Audio-Vestibular and Neurological Correlates in Patients with Auditory and Peripheral Neuropathy

Transcription

1 Audio-Vestibular and Neurological Correlates in Patients with Auditory and Peripheral Neuropathy Azza Abdel-Nasser 1, Naglaa M. Elkhayat 1, Salma H. Khalil 1, Lobna H. Mahmoud 2 Departments of Neuropsychiatry 1, Audiology 2, Ain Shams University ABSTRACT Background: Auditory neuropathy (AN) is a specific hearing disorder with abnormal auditory neural responses in the presence of normal cochlear function. Affection of vestibular portion of cochleo-vestibular (VIII) nerve as well as other peripheral nerves was only reported in few studies. Aim: This work aimed at investigating such issue in an attempt to understand the nature and the site of the underlying pathology. Methods: The study was conducted on fifty (AN) patients and twenty Peripheral Neuropathy (PN) patients of different etiologies diagnosed in Audiology and Neurology department, respectively, Ain Shams University. All subjects were submitted to: full audiological test battery; history taking, clinical otological examination, basic audiological evaluation, Auditory Brainstem Response (ABR), Transient Evoked Otoacoustic Emissions (TEOAEs) with and without using contralateral acoustic stimulation, Vestibular test battery; [ENG test battery, rotational chair testing (SHA), and Computerized Dynamic Posturography (CDP)], and neurological evaluation; [clinical examination, Nerve Conduction Studies (NCS) and Somatosensory evoked Potentials (SSEPs)]. Results: Audiological test battery confirmed the audiological criteria for auditory neuropathy reported in the literature. Pure-tone thresholds and discrimination scores of (AN) patients were statistically significant than those of (PN) patients. Vestibular test battery results showed that 44% of (AN) patient had bilateral extensive peripheral vestibular lesion even though only 9 (18%) complain of dizziness complaint. Neurological evaluation revealed that (AN) patients had subtle peripheral neuropathy only detected by NCS, and SSEPs abnormalities in the central somatosensory pathway as well. Conclusion: Despite that peripheral nerves affection in (AN) patients was significantly milder than (PN) group, it could indicate that auditory neuropathy is a part of generalized process rather than isolated auditory nerve affection. The difference between (AN) and (PN) groups would be related to the different underlying genetic factor, especially that consanguinity of the parents or other members in the family were affected in 40% of (AN) patients. (Egypt J. Neurol. Psychiat. Neurosurg., 2006, 43(1): ) INTRODUCTION Auditory neuropathy is a recently described clinical entity characterized by sensorineural hearing loss in which the auditory brainstem response (ABR) shows absent waves or is severely abnormal but the otoacoustic emissions (OAEs) are present. Most of the auditory neuropathy patients complain of difficulty in understanding speech particularly in the presence of background noise 1. These findings have been identified in earlier studies and were previously described as paradoxical absence of auditory brainstem response in patients with slightly impaired hearing 2,3. Soliman 4 reported also similar findings in a group of patients with predominantly low frequency hearing loss and poor speech discrimination out of proportion to the hearing loss. Such audiological profile was termed low frequency sensorineural hearing loss syndrome. While this characteristic pattern of auditory neuropathy points to VIII cranial nerve affection, yet the specific sites and mechanisms of auditory neuropathy have not been exactly determined 5. Moreover, the specific risk factors for auditory neuropathy are not clearly understood. Accordingly, this work was designed to address the issues related to vestibular and neurological affection in auditory neuropathy 253

2 Egypt J. Neurol. Psychiat. Neurosurg. Vol. 43 (1) Jan 2006 patients to outline a comprehensive diagnostic picture, in an attempt to understand the nature, the specific sites and mechanisms of auditory neuropathy, and so the underlying pathology. SUBJECTS AND METHODS I. Subjects: The studied patients consisted of 2 groups; fifty auditory neuropathy patients group (21 males and 29 females), selected and diagnosed in Audiology Unit-Ain Shams University with the following criteria: (Starr et al., 1996): 1. Sensorineural hearing loss of any degree 2. Poor speech discrimination out of proportion to the degree and configuration of hearing loss. 3. Normal middle ear function with abnormal (absent or elevated) acoustic reflexes. 4. Abnormal or absent ABR waves. 5. Preserved Otoacoustic emissions 6. Normal findings in C.T. scan or MRI. The second group included twenty peripheral neuropathy patients (9 males and 11 females) of different etiologies were selected and diagnosed in the Neurology department; Ain shams University. Clinical neurological examination; history and examination were performed searching for: distal weakness and\or atrophy with diminished or lost distal reflexes, gloves and stacking distribution of sensory affection. II. Method: All subjects were submitted to full audiological, vestibular test battery and neurological evaluation. 1. History taking of details of the hearing loss, family history of consanguinity and other affected members in the family. Detailed clinical dizziness history, also dizziness questionnaire was used for detection of subtle symptoms. History for medical conditions as diabetes mellitus, hypertension etc..., past history of noise exposure, ototoxic drug intake or head trauma. 2. Clinical otological examination. 3. Basic Audiological Evaluation: using: a) Puretone Audiometry: This included Air conduction and Bone-conduction. b) Speech Audiometry. c) Immittancemetry: including tympanometry and acoustic reflex thresholds measurement. 4. Auditory brainstem response (ABR): Auditory Brainstem Response (ABR) was performed for all patients using Amplaid MK12 evoked response audiometer. The ABR parameters were set as follows: 10 ms sweep time, Hz bandpass filter, 20 p/s repetition rate, Fpz/ipsilateral mastoid montage and 1000 averaged sweeps. The stimuli were 0.25 ms rarefaction clicks delivered at an intensity of 90 and 70 dbnhl. High repetition rate was done using 70 p/s recording, at an intensity of 90 dbnhl. Bilateral assessment of waves I,III, and V peak latencies, also inter peak wave latency of (I-III) and (III-V). 5. Transient Evoked Otoacoustic Emissions (TEOAEs): TEOAEs were elicited using click stimuli at stimulus intensity 80 db SPL with and without contralateral acoustic stimulation (CAS) using broad band noise (BBN) at 50 and 70 db SPL. TEOAEs were automatically determined. A measure of degree of suppression was taken as the difference between the amplitude in decibels of the response recorded without and with CAS. 6. Vestibular evaluation: a. Electronystagmography (ENG): The system used was Computerized Electronystagmography Micromedical Tec. version 8. ENG test battery searching for spontaneous, gaze evoked, positional and positioning nystagmus was performed. Oculomotor test battery included Random Saccade test, Eye tracking and optokinetic tests. Bithermal Caloric test was performed using open loop water irrigation lasting 30 seconds at temperature of 30 C and 44 C. Unilateral weakness and Directional preponderance were calculated automatically by software 254

3 algorithm. The results were also compared to results of age matched normal individuals. b) Rotational chair testing: The system used was Micro Medical Tec. Version Sinusoidal harmonic acceleration (SHA) test was performed at frequencies 0.01, 0.02, 0.04, 0.08, 0.16, 0.32 and 0.64 Hz, with maximum chair rotation velocity of 60 degrees/second at each frequency. The program software calculated VOR gain, phase & symmetry and presented them graphically with comparisons to normal individuals. c) Computerized Dynamic Posturography (CDP): Subjects and controls were tested by computerized dynamic posturography platform (Equitest system, version 5.05). The protocol consisted of Sensory organization test (SOT), which assess the three sensory components of balance under variety of altered visual and support surface conditions, and the Motor Coordination Test (MCT) which evaluates the autonomic motor reactions provoked by support surface perturbations. Sensory conditions (SOT) were tested by exposing the patient to a progression of six increasingly challenging conditions in which the support surface, the visual surround, or both are moved in functional relation to the patient's sway (i.e. sway-referencing). The first three conditions on a fixed platform using eye opened (C1), eye closed (C2) and stance with a sway referenced visual enclosure (C3). The remaining three conditions were performed on a sway referenced platform using eye opened (C4), eye closed (C5) and a sway referenced visual enclosure (C6). The duration of each trial was 20 seconds. The motor control (MCT) and adaptation (ADT) tests were received by the computer and analyzed to quantify the active force responses of each foot and the sway motions of the body's center of gravity. Test results are automatically documented and presented graphically with comparisons to agematched normal individuals. 7. Neurological evaluation was performed in the neurology department of Ain Shams University Hospital. All patients were submitted to the following: a. Clinical examination: This included complete neurological history and examination to detect any clinical sensory or motor abnormalities. b. Nerve conduction studies (NCSs): NCSs of median nerve in both upper limbs and peroneal nerves in lower limbs were conducted using EVOMATIC 8000 Apparatus made by Dantec of Denmark. Bipolar surface stimulating electrodes were used for stimulating both sensory and motor nerves of the skin, while two types of recording electrodes were used; ring sensory electrodes with an active recording electrode placed at the proximal phalanx and a reference electrode placed at least 2 cms distal to the active electrode, and a surface electrodes were used with an active recording electrode placed over the motor point of the muscle and the reference one placed distally over the tendon (at least 2 cms distal to the active electrode). c. Somatosensory evoked potentials (SSEPs): SSEPs of median nerve in both upper limbs was performed using EVOMATIC 8000 Dantec Apparatus. Stimulating the median nerve alternatively, recording from bilateral cortical areas (C4 and C3) for N20 latency, cervical 2 area for N13 latency, bilateral erb's area for N9 latency, the machine automatically detect the interpeak wave latency; (N13-N20), and (N13- erb's), also inter side difference was assessed. RESULTS This study included fifty (AN) patients, and twenty (PN) patients their age and gender distribution showed no statistically significant 255

4 Egypt J. Neurol. Psychiat. Neurosurg. Vol. 43 (1) Jan 2006 difference between both groups (Table 1). Comparing age and Gender distribution of auditory neuropathy (AN), and peripheral neuropathy (PN) patients, no statistically significant difference was found. As all patients included in this study had auditory neuropathy (100%) with mean duration of 7.5 years, other audio-vestibular symptoms were tinnitus, headache and dizziness in 30 patients (60%), 13 (26%) and 9 (18%) respectively. Ten patients (20%) with (AN) had positive history of parental consanguinity and 9 (18%) patients had other affected family members. While in the 20 (PN) patients, three (15%), three (15%), and ten patients (50%) had hearing loss, tinnitus and dizziness respectively. Among (PN) patients 6 cases (30%) had Hereditary Motor and sensory ataxia, 5 (25%) Freidriech's ataxia, 5 (25%) Diabetes Mellitus, 2 (10%) Metabolic (Mitochondrial PN), 1 (5%) Neurotoxicity, and 1 (5%) Unidentified etiology. 1. Audiological findings revealed that; in Pure-tone audiometry results all (AN) patients had bilateral symmetrical predominantly low frequency sensorineural hearing loss. Pure-tone thresholds ranged from mild to severe degree. Speech discrimination scores (SD%) were disproportionate to the degree and configuration of pure tone thresholds. Mean scores of speech discrimination was very poor (27.3 %). The majority of (AN) patients 47 (94%) had normal tympano-ossicular mobility with absent acoustic reflex bilaterally, only 3 (6%) had elevated acoustic reflexes. ABR results showed that 46 (86%) of (AN) patients showed bilateral absent auditory brain responses. However, 7 (14%) showed absent waves (III &V). All (AN) patients had preserved Transient Evoked Otoacoustic emissions (TEOAEs) with absent contralateral suppression on using 50 & 70 db masking levels. In contrast, the majority of peripheral neuropathy (PN) patients, (80%) showed normal mean of pure-tone thresholds and excellent speech discrimination scores that were proportionate to their pure-tone thresholds. These results were statistically significant when compared to (AN) patients. Their hearing ranged from normal to mild sensorineural hearing loss. Sloping high frequency sensorineural hearing loss was present in two patients with peripheral neuropathy due to Diabetes Mellitus and two patients with Hereditary Sensory and Motor Neuropathy (HMSN). They had normal immittancemetry results. However, similar to findings of (AN) patients, 3 (PN) patients with Freidriech's ataxia had auditory complaint, mild to moderate low frequency sensorineural hearing loss configuration with very poor speech discrimination and absent acoustic reflexes bilaterally. Among (PN) patients 16 (80%) showed normal auditory brainstem response, while one patient with HMSN had abnormally delayed interpeak waves (III-V) latency; their TEOAEs matched the hearing thresholds. They showed contralateral suppression on using both 50 & 70 db masking levels that was statistically significant compared to (AN) patients. On the other hand, the 3 (PN) patients with Freidriech's ataxia, 2 of them had absent ABR waves and one had absent waves (IIIa & V) bilaterally. One of them had absent TEOAES while the other two had preserved TEOAES with absent contralateral suppression. In 4 (20%) of (PN) patients, the audiological findings reflect hearing loss due to sensory element rather than neural affection comparable to (AN) group. 2. Vestibular findings: In (AN) patients the complaint was mainly a sense of unsteadiness and/ or deviation in walking worsened by darkness. On the other hand, (PN) patients had history of unsteadiness which was clinically related to their sensory and motor ataxia that accompanied the peripheral nerves affection and not related to any vestibular affection. Nevertheless, a wide battery of vestibular assessment was done to explore the possible vestibular system affection in (AN) and (PN) patients, including: * ENG test battery: Both (AN) and (PN) patients showed absence of spontaneous gaze 256

5 evoked positional and positioning nystagmus. Oculomotor test revealed normal Saccade velocity, accuracy and latency. Eye tracking and optokinetic tests were normal. These findings exclude the presence of central oculomotor tracts affection. Bithermal caloric irrigation revealed that 15 (30%) patients of (AN) patients had bilaterally reduced caloric response while 7 (14%) had bilaterally absent caloric response. (AN) patients had significant reduced mean of the slow peak velocity in all irrigations compared to the (PN) group. Most of the affected patients did not report any dizziness during caloric irrigation, only one (AN) patient showed unilateral weakness (difference between two ears was >20% with no direction preponderance). Conversely, 16 (80%) of (PN) patient showed normal ENG test battery, only four patients had abnormal test caloric results. One (PN) patient due to neurotoxicity had bilateral reduced response. Two of three patients with Freidriech's ataxia, had absent caloric response bilaterally and one had reduced caloric response bilaterally. * Rotational chair testing; sinusoidal harmonic acceleration test (SHA) revealed that, 22 (44%) of (AN) patients with bilateral absent or reduced caloric responses had further reduction in vestibulo-ocular reflex gain (VOR), the reduction being more at low frequencies ( ) Hz and with symmetrical response and significantly correlated to the age of patients, duration of hearing loss and or the relative duration % (duration of hearing loss relative to the age of patient). Phase abnormality accompanied the presence of low VOR gain at frequencies ( ) Hz. Phase lag was more frequent than phase lead. In contrast to ENG results, (PN) patients showed normal VOR gain, phase and symmetry except in four patients, three of them had Freidriech's ataxia and one with neurotoxicity. They had reduced VOR gain and phase abnormality, and all of them had symmetrical response, similar to (AN) patients. In the light of patients' complaint, ENG test battery and SHA test, 44% (AN) patients had bilateral extensive peripheral vestibular dysfunction. Similar vestibular findings in 20% of (PN) patients were noticed though they were relatively lower in extent than (AN) patients. * Computerized Dynamic Posturography (CDP) test showed that 23 (46%) of (AN) patients had abnormality in the sensory organization test (SOT) in conditions C4, 5 and 6 except for two patients where one had additional abnormal C2 and the other had abnormal C3. In addition, (PN) patients showed abnormal C5 and 6 although they had normal vestibular findings (ENG and rotary chair). Regarding the motor control test (MCT), all affected (AN) patients had prolonged latencies which was bilateral and bidirectional affecting both medium and/ or large displacement of both backward and forwards translations. Their mean of MCT latencies composite scores were prolonged. This pattern also was encountered in (PN) patients but they had significantly more prolonged mean of MCT composite scores than (AN) group. Consequently, (AN) patients had significantly low SOT composite equilibrium scores. Comparable findings were encountered in 12 (60%) of (PN) patients who could perform the CDP testing. They showed abnormal SOT C4, 5 and 6. Hence, there were no statistically significant difference between (AN) and (PN) in SOT composite equilibrium scores. 3. Neurological findings: Clinical neurological examination revealed that 48 (96%) of (AN) patients had no clinical abnormalities. However, one patient had deep sensory affection as detected by positive Romberg's sign and absent vibration sense in both lower limbs, while the last patient had evident clinical signs of peripheral neuropathy. * Nerve conduction test (NCS) was performed in upper and lower limbs. Latencies (Lat.) and 257

6 Egypt J. Neurol. Psychiat. Neurosurg. Vol. 43 (1) Jan 2006 nerve conduction velocities (CV.) were the parameters measured (Table 2). * Somatosensory Evoked Potentials (SSEPs) test was performed in upper limbs (of the median nerve) in both (AN) and PN patients and revealed that total number of affected patients were in (AN) 31 (62%), and in(pn) patients 15 (65%). There was no statistically significant difference between right and left side in each (AN) and (PN) patients. The following table shows that there was no statistically significant difference between (AN) and (PN) patients except in Erb's latency (Table 3). Correlation between age, duration of hearing loss (D.HL) Relative D.%, speech discrimination scores (DS %), pure tone Average PTA and the nerve conduction results in upper (1) and lower limbs (2) using distal latency and conduction velocity tests. Correlation between Vestibular and Neurophysiologic findings in (AN) patients showed no statistically significant correlation between Total eye speed, SOT, MCT composite and the nerve conduction results in the upper and lower limbs, while correlation of the above mentioned vestibular findings and SSEPs showed a statistically significant (+ve) correlation between (Erbs-N13) latency and the total eye speed values (Tables 6, 7 & 8). Comparing SSEPs and vestibular caloric response findings in AN patients; those with normal caloric response; 28 patients (group1) and those with bilateral abnormal caloric response; 22 patients (group2), show that there was no statically significant difference between the two groups except in the inter-peak latency Erbs-N13 (Table 9) Table 1. Demographic data of patients included in the study. Age Gender Mean SD range Females Males No % No % Total No. (AN) patients (PN) Patients Table 2. Mean, standard deviation (SD), t and P values of sensory and motor conduction velocity (CV), latency (Lat.) of the upper limb (1) and lower limb (2) in (AN) and (PN) patients. (AN) (PN) Mean SD Mean SD t P Motor CV CV ** Lat Lat ** Sensory CV ** CV ** Lat ** Lat * There was a statistically significant difference between (AN) and (PN) patients in the Motor CV and Motor latency in the lower limb, and a statistically significant difference between (AN) and (PN) patients in the Sensory CV and Sensory latency in both the upper and lower limbs. 258

7 Table 3. Mean, standard deviation (SD), t and P values of Somatosensory evoked potentials at different levels of median nerve in the (AN) and (PN) patients. (AN) (PN) Mean SD Mean SD T P Erbs * N Erbs-N N N ISD (N13-20) Fig. (1): Normal SEPS response. Fig. (2): Abnormal SEPs response (Bilateral delayed N20, increased Erbs-N13 259

8 Egypt J. Neurol. Psychiat. Neurosurg. Vol. 43 (1) Jan 2006 on Rt side, bilateral delayed N13-N20). Table 4. Correlation between Audiological and Neurophysiologic findings in (AN) patients. Age D.HL Relative D.% PTA DS% Motor CV CV Lat Lat Sensory CV CV Lat.1.34*.36** Lat.2.29*.51**.3* * Statistically significant correlation ** Very high statistically significant correlation. There was a statistically significant (+ve) correlation between sensory latencies of both upper and lower limbs and the age and the duration of hearing loss. Table 5. Correlation between age, duration of hearing loss (D.HL) Relative D.%, speech discrimination scores (DS %), pure tone Average PTA and the results of Somatosensory evoked potentials (N13 N20 and interside difference). Age D.HL Relative D.% DS% PTA Erbs N13.30*.36*.32* Erbs-N *.30* N20.38**.48**.34** N *.42**.31* ISD (N13-20) *.06 * Statistically significant correlation ** Very high Statistically significant correlation There was a statistically significant (+ve) correlation between (N13, Erbs-N13, N20 & N13-20) latencies, age and the duration of hearing loss. There was a statistically significant (-ve) correlation between ISD of N13-20 and the DS% Table 6. Correlation between Total eye speed, SOT, MCT composite and SSEPs. Tot. eye speed SOT comp. MCT comp. Erbs N Erbs-N * N N ISD (N13-20)

9 Table 7. Correlation between VOR gain and the nerve conduction results in the upper (1) and lower limbs (2). Frequency (Hz) Motor CV CV Lat ** -.27* -.33* -.33* -.25 Lat Sensory CV CV Lat * -.27* Lat * * * -.16 Table 8. Correlation between VOR gain and SSEPs. Frequency (Hz) Erb's N Erbs-N * -.32* -.36* -.35*.06 N N ISD (N13-20) There was a statistically significant (+ve) correlation between (Erbs-N13) latencies and the VOR gain from ( H). Table 9. Correlation between SSEPs and vestibular caloric response findings in both groups of patients. Group 1 Group 1I Mean SD Mean SD T P Erb's N Erbs-N * N N13-20 (RT) ISD (N13-20) DISCUSSION In the present study Auditory Neuropathy patients fulfilled the audiological criteria for auditory neuropathy reported in the literature 1,4. A positive history of consanguinity and affection of other family members of (AN) patients agrees with the possible genetic basis for neuropathy that has been identified in families with isolated auditory neuropathy 6,7. Also a positive sensorineural hearing loss found in Peripheral Neuropathy patients of different etiologies e.g. Diabetes Mellitus, hereditary motor and sensory ataxia as well as toxic neuropathies, was previously reported 8,9. The variability of hearing affection among HMSN type would be related to 261

10 Egypt J. Neurol. Psychiat. Neurosurg. Vol. 43 (1) Jan 2006 their wide variability in genetic inheritance and gene expression itself 10. However, the 3 (PN) patients with Freidriech's ataxia, had audiological findings consistent with the presence of (AN) and agreed with previous reports that auditory neuropathy could be a consequence of Freidriech's Ataxia 11,12. ABR abnormalities were encountered one out of 6 patients HMSN 13. Similarly, balance instability was observed by Kaga et al. 14, in two patients with auditory neuropathy. However, Fujikawa & Starr 15 reported that despite the affection of vestibular nerve in (AN) patients, they did not experience any vestibular symptoms. This was attributed to the slow and gradual affection of the vestibular nerve that would provide efficient time for central compensation mechanisms to operate. The abnormal caloric findings in (AN) patients was also reported, as significant vestibular caloric abnormalities in 14 (64%) examined (AN) patients were found, with either absent or reduced caloric response 15. Furthermore, it was Sheykholeslam et al. reported the absence of response to ice irrigation in three (AN) patients 16. In the present work, the combined absence of spontaneous, positioning and positional nystagmus together with normal oculomotor test findings in the presence of abnormal caloric test results reflects the peripheral nature of vestibular system affection in (AN) patients. In agreement to results of vestibular abnormalities, Lopez et al. reported similar results in two patients with Freidriech's' ataxia 12. Also, Peripheral vestibular dysfunction was reported in patients suffering from peripheral sensory neuropathy of different etiologies 17, however, a higher percentage of caloric test abnormalities (53.2%) than in this study (%) were found, as all of their patients had dizziness. The reduction in vestibulo-ocular reflex gain in (AN) patients documents the fact that the VOR gain measures clinically the extent of bilateral reduction in peripheral system responsiveness 18. Hence, these findings would reflect the extent and severity of peripheral vestibular loss in (AN) patients. Phase lag abnormality indicates that the VOR respond too slowly to keep the head on target, while, phase lead abnormality indicates the abnormal low time constant this strongly suggests pathology in the peripheral vestibular system. However, damage of vestibular nuclei in the brainstem may also result in low time constant 18. Bilateral symmetrical abnormalities of SHA test in (AN) patients confirmed the presence of a peripheral vestibular lesion. Similar vestibular findings in 10 (20%) of (PN) patients were noticed (though were relatively lower in extent than (AN) patients), which reflects that the underlying pathology of vestibular lesion could be confined to cochleo-vestibular nerve or part of general pathological process affecting peripheral nerves. Though CDP testing is not a localizing tool, but it is useful in detecting the pattern of balance dysfunction. The abnormal scores found in C4, 5 and 6 reflected both visual and vestibular dysfunction, which indicates that patients had difficulty in using accurate visual information together with vestibular information or vestibular information alone. Moreover, one (AN) patient showed abnormal C3 in additional to abnormal C5 and C6, a finding reflecting abnormal reliance on visual information in addition to abnormal vestibular function. Patients with bilateral peripheral vestibular deficit could have abnormal C5 and C6 19. However, normal CDP findings were reported by Shepard and Telian 18 in 50% of patients with such pattern of dysfunction. Accordingly, abnormal SOT equilibrium scores in (AN) and (PN) patients could be attributed to vestibulospinal (long loop) dysfunction. Furthermore, abnormal C4 finding indicated that (AN) patients could not rely on their vision, an issue that needs thorough investigation for possible visual pathway affection. The previously mentioned MCT abnormalities in moving platform could not be attributed to severe disturbance of caloric testing and rotary chair 20. Combined SOT abnormalities with MCT latencies would indicate injuries beyond the vestibular system to include portions of sensory-motor control pathway 21. This pattern of bilateral 262

11 affection and bidirectional prolongation of MCT latencies might be attributed to the peripheral nerves affection in (PN) and (AN) patients documented by electrophysiological studies NCS and SSEPs. The positive correlation of the age, duration of hearing loss and or the relative duration % (audiological findings) to the decrease of SOT equilibrium scores, VOR gain at frequencies higher than (0.01) Hz reflects that vestibular dysfunction is a gradual and progressive process. Also, a significant correlation with VOR reflex at frequencies higher than (0.01) Hz reflects that extensive dysfunction could be detected in older patients with longer duration of hearing loss. Indeed, Sheykholeslami et al. 16, reported significant vestibular dysfunction with dizziness complaint in three (AN) patients with long duration of hearing loss which was relatively longer than mean duration of hearing loss in our (AN) patients. Similarly, abnormal caloric responses were among older (AN) patients. Absence of a significant correlation between puretone thresholds, discrimination scores and the vestibular test results (Total eye speed, SOT, MCT and VOR gain) could be due to dyssynchronization which may affect auditory nerve function earlier with smaller diameter than vestibular nerves 13. Though the history of dizziness was present in only 9 (18%) of (AN) patients, yet it was strongly related to the severity of hearing loss, thus dizziness could be attributed to the progression of auditory nerve affection as well as the severity of vestibular nerve affection. This could be supported by the absence of ice caloric response in three (AN) patients examined by Sheykholeslami et al. 16, and had vestibular symptoms, as patients do not complain unless there is an extensive vestibular lesion particularly when other additional modalities like visual or sensory-motor system or both become affected. Thus, dizziness complaint could be a reliable sign of the disease severity. In this study, the abnormalities of NCS results of (AN) patients agree with El-Danasoury and Hasab El-Nabi 22, who found electrophysiological abnormalities in one or more nerves in all fifty (AN) patients examined reflecting generalized neuropathic affection in (AN) patients. The higher percentage of lower limbs affection in (AN) patients agrees with the previous reports on neurological findings in patients with HMSN 23. Baethmann et al. 24, reported marked slowing of nerve conduction velocities in asymptomatic HMSN patients with profound sensory affection in the feet. NCS even remained unchanged with further deterioration of both sensory and motor function over time. They assumed that the primary pathogenic mechanism is a demyelinating process followed by secondary axonal loss which is the major contributor to clinical manifestation. Comparison between the electrophysiological findings of (AN) and (PN) patients revealed that, (PN) patients had significant slower conduction velocities and prolonged latencies for both upper and lower limbs, (Table 2). These findings together with the absence of symptoms and normal clinical examination would reflect the mild and subtle affection of peripheral nerves in (AN) patients. The prolonged latencies and slowing of nerve conduction velocity reflect that the underlying pathology would be demyelinating neuropathy. Somatosensory evoked potentials (SSEPs) have an advantage for detecting dysfunction of somatosensory pathway at both peripheral and central levels. SSEPs of Median nerve in (AN) patients revealed prolongation in inter-peak latencies (Erbs-N13, N13-N20), N20 latency and increased inter-side difference of N13-N20) (Tables 32 & 33). Such pattern of abnormalities in the presence of normal peripheral (Erb's) latencies reflects central SSEPs pathway affection. Similar findings of central SSEPs in (AN) patients were reported 22. Absence of a significant statistical difference between (AN) and (PN) patients reflects similar pattern of somatosensory dysfunction in both groups. Abnormal or absent SSEPs could be encountered in patients with generalized neuropathy. Butinar et al. 25, found absence of SSEPs in three Gypsy patients with HMSN. While 263

12 Egypt J. Neurol. Psychiat. Neurosurg. Vol. 43 (1) Jan 2006 Lopez et al. 12 found absent SSEPs in one patient and abnormal central SSEPs in the other patient with Freidriech's ataxia. Starr et al. 1, reported absent SSEPs in (AN) patients as well. In this study, affection of central SSEPs pathways together with other peripheral nerves affection (by NCS) may reflect that there is demyelinating process affecting both peripheral and central myelin. This is could be supported by Bahr et al 10 who reported involvement of central visual, acoustic and motor pathways in Charcot Marie Tooth (CMT) family. They attributed that to the mutation found in connexin 32 gene which is expressed in both Schewann cells (peripheral) and oligodentrites (central) myelin. Correlation between Audiological and Neurological findings in (AN) patients revealed a significant correlation regarding age of (AN) patients, duration of hearing loss or the relative duration % (duration of hearing loss relative to the age of patient) and the prolonged sensory latencies in the upper and lower limbs (by NCS), (Table 4) as well as SSEPs (N13, Erbs-N13, N13-20), (table5). This reflects that both peripheral and central nervous affection are gradual and progressive. Conversely, pure-tone thresholds and discrimination scores, showed no significant correlation with NCS. This may reflect that peripheral nerve functions are not heavily affected as the auditory nerve by neural dyssynchronization. On the contrary, inter-side latency difference of SSEPs (N13-20) had significant negative correlation with the speech discrimination scores (Table 3). As Speech discrimination depends heavily on temporal synchronization, the significant correlation between speech discrimination scores and (N13-20) of SSEP may be indicative of a similar effect of temporal dys-synchronization on central SEP pathway as well. Correlation between Vestibular and Neurological findings in (AN) patients showed insignificant correlations between caloric; total eye speed, SOT equilibrium scores, MCT scores and NCS. However, prolongation of sensory latencies of both upper and lower limbs significantly correlated with the reduced VOR gain at frequencies higher than (0.01) Hz. (Table 7). Meanwhile, there were no significant correlations between SOT equilibrium scores, MCT scores and SSEPs, prolongation of SSEPs (Erbs-N13) inter-peak latency was significantly correlated with reduced caloric response; total eye speed (Table 6) and with the reduced VOR gain at frequencies higher than (0.01) Hz (Table 8). As further affection of VOR gain in rotary chair testing reflects the extent of vestibular dysfunction, such significant correlation with NCS would indicate that affection of peripheral nerves occurs later in the disease and is present more frequent in patients with extensive vestibular dysfunction. Hence, this would reveal that peripheral neuropathy even though mild but it is late manifestation; hence, NCS could be a useful sign of the disease severity. This agrees with previous findings reported by Starr et al. 1, who documented development of peripheral neuropathy several years later in eight (AN) patients. It also agrees with Fujikawa and Starr 15 who reported that severe vestibular dysfunction was more concomitant with older patients who had peripheral neuropathy as well. Conversely, SSEPs (Erbs-N13) inter-peak latency which reflects cervico-medullary conduction time (conduction time from peripheral to central somatosensory pathway) had a significant correlation with the caloric response in addition to VOR gain in rotary chair testing. This would underlie peripheral SSEPs nerves affection which occurs earlier than other peripheral nerves and is an early sign of peripheral nerves affection. Since, both NCS and SSEPs strongly correlated to VOR gain and/or caloric response; the (AN) patients were divided according to their caloric test results into two groups. Group I with normal caloric response and group II with abnormal (reduced or absent) caloric response this helps to compare further their neurological findings. T-test revealed that there was no statistical significant difference between the two groups regarding the NCS. However, the 264

13 prolonged sensory latencies in the lower limbs in group II were of clinical significance, (Table 6). On the other hand, there were both statistical and clinical significant prolonged SSEPs (Erbs-N13) latency in group II (Table 9). These findings emphasize the previous correlation studies and indicate again that affection of both peripheral nerves and peripheral SEP pathways would reflect the severity of vestibular dysfunction. From the anatomical point of view acoustic nerve fibers have relative small diameters (3-11 µm), vestibular fibers are somewhat larger (3-15 µm), whereas large axons of peripheral nerves exceed 20 µm 13. This would explain why the auditory symptoms appear first regardless the underlying pathophysiology (axonal, demyelinating or both). The relatively larger diameter vestibular nerve fibers manifest later as the gradual process gives time for central compensation mechanisms and patients do not complain unless there is extensive vestibular lesion especially if other additional modalities like visual or sensory-motor system or both become affected. The quite larger peripheral nerves would take much longer time to give an overt manifestation especially if the disease process is inherently very slow. However, other factors as genetic determinant of the pathological process should be highly considered. Acoustic nerve is a pure sensory nerve and is early affected. In conclusion, the present study included fifty (AN) patients who had the characteristic hearing loss of (AN). Twenty three (46) % of them had abnormal vestibular findings, even though the majority did not have dizziness. Only two of them had neurological complaint while 50% of them had subtle peripheral nerves affection as revealed by NCS. Central SSEPs pathway affection was present in 62% of patients. Although, peripheral nerves affection in (AN) patients were significantly milder than (PN) group but it was suggestive of a generalized process rather than isolated auditory nerve pathology. Results of NCS pointed to that nerve demyelination could be the possible underlying pathological process. The difference between (AN) and (PN) groups would be related to the different etiologies among (PN) group and the different pathological processes accordingly. Also, it would be related to the underlying genetic factor responsible for the disease expression. REFERENCES 1. Starr, A.; Picton, T.W.; Sininger, Y.; et al. (1996): Auditory neuropathy. Brain, 119: Cacace, A., Staya-Murti,S. and Grimes,C. (1983): Frequency selectivity and temporal processing in Friedreich's ataxia; clinical aspects in two patients. Annuals of Otology, Rhinology, and Laryngology, 92: Jabbari, B., Schwartz, D., McNeil D., et al. (1983): Early abnormalities of brainstem potentials in Friedreich's ataxia: evidence of primary brainstem dysfunction. Neuorology, Cleveland, 33: Soliman, S. (1987): Low frequency sensorineural hearing loss: A syndrome. Audiology, 26 (6): Hood, L..(1998): Auditory neuropathy: What is it and what can we do about it? The Hearing Journal, vol.51, No.8 6. Varga, R., Kelley, P., Keats, B., et al. (2003): Non-syndromic recessive auditory neuropathy is the result of mutations in the Otoferlin (OTOF) gene. Journal of Medical Genetics, 40: Wang, Q., Gu, R., Han, D. et al (2003): Familial auditory neuropathy. Laryngoscope; 113 (9): Ferrer, J.; Birrun, O.; Lorenete, J., et al. (1991): Auditory function in young patients with type I diabetes mellitus.diabetes Research and Clinical Practice.,11, Hanft, K. and Haddad, J. (1994): Progressive sensorineural hearing loss (SNHL) in peripheral neuropathy: A case report. International Journal of Pediatric Otorhinolaryngology, 28, Bahr, M., Andres, F., Timmerman, V., et al. (1999): Central visual, acoustic, and motor pathway involvement in a Charcot-Marie-Tooth family with an Asn205Ser mutation in the connexin 32 gene. J. Neurol Neurosurg. Psychiatry, 66: Doyle, K., Sininger, Y. and Starr, A. (1998): Auditory neuropathy in children. Laryngoscope, 108: Lopez-Diaz E., Silva-Rojas A., Ysunza A., et al (2003): Auditory neuropathy in Friedreich ataxia. A report of two cases.int J Pediatr Otorhinolaryngol; 67 (6):

14 Egypt J. Neurol. Psychiat. Neurosurg. Vol. 43 (1) Jan Rapin, I. and Gravel, J. (2003): "Auditory neuropathy": physiologic and pathologic evidence calls for more diagnostic specificity. Int J Pediatr Otorhinolaryngol.; 67: Kaga, K., Nakamura, M., Shinogami, M., et al. (1996): Auditory nerve disease of both ears revealed by auditory brainstem responses, electroencephalograghy and otoacoustic emissions.scand. Audiol., 25: Fujikawa, S. and Starr, A. (2000): Vestibular neuropathy accompanying auditory and peripheral neuropathies. Arch Otolaryngol HNS (126): Sheykholeslam, K., Kaga, K., Murofushi, T., et al. (2000): Vestibular function in auditory neuropathy. Acta Otolaryngol 120 (7): Samaha, M. and Katsarkas, A. (2000): Vestibular impairment in peripheral sensory neuropathies. J Otolaryngol. ; 29(5): Shepard, N. and Telian, S. (1996): Rotational chair testing. In: Practical Management of Balance Disorder Patient. Singular pub., San Diago. Chap 7: Nashner, L. (2001): Computerized Dynamic Posturography. In Practical management of dizzy patient, (ed) Joel A Goebel. Lippincott Williams and Wilkins, Philadelphia, pp Di Fabio, R. (1995): "Sensitivity and specificity of platform posturography for identifying patients with vestibular dysfunction." Phys Ther 75(4): Nashner, L. (1992): Computerized Dynamic Posturography: Clinical Application. In: Handbook of Balance functions testing. Jacobson,G., Newman,C., and Kartush, J.(eds). Mosby Year Book. Chap. 14: El Danasoury, I. and Hassab El Naby, M. (2001): Neurophysiological profile of auditory neuropathy. Egypt. Rheumatol. Rehab.: Wilbourn, A. and Shields, R. (1998): Generalized polyneuropathies and other nonsurgical nervous system disordes. In; Management of peripheral nerve problems. Omar,G.; Spinner, M. and Bee, A. (eds.). 2 nd edition. Chapter 64 p: Baethmann M., Gohlich-Ratmann G., and Schroder J. (1998): HMSN-LOM in a 13-yearold Bulgarian girl. Neuromuscular Disorder; 8: Butinar, D., Zidar, J., Leonardis, L., et al. (1999): Hereditary Auditory, Vestibular,Motor, and Sensory Neuropathy in a Slovenian Roma (Gypsy) Kindred. 266

15 الملخص العربي وظائف السمع و االتزان و األعصاب فى مرضى االعتالل العصبى السمعى والطرفى