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Coexistent Vestibular Schwannoma and Creutzfeldt–Jakob Disease

Recognition and Infection Control

Thomas, Andrew J.*; Casazza, Geoffrey C.*; MacDonald, Joel D.; Gurgel, Richard K.*

doi: 10.1097/MAO.0000000000002136
MEDICAL NEUROTOLOGY
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Objectives: We describe the first known case of coexistent vestibular schwannoma (VS) and Creutzfeldt–Jakob disease (CJD). Our objectives are to use this case as a general lesson for the subspecialist otolaryngologist to remain vigilant to alternative diagnoses, and to specifically improve understanding of the diagnosis and management of CJD as relevant to the practice of otolaryngology and skull base surgery.

Methods: Retrospective case review performed in June 2016 at an academic, tertiary, referral center.

Results: A 55-year-old man presents with one month of worsening disequilibrium and short-term memory loss. Magnetic resonance imaging (MRI) (T1, T2) identified a 4 mm left VS which was then surgically resected. Postoperatively, his neurological status decline continued, and subsequent MRI identified patterns of FLAIR hyperintensity and diffusion restriction consistent with CJD. While CSF analysis (tau and 14-3-3) and EEG was inconclusive, serial imaging and the clinical course were highly suggestive of CJD. A probable diagnosis was made, surgical instruments quarantined, and infection control involved to minimize transmission risk. The patient died 6 months after symptom onset.

Conclusions: Patients with CJD may initially present with otolaryngologic symptoms. MRI signal abnormality in the basal ganglia on diffusion weighted imaging and FLAIR sequences in conjunction with physical findings and clinical course may help make a probable diagnosis CJD. Prions are resistant to traditional sterilization and additional measures must be taken to prevent iatrogenic transmission.

Level of Evidence: Level 4—Case series

*Division of Otolaryngology—Head and Neck Surgery, Department of Surgery

Department of Neurosurgery, University of Utah, Salt Lake City, Utah

Address correspondence and reprint requests to Andrew J. Thomas, M.D., University of Utah, Division of Otolaryngology —Head and Neck Surgery, 50 North Medical Drive, Room 3C120, Salt Lake City, UT 84132; E-mail: andrew.thomas@hsc.utah.edu

Funding and conflict of interests: This work was not supported by any funding and the authors have no relevant conflicts of interest to disclose.

Meeting: Presented September 12, 2017 at the 121st Annual Meeting of the American Academy of Otolaryngology-Head and Neck Surgery in Chicago, IL.

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INTRODUCTION

Although rare, patients with vestibular schwannomas (VS) are commonly evaluated and managed by otolaryngologists. VS has an estimated incidence of approximately 1 per 100,000 person years (1), but more frequent use of magnetic resonance imaging (MRI) has increased the incidental discovery rate of asymptomatic VS (2). VS is a slow-growing, benign tumor with gradual symptom progression, and a median age at diagnosis of 50 years (1). The most common presenting symptoms are asymmetric hearing loss and tinnitus (95%); (3) second most common are vestibular symptoms (about 60%), which are usually unsteadiness (not vertigo) (3).

Even more rare and less familiar to the otolaryngologist is Creutzfeldt–Jakob disease (CJD). CJD is a rare prion disease which exists in different forms including sporadic (sCJD), variant (vCJD), familial (fCJD), and iatrogenic (iCJD); most cases are sporadic (approximately 83–88%) (4–6). The annual incidence of sCJD is approximately 1 per 1,000,000 person years (4,5,7). The presenting symptoms of CJD are variable, but a common feature in all cases is rapidly progressive dementia without other identifiable cause and development of broad neurologic deficits (5,7,8). The most common neurologic finding of CJD is myoclonus, but other frequent findings include visual change, ataxia, and eventually akinetic mutism (5), as reflected in the CDC diagnostic criteria for CJD (9). Although incidence increases with age, average age at diagnosis is 60 to 70 years (5,7). The progressive decline with sCJD is so rapid that the median time from symptom onset to death is 5 months (5).

Here we present an extremely rare event which has not been previously reported: A patient with coexistent VS and CJD. Principals of CJD diagnosis and infection control, specifically relevant to the otolaryngologist, are reviewed.

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Case Report

A 55 year old, previously healthy, man first developed intermittent vertigo which progressed to a constant imbalance over approximately 3 months (Fig. 1). He then developed memory loss, which progressed rapidly with daily decline in memory and cognitive function. Evaluation by his primary care provider included magnetic resonance imaging (MRI) which identified a left 4 mm internal auditory canal (IAC) lesion consistent with a vestibular schwannoma (VS; also known as acoustic neuroma) and no other findings (Fig. 2, row A). He was referred to a neurotologist. Disequilibrium and memory impairment were attributed to the VS, the only imaging finding, and explained as cognitive overload from abnormal vestibular signals. He had normal hearing levels and 100% speech discrimination bilaterally.

FIG. 1

FIG. 1

FIG. 2

FIG. 2

A resection of the VS by middle fossa approach (to preserve hearing) was performed, but afterward his symptoms continued to rapidly progress and he developed global ataxia. By 10 days postop he was requiring a two-person assist to walk and was unable to feed himself due to severe coordination deficits. Given this rapid decline, further evaluation including neurology consultation, electroencephalogram (EEG), cerebrospinal fluid (CSF) studies by lumbar puncture (LP), and MRI, led to a presumptive diagnosis of Creutzfeldt–Jakob disease (CJD). The postoperative MRI performed 40 days after the preop MRI demonstrated new findings consistent with CJD (Fig. 2, row B), including T2 FLAIR hyperintensity with associated diffusion restriction involving the right greater than left caudate, putamen, posterior thalami, mesial temporal lobes, amygdala, the cortex of the anterior cingulate gyrus and the cerebellar gray matter. CSF studies (tau and 14-3-3 protein) were inconclusive due to recent intradural surgery, and the EEG failed to identify CJD-associated findings. The patient passed away after 2 months after surgery due to rapidly progressive neurologic decline consistent with CJD, only two and a half months after his neurologic symptoms had brought him to our medical attention. Brain biopsy was declined by the family and therefore the diagnosis of CJD could not be neuropathologically confirmed.

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DISCUSSION

We have reported for the first time, a case of coexistent VS and CJD. The patient's most prominent symptom at presentation was dizziness, and with the finding of a small 4 mm VS on imaging, all symptoms had been attributed to his acoustic tumor. The patient's symptoms of progressive disequilibrium and memory loss are attributable to CJD in retrospect, but had been related to cognitive impact of his unilateral vestibular pathology at his initial presentation.

There is an association between hearing loss and dementia (10,11), and some evidence for psychologic disturbance related to hearing loss (12), though our patient presented with normal hearing. Patients with VS will have elevated stress hormones, which can modulate neurotransmitters responsible for anxiety and depression. These neurotransmitters (glutamate, acetylcholine, GABA, and glycine), are known to play a role in cognition and may explain the cognitive changes associated with VS (13,14)—although not necessarily to the degree that our patient presented. Other proposed mechanisms linking VS and psychologic dysfunction include chronic hydrocephalus, psychologic reaction to illness and facial paralysis, as well as disruption of paratentorial structures from tumor growth or surgery (12). Tumors of the cerebellopontine angle (CPA), such as VS with a large CPA component, may impact the cerebellum resulting in disturbance of motor function, executive functioning and memory (15,16). None of these explanations are appropriate for our case of a small VS confined to the IAC. Other potential causes of our patient's symptoms, distant or regional metastasis, paraneoplastic syndromes, and cognitive decline from Alzheimer's or severe dementia were considered, but thought to be less likely given the patient's lack of additional symptoms or risk factors.

Patients with VS and rapidly progressive dementia and neurologic deficits beyond hearing loss and vestibular symptoms, should be assessed for sCJD so that this condition is not missed. We recommend starting this evaluation by consulting with neurology for comprehensive neurologic assessment, and obtaining an MRI of the brain with T2-FLAIR and diffusion weighted imaging (DWI) sequences. The diagnosis of sCJD can be further pursued with CSF studies, EEG, and potentially brain biopsy (for definitive diagnosis). EEG findings (periodic sharp waves pattern associated with CJD) and positive 14-3-3 CSF assay are supportive of a CJD diagnosis, but lack specificity. A positive result on at least one test among EEG, 14-3-3, or MRI, is required for a “probable” CJD diagnosis by CDC criteria (9).

Management of the patient was largely guided by his initial imaging findings on MRI, which included traditional sequences and gadolinium contrast. Although often appropriate for general intracranial evaluation, T1 sequences are usually normal in CJD and gadolinium enhancement is not a feature of CJD (8). Changes associated with CJD may be seen on T2 sequences, and even more so on T2-FLAIR, but DWI demonstrates CJD-associated changes earlier in the disease process than any other sequence (5,8). Patterns of findings on FLAIR and DWI MRI may differentiate sCJD from other nonprion rapidly progressive dementia with a sensitivity of 98% and specificity of 93%; DWI sequences were concluded to be the most important for diagnosis with key findings associated with sCJD including prevalence of DWI versus T2 abnormality, particularly diffusion restriction in the basal ganglia (17). These basal ganglia DWI changes associated with sCJD increase in extent of involvement and signal intensity with greater duration of disease (18). The initial MRI did include DWI, which does not take into account directionality imposed on diffusion by tracts of neurons, but the post-op MRI included diffusion tensor imaging (DTI). DTI provides more physiologically accurate information about diffusion though not associated with unique findings compared to DWI for sCJD, and can be interpreted similarly for the purposes of this study (19). Diffusion findings are supported also by development of corresponding T2 FLAIR abnormalities (17,18).

CJD is an unlikely cause for dizziness in general, but the otolaryngologist may be one of the first doctors to assess these patients if dizziness is their primary symptom. Initial presentation of sCJD as dizziness without dementia has been reported in the literature, though appears uncommon as dizziness/vertigo is the initial manifestation of CJD in only 2.6% of cases (20). Although rare, the true prevalence of CJD may be greater than is known. And despite no current treatment, identifying at-risk patients is critical for avoiding iatrogenic transmission to other patients via otolaryngologic and neurosurgical procedures.

Iatrogenic transmission of prion disease in otolaryngology is most likely when brain, dura matter, trigeminal ganglia, and pituitary gland are encountered, as these are considered high infectivity tissues for transmissible spongiform encephalopathy (TSE) by the World Health Organization (WHO). Coexistent VS and unrecognized CJD is a particularly high risk situation as the surgical resection for VS involves high infectivity tissues. Unlike other infectious agents, prion proteins are resistant to usual sterilization processes and special precautions must be taken (guidelines are published by WHO and CDC: https://www.cdc.gov/prions/cjd/infection-control.html). Traditional sterilization techniques including alcohol, formaldehyde, and glutaraldehyde are unlikely to reduce prion infectivity on instrumentation and operative surfaces and floors (21). Effective sterilization techniques rely on chaotic disruption of protein structure. Immersion of instruments or flooding of operative surfaces and floors in sodium hydroxide or sodium hypochlorite, both hazardous substances, followed by standard autoclaving of instruments or water dilution of operative surfaces are recommendations for managing prion sterilization (21). Whenever possible disposable instrumentation should be utilized and subsequently incinerated.

CJD transmission has been reported in two cases of otologic surgery, both involving tissue grafts (7,22,23). Potential transmission via aerosolized temporal bone dust has been suggested, as neural tissue has been identified in the dust despite avoiding contact with dura or nerve (7). More common otolaryngologic procedures may also carry some theoretical risk of iatrogenic transmission as peripheral nerve, tonsil, lymph nodes, skeletal muscle, tongue, blood/blood vessels, nasal mucosa, and salivary glands all contain prion proteins in cases of TSE (7). Although rare, prion disease may be encountered by the otolaryngologist and identification of at-risk patients is critical in order to take precautions to avoid potentially devastating iatrogenic consequences to other patients.

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CONCLUSION

Patients with CJD may present with otolaryngologic symptoms. MRI signal abnormality in the basal ganglia on DWI and FLAIR sequences in conjunction with physical findings and clinical course may help make a probable diagnosis CJD. Physicians should remain vigilant to possible CJD, particularly when considering procedural interventions, in order to prevent iatrogenic infection of other patients as unique sterilization procedures are required to remove prions.

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Keywords:

Acoustic neuroma; Creutzfeldt–Jakob disease; Vestibular schwannoma

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