Auditory Deficits in Neurological Disorders Ubytki Słuchu W Chorobach Neurologicznych

artykuł oryginalny / original article

Auditory deficits in neurological disorders Ubytki słuchu w chorobach neurologicznych

1DBAE 2BCE 3BC 4BDF Authors’ Contribution: Tomasz Przewoźny , Anna Gójska-Grymajło , Tomasz Szmuda , Karolina Markiet A – Study Design B – Data Collection 1 C – Statistical Analysis Department of Otolaryngology, Medical University of Gdańsk, Smoluchowskiego 17, 80-214 Gdańsk, Poland D – Data Interpretation 2 E – Manuscript Preparation Department of Neurology of Adults, Medical University of Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland F – Literature Search 3Department of Neurosurgery, Medical University of Gdańsk, Smoluchowskiego 17, 80-214 Gdańsk, Poland G – Funds Collection 4II Department of Radiology, Medical University of Gdańsk, Smoluchowskiego 17, 80-214 Gdańsk, Poland

Article history: Received: 04.08.2015 Accepted: 16.08.2015 Published: 30.10.2015

ABSTRACT: Neurological diseases present with diverse and often complex symptomatology. Focal neurological signs such as paresis, aphasia or visual field deficits together with often serious general state of a neurological patient usually push auditory symptoms into the background. Here, we present a review of literature on central and peripheral auditory disturbances that can appear in the course of most common neurological diseases. We present: cerebral stroke, cochleovestibular nerve compression syndrome, cerebral palsy, multiple sclerosis, epilepsy, myasthenia gravis and brain tumors. We focus on the neuroanatomical basis of auditory dysfunctions, their character and prevalence typical for the abovementioned diseases. Theoretical considerations are supported by broad audiological and neuroimaging studies of our patients. Auditory symptoms in neurological diseases seem to be rare. However, knowledge of these symptoms and their origin can be helpful in proper diagnosis and comprehensive patient management. KEYWORDS: multiple sclerosis, ischemic cerebral stroke, epilepsy, sensorineural hearing loss, sudden deafness, tinnitus

STRESZCZENIE: Choroby neurologiczne objawiają się w sposób różnorodny i złożony. Ogniskowe objawy neurologiczne, takie jak niedowłady, afazja, ubytki w polu widzenia, którym bardzo często towarzyszy pogorszenie stanu pacjenta sprawiają, że objawy słuchowe schodzą na drugi plan. W niniejszym artykule przedstawiamy przegląd literatury dotyczącej ośrodkowych oraz obwodowych zaburzeń słuchu w przebiegu najczęstszych chorób neurologicznych. Opisujemy udar mózgu, konflikt naczyniowo-nerwowy nerwu przedsionkowo-ślimakowego, porażenie mózgowe, stwardnienie rozsiane, padaczkę, miastenię oraz guzy mózgu. Zwracamy uwagę na neuroanatomiczne podstawy zaburzeń słuchu, ich charakter oraz częstość występowania w wymienionych wyżej chorobach. Rozważania teoretyczne uzupełnione zostały prezentacją wyników licznych badań audiologicznych i neuroobrazowych wykonanych u naszych pacjentów. Objawy słuchowe w chorobach neurologicznych wydają się rzadkie, jednakże wiedza dotycząca ich pochodzenia może być pomocna w postawieniu właściwej diagnozy i zastosowaniu kompleksowego leczenia SŁOWA KLUCZOWE: stwardnienie rozsiane, udar niedokrwienny mózgu, padaczka, niedosłuch odbiorczy, nagła głuchota, szum uszny

INTRODUCTION ogy to support diagnostic and therapeutic decisions in different clinical fields. The usefulness of these methods in certain Neurological diseases have complex symptomatology, with au- diseases, especially neurological ones, is regarded comparable diological symptoms included. However, audiological signs are to neuroimaging studies. often neglected by neurologists and otolaryngologists, which may result in a late or wrong diagnosis. In the last 30 years Audiological symptoms of neurological diseases are com- there has been substantial progress in the development of the bined with pathology of different levels of the auditory system, auditory diagnostics based on the electrophysiological mod- from the middle ear to the cerebral cortex. They include more els. These diagnostics are commonly used in modern audiol- commonly diagnosed - hearing loss or tinnitus [1, 2] togeth------

OTOLARYNGOLOGIA POLSKA, TOM 69, NR 5 (2015), p. 29-43 DOI: 10.5604/00306657.1170416 29 artykuł oryginalny / original article

er with less often found higher auditory dysfunctions such as between these two groups. Other authors confirmed correla- the impairment of understanding speech, sound localization tions between ischemic cerebral processes and hearing loss [1, disability, hearing hypersensitivity, phonophobia or auditory 2, 10, 11]. Sudden hearing loss in cerebral stroke may be com- hallucinations [3-6]. plete and it can affect 1.4 to 21% patients, depending on the inclusion/exclusion criteria of the performed studies [1, 2, 10, The aim of the following article was to present audiological 11]. Huang et al. [12] in a study on 503 stroke patients, found symptoms typical for common neurological diseases: cerebral sudden bilateral hearing loss in 7 (1.4%) subjects. Yamasaba et stroke, cochleovestibular nerve compression syndrome, cer- al. [10] found sudden hearing loss and vertigo in 15 (21%) of ebral palsy, multiple sclerosis, epilepsy, myasthenia, cerebel- 70 patients with transient ischemic attack in the vertebrobasi- lopontine angle tumors and cerebral tumors. The authors, on lar territory. Lee et al. [11] described 16 patients with AICA the basis of available literature, present the type, prevalence stroke - 5 (31%) had acute hearing symptoms (hearing loss and pathological background of the auditory dysfunctions in and vertigo). Interestingly, the symptoms appeared 1-10 days the abovementioned diseases. before the onset of other brainstem and cerebellar symptoms. The authors distinguished two acute hearing syndromes: 1) recurrent, transient hearing loss with or without tinnitus that CEREBROVASCULAR DISEASES lasted for several days; and 2) single, prolonged hearing loss with or without tinnitus. The most commonly affected brain Cerebral stroke area in this study was the middle cerebellar peduncle. In four Stroke can affect the territory of the main cerebral arteries: of the five patients hearing loss of variable degree was found the internal carotid artery and its two branches – the middle and all the patients presented vestibular damage in the caloric cerebral artery and the anterior cerebral artery, and of the pos- testing on the side of the ischemic lesion. terior cerebral arteries and the basilar artery. Cerebral tissue ischemia begins 25 seconds after vessel closure and leads to irreversible tissue and metabolic damage after 4-5 minutes. It is the territory of the middle cerebral artery where the vascular incidents are most common. The internal ear and the vestibulocochlear nerve are vascularized by the labyrinthine artery, a branch of the anterior inferior cerebellar artery (AICA) (in 60% of cases) or less often of the basilar artery (40% of cases). The internal ear is particularly susceptible to ischemia due to its high metabolic rate and lack of collateral circulation [7]. On the contrary, the vestibulocochlear nerve (the VIII cranial nerve) has an additional collateral circulation.

According to WHO the cerebrovascular diseases are divid- ed into the ischemic and hemorrhagic stroke, and the sub- arachnoidal bleeding, where 80% of the incidents are due to the ischemic stroke. Auditory symptoms such as the hearing loss, tinnitus and vertigo appear in the posterior cerebral artery strokes. First description of these symptoms was given by Adams in 1943 [8] – vertigo, hearing loss, facial nerve palsy, ataxia, nystagmus and hypoesthesia were caused by AICA occlusion. Since then many clinical descriptions of the cerebral stroke patients with auditory symptoms have appeared, Fig. 1. Horizontal minimum audible angle test (HMAAT) results and MRI however, most of them are case reports. Clinical analyses of findings in a 45-year-old patient with bilateral symmetric mild bigger groups of stroke patients with auditory symptoms are sensorineural hearing loss and poor speech discrimination on the seventh scarce [1, 2, 9, 10], and the results are inconsistent, mainly due day after the incident of stroke. (A) Black line-95th percentile values for the age-matched subgroup of controls, red dotted line-results of the patient; to variable location of stroke lesions. Hariri et al. [9], who com- (incorrect result for all azimuths: 0°[9°]; 45° [24°]; 90° [21°]; 180°[24°]; pared hearing by pure tone audiometry (PTA) in 25 stroke pa- 225°[20°]; 270°[16.5°] and 315°[18°]. (B) Axial FLAIR image shows a diffuse, tients aged 58 to 85, with hearing of 25 healthy individuals of periventricular area of hyperintensity. Axial FLAIR image (C) and coronal T2-weighted image (D) show the extent of ischemic lesions. the same age, did not find statistically significant differences - - - - -

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Fig. 2. Anatomical structures of the cerebellopontine angle. Neurovascular conflict between the VIII and VII cranial nerves and the anterior inferior cerebellar artery. Abbreviations: CN-cranial nerve, AICA-anterior inferior cerebellar artery, PICA-posterior inferior cerebellar artery, FL-flocculus, LA-labyrinthine artery, NI- intermediate nerve.

In a comprehensive study by Lee-Baloh et al. [1], sudden hearing speech. Multiple crossings of the auditory pathways are ing loss was found in 29 subjects (8%) of 364 patients, and the the reason for a vascular lesion to cause both ipsilateral and hearing loss correlated mostly with the posterior circulation contralateral hearing deficits. Disturbed recognition of ver- infarct (POCI, according to the Oxford Community Stroke bal stimuli (auditory verbal agnosia) and/or non-verbal audi- Project classification). Some authors regard hearing symptoms tory stimuli with proper hearing (acoustic agnosia) is usually that appear in time of 10 days before the incidence of other found in uni- or bilateral damage of the temporoparietal re- symptoms, as stroke symptoms [1]. However, other authors gion. Similar topography of injury correlates also with specif- claim that such symptoms can be regarded in terms of stroke ic hearing disorders such as the disturbed localization of an if they appear together with other neurological symptoms [12]. acoustic stimulus or recognition of its affective components, and complete hearing loss (cortical deafness). In amusia it is First reliable description of hearing signs correlated with the the music processing that is disturbed, however with the right anterior circulation infarction was given by Wernicke and hemisphere injury it is the recognition of the melody and rythm Friedländer [13] in 1883. They described a woman with bilat- that is disturbed most. eral stroke of the temporal lobes that was confirmed by autop- sy. She presented aphasia (left temporal lobe lesion) and con- Sound localization ability can also be distorted by stroke. Struc- tralateral complete hearing loss (right temporal lobe lesion). tures of the auditory pathway such as the nuclei of the lateral lemniscus or the nucleus of the inferior colliculus allow sound locali- Vascular incidents can cause different combinations of hearing zation due to differences between time and intensity of perceived deficits dependent on the level of the auditory pathway damage. sounds [14]. Thus, brainstem strokes can cause sound localization Clinical studies supported by MRI findings prove that stroke disturbances [15]. Regions of hemispheres responsible for sound in the region of the tectal lamina and the inferior colliculi may localization is the planum temporale and the parieto-temporal cause bilateral hearing loss and problems with understand- operculum. It was proved that stroke of the temporal and parietal - - - - -

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Fig. 3. Neurovascular conflict in a 52-year-old female patient with pulsating tinnitus in the left ear. MRI, non-contrast-enhanced time of flight (TOF) sequences in axial (A, B) and oblique (C) planes show anterior inferior cerebellar artery (arrows) running closely to the left VIII cranial nerve (short arrow) (A) in the cerebellopontine angle and making a loop over the nerve (B, C). Patient presented with left-sided sensorineural hearing loss (D, E). O,∆-air conduction, ]-bone conduction.

lobes cause ipsi-, contra- and bilateral sound localization distur- or other sound characteristics such as paliacusia – words are bances [15, 16]. Some significance in sound localization was given heard in a repetitive manner, paracusia – words seem too loud also to the frontal cortex, but only bilateral injury seems to have or too silent, and hiperacusis – sounds are recognized loud- substantial impact on this function. However, it is the multiple, er than they truly are. Auditory hallucinations, usually music bilateral and lacunar character of ischemic lesions that influence ones, were reported in cases of hemorrhagic brainstem stroke. the sound localization ability most [17]. (Fig. 1) The cochleovestibular nerve compression syndrome Sudden tinnitus can be another auditory symptom of ischemic (CNCS) stroke [2]. Lee et al. [1] reported that tinnitus was a prodromal The cause of a nerve vascular compression syndrome is the symptom in 6 (20.7%) of the 29 patients with sudden deafness compression of a cranial nerve by a vessel. This conflict usually caused by vertebrobasilar insufficiency. It is regarded that in affects the following cranial nerves: V, VII, VIII and IX. Hear- most patients (80%) tinnitus is caused by cochlear damage and ing problems are of course due to vascular compression of the it is rarely combined with cortical injury. vestibulocochlear nerve [18]. Many authors regard AICA as the vessel responsible for the cochleovestibular nerve com- Other hearing symptoms in vascular brain injury are rare. Ex- pression syndrome (CNCS) [19, 20]. It is a branch of the basi- amples of them include inappropriate recognition of loudness lar artery, and has 3 segments in the region of the cerebello------

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Fig. 4. A 17-year-old patient with cerebral palsy and profound mental retardation. MRI axial FLAIR image (A) and sagittal T2-weighted image (B) show diffuse areas of gliosis, white matter volume loss and accompanying ventriculomegaly associated with hypoxic-ischemic encephalopathy involving the primary auditory cortex (arrows). BAEPs (click 2-4 kHz) proved moderate bilateral sensorineural hearing loss (black arrows indicate hearing levels) (C). Fitting hearing aid was unsuccessful.

pontine angle: 1) after branching off from the basilar artery it where the central type myelin sheath changes into the periph- runs around the brainstem and between the VII and the VIII eral one. Compression of the nerve causes demyelination and cranial nerve; 2) then it gives off small branches that supply secondary axonal damage that causes ectopic excitation of the the internal auditory meatus and the choroid plexus; 3) final- VIII nerve in both directions. The effect is an additional stimu- ly it runs near and supplies the flocculus and the middle cere- lation of the cochlear and vestibular nuclei of the VIII nerve in bellar peduncle [19] (Fig. 2). The most important pathophys- the brainstem [20]. This additional inappropriate impulsation iological aspect of the CNCS is the adhesion of AICA to the usually causes unilateral sensorineural hearing loss and more transition zone of the VIII nerve (Redlich-Obersteiner’s zone), often pulsatile, refractory tinnitus (Fig. 3). - - - - -

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Fig. 5. A 29-year-old man with MS and paresis of the upper right limb as the initial symptom, without auditory symptoms - PTA results normal (A), BAEPs (click 2-4 kHz) latencies (B-right side, C-left side) symmetrical, normal. After 11 months he developed left-sided sensorineural retrocochlear high frequency hearing loss (D). Latency of wave V in BAEPs on the left side was delayed with prolonged III-V inter-peak latency (E, F). MRI, T2-weighted images in axial (G, H) and coronal (I) planes show bilateral linear/ovoid hyperintensities, corresponding to multiple sclerosis plaques in the periventricular region (G, arrow), in the posterior fossa (H, arrow) and in the subcortical white matter (I, arrow). Tympanometry and Otoacoustic Emission tests were normal; Stapedius reflex: no contralateral response (left)-data not shown. O,X-air conduction, >,<-bone conduction.

In cases of CNCS, electrophysiological studies show extra- Cerebral palsy cochlear pathology together with reduced cochlear excitabil- Vascular degenerative changes in cerebral palsy (CP) can ity. The only effective treatment of CNCS is the microsurgical also lead to sensorineural hearing loss. Various sources claim decompression of the nerve with the use of a special teflon that it is present in 4% to 47% of children with CP [22-24]. or gore tex tile placed between the nerve and the vessel [21]. In 2011, Reid et al. [22], made a review of published litera- It is worth mentioning, that the reliable diagnosis of CNCS ture from years 1980-2010 and chose 14 studies from the 380 can be made only after the neurosurgery procedure resolves available ones. It was possible to define the type of hearing the symptoms. loss in 48 children out of 685 with CP (60% - sensorineu------

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Fig. 6. A 30-year-old woman with idiopathic epilepsy since 5 years of age, treated with valproic acid and with partial seizures once a month. The patient presented progressive bilateral asymmetric sensorineural cochlear hearing loss (C); primarily hearing loss was present only in the right ear (A), the left ear was aided 10 years ago (B). The patient did not decide to undergo cochlear implantation. She suffered from left-sided tinnitus for the last 3 years. MRI, T2-weighted coronal image shows typical appearance of polymicrogyria involving the left perisylvian region and the left temporal lobe. Note the loss of normal gyral architecture, thickened cortex and indistinct cortical-white matter interface. Cortical dysplasia-subependymal heterotopic gray matter lining the left temporal horn (D). EEG changes with irregular theta waves, single sharp 5-6 Hz waves and groups of sharp waves in the fronto-temporal areas with predominance in the left hemisphere and tendency for synchronization (E). Audiologic examination: tympanometry-type A; stapedius reflex-bilateral no response; otoacustic emission-bilateral no response; BAEPs (click 2-4 kHz) symmetric responses, normal morphology, 110 dBnHL-left, 80 dBnHL-right-data not shown. MTRNR1 gene mutation was not found (m.1555A>G and m.1438 A>G responsible for 71% of mitochondrial hearing loss). ,∆,X-air conduction, >,<-bone conduction.

ral, 29% - mixed type, 25% - conductive hearing loss). The extrapiramidal CP type, and the severe sensorineural hear- authors concluded that unaided hearing loss >40 dB HL in ing loss (> 70 dB) was mainly found in spastic quadriplegic the better ear across frequencies 500-4000 Hz occurs ap- or dyskinetic type. proximately in 4% to 8% of individuals with CP, and hearing loss >70 dB HL in approximately 2% to 4% of individuals. Shevell et al. [23] reported that in CP children severe auditory Moraleas Angulo et al. [24] found similar percentages in impairment is less common than lack of speech development their study - 18 (60%) out of 30 patients with CP who had (22.2%) or active afebrile seizure disorder (16.9%), but more undergone audiological testing, had sensorineural hearing common than cortical blindness (9.5%) and gavage feeding loss. Sensorineural hearing loss generally accompanies the requirement (7.8%). - - - - -

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Fig. 7. A 49-year-old patient with myasthenia diagnosed 7 years earlier, treated with pirydostygmine. He presented right-sided mixed type hearing loss (conductive component for low frequencies (0.25-1 kHz) and sensorineural component for high frequencies (3-8 kHz) (C). Tympanometry-type C bilaterally (A, E) typical for auditory tube dysfunction (present also in the left ear with normal hearing) due to malfunction of the levator and tensor veli palatini muscles. Stapedius reflex absent bilaterally (B,F) despite normal hearing threshold in the left ear in PTA (G). High resolution computed tomography (HRCT) of the temporal bone showed no pathologies within both middle ears-arrow points to the right stapes (D). O,X-air conduction, [,>-bone conduction.

It is regarded that hearing deficits in CP children are mainly formed, it is possible to construct tonal audiogram on the basis due to cochlear or vestibulocochlear nerve damage. However, of BAEPs by finding the pure tone hearing thresholds (500, 1000, approximately 20% of children present abnormal Brainstem 2000 Hz). This has crucial impact on fitting suitable hearing aids Auditory Evoked Potentials (BAEPs) which prove central audi- in CP children, since many children are eligible for a standard tory pathways disturbance [25]. Abnormalities in those BAEPs hearing aid or even cochlear implant [26]. (Fig. 4). studies were defined as latencies of III and V waves (inter-peak latencies of waves I-III, III-V and I-V) that were ≥2.5 standard deviation for normal results. NEURODEGENERATIVE DISEASES

BAEPs can be helpful in CP children if a child is not eligible for Multiple sclerosis PTA testing. PTA usually shows either high-frequency hearing Hearing loss is a rare MS symptom. About 0.5-6% of patients loss or loss in all frequencies. If subjective testing cannot be per- report hearing loss as the first symptom of MS [3, 27]. Deafness - - - - -

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Fig. 8. A 42-year-old patient with acoustic schwannoma. She complained about persistent tinnitus in the right ear, that first appeared one year ago. MRI revealed an enhancing cerebellopontine angle tumor - an acoustic schwannoma (A). PTA showed mild sensorineural hearing loss in the right ear (arrow) (B). Horizontal minimum audible angle test (HMAAT) showed an incorrect result for right-sided azimuths: 45° [13°]; 90° [19°] and frontal azimuth 0°[13.5°] (C). BAEPs (click 2-4 kHz) showed prolongation of interval I-III on the right side, which proves injury of the proximal part of the VIII cranial nerve and the cochlear nuclei region (D, E).

due to MS is extremely rare, and most of acute hearing loss is BAEPs results are abnormal in most cases of confirmed transient. Tinnitus, hyperacusis and phonofobia are also rare in MS, and it is the prolongation of latencies or interlaten- MS patients. Nevertheless, 80% of MS patients present abnor- cies that are most common. Lack of certain waves or their mal neurootological results – disorders are present both in the deformation and amplitude reduction are less common. visual and the vestibular control system [3, 28]. As much as 33-82% of patients have abnormal BAEPs, with 20% of the patients being without symptoms from It is regarded that sudden hearing loss may be due to a demy- the brainstem [29]. These abnormalities usually concern elinating process of the VIII nerve, similarly to optic nerve wave V that is generated in the lateral lemniscus, some- demyelination that is very common in MS. MRI images show times also wave II (proximal part of the VIII nerve) and small hiperintensive lesions in the vestibulocochlear nerve wave III (the cochlear nuclei) [30] (Fig. 5). Studies prove and in the brainstem. Hearing loss may be sudden or develop a high correlation of BAEPs results with clinical assess- gradually. It is usually unilateral with a fluctuating course. MS ment and MRI images. Some scientists suggest that ab- patients present various types of audiograms in PTA. normal BAEPs result from desynchronization of bioelec------

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Fig. 9. A 61-year-old patient with malignant brain tumor (glioblastoma) in the left superior temporal gyrus. The tumor was diagnosed after the first epileptic seizure. Head T1-weighed MRI shows a contrast-enhancing tumor mass (white arrow) in the axial plane (A). Directionally encoded colors of diffusion tensor tractography (DTT) imaging (A, B, C). To visualize the auditory pathway the start point was set in the Heschl’s gyrus (red arrow) (B). A relatively small auditory pathway is crossed by a large bundle of the arcuate fasciculus (yellow arrow), therefore the role of DTT in tracking Heschl’s gyrus connections is substantially limited (C). Speech audiometry shows central-type curve of speech discrimination on the right side (D). -right ear, X-left ear.

tric potential on the level of type I auditory neuron in the Epilepsy spiral ganglion [31]. Simple tones but also words, sentences or even melodies can be produced in patients with epilepsy due to irritation Sound localization impairment seems to be more common of the temporal lobe cortex, especially its superior and lat- in MS patients than the hearing loss. It was present in near- eral parts. Complex musical hallucinations were described ly 80% of patients and concerned both frontal and lateral also in cases of epileptic lesions localized in the frontal cor- hemispaces, and vertical plane [15, 32]. The neuroanatom- tex. However, hearing loss is a rare symptom present in id- ical structures involved in sound localization are the nuclei iopathic epilepsy and was described in single cases [33, 34] of the trapezoid corpus, nuclei of the lateral lemniscus, the (Fig. 6). PTA results in patients with epilepsy are usually superior nucleus of the oliva and the nucleus of the inferior normal and only electrophysiological and psychological colliculus of the tectal lamina [14]. Demyelinating lesions can studies prove certain hearing abnormalities. Soliman et al. impair sound localization substantially because they restrict [34] in a study on 49 epilepsy patients with normal hearing the broad stream of information going to the upper levels of in PTA, reported higher hearing thresholds in BAEPs (re- the central nervous system (CNS). Levine et al. [28] suggest- sponses from the VIII nerve and the brainstem) in 30% of ed that the process of disruption of auditory pathways in MS the patients and in the Middle Latency Responses (MLR) patients that causes sound localization impairment, must af- (auditory responses from the cortex, the medial geniculate fect the medial superior olive, which sends projections to such nucleus and the inferior colliculi of the tectum) in 40% of structures as the lateral lemniscus, and acts as a pontine time the patients. Incecik et al. [34] studied 21 patients with ep- comparator of bilateral microphonic potentials. In their study, ilepsy that were treated with valproic acid and PTA testing sound localization disturbances always coexisted with an ab- (125-16 kHz) did not show differences compared to healthy normal wave V in BAEPs (the level of the lateral lemniscus). controls. Similarly, in 2007 Li et al. [35], did not find PTA - - - - -

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Fig. 10. Neurological diseases can affect different levels of the auditory pathway. TC-tympanic cavity, CO-cochlea, CN VIII-cranial nerve VIII, VCN-ventral cochlear nucleus, DCN-dorsal cochlear nucleus, SOC-superior olivary complex, TB-trapezoid body, IC-inferior colliculus, MGB-medial geniculate body, AC-auditory cortex

differences between 9 patients with temporal lobe epilepsy Sound localization ability was also studied in patients with and healthy subjects, but epilepsy patients presented pro- temporal lobe epilepsy. Their sound lateralization perfor- longation of wave V latency in BAEPs. Han et al. [36] studied mance was significantly lower than in normal subjects in higher auditory functions such as the ability to differentiate the Interaural Intensity Difference (IID) test [37]. the sound frequency and duration in patients with temporal lobe epilepsy, and found serious distortion of these func- Reasons for epilepsy patients to develop the abovementioned tions in the Frequency Pattern Test (FPT) in 78.6% and in abnormalities remain unknown. However, hearing loss in cer- the Duration Pattern Test (DPT) in 57.1% of these patients. tain patients with temporal lobe epilepsy was correlated with - - - - -

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genetic syndromes. Bockenhauer et al. [38] found mutation in tory tube (the tensor and levator veli palatini muscles) and the KCNJ10 gene on the 1q23 chromosome (that codes potas- can indirectly cause conductive hearing loss since reduc- sium channel in the brain, inner ear and the kidney), in 5 chil- tion of pressure in the tympanic cavity leads to accumula- dren with epilepsy, ataxia and moderate sensorineural hearing tion of exudate (Fig.7). Interestingly, there are also some re- loss (EAST syndrome). Ramelli et al. [39] and Tuppen et al. ports on negative influence of myasthenia on the inner ear [40] described single cases of mitochondrial DNA mutations function, correlated with reduced contractility of hair cells that correlated with epilepsy, sensorineural hearing loss and [44]. This effect can be partly reversed by acetylocholinest- psychomotor retardation. erase inhibitors.

Another important issue is the influence of cochlear implantation on epilepsy. Electrical stimulation of the VIII nerve in NEOPLASMS children with hearing loss who underwent cochlear implant surgery was proved to be safe and did not increase the risk Cerebellopontine angle tumors (CPAT) of epilepsy. Cerebellopontine angle tumors, and especially acoustic neu- roma that constitute up to 85% of the tumors, present with robust audiological and neurological symptomatology. The NEUROMUSCULAR DISEASES tumors have a slow and long-term growth rate. Early stages of the tumor usually present with tinnitus which precedes hearing Myasthenia gravis loss and is caused by irritation of the cochlear part of the VIII Myasthenia can influence the auditory system indirectly by nerve. If the hearing loss appears it is sensorineural in charac- reducing the force of two middle ear muscles – the tensor ter and caused by compression of the VIII nerve [45]. BAEPs tympani and the stapedius muscle. The disease causes reduc- studies show elongation of intervals: I-III (the vestibulococh- tion of striated muscle tone and thus may cause the increase lear nerve level), III-V (the brainstem level) and I-V (both lev- of the threshold of the reflexes from these two muscles [41]. els) (Fig. 8). Furthermore, a tumor growing inside the internal Normal auditory reflex threshold is 70-90 dB HL above the auditory canal may press the labyrinthine artery and cause is- hearing threshold for specific audiometric frequency. The chemia of the cochlea which in turn may cause typical coch- afferent information of the reflex is carried by the VIII nerve lear hearing loss (Fig. 2). If the tumor diameter exceeds 2 cm, and the efferent information by the VII nerve for the stape- symptoms of the V, VI and VII nerve compression may appear dius muscle and by the V nerve for the tensor tympani. The such as facial pain, facial palsy, decreased corneal reflex, lack standard test is performed for 0.5-1-2-4 kHz. In myasthenia, of taste on the anterior 2/3 of the tongue (chorda tympani) or reflex thresholds for these frequencies can be increased sub- lack of the acoustic reflex [46]. stantially (up to 130 dB) or the reflex can be absent [41, 42]. Myasthenia can increase the risk of hearing loss in cases of Tumors of the VIII nerve may also cause higher auditory chronic noise exposure due to “fatigue” of the reflex. It is the process dysfunction. Patients with CPAT present problems Acoustic Reflex Decay (ARD) that is used to find the exhaus- with understanding speech in speech audiometry, which is tion of the reflex by means of prolonged acoustic stimulation. in discordance with usually mild hearing loss. This phenom- Normal reduction of amplitude of contraction in the stapedius enon is called schisoacusis. Additionally, even if the hearing muscle does not exceed 10-30%. If the amplitude is reduced is still normal CPAT patients can present disturbed sound more than 50% during 10 sec of 1 kHz frequency stimulation localization ability [14]. It seems that the sound localization the result is regarded as abnormal. Tensor tympani reflex is problems depend on the stage of the disease. At the begin- not used routinely because of its high threshold (105-110 dB), ning of the tumor growth sound localization disability is ip- relatively long latency and physiological wearing off after 1-2 silateral, in more advanced stages it may become bilateral, sec. The tests are not always abnormal in patients with myas- especially in 90º and 270º azimuths, or the function can be thenia [41, 43]. Sometimes patients need to be stimulated in lost completely [47]. fast and repetitive manner in order to register the reduction of amplitude in ARD. However, this test often allows early Brain Tumors diagnosis of myasthenia and differentiation between the cho- Auditory dysfunctions in patients with brain tumors are var- linergic crisis and myasthenic crisis [42]. iable and depend on the side, volume and level of the lesion [5]. Unilateral tumors in the temporal lobe cortex may remain Due to its influence on striated muscles myasthenia can also silent or cause subtle hearing deficits such as understanding influence the work of muscles that open and close the audi- speech impairment. However, it is the bilateral injury of the - - - - -

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auditory cortex that is destructive enough to cause substantial accompanied by tinnitus. Additionally, strokes of the tem- hearing loss, detectable by PTA. Bilateral tumors of the temporal and parietal lobe were often associated with acoustic poral lobes may also cause pure tone hearing loss [48] or pure agnosia, cortical deafness and sound localization impair- tone and verbal hearing loss [49]. In certain cases of bilateral ment. The cochleovestibular nerve compression syndrome temporal lobe tumors the cortical hearing loss presented itself can cause unilateral extracochlear hearing loss and pulsatile as speech or sound agnosia, with only small hearing deficits in tinnitus. The sensorineural hearing loss can also be found in audiometric testing [6]. 4 to 7% of the cerebral palsy patients. However, serious hearing deficit is less common than speech development prob- Brain tumors of the temporal lobe can also substantially influ- lems. Approximately 1/5 of the cerebral palsy patients have ence the sound localization ability. In a study by Sanchez-Lon- abnormal BAEPs that suggest central auditory processing go et all [5] 19 out of 21 patients with tumor located in the disorders. Hearing loss is found in up to 6% of MS patients, temporal lobe, presented sound localization problems, usual- with abnormal BAEPs and sound localization impairment be- ly contralateral ones. Furthermore, brain tumors can change ing present in up to 82% of those patients. Epilepsy is rarely BAEPs results. Elongation of wave V latency was found to be combined with hearing loss, which is more typical for com- ipsilateral and/or contralateral in cases of brainstem compres- plex genetic syndromes. However, 30-40% of patients with sion by oedema or expansion of a tumor [30]. epilepsy have abnormal auditory electrophysiological results and 50-70% present central auditory processing disorders. Brain tractography is very sensitive in detecting various pathol- Miasthenia can cause conductive hearing loss and increas- ogies of the brain pathways, with the auditory pathway includ- es the risk of acoustic injury due to ear muscle dysfunction. ed. In Figure 9 (Fig. 9) we present Diffusion Tensor Tractogra- Cerebellopontine angle tumors usually cause unilateral ex- phy (DTT) in a patient with temporal lobe tumor and discrete tracochlear sensorineural hearing loss, but they can also be problems with understanding speech. associated with speech understanding and sound localization impairment. Cerebral tumors usually remain silent or cause subtle auditory deficits. Auditory agnosia was proved in rare CONCLUSIONS cases of bilateral temporal tumors.

The described neurological diseases have diverse auditory The character and severity of auditory symptoms depend on symptomatology of central and peripheral origin. Auditory the level of the auditory pathway injury (Fig. 10). Hearing loss symptoms in neurological diseases seem to be rare (stroke, and tinnitus are common complaints or can be diagnosed MS) or very rare (epilepsy, myasthenia gravis) and are often during an examination. However, there are multiple discrete dominated by neurological signs that result from an injury of symptoms of auditory dysfunction such as problems with un- motor and sensory centers. derstanding speech, sound localization impairment or auditory hallucinations. Knowledge of these symptoms and their Sudden deafness can be a prodromal sign of anterior inferior origin can be helpful in proper diagnosis and comprehensive cerebellar artery ischemia in 1-21% of patients and is often patient management.

REFERENCES 1. Lee H, Baloh RW. Sudden deafness in vertebrobasilar ischemia: clinical features, vascular topographical patterns and long-term outcome. J Neurol Sci. 2005;228:99-104. 2. Przewoźny T, Gąsecki D, Narożny W, Nyka W. Risk factors of sensorineural hearing loss in patients with ischemic stroke. Otol Neurotol. 2008;29:745-50. doi: 10.1097/MAO.0b013e318181336c. 3. Daugherty WT, Lederman RJ, Nodar RH, Conomy JP. Hearing loss in multiple sclerosis. Arch. Neurol. 1983;40:33-5. 4. Józefowicz-Korczyńska M, Gryczyński M, Starska K, Pietruszewska W, Durko M, Łukomski M. Clinical ocular-motor disturbances in multiple sclerosis. [Ar- ticle in Polish]. Otolaryngol Pol. 2009;63:126-30. doi: 10.1016/0030-6657(09)70092-7. 5. Sanchez-Longo LP, Forster FM. Clinical significance of impairment of sound localization.Neurology 1958;8:119-25. 6. Goldstein MN. Auditory agnosia for speech (“pure word deafness”). A historical review with current implications. Brain Lang. 1994;1:195-204. 7. Baloh R. Vertebrobasilar insufficiency and stroke.Otolaryngol. Head Neck Surg. 1995;112:114-17. 8. Adams RD. Occlusion of the anterior inferior cerebellar artery. Arch NeurPsych. 1943;49:765-70. doi:10.1001/archneurpsyc.1943.02290170135010. 9. Hariri MA, Lakshmi MV, Larner S, Connoly MJ. Auditory problems in elderly patients with stroke. Age Ageing 1994;23:312-6. 10. Yamasaba T, Kikuchi S, Higo R. Deafness associated with vertebrobasilar insufficiency.J Neurol Sci. 2001;187:69-75. - - - - -

OTOLARYNGOLOGIA POLSKA, TOM 69, NR 5 (2015), p. 29-43 41 artykuł oryginalny / original article

11. Lee H, Cho Y W. Auditory disturbances as a prodrome of anterior inferior cerebellar artery infarction. J Nerol Neurosurg Psychiatry 2003;74:1644-8. 12. Huang MH, Huang CC, Ryu SJ, Chu NS. Sudden bilateral hearing impairment in vertebrobasilar occlusive disease. Stroke 1993;24:132-7. 13. Wernicke C, Friedländer C. Ein Fall von Taubheit in Folge von doppelseitiger Laesion des Schläfelappens. Fortschr Med. 1883;1:177-85. 14. Przewoźny T. Anatomy and physiology of directional hearing. Folia Morphol. 2015;74:9-15. 10.5603/FM.2015.0002 15. Häusler R, Colburn S, Marr E. Sound localization in subjects with impaired hearing. Spatial-discrimination and interaural-discrimination tests. Acta Oto- laryngologica Suppl 1983;400:1-62. 16. Sonoda S, Mori M, Goishi A. Pattern of localisation error in patients with stroke to sound processed by a binaural sound space processor. J Neurol Neuro- surg Psychiatry 2001;70:43-9. 17. Przewoźny T, Gójska-Grymajło A, Gąsecki D. Auditory spatial deficits in the early stage of ischemic cerebral stroke. J Stroke Cerebrovasc Dis. 2015;24:1905- 16. doi: 10.1016/j.jstrokecerebrovasdis.2015.05.001 18. Jannetta PJ. Neurovascular cross-compression in patients with hyperactive dysfunction symptoms of the eighth cranial nerve. Surg Forum 1975;26:467-9. 19. De Ridder D, Ryu H, Møller AR, Nowé V, Van de Heyning P, Verlooy J. Functional anatomy of the human cochlear nerve and its role in microvascular decom- pressions for tinnitus. Neurosurgery 2004;54:381-388; discussion 388-90. 20. Gierek T, Markowski J, Majzel K, Wardas P. Disabling positional vertigo (DPV): syndrome of vestibulo-cochlear organ impairment during vascular compression of the vestibulo-cochlear nerve (VCS). [Article in Polish]. Otolaryngol Pol. 2005;59:403-7. 21. Artz GJ, Hux FJ, Larouere MJ, Bojrab DI, Babu S, Pieper DR. Endoscopic vascular decompression. Otol Neurotol. 2008;29:995-1000. doi: 10.1097MAO. b013e318184601a. 22. Reid SM, Modak MB, Berkowitz RG, Reddihough DS. A population-based study and systematic review of hearing loss in children with cerebral palsy. Dev Med Child Neurol. 2011;53:1038-45. doi: 10.1111/j.1469-8749.2011.04069.x. 23. Shevell MI, Dagenais L, Hall N, REPACQ Consortium. Comorbidities in cerebral palsy and their relationship to neurologic subtype and GMFCS level. Neu- rology 2009;16:2090-6. doi: 10.1212/WNL.0b013e3181aa537b. 24. Morales Angulo C, Azuara Blanco N, Gallo Terán J, González Aledo A, Rama Quintela J. Sensorineural hearing loss in cerebral palsy patients. Acta Otorri- nolaringol Esp. 2006;57:300-2. 25. Zafeiriou DI, Andreou A, Karasavidou K. Utility of brainstem auditory evoked potentials in children with spastic cerebral palsy. Acta Paediatr. 2000; 89:194-7. 26. Hilgenberg AM, Cardoso CC, Caldas FF, Tschiedel Rde S, Deperon TM, Bahmad F Jr. Hearing rehabilitation in cerebral palsy: development of language and hearing after cochlear implantation. Braz J Otorhinolaryngol. 20015;81:240-7. doi: 10.1016/j.bjorl.2014.10.002. 27. Hellmann MA, Steiner I, Mosberg-Galili R. Sudden sensorineural hearing loss in multiple sclerosis: clinical course and possible pathogenesis. Acta Neurol Scand. 2001;124:245-9. doi: 10.1111/j.600-0404.2010.01463.x. 28. Levine RA, Gardner JC, Stufflebeam SM, Fullerton BC, Carlisle EW, Furst M et al. Binaural auditory processing in multiple sclerosis subjects. Hear Res 1993;68:59-72. 29. Baumhefner RW, Tourtellotte WW, Syndulko K, Waluch V, Ellison GW, Meyers LW et al. Quantitative MS plaque assessment with MRI. Its correlation with clinical parameters, evoked potentials and intra-blood-brain barrier IgG synthesis. Arch Neurol. 1990;47:19-26. 30. Kochanek K. Usefullnes of brainstem auditory evoked potentials in diagnostics of retrocochlear hearing loss. [Article in Polish]. Otorynolaryngologia 2001;1:167-171. 31. Marangos N. Hearing loss in multiple sclerosis: localisation of the auditory pathway lesion according to electrocochleographic findings.J Laryngol Otol. 1996;110:252-7. 32. Furst M, Levine RA, Korczyn AD, Fullerton BC, Tadmor R, Algom D. Brainstem lesions and click lateralization in patients with multiple sclerosis. Hear Res. 1995;82:109-24. 33. Soliman S, Mostafa M, Kamal N, Raafat M, Hazzaa N. Auditory evoked potentials in epileptic patients. Ear Hear 1993;14:235-41. 34. Incecik F, Akoglu E, Sangün O, Duman T. Effects of valproic acid on hearing in epileptic patients.Int J Pediatr Otorhinolaryngol. 2007;71:611-4. 35. Li L, Wang NY, Zhang H, Ge XH, Li JL, Xie Q et al. Primary investigation of central auditory function in patients with temporal lobe epilepsy. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2007;42:664-8. 36. Han MW, Ahn JH, Kang JK, Lee EM, Lee JH, Bae JH et al. Central auditory processing impairment in patients with temporal lobe epilepsy. Epilepsy Behav. 2001;20:370-4. 37. Irsel Tezer F, Ilhan B, Erbil N, Saygi S, Akalan N, Ungan P. Lateralisation of sound in temporal-lobe epilepsy: comparison between pre- and postoperative performances and ERPs. Clin Neurophysiol. 2012;123:2362-9. doi: 10.1016/j.clinph.2012.06.015. 38. Bockenhauer D, Feather S, Stanescu HC, Bandulik S, Zdebik AA, Reichold M et al. Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations. N Engl J Med. 2009;360:1960-70. 39. Ramelli GP, Gallati S, Weis J, Krähenbühl S, Burgunder JM. Point mutation tRNA(Ser(UCN)) in a child with hearing loss and myoclonus epilepsy. J Child Neurol. 2006;21:253-5. 40. Tuppen HA, Naess K, Kennaway NG, Al-Dosary M, Lesko N, Yarham JW et al. Mutations in the mitochondrial tRNA Ser(AGY) gene are associated with deafness, retinal degeneration, myopathy and epilepsy. Eur J Hum Genet. 2012; 20:897-904. doi: 10.1038/ejhg.2012.44. 41. Szmeja Z, Obrębowski A, Pruszewicz A, Mularek J. The value of stapedius reflex examinations in patients with myasthenia gravis. [Article in Polish]. HNO 1978;26:198-200. - - - - -

42 WWW.OTOLARYNGOLOGYPL.COM artykuł oryginalny / original article

42. Morioka WT, Neff PA, Boisseranc TE, Hartman PW, Cantrell RW. Audiotympanometric findings in myasthenia gravis.Arch Otolaryngol. 1976;102:211-3. 43. Johns ME, Ruth RA, Jahrsdoerfer RA, Cantrell RW. Stapedius muscle function tests in the diagnosis of neuromuscular disorders. Otolaryngol Head Neck Surg,. 1979;87:261-5. 44. Di Girolamo S, d’Ecclesia A, Quaranta N, Garozzo A, Evoli A, Paludetti G. Effects of contralateral white noise stimulation on distortion product otoacoustic emissions in myasthenic patients. Hear Res. 2001;162:80-4. 45. Benoudiba F, Toulgoat F, Sarrazin JL. The vestibulocochlear nerve (VIII). Diagn Interv Imaging 2013;94:1043-50. doi: 10.1016/j.diii.2013.08.015. 46. Boessert P, Grüttner C, van Ewijk R, Haxel B. Changes in taste ability in patients with vestibular schwannoma. Laryngorhinootologie 2014;93:450-4. doi: 10.1055/s-0034-1375658. 47. Szmeja Z, Pruszewicz A. Clinical value of examination of sound localization. [Article in Polish]. Otolaryngol. Pol. 1977; 31:229-38. 48. Goldstein MN, Brown M, Hollander J. Auditory agnosia and cortical deafness. Analysis of a case with three year follow-up. Brain Lang. 1975;2:324-332. 49. Wohlfart G, Lindgren A, Jernelius B. Clinical Picture and norbid anatomy in a case of “pure word deafness”. J Nerv Ment Dis. 1952;116:818-27.

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Corresponding author: Tomasz Przewoźny, PhD, Department of Otolaryngology, Medical University of Gdańsk, Smoluchowskiego 17, 80-214 Gdańsk, Poland, phone: +48 58 349 31 10, fax: +48 58 349 31 20, email: [email protected]

Competing interests: The authors declare that they have no competing interests.

Cite this article as: Przewoźny T., Gójska-Grymajło A., Szmuda T., Markiet K.: Auditory deficits in neurological disorders. Otolaryngol Pol 2015; 69 (5): 29-43

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