Meniere's Disease
and Syndrome
Vertigo is Curable
@Mitsuo Shichinohe, M.D., Ph.D @Sapporo Towa Hospital @TEL 81-11-784-1118 @FAX 81-11-784-1119 @30-18-8-1, Kita, Higashiku, Sapporo, Hokkaido, @065-0030, JAPAN @E-mail : ms-7@white.zero.jp |
An alternative interpretation of gBenign Paroxysmal Positional Vertigo.h
--- Possibility of Central Paroxysmal Positional Vertigo
Morito Nakayama, M.D.
Department of
Internal Medicine, Nukada Memorial Hospital
mAn examplen
@A mail from U.S.A.
@Date : 5 Nov. 2003
@Sex : Male
@Age : ?
@Address : WA. U.S.A.
@The name of disease : Meniere's disease
@Effect : !!!!!!
@Dr. Mitsuo Shichinohe
@I have had Meniere's for 3 years and I just found out about
your research two weeks ago. My doctor agreed it let me try it
out so I took Famvir(500mg three times a day) last week and I
have been symptom free for 6 days now !!!!!!
@So I may be premature in thanking you, but I want to say THANK
YOU! THANK YOU! THANK YOU! THANK YOU! for your research. I feel
like it has saved my life.
@Forever indebted to you.
m‚l‚…‚„‚‰‚ƒ‚‚Œ@‚q‚…‚‚‚’‚”@‚‚”@Chinese Medical
Association-Taipein
@2005 Annual Meeting of Chinese Medical Association
@‚c‚‚”‚…@F@26@‚i‚•‚Ž@2005
›‚r‚•‚‚‚‚’‚™
Experience of Antiviral Drug Treatment for Menierefs Syndromes
Mitsuo Shichinohe,M.D.,Ph.D. Director, Shichinohe Clinic,
Sapporo, Japan
Despite a variety of proposed causes of Menierefs syndromes ( MS
), such as allergy, autonomous nerve disorders, stresses, etc.,
the real etiology is still indefinite. Viral etiology has also
been suggested, however, no trial of anti-viral treatments has
been reported except my previous papers. The resemblance of the
process and symptoms of MS to those of Bellfs palsy and Ramsay-
Hunt syndromes which proved to be caused by Herpes virus
infection, led me to the idea that the majority of MS is caused
by viral infection, probably Herpes virus infection in
vestibulocochlear nerve.
I attempted to administer Acyclovir (ACV) to treat patients with
MS and could obtain a dramatic therapeutic effect. In the first
clinical series (1990~1997), 301 patients were administered ACV
with the dose of 2,000mg/day for 2 weeks. The effectiveness was
evaluated mainly by symptoms of patients with a definite
criterion. More than 80% of MS patients treated with ACV were
evaluated as gmarked effecth or geffectiveh. It was quite
impressive that ACV was very effective to vertigo, especially
for fresh cases. Most of the patients treated, revealed
improvement of clinical symptoms 3-7 days after the
administration of ACV. After 10 to 14 days, the patients
recovered rapidly and their clinical symptoms disappeared. Side
effects of ACV were extremely rare in this series. Follow-up
studies of a long period could be performed in many patients.
Recurrences were often observed. These cases were re-treat with
ACV and could be cured with lowered doses of ACV usually making
interval of recurrence longer.
In the second series (2003-2004), several hundred patients with
MS were treated with ACV or Valacyclovir. The effectiveness was
evaluated by the same criteria as the first series referring
AAO-HNS. The results were essentially the same as in the first
series. Since 1991, about 3,000 patients with MS have been
treated with ACV or Valacyclovir in my clinic, showing the same
effectiveness.
Serum antibody to HSV-1 and VZV were determined in patients with
MS, however, so far, no significant difference among patients
with various symptoms. In randomly selected 70 MS cases, HSV-1
and VZV-DNA were investigated with PCR. Frequency of viral DNA
detection in MS cases was not high, while no viral DNA was found
in control cases. No significant correlation was found among
symptoms of virus-detected and ?non-detected cases.
mAntiviral Drug Treatment for Menierefs Diseasen
Mitsuo Shichinohe, M.D.,Ph.D Director, Shichinohe Clinic,
Sapporo, Japan
‚PD Definition of Menierefs Disease
Menierefs disease (MD) is defined as the idiopathic syndrome of
endolymphatic hydrops. Itfs symptom is characterized by spells
of vertigo, tinnitus, hearing loss, and a sensation of aural
fullness. Detailed definition is described by the American
Academy of Otolaryngology- Head and Neck Surgery (AAO-HNS)
guidelines (1). In this article, the author defines MD as the
disease with symptoms of vertigo, ear tingling (tinnitus
aurium), and impaired hearing. Most of the patients listed in
this study was diagnosed by the specialists of otolaryngology
and the author accepted the diagnosis. It includes Menierefs
syndrome (MS), which may be MD but cannot completely exclude
other basic diseases, according to the specialists of
otolaryngology. Neither MD nor MS has been the target of the
treatment by antiviral drugs.
2. Viral Theory of Menierefs Disease
The pathogenesis of Menierefs disease (MD) has remained
controversial since 1900s. Many investigators have recognized
hydrops or fibrosis of endolymphatic sac of the inner ear as a
pathologic feature associated with MD (2,3). Vestibular ganglia
have also been postulated as the target tissue of MD (4,5). A
number of theories for development of MD have been presented
such as allergy, disorder of the autonomic nervous system,
autoimmunity, stress, etc.
Viral infection has also been suggested. By immunological
techniques, Williams, et al (6) found significant elevations of
both humoral and cellular immune responses to viral antigens of
herpes simplex (HSV-1), varicella-zoster (VZV), etc. Bance and
Rutka (7) reported a case history of a patient who initially had
an idiopathic facial palsy that years later developed into a
spectrum of vestibular dysfunction associated with the clinical
stigmata of herpes zoster. Based on this case and reviewing
previous reports, they postulated that Bellfs palsy and other
inner ear disorder might have a common underlying viral etiology
involving multiple cranial nerves. Serum antibodies in patients
with MD were reported using various immunologic techniques such
as enzyme-linked immunosorbent assay (8), radioallergosorbent
test (9). However, it might be rather difficult to detect immune
reactions to viral infection in the serum of patents with MD,
which may affect a local lesion in the inner ear. Arnold and
Niedermeyer (10) detected IgG antibodies to HSV in the serum and
perilymph of patients with MD collected during therapeutic
vestibulotomy.. Compared with the corresponding serum sample,
the perilymph from the patients with MD showed a higher level of
specific anti-HSV IgG. The results supported the hypothesis that
HSV might play an important role in the pathogenesis of MD.
Takahashi, et al (11), examined the existence of HSV-1 or VZV
DNA by nested polymerase chain reaction (PCR) in peripheral
blood mononuclear cells (PBMC) of patients with MD. They
detected HSV-1 or VZV DNA in PBMC of three of 28 patients, but
detected in none of the control group. Vrabec (5) investigated
vestibular ganglia obtained from archival surgical pathology
specimen from patients with Menierefs disease undergoing
vestibular neurectomy. Using nested PCR HSV DNA was more
commonly detected in vestibular ganglia of patients with MD than
the general population.
These studies of immunology and molecular biology may provide
supportive evidence for a viral etiology of MD.
3. Experience of Antiviral Drug Treatment for Menierefs Disease.
Treatment for MD have generally centered to improve symptoms,
for example, diuretics, vasodilatators, steroids, other
chemicals, surgical labyrinthectomy, endolymphatic shunt,
intratympanic gentamycin treatment, etc. However, none of these
treatments have been decisively effective.
@@@As described above, virus etiology, especially HSV-infection,
of MD (including MS) have been postulated by a considerable
number of investigators, however, no trial of antiviral
treatments have been reported except the authorfs previous
papers (12-14) and one paper (15) recently published. Therefore,
the author will describe his own experience of antiviral
treatments for MD.
1) Idea
More than fifteen years, the author has independently had the
idea that MD is
developed by HSV infection in the inner ear. The process of MD
resembles that of a latent infection and recurrence in herpes
labialis and herpetic gingivostomatitis and time-course of the
symptoms of MD is similar to latent virus that reactivates,
causes inflammation and then returns to latent status. Bellfs
palsy and Ramsay-Hunt syndrome are now considered to be involved
by HSV infection in the facial nerve and VZV infection in the
trigeminal nerve, respectively. For these diseases, Acyclovir
(ACV) is commonly used. HSV and VZV may invade other cranial
nerves, such as vestibulocochlear nerve. As Bance and Rutka (7)
postulated, a number of inner ear disorders might have a common
underlying viral etiology with facial palsy showing a spectrum
of vestibular dysfunction. The use of antiviral agents has the
potential to treat one possible agent inducing MD and provide
more than symptomatic relief. Based on this idea, the author has
administered ACV to patients with MD. Since 1991, about 3000
patients with MD have been treated with ACV or Valaciclovir in
the authorfs clinic, showing almost the same effectiveness. In
this article, experience in the first series of 301 cases will
be mainly described, second series of 574 cases will be also
reported and both series will be compared.
@@@@2) Observations of the First Series
@@@@a) Patients
@@@@ Three hundred and one patients who visited Shichinohe
Clinic, between 1990-1997, with symptoms of vertigo, ear
tingling and impaired hearing were studied. In this study, the
author accepted the test results and diagnoses of specialists of
otolaryngology, neurology and neurosurgery, where the patients
experienced such test as CT, MRI, intelligence tests,
psychoanalyses, etc, except 10 cases which the author diagnosed
according to the typical clinical symptoms of the patients. Out
of 301 cases, 135 were diagnosed as MD, 99 as Menierefs syndrome
(MS), 52 as vestibular dysfunction and 15 as others. These
diagnoses were made mainly by the otolaryngologists, however, it
may be possible that the patients diagnosed as MD, MS and
vestibular dysfunction were affected by the same pathologic
agents. Ninety-six were male ranging from 13 to 81 years of age
and 205 were female ranging from 19 to 84 years of age. Duration
of the disease (the period between the first attack and the
administration of ACV) varied from 1-20 days for the patients
with first attack to 1-30 years for the chronic patients who had
repeated attacks, exacerbation, recurrences and partial
remissions.
b) Treatment with ACV
The dosage and the duration of administration of ACV were
determined in accordance with the treatment of herpes simplex,
genital herpes or herpes zoster. Patients diagnosed as MD, MS or
vestibular dysfunction were usually administered ACV with the
dose of 2,000mg/day for 2 weeks. Patients whose body weight was
less than 50kg were given less dose of ACV. This dose seems
appropriate considering the clinical results and in the 15 years
experience of the author. No serious adverse events were
observed.
c) Evaluation of effectiveness of the treatment
The randomized well-controlled study should be required to
determine the effectiveness of the new trial of treatment for a
disease. However, the author could not carry out a
double-blinded controlled study in his private clinic. A
guideline for evaluating improvement of dizziness, hearing and
equilibrium in MD (AAO-HNS criteria) has been reported(1),
however, assessment of hearing loss could not always be made for
all of the patients, In this study, the author used his own
criteria. The process of the disease was recorded in detail in
the records of the patients. The subjective symptoms were told
and described by the patients themselves and objective findings
by the family members and recorded by the author. Special
attention was paid to frequency and severity of spells of
vertigo, intensity of tinnitus, which were described by the
patients, referring to AAO-HNS criteria. Many patients were sent
to otolaryngologists and examined with audiogram tests.
Effectiveness of the treatment was evaluated by the improvement
of symptoms (frequency and severity of spells of vertigo,
intensity of tinnitus and hearing disorder) by the ACV
treatment. The results were described as follows; Marked effect;
vertigo and tinnitus completely disappeared, effective: vertigo
disappeared, tinnitus and hearing improved, Unclear effect:
vertigo and tinnitus improved, hearing not improved, No effect:
vertigo, tinnitus and hearing not improved. Not evaluatable: no
follow-up information was obtained. These criteria are clear to
judge and seem to work well.
d) Results of ACV treatment. (Table)
Out of 301 cases treated with ACV, 250 cases were evaluatable.
Fifty one patients did not contact with doctors after the
treatment and were non-evaluatable. Eight nine cases showed g
marked effecth and 116 cases were g effectiveh, indicating total
205 effective cases out of 250 evaluatable cases (205/250,
82.0%). Twenty-four cases were g unclear effect g (24/250,
9.6%). Only 21 cases (21/250, 8.4%) were g no effecth. (Table)
About the same frequencies of g marked effect g plus geffectiveh
were obtained in patients diagnosed as MD (94/114, 82.5%), MS (
69/80, 85.0% ) and vestibular dysfunction ( 41/46, 89.1% ),
indicating the existence of similar causes among cases diagnosed
differently.
It was quite impressive that ACV was extremely effective to
vertigo. Relatively smaller effects were observed for hearing.
Most of the patients treated revealed improvement of clinical
symptoms 3-7 days after the administration of ACV. After 10 to
14 days, many patient rapidly recovered and clinical symptoms
disappeared.
There was a significant relationship between effectiveness of
ACV therapy for MD and duration of the disease. The ACV
treatment was more effective for patients with shorter duration
of the disease from onset than for patients with longer
duration. In other words, the longer duration the cases had, the
more number of ineffective cases increased. Cases with duration
of less than 6 months included 43 cases (95.6%) out of 45 cases
of gmarked effect g plus geffectiveh, whereas cases with
duration of more than 10 years revealed the increase of
ineffective cases showing 19 cases (28.3%) out of 67 cases of
gunclear effecth plus gno effecth.
e) Recurrences
Recurrences were often observed. Out of 250 effective cases, 39
cases (19.0%) re-visited the authorfs clinic having recurrences
in the period of 4-24 months after the ACV treatment but they
usually cured by ACV treatment with lower doses (less than half
of the first administration of ACV) within shorter period (less
than half period of the first ACV treatment). The second
recurrence, if it occurs, is usually delayed about twice longer
period compared to the first recurrence. If MD would be caused
by HSV, it should be natural to presume recurrences occur. In
the case of HSV infection, it is known that re-treatment with
ACV make the interval of recurrences longer or prevent
recurrences for several years. It is confirmed that the same is
true in ACV-therapy of MD.
@@@3) Observation of the second series
In the second series (2003-2004), 574 patients with MD were
treated with ACV or Valaciclovir. Four hundred seventy-six
patients were entered for evaluation (Table). The effectiveness
was evaluated by the same criteria as the first series referring
AAO-HNS Guideline. The results were essentially the same as in
the first series as shown in the Table. The percentage of g
marked effect g plus geffectiveh was 81.1% and g no effect g was
8.0%, which was confirmed almost the same as in the first
series. Percentage of effective cases of patients diagnosed as
MD, MS or vestibular dysfunction was 85% (84/99), 81% (76/93) or
88% (56/64), respectively, suggesting these categories of
disease might be induced by a common causative factor (patients
in 2003). Recurrences were 180 cases (47%) out of 386 effective
cases within 16 months after the treatment. The higher frequency
of recurrences might be ascribed to that the patients realized
the ACV effect and visited the authorfs clinic, wishing to be
re-treated with ACV. Generally speaking, recurrence of the
disease of the patients treated with ACV or Valaciclovir could
be cured by about half doses making the intervals of the spell
twice longer.
@@@ Since 1991, almost 3000 patients with MD have been treated
with ACV or Valaciclovir in the authorfs clinic showing about
the same effectiveness as described in the first series as shown
in the Table.
@@@
4) Immunological and Molecular Biological investigation of the
Present Cases
The dramatic effects of the treatment with ACV for MD strongly
suggested that MD is caused by the viral infection. Judging from
the pharmacological effect of ACV, HSV and VZV are suggested to
be causative agents. Serum antibody to HSV and VZV were
determined in patients with MD, however, so far no significant
difference among patients with various symptoms. As described
above, Takahashi, et al (10) examined the patients with MD in
the authorfs clinic, and detected HSV or VZV DNA in PBMC using
nested PCR. Though the frequency of HSV or VZV detection was low
in the patients with MD, these findings may imply that
reactivation of HSV-1 or VZV may be associated with the
development of some cases of Menierefs disease. In randomly
selected 70 MD cases in the authorfs clinic, HSV-1 and VZV DNA
in PBMC were investigated with PCR by Light Cycler.. Frequency
of viral DNA detection in MD cases was not high, while no viral
DNA was found in control 100 cases. No significant correlation
was found among symptoms of virus-detected and non-detected
cases. Difficulties to detect the involvement of HSV might be
attributed to that the lesion of MD is restricted locally in
inner ear.
5) Hope to Antiviral Treatment for Menierefs Disease
In spite of a considerable amount of suggestions of the viral
etiology of MD, there have been no reports of antiviral drug
treatment for MD except the authorfs previous papers (11-14) and
one paper (15) recently published. Derebery, et al (15)
conducted a randomized, double-blinded placebo-controlled trial
of Famciclovir (anti-herpetic drug) for symptoms MD diagnosed
according to AAO-HNS guidelines. Twelve subjects in the
treatment and 11 in the placebo arm were examined. Effectiveness
was assessed by AAO-HNS guidelines. Twenty-five percent of the
treatment (250 mg, 3 times a day for 10 days, followed by 250mg
twice a daily for 80 days) group and 18% of the placebo group
showed a reduction in number of spells. This difference was not
statistically significant and no dramatic effects of Famciclovir
were found on vertigo or dizziness. They concluded that
Famciclovir might suppress the fluctuation of hearing in MD but
had minimal effects on vertigo or dizziness symptoms in this
study, and further studies required to be conducted to determine
the effects of antiviral medications. This study was conducted
by well-controlled design and should be evaluated highly, since
this was the first paper dealing with antiviral drug therapy for
MD except the authorfs previous papers. The results were rather
disappointing, however, these did not mean to deny the
effectiveness of antiviral drug on MD. There are many points,
which should be considered to reach the right and reasonable
evaluation of antiviral treatment of MD. The author believes
that evaluation of effectiveness of anti-MD drug should be the
same as that of acute or chronic infectious diseases, just like
judgment of effects of antibiotics on pneumonia. From this
viewpoint, AAO-HNS guideline seems inappropriate as far as
evaluation of effectiveness of treatment for MD concerned.
Therefore, selection of cases entered in evaluation and criteria
of improvement of symptoms should be changed. The author
sincerely hope that many investigators will try to prove the
viral theory of MD and many clinicians will conduct antiviral
treatment of MD and evaluate the real effectiveness of the
antiviral drug therapy.
Lastly, let the author transcribe here a e-mail from a patient
(female, age not known) who was treated with Famciclovir in US.
g----- I have had Menierefs for 3 years and I just found out
about your research two weeks ago. My doctor agreed to let me
try it out so I took Famvir (500mg three times a day) last week
and I have been symptom free for 6 days now !!!!!
So I may be premature in thanking you, but so happy to be not
dizzy or nauseous that I want to say THANK YOU ! THANK YOU!
THANK YOU! THANK YOU! for your research. I feel like it has
saved my life.
Forever indebted to you,
@@@@References
1. Pearson BW and BrackmannDE. Committee on hearing and
equilibrium guidelines for reportingtreatment results in
Menierefs disease. Otolaryngol Head Neck Surg. 1985;93:579-81
2 Wackym,P.A.@Histopathologic finding in Menierefs disease.
Otolaryngol Head Neck Surg. 1995; 112: 90-100
3 Paparella MM, Djalilian HR. Etiology, pathophysiology of
symptoms, and pathogenesis of Menierefs disease. Otolaryngol
Clin North Am. 2002; 35: 529-45
4 Furuta Y, Takasu T, Fukuda S, Inuyama Y, Sato KC, Nagashima K.
Latent herpes simplex rirus type 1 in vestibular ganglia. Acta
Otolaryngol Suppl. 1993; 503; 85-9
5 Vrabec JT. Herpes simplex virus and Menierefs disease.
Laryngoscope. 2003; 113; 1431-8
6 Williams LL, Lowery HW, Shannon BT. Evidence of persistent
viral infection in Menierefs disease. Arch Otolaryngol Head Neck
Surg. 1987; 113: 397-400
7 Bance M, Rutka J. Speculation into the etiologic role of
viruses in the development of Bell palsy and disoders of inner
ear dysfunction a case history and review of the literature. J
Otolaryngol. 1990; 19: 46-9
8 Bergstrom T, Edstrom S, Tjellstrom A Vahlne A. Menierefs
disease and antibody reactivity to herpes simplex virus type 1
polypeptide. Am J Otolaryngol. 1992; 13: 295-300
9 Calenoff E, Zhao JC, Derlackki EL, Harrison WH, Selmeczi K,
Dutra JC, Olson IR, Hanson DG. Patients with Menierefs disease
possess IgE reacting with herpes family viruses. Arch
Otolaryngol Head Neck Syrg 1995; 121: 861-4
10 Anold W, Niedermeyer HP. Herpes simplex virus antibodies in
the perilymph of patients with Menierefs disease. Arch
Otolaryngol Head Neck Surg 1997; 123: 53-6
11 Takahashi K, Aono T, Shichinohe M, Tamura M, Iwata Y,
Yamanishi K, Shigeta S, Herpes virus DNA in peripheral blood
mononuclear cells of some patients with Menierefs disease.
Microbiol Immunol. 2001; 45: 635-8
12 Shichinohe M. Effectiveness of ACVG for Menierefs disease.
Igaku no Ayumi (J Clin Exp Med ) 1994; 169: 796-7
13 Shichinohe M. Effectiveness of ACV for Menierefs disease‡U.
Report of 10 cases. Shindan to Chiryo (Diagnosis and Treatment)
1994; 82: 1860-4
14 Shichinohe M Effectiveness of acyclovir on Menierefs
syndrome‡V Observation of clinical symptoms in 301 cases. Sapporo
Med J. 1999; 6871-7
15 Derebery MJ, Fisher LM, Iqbal Z. Randomized double-blinded,
Placebo-controlled clinical trial of famciclovir for reduction
of Menierefs disease symptoms. Otolaryngol Head Neck surg. 2004;
131: 877-84
›@m‚q‚…‚“‚•‚‚…@‚‚†@‚l‚‰‚”‚“‚•‚@‚r‚ˆ‚‰‚ƒ‚ˆ‚‰‚Ž‚‚ˆ‚…n
Mitsuo Shichinohe, M.D.,Ph.D., Curriculum Vitae
Present Position and Institution
Director, Shichinohe clinic
Date and place of Birth; February 26, 1931. Esutoru mati,
Karafuto,Japan
@@@@@@@@@@@@@@@@@@@@
Marital Status; Married, two sons
Education;
1958 M.D Sapporo Medical University, Sapporo
1958-1963 Graduate,School, Department of
Physiology(pharmacology),Sapporo Medical@University, Sapporo
1973-2005 Opened Shichinohe Clinic in Sapporo,Japan
1900 The first administration of Acyclovir ( anti-viral drug )
to a patient with Menierefs disease.
1994 Publication in theh Journal of Clinical and Experimental
Medicine
( Igaku no ayumi)
1996 Presentation at theh 9th International Conference on
Antiviral Research (ICAR) on 179 cases. Fukushima Japan
@
@1998 Presentation at the g 11th ICAR on 301 cases. San-Diego
USA
1999 Effectiveness of Acyclovir on Menierefs Syndrome 111
Observation of Clinical Symptoms in 301 Cases.
( The Sapporo Medical Journal Vol. 68, No. 4-6, December, 1999
2004 Vertigo is Curable Apublished from the BUNGEISHUNJU Co.Ltd.
During the above period, the treatment was widely introduced in
a number of health magazines. My home-page is visited by about
100,000 patients now. My clinic received anxious patients from
all over Japan. I have received and replied to e-mail inquiries
from patients in Japan, USA, Canada, Australia, Italy, ext.