[A man in his fifties with near-syncope episodes and persistent dizziness]. / En mann i 50-årene med nærbesvimelser og vedvarende svimmelhet.

BACKGROUND: A previously healthy male patient in his fifties presented with subacute onset of severe, diffuse dysautonomia with orthostatic hypotension as the main symptom. A lengthy interdisciplinary workup revealed a rare condition. CASE PRESENTATION: Over the course of a year, the patient was twice admitted to the local department of internal medicine because of severe hypotension. Testing showed severe orthostatic hypotension with normal cardiac function tests and no apparent underlying cause. On referral to neurological examination, symptoms of a broader autonomic dysfunction were discovered, with symptoms of xerostomia, irregular bowel habits, anhidrosis and erectile dysfunction. The neurological examination was normal, except for bilateral mydriatic pupils. The patient was tested for ganglionic acetylcholine receptor (gAChR) antibodies. A strong positive result confirmed the diagnosis of autoimmune autonomic ganglionopathy. There were no signs of underlying malignancy. The patient received induction treatment with intravenous immunoglobulin and later maintenance treatment with rituximab, resulting in significant clinical improvement. INTERPRETATION: Autoimmune autonomic ganglionopathy is a rare but likely underdiagnosed condition, which may cause limited or widespread autonomic failure. Approximately half of the patients have ganglionic acetylcholine receptor antibodies in serum. It is important to diagnose the condition as it can cause high morbidity and mortality, but responds to immunotherapy.

[SENSORINEURAL HEARING LOSS AND VERTIGO DUE TO INTRA-COCHLEAR HEMORRHAGE].

INTRODUCTION: Intra-cochlear hemorrhage is a rare cause of sudden sensorineural hearing loss (SSNHL) which may be accompanied by diverse labyrinthine symptoms. In these cases, we expect magnetic resonance imaging (MRI) to demonstrate a high signal intensity in the labyrinth on unenhanced T1-weighted images as well as in fluid-attenuated inversion recovery (FLAIR) images. AIMS: To describe an experience with a case of intra-cochlear hemorrhage in a patient treated with anticoagulation, causing SSNHL and vertigo. METHODS: Case report and literature review. RESULTS: An 85-year old patient treated with anticoagulation therapy presented with right SSNHL, tinnitus and vertigo. Physical examination revealed: bilateral normal otoscopic examination, lateralized left Weber tuning fork test and a spontaneous left horizontal nystagmus. MRI performed demonstrated a high signal intensity inside the cochlea on unenhanced T1-weighted images. CONCLUSIONS: Performing an MRI is necessary in order to rule out frequent causes of SSNHL including benign as well as malignant tumors, malformations, trauma and more. The finding of an intra-labyrinthine hemorrhage causing SSNHL is rare, and should be taken into consideration when treated by anticoagulation therapy.

Neurovascular compression syndrome of the brain stem with opsoclonus-myoclonus syndrome combined with vestibular paroxysmia and autonomic symptoms.

We describe a rare case of neurovascular compression syndrome (NVCS) of the brain stem and opsoclonus-myoclonus syndrome (OMS) complicated with vestibular paroxysmia (VP) and autonomic symptoms. Moreover, we discuss the case with respect to the available information in medical literature. A 36-year-old man with vertigo and nausea had difficulty standing, and was transported by an ambulance to our hospital. He had VP, opsoclonus, cervical myoclonus, anxiety, and restless legs syndrome. Magnetic resonance imaging at hospitalization showed that the dolichoectatic vertebral artery was in contact with the postero-lateral side of the pontomedullary junction. He was diagnosed with NVCS of the brain stem (most likely of the input to the vestibular nucleus) associated with contact with the dolichoectatic vertebral artery. Combination therapy using multiple antiepileptic drugs, such as low-dose carbamazepine, clonazepam, and lacosamide, improved his clinical symptoms. He was finally able to walk and was discharged on day 42 after admission. He is being routinely followed-up since then. Further research is needed to confirm the validity of the combination therapy.

Proteome of normal human perilymph and perilymph from people with disabling vertigo.

The vast majority of hearing loss, the most common sensory impairment, and vertigo, which commonly causes falls, both reflect underlying dysfunction of inner ear cells. Perilymph sampling can thus provide molecular cues to hearing and balance disorders. While such "liquid biopsy" of the inner ear is not yet in routine clinical practice, previous studies have uncovered alterations in perilymph in patients with certain types of hearing loss. However, the proteome of perilymph from patients with intact hearing has been unknown. Furthermore, no complete characterization of perilymph from patients with vestibular dysfunction has been reported. Here, using liquid-chromatography with tandem mass spectrometry, we analyzed samples of normal perilymph collected from three patients with skull base meningiomas and intact hearing. We identified 228 proteins that were common across the samples, establishing a greatly expanded proteome of the previously inferred normal human perilymph. Further comparison to perilymph obtained from three patients with vestibular dysfunction with drop attacks due to Meniere's disease showed 38 proteins with significantly differential abundance. The abundance of four protein candidates with previously unknown roles in inner ear biology was validated in murine cochleae by immunohistochemistry and in situ hybridization: AACT, HGFAC, EFEMP1, and TGFBI. Together, these results motivate future work in characterizing the normal human perilymph and identifying biomarkers of inner ear disease.

[Diagnosis of Cochleovestibular Neurovascular Compression Syndrome:A Scoring System Based on Five Clinical Characteristics].

The optimal method for diagnosing cochleovestibular neurovascular compression syndrome(CNVC)remains controversial, and the aim of this study is to develop a standard diagnostic instrument for the condition. The clinical features of 53 sides of 50 patients with a combination of vertigo, tinnitus, and/or hearing loss were retrospectively evaluated. The following five clinical features were evaluated and given a score of 1 or 0:1)a long history of recurrent vertigo, tinnitus, or hearing loss;2)neurological findings related to positional vertigo, nystagmus, tinnitus, or hearing loss;3)neuro-otological findings involving tinnitus, audiometry, or vestibular testing;4)auditory brainstem response(ABR)evaluation with the detection of a low 25-75% II wave amplitude on the contralateral side and delayed interpeak latency in the I-III or I-V waves(usually low II wave amplitude combined with double peaks and a wide-based form)during ABR evaluation using 80 and 90dB clicks;and 5)the detection of vascular contact with the eighth cranial nerve on magnetic resonance imaging-constructive interference in steady state or air computed tomography imaging. Finally, the sum of these scores was evaluated. For cases in which more than one of the features of the items 1), 2), or 3) were present, the score was evaluated based on the most representative of the items. RESULTS: The patients were divided into those with scores of 4-5 and those with scores of 2-3. All the patients with scores of 4-5 exhibited CNVC, while those with scores of 2-3 had other diseases. Therefore, CNVC should be suspected in patients with scores of 4-5, but can be ruled out in those with scores of 2-3.

Central positional nystagmus associated with cerebellar tumors: Clinical and topographical analysis.

PURPOSE: Positional nystagmus is usually caused by peripheral vestibular disorder, mostly benign paroxysmal positional vertigo (BPPV). However, positional nystagmus is also encountered in central lesions. We aimed to determine clinical characteristics of the structures responsible for central positional nystagmus (CPN) associated with brain tumors. METHODS: All four patients (3 men; range=19-77years) had an evaluation of spontaneous and positional nystagmus using video-oculography. Brain MRIs were performed in all patients. RESULTS: All patients showed apogeotropic positional nystagmus during supine roll tests, and had an initial diagnosis of BPPV. Except for the positional nystagmus, findings of neurological examination were normal. Because all subjects were initially diagnosed with BPPV, canalith repositioning maneuvers were applied repeatedly but without a success. Brain MRI finally disclosed brain tumors involving the midline cerebellar structures around the fourth ventricle and the nodulus. The pathological diagnosis was hemangioblastoma in two and metastatic tumor in the others. CONCLUSIONS: An apogeotropic type of CPN may be an isolated finding in patients with a cerebellar tumor. Even in patients with isolated apogeotropic positional nystagmus, a central lesion should be sought especially when refractory to repeated canalith repositioning maneuvers.

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.

Vertigo by Breast Cancer Metastasis 33 Years after Treatment.

A 76-year-old woman complained of vertigo for two years. She manifested left deafness, loss of caloric response, and right-beaten nystagmus. An imaging study revealed a tumorous lesion located from the clivus to the left temporal bone with inner ear destruction. A tumor biopsy was performed endonasally and the patient was diagnosed with adenocarcinoma mimicking breast cancer. She had undergone surgery for breast cancer 33 years previously, and the current biopsy specimen showed identical pathology. Breast cancer may metastasize to the skull base; however, metastasis 33 years after surgery is very rare.

Refractory Positional Vertigo With Apogeotropic Horizontal Nystagmus After Labyrinthitis: Surgical Treatment and Identification of Dysmorphic Ampullae.

OBJECTIVES: To describe the rationale, intraoperative details, and histopathologic findings discovered when treating an unusual case of apogeotropic horizontal canal positional vertigo with a transmastoid labyrinthectomy. PATIENT: A single case report. INTERVENTION: Therapeutic. MAIN OUTCOME MEASURES: Resolution of apogeotropic nystagmus and improvement of positional vertigo. RESULTS: The apogeotropic variant of horizontal canal positional vertigo can be a difficult entity to treat. This report describes a patient who developed profound sensorineural hearing loss and vertigo after an acute left labyrinthitis. Ten months later, she developed vertigo with apogeotropic positional nystagmus involving the left horizontal semicircular canal. Particle repositioning maneuvers and vestibular physical therapy were unsuccessful. In addition, she developed intermittent positional vertigo affecting the ipsilateral vertical semicircular canals. Given the persistence of her vertigo, multiple canal involvement, and patient preference for definitive treatment, a transmastoid labyrinthectomy was performed. Intraoperatively, the ampulla of the horizontal canal as well as that of the other canals was grossly abnormal as later confirmed on histology. After surgery, her apogeotropic nystagmus and vertigo resolved, and her balance ability gradually improved to a highly functional level. CONCLUSION: This case illustrates a unique form of positional vertigo that developed and persisted after acute labyrinthitis. Conservative measures were unsuccessful and a transmastoid labyrinthectomy documented dense inflammatory tissue involving all three ampullae. We postulate that the post-labyrinthitic inflammatory changes resulted in mass loading of the membranous ampullae, causing abnormal nystagmus patterns and positional vertigo, which resolved after the labyrinthectomy.

Pathogenesis, Diagnosis, and Treatment of Cervical Vertigo.

Cervical vertigo is characterized by vertigo from the cervical spine. However, whether cervical vertigo is an independent entity still remains controversial. In this narrative review, we outline the basic science and clinical evidence for cervical vertigo according to the current literature. So far, there are 4 different hypotheses explaining the vertigo of a cervical origin, including proprioceptive cervical vertigo, Barré-Lieou syndrome, rotational vertebral artery vertigo, and migraine-associated cervicogenic vertigo. Proprioceptive cervical vertigo and rotational vertebral artery vertigo have survived with time. Barré-Lieou syndrome once was discredited, but it has been resurrected recently by increased scientific evidence. Diagnosis depends mostly on patients' subjective feelings, lacking positive signs, specific laboratory examinations and clinical trials, and often relies on limited clinical experiences of clinicians. Neurological, vestibular, and psychosomatic disorders must first be excluded before the dizziness and unsteadiness in cervical pain syndromes can be attributed to a cervical origin. Treatment for cervical vertigo is challenging. Manual therapy is recommended for treatment of proprioceptive cervical vertigo. Anterior cervical surgery and percutaneous laser disc decompression are effective for the cervical spondylosis patients accompanied with Barré-Liéou syndrome. As to rotational vertebral artery vertigo, a rare entity, when the exact area of the arterial compression is identified through appropriate tests such as magnetic resonance angiography (MRA), computed tomography angiography (CTA) or digital subtraction angiography (DSA) decompressive surgery should be the chosen treatment.

Pseudopheochromocytoma induced by anxiolytic withdrawal.

BACKGROUND: Symptomatic paroxysmal hypertension without significantly elevated catecholamine concentrations and with no evidence of an underlying adrenal tumor is known as pseudopheochromocytoma. METHODS: We describe the case of a female patient with paroxysmal hypertensive crises accompanied by headache, vertigo, tachycardia, nausea and altered mental status. Previously, she was treated for a longer period with alprazolam due to panic disorder. Causes of secondary hypertension were excluded. Neurological triggers (intracranial tumor, cerebral vascular lesions, hemorrhage, and epilepsy) could not be detected. RESULTS: Setting of the diagnosis of pseudopheochromocytoma treatment was initiated with alpha- and beta-blockers resulting in reduced frequency of symptoms. Alprazolam was restarted at a daily dose of 1 mg. The patient's clinical condition improved rapidly and the dosage of alpha- and beta-blockers could be decreased. CONCLUSIONS: We conclude that the withdrawal of an anxiolytic therapeutic regimen may generate sympathetic overdrive resulting in life-threatening paroxysmal malignant hypertension and secondary encephalopathy. We emphasize that pseudopheochromocytoma can be diagnosed only after exclusion of the secondary causes of hypertension. We highlight the importance of a psychopharmacological approach to this clinical entity.

Management of endolymphatic sac tumors: sporadic cases and von Hippel-Lindau disease.

OBJECTIVE: To analyze the difference between the endolymphatic sac tumors (ELSTs) in sporadic cases and in von Hippel-Lindau (VHL) disease. STUDY DESIGN: Retrospective case review in a tertiary referral center. PATIENTS AND METHODS: Fourteen cases of ELST, occurring since 1998, were reviewed. We analyzed the initial symptoms, characteristics of the tumor, treatment, sequelae, and follow-up for each group. RESULTS: The ELSTs were sporadic in 6 cases and associated with VHL disease in 8 cases. The mean age at the time of the first surgery was 26 years (range, 12-41). All except two of the patients presented with a unilateral tumor. The initial symptoms were hearing loss (n = 9), tinnitus (n = 7), and/or vertigo (n = 5). Hearing loss was more prevalent in the sporadic cases. Preoperative arteriography was performed for 4 patients, with embolization performed for 1 patient. The size of the tumor was significantly larger in the sporadic cases (31.7 mm) than in the cases of VHL disease (19.3 mm). The surgical approach was more extensive in the sporadic cases. The surgeons found 2 types of tumors. Cystic tumors with massive bleeding invading the surrounding structures (the dura mater or jugular bulb) were more common in the sporadic cases. Fibrous tumors that infiltrate the bone and have moderate bleeding were more common in the cases associated with VHL disease.Two patients with small lesions were not operated on but were followed for 6 years without tumor growth. They died of metastasis from gastric and kidney cancer. Four recurrences occurred during the 14 years of follow-up. Four facial palsies and 8 cases of profound deafness were encountered postoperatively. CONCLUSION: Sporadic tumors are more aggressive than those associated with VHL disease. Complete surgical resection should be the goal of treatment. Preoperative angiography with embolization is recommended. In some cases, embolization may be impossible, and preoperative or postoperative radiotherapy should be discussed.

Vulnerability of the vestibular organs to transient ischemia: implications for isolated vascular vertigo.

The aim of this study was to elucidate the mechanism of isolated vascular vertigo by determining selective and relative ischemic vulnerability of the vestibular structures using a global hypoperfusion model in rats. Sprague-Dawley male rats weighing 330-350 g were subjected to transient global ischemia of the brain using a 4-vessel-occlusion (4VO) model. After permanent occlusion of both vertebral arteries (VA) using electrocauterization, both common carotid arteries (CCAs) were occluded for 5-20 min with ligation. One hour after reperfusion of the CCAs, the animals were sacrificed and subjected to c-Fos staining of the entire cerebellum, brainstem, and vestibular ganglion. The rats in the sham group received the same surgical procedures except the vessel ligation. With 4VO for 5-15 min, both the sham and experimental groups showed a weak and scarce c-Fos expression in the medial vestibular nucleus (MVN), neuron Y, and cochlear nucleus. After 4VO for 20 min, only the MVN began to show a significant difference in the number of c-Fos positive neurons between the experimental and sham groups (33.7±17.7 vs.7.1±5.1, Wilcoxon rank test, p=0.005). With 4VO for up to 20 min, c-Fos positive neurons were not found in other areas of the brainstem and cerebellum, including the superior, lateral, and spinal vestibular nuclei, the vestibular ganglion, the cerebellar cortex, and the deep cerebellar nuclei. The vestibular structures appear to be vulnerable to ischemia more than any other structures in the brainstem and cerebellum. Of the vestibular structures, the MVN is most vulnerable to ischemic insults in rats. These findings are consistent with the common findings of vertigo as an initial and isolated symptom of posterior circulation ischemia in human.

Primary inner ear schwannomas: a case series and systematic review of the literature.

OBJECTIVES/HYPOTHESIS: To describe the natural history of primary inner ear schwannomas (PIES) and evaluate management outcomes and relationship between PIES location, clinical presentation, and time to diagnosis. STUDY DESIGN: Retrospective chart review and systematic review of the literature. METHODS: Vestibular schwannoma confined to or arising from the inner ear were included. PIES classification was based on anatomic subsite(s) involved. Detailed clinical history and outcomes were recorded. RESULTS: In a systematic review (1933-2011), including 14 patients from the authors' institution (1999-2009), a total of 72 studies comprising 234 patients were evaluated. Mean follow-up was 32.8 ± 39.1 months (range, 0-183 months). The cochlea was the most commonly involved subsite (51%). Hearing loss was the most frequent presenting symptom (99%). Vertigo and abnormal balance were more common among tumors involving the vestibular system (P < .01). Average delay between symptom onset and diagnosis was 7.0 ± 8.0 years (median, 5 years; range, 0-40 years). Recent onset hearing loss was more likely to elicit an earlier diagnosis (P = .01). The majority of patients were observed without treatment (53%). Tumor progression was seen in 52% of patients. CONCLUSIONS: PIES are rare tumors and most commonly involve the cochlea. Tumor location is often associated with clinical presentation and correlates with delay between symptom onset and diagnosis. A watch-and-scan approach is the management strategy of choice in the absence of intractable vertigo or extensive tumor growth. The majority of patients report stable or improved symptoms over time, regardless of treatment.

Prospective evaluation of the clinical profile and referral pattern differences of vestibular schwannomas and other cerebellopontine angle tumors.

OBJECTIVE: To evaluate the clinical profile, referral pattern, delay in diagnosis, and impact of tumor size of cases involving vestibular schwannomas (VS) versus other cerebellopontine angle (CPA) tumors in an Egyptian population. STUDY DESIGN: Case series study. SETTING: Tertiary referral center. PATIENTS: A prospective study of possible retrocochlear lesions was conducted from 2008 to 2010. INTERVENTION(S): Patients were subjected to a full clinical history, complete otorhinolaryngological examination, a basic audiologic evaluation, auditory brainstem response assay, and gadolinium-enhanced magnetic resonance imaging. According to the findings of magnetic resonance imaging, patients with retrocochlear lesions were divided into 2 groups: those with VS (n = 17) and those with other CPA lesions (n = 14). MAIN OUTCOME MEASURE(S): Diagnostic delay and criteria of VS and CPA tumors. RESULTS: Unilateral hearing loss and tinnitus were presented in 52.9% of VS cases with a diagnostic delay of 15.5 months. For cases involving other CPA lesions, a combination of otologic symptoms was observed in 9 (64%) of 14 cases, and a diagnostic delay of 47.5 months was experienced. An absence of auditory brainstem response waves was identified significantly (p < 0.05) for the affected ears of both groups. Only differences in Wave V latency were significant between the 2 groups (p < 0.05). CONCLUSION: A longer diagnostic delay was associated with cases involving other types of CPA lesions versus cases of VS, and tumor size and volume did not affect the diagnostic delay of the former. Moreover, the only significant difference in clinical presentation for these 2 groups of intracranial tumor involved Wave V latency.

Disorders affecting the fourth ventricle: etiology and clinical correlates.

OBJECTIVE: The fourth ventricle encompasses many vital structures including the brainstem as its floor and the cerebellum as its lateral wall and roof. Therefore, lesions affecting the fourth ventricle may present as cerebellar or brainstem manifestations. Herein, we presented our experience in the diagnosis of disorders affecting the fourth ventricle during the past 15 years. STUDY DESIGN: Retrospective study. SETTING: University hospital. SUBJECTS: From September 1995 to August 2010, 24,838 patients with vertigo/dizziness visited the clinic. Of them, 13 patients (0.5%) had tumor/stroke affecting the fourth ventricle. MAIN OUTCOME MEASURES: All patients underwent a battery of audiovestibular function test. RESULTS: All patients had vertigo (100%) and then ataxia (92%) and nausea/vomiting (85%). Eight patients (68%) displayed persistent nystagmus. Most (>75%) patients showed central signs in electronystagmographic recordings and abnormal caloric coupled with visual suppression test. Three patients underwent both ocular and cervical vestibular-evoked myogenic potential tests, and abnormal results were noted in all 3 patients indicating a brainstem involvement. However, magnetic resonance imaging failed to demonstrate brainstem lesion in these 3 patients. Final diagnoses consisted of the following: cavernoma, n = 3; metastatic cancer, n = 3; astrocytoma, n = 2; meningioma, n = 2; epidermoid cyst, n = 1; ependymoma, n = 1; and lymphoma, n = 1. The prognosis was poor as 10 patients (77%) died within 2 years. CONCLUSION: When a vertiginous patient displayed ataxia, persistent vomiting, and persistent nystagmus, lesion affecting the fourth ventricle should be kept in mind because its prognosis is poor. Abnormal results in electronystagmography and in ocular and cervical vestibular-evoked myogenic potentials may serve as a supplementary to magnetic resonance imaging to delineate the involvement of the lesion.

[To analyze the etiology of benign paroxysmal positional vertigo].

OBJECTIVE: To analyze the occurrence and probable etiological factors of benign paroxysmal positional vertigo (BPPV). METHOD: one hundred and twenty four BPPV cases were inquired histories, classified into different groups and analyzed relevant diseases. All patients were taken Caloric tests before Canal repositioning procedure, and compared the differences of unilateral weakness (UW) and semicircular canal involved between BPPV patients with and without relevant diseases. RESULT: There were 97 (78.2%) patients with relevant diseases while 27 (21.8%) without. Ninety-two (74.2%) patients with abnormal UW. To compare the normal and abnormal UW, posterior canal and lateral canal with abnormal UW values, unilateral or bilateral of abnormal UW values, consistency of abnormal UW side and BPPV side between BPPV patients with and without relevant diseases, there were no significant differences (Chi-square values were 0.000, 0.000, 0.306, 0.027, P>0.05). CONCLUSION: BPPV patients with relevant diseases are common, which mainly occurs in middle-aged or aged people and female. Otolith ecclesiis and dysfunction of semicircular canal may have the same etiological factors. Caloric tests may do help to analyze the BPPV etiological factors.