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Table of Contents    
Year : 2020  |  Volume : 68  |  Issue : 1  |  Page : 72-75

Blink Reflex is Significantly Altered in Patients with Multisystem Atrophy Compared to Patients with Progressive Supranuclear Palsy, Alzheimer's Disease, and Frontotemporal Dementia ‑ A Pilot Study

1 Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
2 Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
3 Department of Lab Technician, ENMG Lab, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
4 Department of Biostatistics, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India

Date of Web Publication28-Feb-2020

Correspondence Address:
Dr. Sadanandavalli R Chandra
Faculty Block, Neurocentre, National Institute of Mental Health and Neurosciences, Bengaluru - 560 029, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.279678

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How to cite this article:
Chandra SR, Ramanujam NC, Gohel A, Mailankody P, Nagaraj B C, Mondal MS, Philip M. Blink Reflex is Significantly Altered in Patients with Multisystem Atrophy Compared to Patients with Progressive Supranuclear Palsy, Alzheimer's Disease, and Frontotemporal Dementia ‑ A Pilot Study. Neurol India 2020;68:72-5

How to cite this URL:
Chandra SR, Ramanujam NC, Gohel A, Mailankody P, Nagaraj B C, Mondal MS, Philip M. Blink Reflex is Significantly Altered in Patients with Multisystem Atrophy Compared to Patients with Progressive Supranuclear Palsy, Alzheimer's Disease, and Frontotemporal Dementia ‑ A Pilot Study. Neurol India [serial online] 2020 [cited 2020 Jul 11];68:72-5. Available from:

Neurodegenerative disorders form a group of progressive disorders where multiple functions become affected and mostly do not have a cure. The prognosis depends on the extent of involvement of the circuits and structures which become diseased in the process. Many disorders have specific phenotypes, but yet a large group has overlapping features. Therefore, treatment options and prognosis varies in these patients. Simple tools are needed to know the extent of circuit break down early in disease. With this in mind, the authors decided to generate data using the blink reflex in 4 classical degenerative diseases, 2 involving the cortex and 2 involving the brainstem to know if this simple tool shows different patterns.

Patients who qualified for probable AD, FTD, PSP and MSA by appropriate criteria were evaluated with blink reflex after informed consent. Data was subjected for null hypothesis testing.

Blink reflex is commonly done to test the integrity of trigeminal and facial nerve. The supraorbital or infraorbital nerve is stimulated transcutaneous and the reflex closure of orbicularis oculi is tested with surface electrodes placed over the orbicularis oculi. Two CMAPs are seen. The first is ipsilateral R1 occurring approximately in 10 seconds after the stimulus and R2 30 seconds after the stimulus. The contralateral R2 comes still 5 seconds later. Both R1 and R2 come from facial motor nucleus, but R1 is from the pons in the vicinity of the neurons of pontine sensory part of 5th nerve. R2 is from the reflex pathway in the pons. If blink reflex is normal, it indicates that the 5th nerve, interneurons in pons, caudal medulla and 7th nerve are not interrupted in the above pathway. In brain stem disorders, the data is less and results are inconsistent as it involves polysynaptic pathways in brainstem reticular formation. Prolonged latencies of R2 (both ipsilateral and contralateral) is likely to be more sensitive than clinical evaluation in in the early stage. A study comparing PD, MSA-P, MSA-C and PSP reported 19.2% of patients showed abnormal R2 latencies in individuals with PD. However, the mean values of R2 latencies were within normal limits.[1]

Blink stimuli passes through the main sensory nucleus in the pons and nucleus of spinal tract of trigeminal nerve at medulla. This reaches the ipsilateral and contralateral facial nuclei through multiple interneurons in pons and medulla and travel bilaterally. The first response seen is labelled as R1, which is seen ipsilateral to the site stimulated. A late response, R2 is found bilaterally. R1 is a disynaptic reflex from the trigeminal nerve to ipsilateral facial nucleus in lower pontine tegmentum. R2 responses are generated by polysynaptic pathway between spinal nucleus of trigeminal in ipsilateral pons and medulla and its connections to ipsilateral and contralateral facial nuclei.[2] The impulse travels through 5th nerve to main sensory nucleus in mid pons and through spinal tract of trigeminal to lower pons and medulla. The stimulation reaches the facial nucleus in pons in both sides by multiple interneurons in pons and medulla. After that, the impulse travels from 7th nerve nuclei bilaterally and 2 responses are generated. Normal values are mean latency plus 2 standard deviations and usually in an adult is around 12.5 milliseconds. R2 is not more than 40 milliseconds ipsilateral and 41-45 milliseconds contralateral.[3],[4]

There were 13 patients with MSA, 6 patients with PSP, 13 patients with FTD and 9 patients with AD who qualified as probable cases as per consensus criteria. All of them underwent Blink Reflex with the Keypoint.NET EMG and EP system. Stimulation of supraorbital nerve produces contraction of orbicularis oculi, which was picked up through surface electrodes placed over orbicularis oculi in upper eyelids and reference electrode at outer canthus. The patient lies supine with closed eyes. Stimulation is given in such a way that the cathode of the stimulator lies over the supraorbital foramen and anode two centimetres above that. Ground electrode is applied around the arm. Reproducible R1 is identified by repeated trials. Stimulation is given with 50 to 150 mV current for 0.1 milliseconds. The rate of stimuli 0.5 Hz with interstimulus interval of 30 to 50 milli second, bandwidth of 20 Hz to 10 kHz, latency of the earliest evoked potential is measured as R1 and subsequent ipsilateral and contralateral potentials as R2. The total number of patients included for this study was 41, out of which patients with FTD were 13, MSA were 13, PSP were 6 and AD were 9, who qualified as probable in the respective groups Among patients with FTD, 92.3% were of the behavioural variant and 7.7% were of the semantic variant. Among AD patients, classical AD was seen in 55.6%, early onset AD in 11.1% and frontal variant in 33.3%. In MSA group 76.9% was MSA-C and 23.1% MSA-P. In the FTD group 61.5% were female and 38.5% male, AD group 77.8% female and 22.2% male, MSA 61.5% male and 38.5% female and PSP 100% male. Hypothesis testing using comparison of latency between ipsilateral R1 and R2 and ipsilateral R1 and contralateral R2 showed significant delay in MSA group and was within normal limits in AD, FTD and PSP. The absolute R1 latency, R2 (ipsilateral)-R2 (contralateral) latency differences were not significantly altered in any group [Table 1] hypothesis testing). When compared across groups, left-sided latency between ipsilateral R1 and R2 was significantly different between MSA and AD [Table 2] and [Figure 1] and ipsilateral R1 and contralateral R2 showed trend [Figure 2], but no statistical significance was seen in right-sided stimulation [Table 3]. Blink reflex in sample MSA cases is shown in.[2] Blink reflex in sample AD, FTD and PSP cases is shown in [Figure 3]. Comparison of blink latencies among patients with MSA, FTD, AD and PSP.
Table 1: Shows hypothesis testing of the results showing significant prolongation of R1 to R2 ipsilateral and R1 to R2 contralateral in patients with MSA

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Table 2: Shows data comparing latencies between patients with AD and MSA

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Figure 1: Shows Blink reflex graphs in our patients with MSA (Sample cases)

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Figure 2: Shows ipsilateral R1 and R2 latencies on the left side between patients with MSA and AD

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Table 3: Shows ipsilateral R1 to R2 latency differentially involved in MSA and AD patients on the left side

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Figure 3: Shows Blink reflex graphs of sample cases of AD, FTD and PSP

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Our study reveals in this that R1 latency and ipsilateral R2 to contralateral R2 is not differentially involved in all the 4 groups studied. This indicates that the disynaptic pathways between main sensory nucleus of 5th nerve and ipsilateral facial nucleus in pontine tegmentum as well as the interneurons between ipsilateral to contralateral facial nuclei are not differentially affected in all these 4 groups of patients. But the polysynaptic pathways between the ipsilateral 5th nerve nucleus to ipsilateral and contralateral facial nucleus are differentially affected even in very early course in patients with MSA but not in patients with AD, FTD and PSP.

Blink reflex latency from R1 to ipsilateral and contralateral R2 are significantly prolonged in MSA as compared to patients with AD, FTD and PSP. Absolute R1 latency and inter R2 latency is unaffected in all of these conditions. This indicates early involvement of brainstem polysynaptic pathways in the pons and medulla in MSA patients with sparing of the ipsilateral disynaptic pathways. Both disynaptic and polysynaptic pathways are spared in patients with FTD, AD and PSP. This study can be carried out in a larger number of patients in all groups with normal healthy controls. Later, longitudinal follow-up of all these patients can be done as the next phase of the study is to find out the phenotypic and electrophysiological correlations with patients who converted to overlap syndromes and those who remained pure cases. The following information can serve as a biomarker for picking up overlapping cases early using reflex: 1. Patients with normal blink continuing to remain as pure AD, FTD and PSP during longitudinal follow-up. 2. Patients clinically resembling the above mentioned features but with prolonged R1-R2 latency (ipsilateral or contralateral) converted to overlap syndrome. If blink latency in early stages is differentially affected in those patients who converted to overlap and remained pure over time, this will serve as a useful prognostic tool for those who are likely to convert to overlap syndromes. This hypothesis needs further testing, both cross sectional and longitudinally in a larger cohort of patients. This is a cheap, easily available and non-invasive simple test can be repeated with minimal patient cooperation and will be a quick screening tool in difficult clinical situations.


National Institute of Mental Health and Neurosciences (NIMHANS); Bangalore, Karnataka State.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Szmidt-Salkowska E, Gawel M, Jamrozik Z, Salkowska-Wanat J, Gawel D, Kaminska A. Diagnostic value of blink reflex in multisystem atrophy, progressive supranuclear palsy and Parkinson disease. Neurol Neurochir Pol 2016;50:336-41.  Back to cited text no. 1
Esteban A. A neurophysiological approach to brainstem reflexes. Blink reflex. Neurophysiol Clin 1999;29:7-38.  Back to cited text no. 2
Nisticò R, Salsone M, Vescio B, Morelli M, Trotta M, Barbagallo G, et al. Blink reflex recovery cycle distinguishes essential tremor with resting tremor from de novo Parkinson's disease: An exploratory study. Parkinsonism Relat Disord 2014;20:153-6.  Back to cited text no. 3
Valls-Solé J. Neurophysiological assessment of trigeminal nerve reflexes in disorders of central and peripheral nervous system. Clin Neurophysiol 2005;116:2255-65.  Back to cited text no. 4


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2], [Table 3]


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