|Year : 2021 | Volume
| Issue : 3 | Page : 131-135
Pattern reversal and flash visual evoked potentials in essential tremor
ªencan Buturak1, Halit Fidanci2
1 Department of Neurology, Adana City Training and Research Hospital, Adana, Turkey
2 Department of Neurology, Division of Clinical Neurophysiology, Adana City Training and Research Hospital, Adana, Turkey
|Date of Submission||30-Nov-2020|
|Date of Decision||26-Jan-2021|
|Date of Acceptance||10-May-2021|
|Date of Web Publication||21-Oct-2021|
Dr. Halit Fidanci
Department of Neurology, Division of Clinical Neurophysiology, Adana City Training and Research Hospital 01060, Yüregir, Adana.
Source of Support: None, Conflict of Interest: None
BACKGROUND: There is evidence that nonmotor clinical findings may occur in essential tremor (ET). The aim of the study was to determine whether there is a subclinical impairment of visual pathways in ET by conducting visual evoked potential (VEP) studies on patients with ET. METHODS: Healthy individuals and patients with ET were included in the study. Individuals with visual impairment, eye disease, neurodegenerative diseases, or migraine were not included in the study. Pattern reversal VEP (PrVEP) and flash VEP (FVEP) were applied to all individuals. N75, P100, and N135 waves were obtained by PrVEP, whereas N1, P2, N2, P2, N3, and P3 waves were obtained by FVEP. The latencies and amplitudes of these waves were analyzed. RESULTS: Thirty-five healthy individuals (12 male, 23 female) and 29 patients with ET (16 male, 13 female) were included in the study. The mean age of the patients in the control group and the patients with ET was 33.9 ± 8.5 and 35.9 ± 16.8 years, respectively. Age and gender were not statistically significantly different between the two groups. The mean right/left P100 wave latencies of the control group and ET group were 90.3 ± 7.3/91.5 ± 6.1 ms and 99.4 ± 9.1/101.1 ± 7.8 ms, respectively (P = 0.009/P < 0.001). The mean right/left P2 wave latencies of the control group and ET group were 104.9 ± 15.1/104.8 ± 13.8 ms and 117.6 ± 15.4/118.3 ± 15.6 ms, respectively (P = 0.001/P = 0.001). CONCLUSION: This study showed that subclinical involvement of visual pathways may occur in ET.
Keywords: Essential tremor, flash visual evoked potential, pattern reversal visual evoked potential
|How to cite this article:|
Buturak ª, Fidanci H. Pattern reversal and flash visual evoked potentials in essential tremor. Ann Mov Disord 2021;4:131-5
|How to cite this URL:|
Buturak ª, Fidanci H. Pattern reversal and flash visual evoked potentials in essential tremor. Ann Mov Disord [serial online] 2021 [cited 2023 May 29];4:131-5. Available from: https://www.aomd.in/text.asp?2021/4/3/131/328961
| Key Messages:|| |
ET may have nonmotor features, such as impairment of visual pathways.
| Introduction|| |
Essential tremor (ET) is a common movement disorder that is characterized by postural and kinetic tremor. Findings such as the presence of Lewy bodies in the brainstem of patients with ET and the manner of progression of ET over several years have suggested that ET may be a neurodegenerative disease such as Parkinson’s disease (PD).,, In addition, the development of PD in some patients with ET supports this observation.,, Similar to cases of PD, some nonmotor symptoms such as neuropsychiatric symptoms can be seen in patients with ET., In addition, subclinical retinal involvement may be present in patients with ET.,, Studies have shown that patients with ET may have abnormalities in their retinal nerve fiber layer thickness, similar to patients with PD.,, There is also evidence that there may be abnormalities in the occipital cortex and visuospatial process in ET.,, All these results indicate that visual impairments may be a condition of ET. Therefore, using visual evoked potential (VEP) studies, the goal was to determine whether the visual pathways of patients with ET are affected.
| Materials and Methods|| |
Study design, and participants
Patients with ET as well as healthy individuals aged 18 years and older who applied to our neurology clinic between April 2019 and April 2020 were included in this prospective study. Ethics committee approval was obtained from the Adana City Training and Research Hospital Ethics Committee (number: 29/387). Written consent was obtained from all participating individuals. It was decided to include at least 25 individuals in each group (Type 1 error, 95% confidence interval)., Patients with ET according to recommended diagnostic criteria were included in the ET group. The criteria for ET were as follows: (1) Disease duration should be longer than three years; (2) action tremor in the upper extremities; and (3) absence of neurological signs, such as dystonia or Parkinsonism More Details. Individuals with neurodegenerative disease, diseases such as diabetes mellitus that may cause retinal disorders, migraine, and eye diseases such as cataracts or glaucoma were excluded from the study. Patients with a visual acuity of 20/30 or better obtained using the Snellen card were included in the study. In addition, visual acuity was expressed as log of the minimum angle of resolution (LogMAR). The severity of postural tremor was analyzed when the arms were extended straight forward in patients with ET. The severity of the kinetic tremor was also analyzed by the finger-nose test and by pouring water from glass to glass. Tremor severity was scored after the tremor was observed for at least 30 s. Tremor severity was scored as follows: 0 = if there is no tremor; 1 = mild tremor; 2 = moderate tremor; and 3 = high amplitude and severe tremor.
Visual evoked potential study
The VEP study was performed with a Cadwell Sierra Summit EMG unit (Cadwell Laboratories, Kennewick, Washington, USA). Pattern reversal VEP (PrVEP) and flash VEP (FVEP) were applied to individuals using recommended techniques. The high-pass and low-pass filters were set to 1 Hz and 100 Hz, respectively. Sweep speed and sensitivity were 25 ms/division and 2.5 µV/division, respectively. The recording was made with silver cup electrodes. Oz and Fz points were located as recommended in the international 10–20 electroencephalography system. Active electrodes and reference electrodes were placed at Oz and Fz points, respectively. It was required that impedances be less than 5 kΩ for all electrodes in order to perform the VEP test. The stimulus rate was 1 Hz. A CBOX 18.5″ LED monitor and Cadwell LED Goggles were used for PrVEP and FVEP, respectively. A white–black checkerboard (8 × 8) was used for PrVEP. The point in the middle of the checkerboard was red. The distance between the monitor and the eyes of the participants was 100 cm. The check size was 41 min of arc. Since an LED monitor was used for PrVEP instead of a cathode ray tube monitor, there was an interval between the participant observing the white checkerboard change to black on the screen (or vice versa) and the delivery of the stimulus. The software program could calculate this interval with the sensor placed on the LED monitor. This interval was 56 ms. The latencies of the PrVEP potentials were corrected by the software program while considering this interval. The average of two hundred potentials was taken twice for each eye. In the PrVEP study, N75, P100, and N135 waves were obtained and the latencies of these potentials were recorded. The latencies of N1, P1, N2, P2, N3, and P3 potentials obtained by FVEP were analyzed. P100 wave amplitude was measured from the N75 wave to the P100 wave, and P2 amplitude was measured from the N2 wave to the P2 wave [Supplementary Table 1].
The Shapiro-Wilk test was used to determine the distribution of the data. Pearson’s Chi-squared test was used to analyze categorical variables. The Mann-Whitney U test was used for group comparisons. The Spearman correlation test was used for correlation analysis. Mean ± standard deviation (SD) and median were calculated for descriptive statistics. The upper limits of the VEP latencies obtained from the controls were calculated as mean + 2 SD. If P value was <0.05, it was considered statistically significant. The Statistical Package for the Social Sciences (SPSS IBM Corp; Armonk, NY, USA) 22.0 was used to perform the statistical analysis.
| Results|| |
Thirty-five healthy individuals (12 male, 23 female) and 29 patients with ET (16 male, 13 female) were included in the study. The mean age of the control group and the patients with ET was 33.9 ± 8.5 (range: 19–54) and 35.9 ± 16.8 (range: 18–70) years, respectively. Age and gender were not statistically significantly different between the groups (P = 0.530, P = 0.130). Twelve patients reported tremor as being unilateral at the onset of ET (seven patients with tremor in the right upper extremity, five patients with tremor in the left upper extremity). Seven patients reported as bilateral. Ten patients could not clearly state in which area of the body the tremor was present at the onset of the disease. The mean duration of the disease in patients with ET was 6.1 ± 1.7 (range: 5–10) years. Family history of ET was present in 14 (48%) patients. The mean score of right/left kinetic and postural tremor severity was 1.7 ± 0.7/1.7 ± 0.8 and 1.2 ± 0.9/1.0 ± 0.9, respectively. There were no patients with head or lower extremity tremor. The number of patients using primidone and propranolol for ET was 5 and 11, respectively. Thirteen patients were not receiving treatment for ET. The LogMAR values for the right/left eye of patients with ET and controls were 0.041 ± 0.050 (range: 0.00–0.2, median: 0.00)/0.038 ± 0.056 (range: 0.00–0.2, median: 0.00) and 0.029 ± 0.057 (range: 0.00–0.2, median: 0.00)/0.026 ± 0.056 (range: 0.00–0.2, median: 0.00), respectively (P > 0.05). In the neurological examination, no participants exhibited limited eye movements or nystagmus.
The FVEP potentials of a patient with ET are shown in [Figure 1]. The PrVEP and FVEP parameters of the control group and patients with ET are shown in [Table 1]. Latencies of the N75, P100, N135, P2, N3, and P3 waves of both eyes and latencies of the N2 waves of the left eye were significantly higher in the ET group compared with the control group [Table 1]. The comparisons of the right P2 latency and the left P2 latency of the two groups are shown in [Figure 2] and [Figure 3], respectively. The upper reference limits for the right/left P100 and P2 wave latencies were calculated as 104.9/103.7 ms and 135.1/132.4 ms, respectively. The P100 wave latency in eight patients with ET (27.6%) and the P2 wave latency in five patients with ET (17.2%) were delayed considering the reference values. No correlation was found between VEP parameters and the scores of tremor severity/duration of ET (P > 0.05) [Supplementary Table 2].
|Figure 1: VEP waves of the left eye of an ET patient obtained by the FVEP study|
Click here to view
|Figure 2: Comparison of right P2 waves obtained by FVEP in ET and control groups|
Click here to view
|Figure 3: Comparison of left P2 waves obtained by FVEP in ET and control groups|
Click here to view
|Supplementary Table 2: Correlation between VEP parameters and scores of tremor severity|
Click here to view
| Discussion|| |
There is ample evidence that ET is not a benign disease and that it may, in fact, be a neurodegenerative disease. This evidence includes the progression of ET over several years, the development of PD in some patients with ET, and the presence of Lewy bodies in the brainstem in postmortem studies of patients with ET.,,,, Also, there may be nonmotor symptoms such as PD in ET., These findings show that ET and PD may have similar clinical features.,, There are studies showing that subclinical visual pathways may be impaired in ET.,,,,, As in PD, the abnormalities of the retinal nerve fiber layer thickness in ET may be an example of visual pathway abnormalities in ET.,, The VEP abnormalities found in this study in ET may be due to thinning of the retinal nerve fiber layer., The VEP abnormalities have also been shown in PD., This study showed that VEP abnormalities may exist in ET. There is an article stating that P100 wave latencies were not different in patients with ET from patients in the control group and patients with PD. Unlike that study, we did not include patients with migraine, and this may account for the different results from those in this study. As has been shown, P100 wave abnormalities may occur in patients with migraine.,
Although the origin of VEP waves is not definitively known, it is believed that the P100 wave originates from the retina to the striate cortex, and the N135 wave originates from the retina to the striate or extrastrate cortex. As a large area of the retina is stimulated with FVEP, a response occurs in a larger area of the brain. Since both PrVEP and FVEP were administered to patients with ET in this study, the findings may indicate that the striate cortex and/or extrastriate cortex and/or other regions of the cortex are affected in ET. Atrophy has been reported in the occipital and other brain areas in patients with ET. In addition, it has been reported that there may be increased gray matter in the occipital cortex and visuospatial areas, as well as abnormalities in the relative cerebral blood flow in the visual cortex., As a result of the spread of neurodegeneration from the brain stem, the thalamic–cerebellar–cortical network may be affected, and there may be involvement in cortical structures. The involvement of the retinal nerve fiber layer and affected cortical structures may have caused VEP abnormalities in ET.
No correlation was found between tremor severity and VEP parameters in this study. This finding did not surprise us, because tremor is a motor finding, whereas subclinical visual impairment is a nonmotor finding.
There is no neurophysiologic test available to diagnose ET. Although VEP latencies were higher in patients with ET than in the control group in this study, the percentage of patients with ET with normal VEP latencies was greater than 70%. Therefore, it may indicate that VEP will not be beneficial in the diagnosis of ET.
There were some limitations in our study. Although patients were selected according to the recommended diagnostic criteria that they do not have PD indicators, some patients may still develop PD over the years. This situation was one of the limitations. We think that a study in which both VEP and a Dopamine Active Transfer scan were applied to patients with ET would be interesting. Second, some patients were using propranolol or primidone and this could have affected the results. It would be interesting to conduct a VEP study that considers drug use in patients with ET. The low number of patients with ET was also a limitation of the study. Although the cranial nervous system examination was roughly normal, eye disorders such as abnormalities in smooth pursuit can be in ET, which can affect VEP parameters. This situation was another limitation. Some methodological differences, such as the use of LED monitors in this study, may have caused differences in VEP parameters between ET and control groups. Finally, there were more female participants in the control group than in the ET group, but it should be taken into account that this difference is not significant.
In conclusion, this study showed that VEP latencies were higher in the ET group than in the control group. Thus, there may be a subclinical impairment in the visual pathways in ET.
All authors contributed to all processes of the article.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
Ethics committee approval
Ethics committee approval was obtained from the ethics committee of Adana City Training and Research Hospital (number: 29/387).
| References|| |
Louis ED, Honig LS, Vonsattel JP, Maraganore DM, Borden S, Moskowitz CB. Essential tremor associated with focal nonnigral lewy bodies: A clinicopathologic study. Arch Neurol 2005;62:1004-7.
Jankovic J. Essential tremor: A heterogenous disorder. Mov Disord 2002;17:638-44.
Louis ED, Faust PL, Vonsattel JP, Honig LS, Rajput A, Robinson CA, et al
. Neuropathological changes in essential tremor: 33 cases compared with 21 controls. Brain 2007;130:3297-307.
Benito-León J, Louis ED, Bermejo-Pareja F; Neurological Disorders in Central Spain Study Group. Risk of incident Parkinson’s disease and Parkinsonism in essential tremor: A population based study. J Neurol Neurosurg Psychiatry 2009;80:423-5.
Louis ED. Essential tremor: From bedside to bench and back to bedside. Curr Opin Neurol 2014;27:461-7.
Louis ED, Benito-León J, Bermejo-Pareja F; Neurological Disorders in Central Spain (NEDICES) Study Group. Self-reported depression and anti-depressant medication use in essential tremor: Cross-sectional and prospective analyses in a population-based study. Eur J Neurol 2007;14:1138-46.
Lee SM, Kim M, Lee HM, Kwon KY, Koh SB. Nonmotor symptoms in essential tremor: Comparison with Parkinson’s disease and normal control. J Neurol Sci 2015;349:168-73.
Cubo E, Tedejo RP, Rodriguez Mendez V, López Peña MJ, Trejo Gabriel Y Galán JM. Retina thickness in Parkinson’s disease and essential tremor. Mov Disord 2010;25:2461-2.
Tak AZA, Şengül Y, Karadağ AS. Evaluation of thickness of retinal nerve fiber layer, ganglion cell layer, and choroidal thickness in essential tremor: Can eyes be a clue for neurodegeneration? Acta Neurol Belg 2018;118:235-41.
Fidancı H, Öksüz N, Öztürk Ş, Adıgüzel U, Kaleağası ŞH, Doğu O. Retinal nerve fiber layer thickness in patients with essential tremor and Parkinson’s disease. J Surg Med 2019;3:865-9.
Daniels C, Peller M, Wolff S, Alfke K, Witt K, Gaser C, et al
. Voxel-based morphometry shows no decreases in cerebellar gray matter volume in essential tremor. Neurology 2006;67:1452-6.
Bagepally BS, Bhatt MD, Chandran V, Saini J, Bharath RD, Vasudev MK, et al
. Decrease in cerebral and cerebellar gray matter in essential tremor: A voxel-based morphometric analysis under 3T MRI. J Neuroimaging 2012;22:275-8.
Czarnecki K, Jones DT, Burnett MS, Mullan B, Matsumoto JY. SPECT perfusion patterns distinguish psychogenic from essential tremor. Parkinsonism Relat Disord 2011;17:328-32.
Büttner T, Kuhn W, Müller T, Heinze T, Pühl C, Przuntek H. Chromatic and achromatic visual evoked potentials in Parkinson’s disease. Electroencephalogr Clin Neurophysiol 1996;100:443-7.
Kaur M, Saxena R, Singh D, Behari M, Sharma P, Menon V. Correlation between structural and functional retinal changes in Parkinson disease. J Neuroophthalmol 2015;35:254-8.
Bhatia KP, Bain P, Bajaj N, Elble RJ, Hallett M, Louis ED, et al
; Tremor Task Force of the International Parkinson and Movement Disorder Society. Consensus statement on the classification of tremors. From the task force on tremor of the international Parkinson and movement disorder society. Mov Disord 2018;33:75-87.
Holder GE, Celesia GG, Miyake Y, Tobimatsu S, Weleber RG; International Federation of Clinical Neurophysiology. International federation of clinical neurophysiology: Recommendations for visual system testing. Clin Neurophysiol 2010;121:1393-409.
Husain AM, Hayes S, Young M, Shah D. Visual evoked potentials with CRT and LCD monitors: When newer is not better. Neurology 2009;72:162-4.
Antal A, Dibó G, Kéri S, Gábor K, Janka Z, Vécsei L, et al
. P300 component of visual event-related potentials distinguishes patients with idiopathic Parkinson’s disease from patients with essential tremor. J Neural Transm (Vienna) 2000;107:787-97.
Liu C, Zhang Y, Tang W, Wang B, Wang B, He S. Evoked potential changes in patients with Parkinson’s disease. Brain Behav 2017;7:e00703.
Sand T, Zhitniy N, White LR, Stovner LJ. Visual evoked potential latency, amplitude and habituation in migraine: A longitudinal study. Clin Neurophysiol 2008;119:1020-7.
Gawel M, Connolly JF, Rose FC. Migraine patients exhibit abnormalities in the visual evoked potential. Headache 1983;23:49-52.
Benito-León J, Serrano JI, Louis ED, Holobar A, Romero JP, Povalej-Bržan P, et al
. Essential tremor severity and anatomical changes in brain areas controlling movement sequencing. Ann Clin Transl Neurol 2019;6:83-97.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]