENOUS DRAINAGE Internal Jugular Vein
Internal auditory vein Vein of cochlear aqueduct Vein of vestibular aqueduct
Superior petrosal sinus Inferior petrosal sinus
Transverse sinus
Sygmoid sinus
Internal Jugular Vein
The venous drainage of the inner ear is carried out by the Internal auditory vein ….

15. Friberg U, Rask-Andersen H.
Vascular occlusion in the en- dolymphatic sac in Meniere’s disease. Ann Otol Rhinol Laryngol 2002;111:237–245.
The described specimens represent pathologic changes that occur after a prolonged disease. A thrombus may recanalize, lyse, prop- agate, or become organized; accordingly, a reverted flow can be temporary or chronic. In the cases reported here, the thrombus appeared as organized and hence indicates a longstanding process, which is consistent with MD for several years.
In theory, repeated microthrombosis could reverse the flow over and over and cause fluctuating symptoms as seen in MD.

16. Laryngoscope 2007 Feb;117(2):194-8
Laryngoscope 2007 Feb;117(2): A potential portal flow in the inner ear. Friis M, Qvortrup K. Source Department of Otolaryngology, Head and Neck Surgery, Unviersity of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
Abstract
Objectives/Hypothesis: The aim of the present study was to visualize the flow direction of blood in the extraosseous part of the vein of the vestibular aqueduct (VVA) and to explore the effect of an induced obstruction in the distal part of the VVA before it merges with the sigmoid sinus. The endolymphatic sac has been implicated as a potential endocrine gland, which venules drain to the VVA. A reversal of the direction of flow in the VVA toward the inner ear could, through vestibular arteriovenous anastomosis, cause portal circulation in the inner ear.
Study Design: The authors conducted an experimental animal study using in vivo fluorescence microscopy.
Results: Obstructing the distal part of the VVA just before it empties into the sigmoid sinus immediately reverses the flow of blood in the VVA toward the inner ear.
Conclusions: After an obstruction of the VVA, the drained venous blood from the endolymphatic sac may enter a portal circulation in the inner ear, which could cause disturbances in the endolymph homeostasis and potentially symptoms as seen in Meniere disease 16 16

17. Conclusions: After an obstruction of the VVA, the drained venous blood from the endolymphatic sac may enter a portal circulation in the inner ear, which could cause disturbances in the endolymph homeostasis and potentially symptoms as seen in Meniere disease

18. Our group worked either on diagnosis and on therapy of CCSVI in MD
Benevento:
A.O Rummo Audiology Department.
Rome:
Sapienza University, ENT Department,
Bologna:
Maggiore Hospital, ENT Department
ITALY
Collect the experience of the three italian centers 18 18

19. Neuroradiology Department (Telese Terme Italy)
Our group are working on diagnosis and therapy of Diagnosis and therapy of CCSVI
in Meniere’s Disease
ECD, MRI, PTA
Clinica Gepos:
Vascular Department
Neuroradiology Department (Telese Terme Italy)

20. Ethics
The experimental study was approved by the local authority and was in accordance with the guiding principles in the care

21. HOWEVER, NO PATIENTS EXPERIENCED NOTABLE IMPROVEMENT
ALL PATIENTS ENROLLED IN THIS STUDY WERE ALREADY IN TREATMENT AT REFERRED ENT DEPARTMENTS AND UNDERWENT ONLY SYNTHOMATIC THERAPY .
SOME OF THEM HAD INTRATHIMPANIC INJECTION OR SURGICAL TREATMENT FOR SYMPTHOMS OF MENIERE DISEASE
HOWEVER, NO PATIENTS EXPERIENCED NOTABLE IMPROVEMENT

22. Neck veins to be examined within the CCSVI Examination Protocol
IJVs – Internal Jugular Veins (examined side Left and Right both sitting 90° and supine 0° position)
VVs – Vertebral Veins (examined side Left and Right both sitting 90° and supine 0° position) 22

23. ECD-TCCS PARAMETERS
1. Bidirectional flow in one or both the IGV and / or the VV in both positions or bi-directional flow in one position with absence of flow in the other (65%)
2. Bidirectional flow in the intracranial veins and sinuses (80%).
3. Intraluminal defects (flaps, septa or valves) associated with hemodynamic changes (blocks, reflux or acceleration) and / or re duction of the area of ​​the IGV in the supine position to 0.3 cm /sq (90%)
4. Absence of flow in the IGV and / or VV and / or absence of flow in one position and bidirectional flow in the other (45%)
5. IGV DCSA increased or unchanged both at 90 ° to 0 °(3%) 23

24. Gadda G, Taibi A, Sisini F, Gambaccini M., Zamboni P., Ursino M.:
A NEW HEMODYNAMIC MODEL FOR THE STUDY OF CEREBRAL VENOUS OUTFLOW
Am.J.Physiol Heart Circ.Physiol 2015 Feb1;308(3): H217-31

25. MATERIAL and METHOD
312 PATIENTS WITH DEFINITE MENIERE’S DISEASE
123 MEN AND 189 WOMEN
Age 58 +/ years
Definite Meniere's disease
Two or more definitive spontaneous episodes of vertigo 20 minutes or longer
Audiometrically documented hearing loss on at least one occasion
Tinnitus or aural fullness in the treated ear
Other cases excluded
102 healthy subjects
48 men and 54 women
Age /- 7.8

26. CCSVI POSITIVITY in definite Meniere's disease
277/312 PATIENTS WITH MD (89%)
12/102 HEALTHY SUBJECTS (12%) 26

27. Acta Oto-Laryngologica
Chronic cerebrospinal venous insufficiency as a cause of inner ear diseases
Giuseppe Attanasio, Laura Cagnoni, Eleonora Masci, Francesco Ciciarello, Francesco Diaferia, Aldo Bruno, Antonio Greco & Marco De Vincentis
Pub Online Nov.2016

28. ANGIO-MRI and CCSVI

29. ARISCI. MALATTIA DI MENIERE BILATERALE CON ESORDIO A SINISTRA NEL 2005
ARISCI. MALATTIA DI MENIERE BILATERALE CON ESORDIO A SINISTRA NEL ECO blocco del flusso a sinistra e reflusso.
Reflusso a dx.

31. GARRONE. SN blocco del flusso alla flebografia. ECO reflusso.

33. Work in progress

34. PTA FOR CCSVI: Personal protocol
Local anesthesia
  Percutaneous trans-femoral venous catheterization (sn / dx)
  Cavography (Lower and Upper)
  Selective catheterization of the internal jugular veins and of the azygos vein
  Selective venography in the three projections and assessment of the empty time
  Sodium heparin 2500 IU
  PTA balloon noncompliant with Ø mm (routine Ø mm) for IGV
and 8-12 for AV
  control angiography
  Manual compression for hemostasis
  Compressive dressing (no need for percutaneous systems of hemostasis)
  Bed rest with leg extended for 12 hours
  Post-operative therapy: LMWH 6000 IU x 2 x 20 days
  Mesoglycan therapy: 100 mg / day for months
  Clinical monitoring and echocolordoppler at 1, 3, 6, 12, 15, 18, 24 months 34

35. The main criteria adopted to define stenosis of the IJV or AV with venography was:
At least 50% stenosis of the vein compared with the diameter of an adjacent segment of the vein.
Emptying time of over 6 seconds in all vein projections.
Intraluminal abnormalities (web, septa, valvular ).
Collateral veins with a faster emptying time compared with IJV or AV.

36. In Meniere’s Disease I have observed mainly Type C and Type B of CCSVI
Type A (4%) stenosis of both proximal segments of the Azygos vein and the IJV with a contralateral IJV size increased (> cross-sectional area)
Type B (35%)hemodynamically significant stenosis of both IJV and proximal Azygos Vein
Type C (60%) bilateral stenosis of the IJV with normal azygos
Type D (1%) multiple azygos and lumbar system lesions .
In Meniere’s Disease I have observed mainly
Type C and Type B of CCSVI
The collateral circulations that occur most frequently are those of the condylar system, pterygoid plexus and thyroid veins

43. Mesoglycan therapy: 100 mg / day for 12-24 months
Post-operative therapy:
LMWH 6000 IU x 2 x 20 days
Mesoglycan therapy: 100 mg / day for months
Clinical monitoring by ENT and echocolordoppler at
1, 3, 6, 12, 15, 18, 24 months,
Dosage: Vit. B12 , Folic Acid, Vit. D, Homocysteine

44. Vascular Surgeon: Aldo BRUNO, Benevento (Italy)
OUR CLINICAL SERIES
Vascular Surgeon: Aldo BRUNO, Benevento (Italy)
From April 2013 to December 2016
N. 105 PROCEDURES
- 53 Male
- 52 Female
Age: average 47 years.
Unilateral Meniere’s Disease : 70 cases
Bilateral Meniere's disease: cases
Onset of the disease from 28 years to 2 years before
All patients with positivity for two/five parameters according to Zamboni Protocol for CCSVI 44 44

45. RESULTS Angiographic success v / s Intention-To-Treat: 103/105 (98.5%)
Major complications: 0% (DVT, rupture, hemorrhage)
Minor complications: five patients 5% (Fibrosis IGV by sonography after one month and one case of inguinal hematoma)
Unchanged: 6% (Seven Patients)
Secondary Clinical deterioration : Nine Patients (9%)
Restenosis: Twelve Patients (Doppler ultrasound each three months after PTA): 11%, Six of which had a secondary clinical deterioration 45

46. Results on Meniere's disease symptoms
ONLY BY
ENT EVALUTATION 46

47. In 3-6-12 month post PTA follow-up we have observed
Improved hearing, reduction or disappearance of tinnitus, disappearance or reduction of dizziness, decreased sensation of fullness in about 80% of cases, improvement of QOL
But:
in a short time follow up the placebo effect could act on results
AAO guidelines recommended the evaluation of therapy after a 24 month follow up 47

48. Chronic Cerebrospinal Venous Insufficiency in Meniere Disease:
Article Published February 2017
J.V.I.R.
The Prevalence of
Chronic Cerebrospinal
Venous Insufficiency in
Meniere Disease:
24-Month Follow-up after Angioplasty
Aldo Bruno, MD, Marisanta Napolitano, MD, PhD, Luigi Califano, MD, Giuseppe Attanasio, MD, Vincenzo Giugliano, MD, Pier Paolo Cavazzuti, MD, Marika Viccaro, MD, Eleonora Masci, MD, Diego Mastrangelo, MD, Francesca Salafia, MD, Salvatore Mazzone, MD, Benedetto Bernardo, MD, Laura Cagnoni, MD, Roberto Filipo, MD, PhD, Marco De Vincentis, MD, Antonio Greco PhD,

49. Vascular Surgeon: Aldo BRUNO, Benevento (Italy)
OUR CLINICAL SERIES
Vascular Surgeon: Aldo BRUNO, Benevento (Italy)
From April 2013 to December 2015
N. 69 PROCEDURES
- 32 Male
- 37 Female
Age: average 47 years.
Unilateral Meniere’s Disease : 45 cases
Bilateral Meniere's disease: cases
Onset of the disease from 28 years to 2 years before
All patients with positivity for two/five parameters for CCSVI 49 49

50. Expected benefits on MD symptoms were:
24 MONTH FOLLOW-UP
Expected benefits on MD symptoms were:
Improvement of hearing
Reduction of the number and degree of spells of vertigo.
Reduction of tinnitus and fullness
Improvement of Quality of Life, measured by DHI 50

51. 40 24 MONTH FOLLOW-UP }70% 51 patients Male Female
Mean duration of MD (months)
Side 40
16(40%)
24 (60%) 74
R: 12
L: 16
Bil: 12 (30%)
}70% 51 51

52. HEARING LOSS Pre- Angioplasty Pure Tone Average: 60.09 dB
PTA kHz
Improved (>10dB)*
* In 5/10 Patients dB
20 (50%)
Unchanged (± 10dB)
16 (40%)
Worsened (>10dB)
4 (10%)
Pure Tone Average is considered improved / worsened if a 10 dB difference is noted
Committee on Hearing and Equilibrium AAO-HNS , 1995
Pre- Angioplasty Pure Tone Average: dB
Post- Angioplasty Pure Tone Average: dB
P=0.0031
In 10/20 patients improvement was dB

53. Vertigo spells 34 (85%) 53 6 (15%) Control level A B C D E F
Avg spells/month post-treatment (24 mon recommended)
x 100 =
Control Level
Avg spells/month pre-treatment (6 mon recommended)
AAO-HNS CHE, 1995
AVG/month pre ± SD
11.9±14.3
AVG/month post±SD
0.97±1.3
Control level A B C D E F
N° Patients 22 12 2 %
55%
30% 5%
A = complete control
B = substantial control
C = limited control
D = insignificant control
E > = worse
F Secondary treatment required due to disabling vertigo 53
34 (85%)
6 (15%)

54. TINNITUS AND FULLNESS: a «brute» subjective evaluation
Disappeared
Improved
14 (35%)
52 (70%)
Unchanged
22 (55%)
12 (30%)
Worse
4 (10%) 54

55. Clinicians measure, patients feel What happened by a very simply
patient-oriented assessment?
Better or worse? This is the question
Better /40
Unchanged /20
Worse /20

56. 56

57. We can affirm that: We cannot affirm that:
CCSVI and MD are frequently associated conditions
PTA procedure cures anatomic and functional CCSVI anomalies
PTA procedure gives a good control of MD symptoms in a two year follow up
We cannot affirm that:
CCSVI is the major cause of MD
PTA “cures” MD 57

58. The venous stasis of the head and neck veins may be considered a further etiopathogenetic mechanism which adds to many other already known mechanisms that define MD as a multifactorial disease 58

60. Research and Knowledge never ends
Research and Knowledge never ends. There are very few certainties to build on our weak knowledge 60