brain stem evoked responses in patients with diabetes mellitus

BRAIN STEM EVOKED RESPONSES IN PATIENTS WITH DIABETES MELLITUS

Ravinder Sharma 1, S. C. Gupta 2, Isha Tyagi 3, Sanjay Kumar 4, Kanchan Mukherjee s,

Key Words : Brain stem evoked response. Diabetes mellitu~. Central neuropathy.

I N T R O D U C T I O N Diabetes mellitus is the most common endocrine disorder, with a incidence of 1-2%, characterized by fasting hyperglycemia with or without gtycosuria. Pathologically it consti tutes the triad of neuropathy, retinopathy, and nephropathy. Basic lesion which contributes to this triad is microangiopathy. Microangiopathic changes are the most important findings in histopathoiogic studies of inner ear in diabetic subjects (Reske Neilson et al, 1965). Diabetics suffer from hearing loss also which tends to be sensorineural, slowly progressive and bilateral with a more severe loss at higher feequencies (Axelsson et al, 1968). The Occulomotor, Trochlear and facial nerve palsy in diabetic subjects (Jorgenson et al, 1962) further suggests that besides autonomic and peripheral neuropathy there is definitely some neuroendocrine defect, which contributes to central neuropathy.

The study of auditory brain stem evoked responses pro- vides an opportunity to evaluate the functional integrity of auditory pa thway f rom inner ear to upper brain stem. Jewett et al, (1970) gave the topographical locat ion of generation centres of waves I-V. However only wave I, III & V are recorded reliably enough to be routinely used in clinical applications (American Electroencephalographic Society i984) and they primarily represent the volume conducted electrical activity from the cochlear nerve, pons and midbrain respectively.

The present study was done with an aim to study auditory brain stem evoked responses changes in patients of diabetes mellitus at 2 KHz, 4KHz, & 6KHz, frequencies. Further an at tempt was made to relate abnormal brain stem evoked responses with the blood glucose level, duration of disease, and peripheralneuropathy.

Senior Resident, 2 Associate Professor & Head, 3 Associate Professor, 4 Audiologist, 5 Senior Resident, Department of Neurosurgery, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow - 226 014, Inaia.

224 Brain Stem Evoked Responses in Patients with Diabetes Mellitus

M A T E R I A L A N D M E T H O D The study was carried out on 25 normal hearing diabetic patients (17 males and 8 females, male : female ratio of 2.12 : 1) with mean age = 44.28 years (ranging from 28 years to 49 years). The mean duration of disease was 9.92 years (ranging f rom 1 year to 20 years). Patients were excluded if they had history of ear discharge, asso- ciated endocrine disorder e.g. myxedema, head injury, neurological deficit, cerebrovascular accident, or noise exposure in the past. The patients with history of drug intake known to cause central neuropathy e.g. reserpine, alpha methyl dopa, phenytoin, & nitrofurantoin were also

excluded from this study.

Complete clinical examinat ion was done in all subjects (with special reference to long term complications of diabetes mellitus). Peripheral neuropathy was present in 56% subjects. Ret inopathy was asessed by fundus-examina- tion. It was present in 8% of cases. Nephropathy was assessed by urinary protein estimation (using Albustics). It was present in 4% of cases.

Fasting and post prandial blood glucose estimation was done in all cases a day before conduct ing brain stem evoked response audiometry. Blood glucose estimation was done before brain stem evoked response audiometry to exclude hypoglycaemia at the t ime of testing. Blood glucose es t imat ion was done by using non enzymat ic method (Asatoor and king 1954). All subjects were sub-

jected to otoscopy and tuning fork tests. Pure tone audiometry was done on ARPHI 700 M K audiometer. Pure tone thresholds ranged between 0-15 dBHL for 500 to 8 KHz.

Brain stem evoked response audiometry was done in a sound t rea ted r o o m unde r s t anda rd condi t ions on E.R.A.T.A. 1000 model. The patient was instructed to be comfortable by all means. The test was carried out in relaxed supine position. First the skin of forehead and of both mastoid process were cleaned with acetone soaked swab. Then electrodes were properly cleaned and stan- dard adhesive paste (conducting medium) was applied in the recess of the electrode and which was then adhered to cleaned surface of their respective sites. The head phone was applied in position. The stimulus rate was set at 20 clicks/sec.,sensitivity was set at 0.2 mv/div. Recording were taken at 80dBHL for 2KHz, 4KHz, & 6KHz frequencies. At least 2 recordings were taken to confirm the re- producibility of wave from and the absolute latencies of wave I, III &V & inter peak latencies I-III, III-V, & I-V were recorded.

The results from the diabetic subjects were compared with those from the age and sex matched control subjects. A total of ten subjects in the age range of 29 years to 49 years (mean age 44.17 years) were evaluated, out of which 7 were males and 3 were females. As the inter aural latency difference was insignif icant in both the

Table - I C o m p a r i s i o n o f abso lu te latencies & interpeak latencies in n o r m a l subjects and in pat ients with diabetes mei l i tus at 2 K H z

Wave Latency

Control Group (N) Mean _+ S. D.

Diabetic Group (N1) Mean _+ S. D.

T-scroe

I 1.10_+0.08 1.29-+0.13 4.28 I I I 3.17_+0.11 3.55_+0.13 6.17 V 5.19_+0.09 5.66_+0.22 3.55 I-III 2.07_+0.04 2.27_+0.17 3.64 III-V I-V

2.11_+0.12 4.38_+0.12

2.02+0.04 4.09_+0.22

2,30 3.20

P-Value

<.001IHSI <.001[HS] <0.01[HS1 <.001 [HSI <0.05[HSI <0.01 [HS]

D a t a are m e a n +_ S .D. , T h e m e a n v a l u e s o f b o t h ea rs w e r e used ,

N - N u m b e r o f c o n t r o l s u b j e c t s (10) , N 1 - N u m b e r o f d i abe t i c pa t i en t s (25),

H S - H i g h l y significant, S-Signifant .

Indian Journal of Otolaryngology and Head and Neck Surgery Vol. 52 No. 3, July - September 2000

Brain Stem Evoked Responses in Patients with Diabetes Mellitus 225

groups, 50 diabetic ears were evaluated against 20 normal ears. The significant differences between the two groups were assessed using student 's t-test for unequal samples.

To evaluate the incidence of abnormal brain stem evoked responses at 2 KHz, 4KHz & 6KHz, the range of normal brain s tem evoked responses was taken as mean wave latency in control group _+ 2SD (95.45% confidence lim- its). I f the value of wave latencies obtained in diabetic subjects was within this range it was considered normal and if it was outside this range it was considered abnormal. Following this criteria the number of diabetic subjects with abnormal values were evaluated with the duration of disease, age of patient and the blood glucose level. Similar cri teria was fol lowed by Buller et al, (1988), Mukhopadhaya et al, (1992), Sharma Y et al, (1987) and D. Fedele(1984).

of wave I, III &V and interpeak latencies I-III, I I I -V & I- V in diabetic subjects as compared to control subjects. The mean values of absolute latencies & interpeak latencies of BAEP in 25 diabetic patients and 10 control subjects are shown in Table - II.

At 6KHz Table III shows that there was a highly significant delay is absolute latencies of wave I, III &V and interpeak latencies I-III, I I I -V & I-V in diabetic patients as compared with the normal subjects.

Incidence of abnormal brain s tem evoked responses in diabetics at 2 KHz, 4KHz & 6KHz The number of diabetic subjects with abnormal values (>Mean wave latency in control subject _+2SD) of absolute latencies of wave I, I II &V and interpeak latencies I-III , I I I -V & I -V were 64% (16/25), 72%(18/25) and

OBSERVATION At 2KHz The absolute latencies of wave I, III &V and interpeak latencies I-III, I I I -V & I-V were significantly greater in diabetic patients than in the control group. Table - I shows the mean and standared deviation of the absolute latencies and interpeak latencies of BAEP in 25 diabetic patients as compared with the normal subjects.

At 4KHz There was a highly significant delay in absolute latencies

Table - II

Comparision of absolute latencies & inter peak latencies in normal subjects and in patients with diabetes mellitus at 4KHz.

Wave Latency Control Group (N) Diabetic Group (N~) t - score P-valve Mean +_S.D. Mean _+S, D.

I 1.14+_.07 i.30+_.09 4.81 <.001 [HS] I I I 3.22+_. 15 3.61 _. 13 7.4 i <.001 [HS] V 5.25+-. 16 5.79__..27 2.18 <.001 [HS 1 I - I I I 2.06_+. 10 2.31 +_.28 4.10 <.001 [HS] I I I -V 2.06_+. 11 2.18_+. 10 3.00 <0.01 [HS] I-V 4.10_+. 11 4.50_+.27 5.75 <.001 [HS]

Data are mean -+ S.D., The mean values of both ears were used, N-Number of control subjects (10), N~ - Number of diabetic patients (25),


226 Brain Stem Evoked Responses in Patients with Diabetes Mellitus

Table -III

Comparision of absolute latencies & inter peak latencies in normal subjects and in patients with diabetes mellitus at 6 KHz

Wave Latency Control Group (N) Diabetic Group (NI) t -score P-Valve Mean_+S. D. Mean _+S. D.

I 1.16_+.07 1.29_+. 10 3.70 <.001 [HS] III 3.23-+. 10 3.71_+. 14 4.73 <.001 [HS] V 5.26-+. 17 5.89_+.36 4.40 <.001 [HS] I-III 2.07_+.06 2.43_+. 14 7.97 <.001 [HS] III-V 2.07-+. 12 2.44_+. 15 5.95 <.001 [HS] I-V 4.14-+. 14 4.61_+.33 4.30 <.001 [HS]

Data are mean _+ S.D., The mean values of both ears were used, N-Number of control subjects (10), N~ - Number

of diabetic patients (25), HS-Highly significant, S-Signifant.

Table-IV

Showing relationship between auditory Brain Stem Evoked Responses at 2 KHz & Blood Glucose Level; in Diabetes mellitus

ABER No. of Subjects Fasting

Mean Blood Level (mg./dl) Post-Prandial Random

Normal BERA 09 235.77 268.81 243.44 Abnormal BERA 16 224.81 264.73 244.37

ABER : Auditory brain stem evoked responses.

Table -V Showing relationship between abnormal brain stem evoked responses at 2KHz and duration of illness

Group Total No. of Subjecets Subjects with abnormal brain stem evoked responses

Diabetics with duration of illness 0-10 years 12 4(25%) Diabetics with duration of illness 10-20 years 13 12(92.31%)

Table-VI Showing

thy. relationship between abnormal brain stem evoked responses at 2KHz and peripheral neuropa-

Group Total No. of Subjecets

11 14

Diabetics withou t peripheral neuropathy Diabetics with peripheral neuropathy

Subjects with abnormal brain stem evoked responses

4(36.36%) 12(85.71%)

Indian Journal of Otolarvngology and Head and Neck Surgery Vol. 52 No. 3, July - September 2000

Brain Stem Evoked Responses in Patients" with Diabetes Mellitus 227

84%(2S/25) at 2KHz, 4KHz & 6KHz respec t ive ly (Fig. - I).

Auditory brain stem evoked responses & blood glucose level In patients with abnormal brain stem evoked responses at 2KHz mean values of fasting post prandial and random blood glucose level were 224.81mg/dl, 262.73mg/dl, and 235.37 mg/dl respectively. Diabetic subjects with normal brain stem evoked responses had slightly higher mean values of fasting, post prandial and random blood glucose, level as shown in Table -IV.

Relationship between abnormal brain stem evoked responses & duration of disease

92.3% of diabetic subjects with duration of disease 10-20 years had abnormal brain stem evoked responses while 25% of diabetic subjects with duration of disease 0-10 years had abnormal responses (Table - V).

Relationship between abnormal brain stem evoked responses & peripheral neuropathy Total number of diabetics with peripheral neuropathy were 14, of these 12 (85.71%) had abnormal brain stem evoked responses. While the number of diabetics without peripheral neuropathy were l l , of these, only 1 (36.36%) had abnormal brain stem evoked responses. (Table - VI).

D I S C U S S I O N A diffuse peripheral polyneuropathy involving autonomic and peripheral nerves is a well known complication of diabetes mellitus. Studies of Reske Neilson et aS, (1965) and Makishima et aS, (197 S) showed degenerative abnor- malities of the brain tissue and atrophy of the spiral gan- glion of the cochlea in patients of diabetes mellitus, thereby suggesting the presence of central neuropathy. Brain stem evoked response audiometry is a noninvasive eSectrophysi-

We found a significant delay (P< .01) in inter peak latencies I -III & I-V while a significant delay (P< .50) in inter peak latency III -V. Virtaniemi et al, (1993) reported similar results.

At 4KHz There was a highly significant (P< .001) delay in absolute latencies of wave I ,III &V and inter peak Satencies of wave I-III, III -V & I - V. No study was available to compare the results obtained.

At 6KHz There was a highly significant (P< .001) delay in absolute latencies of wave I , III &V and'interpeak Satencies of wave I-III, III -V & I - V. No study was available to compare the results obtained.

Incidence of abnormal brain stem evoked responses in diabetics at 2KHz, 4KHz & 6KHz. 64% (16/25) of diabetic patients showed abnormal brain stem evoked responses (delayed absolute latencies of wave I - II, III -V and inter peak latencies I-III, III -V & I - V). The finding was similar with the 64% incidence of abnormal brain stem evoked responses reported in the study of N. Buller et al, (1988) and close to 43% & 44% incidence of abnormal brain stem evoked responses reported in the study of D. Fedele et al, (1987) and Mukhopadhyaya et al, (1992) respectively. However Ashok Verma et al, (1984) reported normal auditory brain stern evoked responses in patients of diabetes mellitus. In three patients with mean duration of illness more than 15 years, he reported de- l ayed r e s p o n s e s s ince n e u r o p a t h y is a t t r i b u t e d to microangiopathy which is a long term sequelae of diabetes mellitus.

72% (18/25) and 84%(21/25) of the diabet ic subject showed abnormal brain stem evoked reponses (delayed Satencies of wave I, I I I & V inter peak latencies I-III, III-

oSogica! too! to detect retrocochSear lesion. Thus it is of V & I-V) at 4 KHz & 6KHz respectively. immense help in guid ing us for de tec t ion of ear ly imparirment of the auditory nerve and of brain stem function (Rowe 1981).

At 2KHz There was a highly significant delay (P<.001) in absolute latencies of wave I, III & V. N. Buller et al, (1988) and D. Fedele et al, (1987) also reported similar results. Ashok Verma et al, (1984) reported non-significant delay (P>0.1) in wave latencies.

The results at 2KHz, 4KHz, & 6KHz showed that as the f requency o f st imulus was increased, abnormal brain stem evoked responses were more common. This can be explained by bilateral high frequency sensorineuraS hearing loss in diabetes mellitus, as reported by Axelson et al, (1988). However the subjects included in this study had normal pure tone audiogram suggesting that subclinical involvement of auditory pathway can be detected earlier in the course of disease at higher frequency level (6KHz).


228 l~rain Stem Evoked Responses in Patients with Diabetes Mellitus

Thus abnormal brain stem evoked responses at 6KHz is a more sensitive indicator of severity of diabetic mellitus as

compared to that at 2KHz & 4KHz.

Abnormal brain stem evoked responses & blood glucose level. There was no relationship between impairment of brain stem evoked responses & blood glucose level in the study group. N. Buller et al, (1988), Ann Sieger et al, (1983) also reported similar results. This can be due to structural d a m a g e of b ra in s t em t i s sue , wh ich is due to microangiopathy (Jorgenson et al, 1962 and Reske Nielson et al, 1965). Ashok Verma et al, (1984), and Yashpaul Sharma et al, (1987) made no attempt to relate abnormal brain stem evoked responses with blood glucose level.

A b n o r m a l brain stem evoked responses and the du- rat ion of illness. Abnormal brain stem evoked responses were more common in patients with duration of illness more than 10 years as compared to patient with duration of illness less than 10 years . J o r g e n s o n et al, (1962) s ta ted that microangiopathy is responsible for diabetic neuropathy, which is a long term complication and this explains a higher incidence of abnormal brain s tem evoked responses in patients with duration of illness more than 10 years. Ashok Verma et al, (1984) noted that the patients with duration of illness more than 15 years showed delayed responses.

A b n o r m a l bra in s tem e v o k e d re sponses & peripheral n e u r o p a t h y There was a direct correlation between peripheral neur- o p a t h y and a b n o r m a l bra in s t em e v o k e d responses . 85.71% subjects with diabetic neuropathy had abnormal brain stem evoked responses while 36.36% subjects without neuropathy had abnormal brain stem evoked responses. Goldsher et al, (1986) reported abnormal brain stern evoked responses in diabetics with neuropathy in 44% cases. Mean age of patient in his study was 33 years while in our study it was 44.28 years. This explains a higher incidence of abnormal brain stem evoked responses in our study. N. Panda & Prabhakar (1987) also suggested that the delay in wave latencies of auditory brain stem evoked responses in definitely related to the presence of neuropathy.

C O N C L U S I O N Diabetic subject can suffer not only from peripheral and autonomic neuropathy but also f rom central neuropathy.

This study suggests that if brain stem evoked response audiometry is carried out at higher frequencies like 6KHz in diabetic patients, involvement of central neuronal axis can be detected earlier. Further studies involving more patient are necessary to corroborate these observations and to clearly establish the role of brain stem evoked responses audiometry in patients of diabetes mellitus.

Central neuropathy in diabetes mellitus is not related to blood glucose level. However duration of illness and presence of peripheral neuropathy are definite risk factors for

the development of central neuropathy.

A C K N O W L E D G E M E N T S I am thankful to Dr. C. M. Pandey, Associate Professor, Biostatistics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow for his kind assistance in Sta- tistical analysis of this work.

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brain stem evoked responses in patients with diabetes mellitus

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