Role of middle latency auditory evoked potentials in parkinsonism: An electrophysiological clue

Anish Mehta; Rohan R Mahale; Nikith Ampar; Purushottam Acharya; Mahendra Javali; Srinivasa R

doi:10.4103/AOMD.AOMD_18_22

ORIGINAL ARTICLE

Year : 2022 | Volume : 5 | Issue : 3 | Page : 183-188

Role of middle latency auditory evoked potentials in parkinsonism: An electrophysiological clue

Anish Mehta¹, Rohan R Mahale², Nikith Ampar¹, Purushottam Acharya¹, Mahendra Javali¹, Srinivasa R¹
¹ Department of Neurology, Ramaiah Medical College, Bengaluru, Karnataka
² Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India

Date of Submission	28-Apr-2022
Date of Decision	31-Jul-2022
Date of Acceptance	10-Oct-2022
Date of Web Publication	14-Dec-2022

Correspondence Address:
Rohan R Mahale
Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bengaluru - 560029, Karnataka
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/AOMD.AOMD_18_22

Abstract

Introduction: Middle latency auditory evoked potentials (MLAEPs) allow the assessment of the function of the central part of the auditory pathway. MLAEP abnormalities have been demonstrated in patients with Alzheimer’s and Parkinson’s disease with dementia. Objective: The objective of our study was to assess the MLAEP findings in patients with idiopathic Parkinson’s disease (IPD) and atypical parkinsonism (AP) and to determine whether MLAEPs could contribute to the differential diagnosis of IPD and AP. Methods: We included 75 participants (25 IPD patients, 25 AP, and 25 age-matched healthy control subjects). MLAEPs were recorded in all patients and control subjects as per the standard procedure for MLAEP recordings. Absent waveforms (Na and Pa waves) and prolonged latencies of individual waves were considered as abnormal MLAEP readings. Results: The Pb waveform was significantly absent in the patients with IPD and AP compared to control subjects (p = 0.02). The Pb waveform was significantly absent in the AP group compared to the IPD group (p = 0.03). The Pb waveform was significantly absent in the AP group without cognitive impairment compared to the IPD group without cognitive impairment (p = 0.003). There was no statistically significant difference between the patients with IPD with and without cognitive impairment (p = 0.07). There was no significant difference among the groups with respect to Na and Pa wave latencies. Other parameters such as Na–Pa amplitude and Nb–Pb amplitudes were not significant among the groups. Conclusion: The absence of Pb potential in AP is an electrophysiological clue for the diagnosis of AP in patients presenting with parkinsonism. MLAEPs can act as an electrophysiological adjunct to the clinical imaging markers in differentiating IPD from AP.

Keywords: atypical parkinsonism, middle latency auditory evoked potentials, Parkinson’s disease

How to cite this article:
Mehta A, Mahale RR, Ampar N, Acharya P, Javali M, Srinivasa. Role of middle latency auditory evoked potentials in parkinsonism: An electrophysiological clue. Ann Mov Disord 2022;5:183-8

How to cite this URL:
Mehta A, Mahale RR, Ampar N, Acharya P, Javali M, Srinivasa. Role of middle latency auditory evoked potentials in parkinsonism: An electrophysiological clue. Ann Mov Disord [serial online] 2022 [cited 2023 May 30];5:183-8. Available from: https://www.aomd.in/text.asp?2022/5/3/183/363462

Introduction

Middle latency auditory evoked potentials (MLAEPs) are a set of functional tests used to assess the function of the central part of the auditory pathway.^[1] They comprise several components that are recorded 10–50 ms after stimulus onset.^[2] Geisler et al., (1958)^[3] first discovered MLAEPs at the Massachusetts Institute of Technology. However, in 1974, different waves of MLAEPs, such as N18 (Na), P30 (Pa), and P50 (Pb), were described.^[4] Na and Pa, with latencies between 10–25 ms and 22–40 ms, respectively, are the most stable components of MLAEPs. ^[5] The other major waves are Nb and Pb.^[6] The Pb potential has been found to be absent in Alzheimer’s disease and Parkinson’s disease with dementia (PDD).^[7],[8],[9] Studies on MLAEPs in patients with PD showed absence of the Pb component in 60% of the patients with PDD, 28.5% of the patients with PDD, and 5% of the patients without cognitive dysfunction.^[10],[11] The aim of this study was to assess the MLAEP findings in patients with idiopathic Parkinson’s disease (IPD) and atypical parkinsonism (AP) and to determine whether MLAEPs could contribute to the differential diagnosis of IPD and AP.

Materials and Methods

The study was a case-control prospective analytical study. A total of 75 participants (25 IPD patients, 25 AP patients, and 25 age-matched healthy controls) were included in the study. IPD patients were recruited from the outpatient/inpatient care at Ramaiah Medical College and Hospitals, Bengaluru, India, over a 2-year period from January 2017 to December 2018. IPD was diagnosed based on the United Kingdom Parkinson’s Disease Society Brain Bank clinical diagnostic criteria.^[12] The exclusion criteria were the presence of psychiatric disease; cerebrovascular illness; auditory disorders; osteoarticular cervical disorders; and other systemic diseases such as heart failure, cardiac arrhythmia, respiratory disorders, etc. The AP group comprised patients with progressive supranuclear palsy (PSP), diagnosed according to the Movement Disorders Society criteria for PSP (2017), and multiple system atrophy (MSA), diagnosed according to the second consensus statement for the diagnosis of MSA (2008).^[13],[14] The participants were evaluated in the “ON” phase to minimize the potential artefacts due to the lack of dopaminergic control on motor symptoms. The study protocol was approved by the Ethics committee (ID protocol Ref number: SS-1/EC/01/2017). Written informed consent was obtained from all the participants.

Clinical data

Detailed medical history was obtained and clinical examination was performed for all participants. The severity of the motor symptoms in patients with IPD and AP was assessed using the United Parkinson’s Disease Rating Scale part III, and the stage of the disease was assessed using the H & Y classification (Hoehn and Yahr scale).^[15],[16] The REM Sleep Behavior Disorder Screening Questionnaire; Geriatric Depression Scale-15; Mini-Balance Evaluation Systems Test; and Epworth Sleepiness Scale were used for detection of REM Sleep Behavior Disorder, depression, balance and postural instability, and day time sleepiness, respectively.^{[17],[18],[19],[20]} The screening for cognition was performed using the mini mental state examination.^[21] Scores below 24 were indicative of cognitive impairment.

Middle latency auditory evoked potentials recording

The vertex electrode is used as the active electrode and the left and right electrodes are used as the reference electrodes for two-channel recordings (channel 1, left; channel 2, right). The upward deflection is recorded as the negative potential.

Recording settings: The MLAEP readings were recorded using 80 decibels nHL click sound to either the left or right ear, and the masking noise was applied to the opposite ear. The recording was performed two times to check for reproducibility. Peak latency was defined as the time from the stimulation onset to the positive or negative peak point of the waveform. The negative waveform “N” and positive waveform “P” and a character “a, b” was added according to the order of appearance [Figure 1].

Figure 1: Normal MLAEP waveforms

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Waveforms

Peak latency of prominent waves, Na and Pa waves, were measured in all subjects. The presence of the Nb wave and Pb wave along with the presence of the P1 wave was noted in all subjects. The criterion for abnormality was absent wave forms (Nb, Pb, Na, and Pa waves) or prolonged latencies (Na and Pa waves), calculated according to the one-standard-deviation deviations calculated from the control group. Among the amplitudes, Na–Pa amplitude and Nb–Pb amplitude were assessed in all the cases.

Statistical analysis

Statistical analysis was performed using SPSS version 22. Categorical variables were expressed as frequency and percentage, while continuous variables were expressed as mean and standard deviation. Student’s t-test was used to compare the mean between the two groups and analysis of variance was used for more than two groups. A p value of <0.05 was considered to be statistically significant.

Results

A total of 75 participants were included in the study. Among these, there were 25 patients with IPD, 25 patients with AP (20 patients with PSP and five patients with MSA), and 25 healthy controls. There were 19 men (76%) in the IPD group, 20 men (84%) in the AP group, and 15 men (64%) in the control group. There was no significant difference in the mean age of patients and the controls in all three groups. There was no significant difference in the mean duration of illness between the IPD and AP groups. The demographic and clinical assessment data of the patient and control groups are summarized in [Table 1]. All the patients with IPD were on levodopa/carbidopa, and six patients with IPD were on additional trihexyphenidyl. All patients with AP were only on levodopa/carbidopa.

Table 1: Comparison of demographic details and clinical scales among the groups

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MLAEP findings

All the patients and controls underwent MLAEP assessments and the waveforms were analyzed. Absent waveforms (Na and Pa waves) and prolonged latencies of the individual waves were considered as abnormal MLAEPs. All waveforms (Nb, Pb, Na, and Pa waves) were recorded in all 25 controls. In the IPD group, the Na wave was not recordable in five cases and the latencies were prolonged in two cases. The Na wave was not recordable in six cases in the AP group and the latencies were prolonged in three cases. In the IPD group, the Pa waveforms were not recordable in six cases and the latencies were prolonged in two cases. In the AP group, the Pa waveforms were not recordable in five cases. All cases in the control group had normal waveform recordings. There was no significant difference between IPD and AP groups with respect to the Na and Pa wave latencies (p=0.38, p=0.11 respectively). Other parameters such as the Na–Pa amplitudes and Nb–Pb amplitudes were not significant between IPD and AP groups (p=0.15, p=0.29 respectively). The MLAEP waveform latencies and amplitudes among the groups are summarized in [Table 2]. The Pb waveform was significantly absent in the IPD and AP groups compared to the control group (p = 0.02). The Pb waveform was significantly absent in the AP group compared to the IPD group (p = 0.03). The Pb waveform was significantly absent in AP group without cognitive impairment compared to the IPD group without cognitive impairment (p = 0.003). There was no statistically significant difference between patients with IPD and those without cognitive impairment (p = 0.07). The Pb waveform among the groups are summarized in [Table 3].

Table 2: Comparison of MLAEP waveforms values among the groups

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Table 3: Comparison of presence of Pb waveform among the groups

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Discussion

Idiopathic PD is an alpha synucleinopathy, characterized by bradykinesia, rigidity, and rest tremor with asymmetric onset of symptoms. This is due to the degeneration of dopaminergic substantia nigra in the midbrain. Apart from the motor symptoms, various non-motor symptoms are well known in PD, which occur as a result of degeneration in the serotonergic, noradrenergic, and cholinergic brainstem nuclei.^[22],[23] AP is a term used to describe a group of neurodegenerative disorders with distinct pathological entities, such as MSA, PSP, and corticobasal degeneration.^[24] In the early stages of the disease, AP is frequently misdiagnosed as IPD. Differentiating IPD from AP is a clinical challenge for neurologists due to their overlapping clinical presentation. An accurate clinical diagnosis is essential for prognostication, as well as for treatment such as deep brain stimulation for IPD and research purposes. Clinical clues called “red flags” help in differentiating AP from IPD. Different brain magnetic resonance imaging studies in patients with IPD and AP have examined the magnetic resonance imaging markers for the accurate differentiation of IPD from AP.^[25] In addition, single photon emission computed tomography and positron emission tomography helps in the differentiating AP from IPD.^[26] The electrophysiological tools used to differentiate IPD from AP are limited. In a resource-poor setting, the usage of single photon emission computed tomography and positron emission tomography is limited in the differentiation due to its cost-effectiveness and availability. The “middle latency” components of the auditory evoked response that occur within 10–100 ms following stimulus onset has not been studied in detail in neurological diseases. There are few studies on the utility of MLAEPs in the differentiation of IPD and AP. ^[11],[27]

This study aimed at evaluating MLAEPs in patients with IPD and AP. MLAEP potentials represent a series of deflections that occur between 10 and 80 ms after the auditory stimulus. They occur beyond brainstem-evoked potentials and precedes later responses, which are related to the cortical and cognitive functions. The anteromesial temporal cortex has a modulating influence on the subcortical generators of Na and Pa potentials. The Nb potential originates in the lateral aspect of the supratemporal gyrus. The Pb potential is considered as an overlapping potential, having a temporal component from each of the supratemporal cortices, and a midline component from the ascending reticular activating system.^[28] Green JB et al. (1992)^[8] reported the absence of the Pb waveform in seven out of 12 demented IPD patients. Normal MLAEP readings have been found in nondemented IPD patients. Pb is abnormal in AP patients, as often as that observed in demented IPD patients. Çelik M et al., (2000)^[11] studied MLAEP findings in IPD and AP. They included 27 patients with IPD, eight patients with AP, and 19 control subjects. Among patients with IPD, Pb was absent in one nondemented patient with young-onset Parkinson’s disease (5%) and in two of seven demented (28.5%) IPD patients. In the AP group, three of the seven (42.8%) nondemented patients and one patient with dementia showed the absence of Pb. The absence of Pb was found to be remarkably higher in patients with AP than in those with IPD. Nojszewska M et al., (2009)^[27] studied MLAEPs in patients with IPD. They found abnormal MLAEP results in 17 out of 27 patients with PD with normal Wisconsin card sorting test (WCST) scores and abnormal MLAEP results in 10 of 14 patients with PD with abnormal WCST scores. The differences in the latencies of all MLAEP components in patients with PD with normal and abnormal WCST scores were not statistically significant. The Pb component was absent in 63% of the patients in the subgroup of normal WCST scores and in 72% of the patients in the subgroup of abnormal WCST scores. In the subgroup of patients who performed poorly on the WCST test, the lack of Pb component was found more frequently compared to that in the subgroup with normal WCST. There was no significant difference in the absence of Pb in patients with IPD with and without cognitive impairment in our study. We used the mini mental state examination as the screening tool for the presence of cognitive impairment, whereas Nojszewska M et al.^[27] used WCST, which is a neurophysiological test for executive function.

This study showed that the Pb waveform was markedly absent in the AP group, with or without cognitive impairment compared to the IPD group. There was no difference between the IPD and AP groups with respect to latency and amplitudes of the Na, Pa, Nb, and Pb waveforms. The strength of our study was the demonstration of the utility of MLAEPs in differentiating IPD from AP in a resource-limited setting. However, the limitation of our study was the relatively small sample size in the IPD and AP groups. The findings of our study need to be confirmed in a larger population.

Conclusion

The absence of the Pb potential in AP is the potential electrophysiological clue for the diagnosis of AP in patients presenting with parkinsonism. The difference in the frequency of abnormal MLAEP findings in IPD and AP may be related to the topographic distribution of the lesions in these two disorders. MLAEPs can act as an electrophysiological adjunct to the clinical imaging markers in the differentiation of IPD from AP.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgement

Nil

Author contribution

Concepts: Anish Mehta, Rohan Mahale; Design: Anish Mehta, Rohan Mahale, Nikith Ampar; Definition of intellectual content: Anish Mehta, Rohan Mahale, Nikith Ampar, Purushottam Acharya, Mahendra Javali, Srinivasa R; Literature search: Anish Mehta, Rohan Mahale, Nikith Ampar; Data acquisition: Anish Mehta, Rohan Mahale, Nikith Ampar, Purushottam Acharya; Data analysis: Anish Mehta, Rohan Mahale, Nikith Ampar, Srinivasa R; Statistical analysis: Anish Mehta, Rohan Mahale; Manuscript preparation: Anish Mehta, Nikith Ampar,; Manuscript editing: Rohan Mahale; Manuscript review: Anish Mehta, Rohan Mahale, Nikith Ampar, Purushottam Acharya, Mahendra Javali, Srinivasa R.

Ethical compliance statement

The procedures followed were in accordance with the ethical standards.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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