Autoimmune vertigo: an update on vestibular disorders associated with autoimmune mechanisms.

The role of the immune system in mediating cochleovestibular pathologies has received increasing attention in recent years. Autoimmune vertigo may be an invalidating condition and may worsen the quality of life of affected patients, especially in the cases of delayed diagnosis. Since the etiopathogenesis is still not clear, also the treatment is not yet completely delineated. According to the clinical presentation, autoimmune vertigo can present as an isolated disorder or in association with systemic autoimmune diseases. The main feature in autoimmune vertigo is the presence of an abnormal immune response, in either absence or presence of systemic autoimmune disease, directed against delicate components of the inner ear. This may determine a functional or anatomical alteration, with an inflammatory reaction often devastating for hearing and balance. Being the exact pathogenesis unknown, the diagnosis of autoimmune vertigo is based either on clinical criteria or on a positive response to steroids. The earlier the diagnosis is made, the sooner the therapy can be installed, giving a chance to the recovery of inner ear damages. Corticosteroids represent the most effective and universally accepted treatment, even if other immunomodulatory drugs are now having a more extensive use. HIGHLIGHTS: Vertigo is relatively frequent in autoimmune diseases; however, it is often misdiagnosed or attributed to central nervous system alterations rather to specific inner ear involvement. Vertigo and other audiovestibular symptoms may be the first manifestation of an autoimmune disease and if correctly addressed could significantly contribute to early diagnosis of the underlying autoimmune disease. Early diagnosis of immune-related vertigo can lead to prompt initiation of targeted therapy with elevate chances of preventing irreversible damages to the inner ear. The presence of alternating phases of well-being and disabling symptoms in patients with vertigo should always been considered, as they could suggest an underlying autoimmune condition.

Update on Vertigo in Autoimmune Disorders, from Diagnosis to Treatment.

The prevalence of autoimmune diseases has been increasing over the last 20 years. The clinical presentation of this large and heterogeneous group of disorders depends on whether the involvement is organ-specific or non-organ-specific. Dizziness, vertigo, and disequilibrium are common symptoms reported by patients with vestibulocochlear involvement. The association of vertigo and autoimmune diseases has been largely documented, suggesting that autoimmune disorders could be overrepresented in patients with vertigo in comparison to the general population. The aim of this review is to present the recent literature findings in the field of autoimmune-mediated diseases with cochleovestibular involvement, focusing on the clinical presentation, diagnosis, and treatment of immune-mediated inner ear diseases including autoimmune inner ear disease (AIED), Meniere's disease, and bilateral vestibulopathy, as well as of systemic autoimmune diseases with audiovestibular disorders, namely, Behçet's disease, Cogan's syndrome, sarcoidosis, autoimmune thyroid disease, Vogt-Koyanagi-Harada syndrome, relapsing polychondritis, systemic lupus erythematosus, antiphospholipid syndrome, IgG4-related disease, and ANCA-associated vasculitides.

Disabling Central Paroxysmal Positioning Upbeat Nystagmus and Vertigo Associated With the Presence of Anti-Glutamic Acid Decarboxylase Antibodies.

An immune attack by anti-glutamic acid decarboxylase (GAD) antibodies is believed to cause a deficiency in gamma-aminobutyric acid-mediated neurotransmission in the cerebellum. This, in turn, leads to several eye movement disorders, including spontaneous downbeat (DBN) and periodic alternating nystagmus. We describe a 68-year-old diabetic woman with disabling paroxysmal positioning upbeat nystagmus (UBN) exclusively in the supine position, associated with asymptomatic spontaneous DBN, alternating skew deviation and hyperactive vestibulo-ocular reflex responses on head impulse testing, in whom high titers of anti-GAD antibodies were detected. After treatment with intravenous immunoglobulin, a complete resolution of positioning UBN and spontaneous DBN occurred, along with a decrease in anti-GAD antibody titers. Positioning UBN in this case may reflect a transient disinhibition of the central vestibular pathways carrying posterior semicircular canal signals, due to lack of normal inhibitory input from the cerebellar nodulus/uvula. Immunoglobulin restored cerebellar inhibitory output, possibly by improving gamma-aminobutyric acid neurotransmission.

[The pilot study of type â allergic reaction in Meniere's disease patients].

Objective: To evaluate the correlation between type Ⅰ allergic reaction and pathogenesis of Meniere's disease. Methods: A total of 35 (10 male vs. 25 female) patients aged between 21-66 years diagnosed with Meniere's disease were recruited to this study, mean age of them was (47.3±13.6) years. The control group consisted of 15 inpatients (5 male vs. 10 female) with pharyngolaryngeal diseases but without otologic and rhinologic abnormity, mean age was 45.4±12.8 years. Allergic prevalence, serous total immunoglobulin E( tIgE ) levels, serous specific immunoglobulin E( sIgE ) levels and subtypes of T lymphocytes were measured and compared in patients with Meniere's disease and the control group. Severity of vertigo, tinnitus and sensation of fullness were compared between Meniere's disease patients with or without allergy. Results: Allergic prevalence were significantly different (Pearson chi-square 5.832, P<0.05) between patients with Meniere's disease and the control group(57.1% vs. 20.0%). Patients with Meniere's disease report higher level of serous tIgE compared with controls, the difference is statistically significant (Z=168.000, P<0.05). However, positive rates of sIgE of food allergens and inhalant allergens were not significantly different between patients with Meniere's disease and the control group. Scores of vertiginous severity, dizziness handicap inventory (DHI) and tinnitus handicap inventory (THI) were significantly different between Meniere's disease patients with or without allergy (P<0.05). Treg and Treg/Th17 levels (Z=26.000) were much higher in Meniere's disease patients with allergy than in the controls(P<0.05). Conclusions: Patients with Meniere's disease report higher rate of allergy than the control group. Type Ⅰ allergic reaction is thought to be one of the possible reasons that may induce endolymphatic hydrops and lead to Meniere's disease.

Progressive multifocal leukoencephalopathy in a patient without apparent immunosuppression.

Progressive multifocal leukoencephalopathy (PML) is a viral demyelinating disease due to the reactivation of the JC virus (JCV), which usually occurs in the context of immunosuppression in HIV infection, malignancy, or in patients on disease modifying therapy for autoimmune diseases, such as multiple sclerosis (MS) and Crohn's disease. Notably, there is growing recognition that PML can occur in patients with transient immune dysfunction. Here, we present a case of a 55-year-old man without history of immunosuppression or evidence of ICL who was diagnosed with PML on brain biopsy. We will discuss the potential etiologies of mild and transient immunosuppression that can lead to PML with non-apparent immunosuppression.

Parasympathetic nervous system involvement in food allergy: description of a paediatric case.

The latest research data emphasize the interaction between the nervous and the immune systems. It has been demonstrated that the central nervous system (CNS) can be involved secondarily due to blood brain barrier (BBB) disruption via pro-inflammatory cytokines released in allergy. More recently it was demonstrated that the parasympathetic nervous system (PNS) could also be equally involved in models of peripheral inflammation such as food allergy; although this last clinical presentation has rarely been described. Herein, the authors report the case of a five-year-old Caucasian female who was admitted to our Pediatric Acute and Emergency Operative Unit for cyclic vomiting. Her vomiting, which was preceded by objective torque vertigo, headache and weakness, had been recurring with constant frequency every two months since she was 3 years old. After a complex diagnostic flow-chart, it was found that this spectrum of neurologic symptoms was due to a food allergy syndrome, which postulates some etiopathogenic hypotheses to explain the relationship between the two mentioned diseases.

Idiopathic bilateral vestibulopathy: an autoimmune disease?

Bilateral vestibulopathy (BV) is the loss of function of both peripheral labyrinths or of the eighth nerves. Its etiology remains obscure in approximately 20% to 50% of cases (so-called idiopathic bilateral vestibulopathy, IBV). Alternatively, the cause could be viral or vascular; to date, causative gene mutations have not been identified. Other potential disease mechanisms include autoimmune disorders. Antibodies have been detected against inner ear tissue (primarily against vestibular membranous labyrinth). The data suggest that the bulk of anti-labyrinthine autoantibodies may be an epiphenomenon, but a small subgroup of organ-specific autoantibodies may synergize with a cellular response to develop vestibular lesions. The two key symptoms of BV are the following: 1. unsteadiness of gait, particularly in the dark or on uneven ground, and 2. oscillopsia associated with head movements. Episodes of vertigo are reported by patients with IBV, particularly early in the development of vestibular loss. Associated hearing loss seldom occurs in the idiopathic type of this condition. Post-mortem examinations revealed a remarkably selective loss of vestibular hair cells in the vestibular end organs but normal hair cells in the cochlea. The diagnosis is made with a simple bedside test for defective vestibular function. The diagnosis can be confirmed by bithermal caloric testing and pendular body rotation. The therapy is based on steroid treatment, and the early initiation of immunosuppression appears to be essential for therapeutic success.

Vertigo and autoimmunity.

Autoimmune inner ear disease probably accounts for less than 1% of all cases of balance disorders, but its incidence is often overlooked due to the absence of a specific diagnostic test. Furthermore, in several systemic autoimmune diseases the vestibulo-cochlear system may be affected. Clinical features comprise generalized imbalance, ataxia, motion intolerance, episodic vertigo and positional vertigo. An autoimmune mechanism seems to be responsible for 6% of unilateral and 16% of bilateral forms of Ménière's disease. Oscillopsia and disequilibrium secondary to a bilateral vestibular paresis are probably caused by an autoimmune response in 5% of cases. Balance disorders of central origin may be due to other immuno-mediated disorders such as multiple sclerosis, brainstem encephalitis and vasculitidis. Aim of this paper is to assess the clinical features of autoimmune vertigo disorders through a systematic literature review.

Autoantibodies against inner ear proteins in patients with delayed endolymphatic hydrops and unilateral juvenile deafness.

CONCLUSIONS: Patients with the contralateral type of delayed endolymphatic hydrops (DEH) may undergo an autoimmune attack against the other inner ear. As patients with unilateral juvenile deafness show no progression, despite lengthy observation, the autoantibody against the 68-kDa protein may be unrelated to the pathogenesis of DEH. OBJECTIVE: The contralateral type of DEH is believed to have an autoimmune etiology, and sometimes develops from unilateral juvenile deafness. The purpose of this study was to determine whether autoantibodies are pathogenetically important in DEH. MATERIAL AND METHODS: Sera from 9 patients with DEH, 18 patients with profound unilateral juvenile hearing loss and 15 control volunteer without inner ear diseases were investigated by means of Western blot assay against rat inner ear proteins. RESULTS: Among 8 patients with the contralateral type of DEH, 6 (75%) showed at least 1 reactive band on Western blotting. The protein that reacted most frequently had a molecular weight of 28 kDa, which was consistent with our previous results. Among 18 patients with unilateral juvenile deafness, 5 (28%) showed reactive bands, exclusively at 68 kDa.

[The importance of IgG auto-antibodies, anti-collagen type II specific in Menière's disease and progressive hearing loss]. / La importancia de los auto-anticuerpos IgG, específicos anticolágeno tipo II en la enfermedad de Menière y pérdida progresiva de la audición.

UNLABELLED: The Meniere's Disease and Progressive Hearing Loss were considered idiopathic. Both entities were produced by endo lymphatic hydrops and disruption of the membrane which contain type II collagen. The inner ear presented widely expression of type II collagen. These pathologies were probably autoimmune diseases. The aim of this work was to study the relationship of specific IgG to type II collagen in Meniere's disease, Progressive hearing loss, and compared with Sudden hearing loss patients, vascular vertigo patients and normal controls. Patients were divided by clinical findings in: 1 degree Meniere's disease (n:27), 2 degrees Progressive Hearing loss (n:20), 3 degrees Sudden hearing loss (n:15), 4 degrees Vascular Vertigo (n:9) and compared with normal controls (n:30) aged and sex matched. We have measured specific IgG to type II collagen by ELISA test. We considered positive the OD two or more SD above the mean of normal controls. RESULTS: 1 degree The Meniere's group presented IgG to type II collagen (+) in 22 out of 27 patients, p < .025; 2 degrees The Progressive Hearing loss presented IgG to type II collagen in all cases (n:20), p < .0005. The Sudden Hearing loss presented IgG to type II collagen (-) in all cases (n:15) p < .00001 and Vascular Vertigo (n:9) presented IgG to type II collagen (-) in 8 out of 9 cases, p < .0005. These results suggest strongly the notion that Meniere's diseases and Progressive hearing loss have specific IgG to type II collagen and these conditions were ascribed with in autoimmune process.

La importancia de los auto-anticuerpos IGG específicos anticolágeno tipo II en la enfermedad de Meniere y pérdida progresiva de la audición / The importance of type II anticollagen specific IGG autoantibodies in the Menieres disease and progressive hearing loss

La enfermedad de Meniere así como la pérdida progresiva de la audición son consideradas como idiopáticas. Las mismas se deben a un hidrops endolinfático y posterior disrupción de diversas estructuras del oído interno, que conducen al vértigo o a la sordera progresiva. Desde hace algún tiempo estas enfermedades han sido consideradas como autoinmunes. La respuesta inmunológica ataca a variadas estructuras, en el ódio interno está presente el colágeno tipo II. El propósito de este trabajo es correlacionar la presencia de IgG anti colágeno tipo II en pacientes afectados de Meniere, pérdida progresiva de la audición y compararlos con pérdia súbita de la audición, vértigo de orígen vascular y controles normales. Para este trabajo hemos estudiados a 71 pacientes con manifestaciones compatibles con diferentes enfermedades relacionadas con el oído interno. Las mismas se dividieron en: Enfermedad de Meniere (n:27), Pérdia progresiva de la audición (n:2)), Pérdida súbita de la audición (n:15), Vértigo vascular (n:9) y 30 controles normales de similar edad y proporciones de sexo. A todos los pacientes y controles se les praticó dosaje de IgG específica para colágeno tipo II por ELISA. Se consideró determinación positiva cuando era más de 2 DS de la media de los normales. Resultados: 1º El grupo Meniere presentó IgG específica para colágeno II (+) en 22 de 27 casos, p<.025. 2º El grupo con Pérdida Progresiva de la Audición presentó IgG especifica para colágeno II (+) en los 29 casos del grupo p<0005. 3º en la Pérdida súbita de la audici

La importancia de los auto-anticuerpos IGG específicos anticolágeno tipo II en la enfermedad de Meniere y pérdida progresiva de la audición / The importance of type II anticollagen specific IGG autoantibodies in the Meniere's disease and progressive hearing loss

La enfermedad de Meniere así como la pérdida progresiva de la audición son consideradas como idiopáticas. Las mismas se deben a un hidrops endolinfático y posterior disrupción de diversas estructuras del oído interno, que conducen al vértigo o a la sordera progresiva. Desde hace algún tiempo estas enfermedades han sido consideradas como autoinmunes. La respuesta inmunológica ataca a variadas estructuras, en el ódio interno está presente el colágeno tipo II. El propósito de este trabajo es correlacionar la presencia de IgG anti colágeno tipo II en pacientes afectados de Meniere, pérdida progresiva de la audición y compararlos con pérdia súbita de la audición, vértigo de orígen vascular y controles normales. Para este trabajo hemos estudiados a 71 pacientes con manifestaciones compatibles con diferentes enfermedades relacionadas con el oído interno. Las mismas se dividieron en: Enfermedad de Meniere (n:27), Pérdia progresiva de la audición (n:2)), Pérdida súbita de la audición (n:15), Vértigo vascular (n:9) y 30 controles normales de similar edad y proporciones de sexo. A todos los pacientes y controles se les praticó dosaje de IgG específica para colágeno tipo II por ELISA. Se consideró determinación positiva cuando era más de 2 DS de la media de los normales. Resultados: 1º El grupo Meniere presentó IgG específica para colágeno II (+) en 22 de 27 casos, p<.025. 2º El grupo con Pérdida Progresiva de la Audición presentó IgG especifica para colágeno II (+) en los 29 casos del grupo p<0005. 3º en la Pérdida súbita de la audición todos los casos (n:15) fueron negativos para IgG específica para colágeno II, p<.00001. 4º Los pacientes con vértigo vascular 1 sobre 9 casos fue (+) para IgG anti colágeno II, p<.0005. Estos resultados sugieren fuertemente que los pacientes con enfermedad de Meniere y/o Pérdida Progressiva de la Audición tienen como mecanismo fisiopatogénico productor de ambas enfermedades a autoanticuerpos para colágeno tipo II.

Lyme borreliosis--an unusual cause of vertigo.

A total of 2055 consecutive vertigo patients were examined in a prospective study in an area endemic for Lyme borreliosis for clinical signs of Lyme borreliosis or serum antibodies against Borrelia burgdorferi. Of these, 41 patients (2%) had positive levels of serum antibodies against B. burgdorferi. The incidence of seropositivity against B. burgdorferi among the vertigo patients did not differ from the incidence of the normal Finnish population. In addition to seropositivity the criteria used for Lyme borreliosis included previous erythema migrans, a positive polymerase chain reaction (PCR) or positive serum immunoblot. Eight patients were diagnosed as having Lyme borreliosis. This disease is a rare but possible cause of vertigo. Seropositivity alone is an insufficient finding for the diagnosis of Lyme borreliosis and should be supported by the clinical findings, the patient's history and other laboratory findings, such as immunoblotting or PCR. Although Lyme borreliosis seems to be a rare cause of vertigo, it must be kept in mind in the differential diagnosis of vertigo.

Use of a screening RAST in a large neuro-otologic practice.

Evidence in the literature emphasizes the role of the immune system in disorders of the inner ear and eustachian tube. We initially investigated the presence of inhalant allergy in selected patients seen for otologic problems by means of a screening radioallergosorbent test (RAST), using either a microscreen or a limited antigen panel. This study analyzed the results of tests performed over a 2-year period on 186 patients seen by one of us (WLM) for treatment of vertigo (66%), tinnitus (63%), hearing loss (49%), aural fullness (48%), Meniere's quadrad (27%), balance disturbance other than true vertigo (21%), and eustachian tube dysfunction (4%). We found an incidence of immunoglobulin E-mediated hypersensitivity of nearly 40% in a patient population selected solely for neuro-otologic symptoms and not for sinonasal symptoms. This figure is more than double that quoted for the general population. We also found a surprisingly high incidence of mold antigen atopy in this selected population. Allergy can contribute to a number of otologic symptoms, including eustachian tube dysfunction, vertigo, tinnitus, hearing loss, aural fullness, and nonspecific balance disturbance. Allergy also has been emphasized as an etiologic factor in a portion of patients diagnosed with Meniere's syndrome. A screening RAST, combined with clinical evaluation, appears to be an excellent tool for evaluating these patients for inhalant allergy as part of a comprehensive workup.

Outbreak of vertigo in Wyoming: possible role of an enterovirus infection.

An epidemiologic investigation was conducted to characterize and evaluate the possibility of a viral aetiology of an outbreak of acute vertigo in Hot Springs Country, Wyoming, during autumn 1992. Case-finding identified Hot Springs County residents who sought medical attention for new onset vertigo during 1 August, 1992-31 January 1993. Thirty-five case-patients and 61 matched controls were interviewed and serum specimens were obtained during January 1993. Case-patients were more likely than controls to report symptoms (e.g. fatigue, sore throat, fever, diarrhoea) of antecedent acute illness. Case-patients did not have a significantly greater prevalence or mean titre of IgG antibodies to respiratory syncytial virus, parainfluenza viruses, Epstein-Barr virus, and cytomegalovirus than controls. Serologic evidence of recent enterovirus infection (IgM antibodies) was found for 74% of case-patients compared with 54% of controls (P < 0.05), suggesting a possible association between vertigo and enterovirus infection. Future studies are needed to define the role of enteroviruses in innerear diseases.