Trigeminal Blink Research Articles

Facial Onset Sensory and Motor Neuronopathy: A Neurodegenerative TDP-43 Proteinopathy? (P03.183)

Objective: We report clinical, electrophysiologic and pathologic features of five new cases of facial onset sensory and motor neuronopathy or FOSMN syndrome. An autopsy performed in one case identified TDP-43 cytoplasmic inclusions. Background Vucic et al. described four adult males in 2006 with facial sensory loss gradually spreading to cervical and brachial dermatomes associated with LMN weakness of cranio-bulbar and upper extremity (UE) distribution. Autopsy in one case suggested a neurodegenerative process affecting motoneurons and sensory ganglia. Design/Methods: A retrospective review of patients referred to Mayo Clinic from 2004 to 2011 identified five males who met the clinical features of FOSMN. Results: The age of onset ranged from 55 to 63 years. The presenting symptoms often years after onset, were facial numbness (5), associated with loss of taste (1), dysphagia (3), and masseter weakness (2). Sensory loss spread to scalp, neck, upper torso and distal UEs. Patients developed facial, masseter, bulbar, neck flexor/extensor and LMN weakness of UEs. Two patients died of respiratory failure 6 and 9 years after onset. Electrodiagnostic studies revealed prolonged to absent trigeminal blink R1 responses, reduced sensory nerve action potentials in UEs, and chronic denervation mainly in cranial and cervical regions. CSF protein elevation (4) ranged from 46 to 96 mg/dL. Brain and cervical MR images were normal. Biopsies of greater auricular and transverse cervical nerves revealed low grade axonal degeneration. A patient aged 65 who died 6 years after onset, came to autopsy. Neuronal loss and gliosis with TDP-43 positive cytoplasmic neuronal and glial inclusions were present in hyploglossal nucleus and cervical motoneurons. Alpha-synuclein positive inclusions were found in substantia nigra, pigmented brainstem nuclei and mesial temporal lobe suggestive of incidental Lewy body disease. Conclusions: FOSMN syndrome joins sporadic ALS, frontotemporal lobar degeneration (FTLD-U) and other neurodegenerative disorders as a TDP-43 proteinopathy. Disclosure: Dr. Bosch has nothing to disclose. Dr. Tracy has nothing to disclose. Dr. Goodman has nothing to disclose. Dr. Dyck has nothing to disclose. Dr. Toro has nothing to disclose. Dr. Giannini has nothing to disclose.

The somatosensory blink reflex in upper and lower brainstem lesions

The brainstem pathways that mediate the somatosensory blink reflex (SBR) are not completely understood. We hypothesized that the circuits of the SBR might be affected separately from those of the trigeminal blink reflex (TBR). We examined 7 patients with mesencephalic lesions and 8 patients with medullary lesions. The SBR was elicited by median nerve stimulation. The TBR was elicited by supraorbital nerve stimulation. In patients with upper brainstem lesions, the TBR was normal, whereas the SBR was generally abnormal. The SBR was either absent or small and was significantly delayed with respect to control subjects. The opposite was the rule in patients with lower brainstem lesions who had delayed or absent TBR and no abnormal findings in the SBR. The SBR is mediated through circuits in the upper brainstem. Study of the SBR can be helpful in the neurophysiological assessment of patients with mesencephalic lesions.

Metaplasticity of the human trigeminal blink reflex

Although synaptic plasticity in the human cerebral cortex is governed by metaplasticity, whether a similar mechanism operates at brainstem level is unknown. In this study in healthy humans we examined the effects and interactions induced by pairing supraorbital nerve high-frequency electrical stimulation (HFS) protocols on the R2 component of the trigeminal blink reflex [Mao, J.B. & Evinger, C (2001) J Neurosci., 21:RC151(1-4)]. Changes in the R2 component were tested by pairing three different priming stimulation protocols inducing long-term potentiation (LTP)-like or long-term depression (LTD)-like effects (LTP-HFS and LTD-HFS), or no change (CONTROL-HFS) with a subsequent test LTP-HFS. Additionally, to examine changes in the R2 component induced by nonspecific factors, two CONTROL-HFS sessions were paired. Priming LTP-, LTD- or CONTROL-HFS potentiated, inhibited or left unchanged the area of the R2 component. Regardless of the type of priming LTP-, LTD- or CONTROL-HFS, the test LTP-HFS induced negligible differences in the R2 component. When two CONTROL-HFS sessions were paired, the test CONTROL-HFS increased the latency and markedly reduced the duration and area of the R2 component. The analysis of the normalized data across the first three experimental sessions, corrected for the inhibitory effects found in the fourth experiment, showed that the test LTP-HFS potentiated the R2 component area of the trigeminal blink reflex only when preceded by a priming LTD-HFS. We propose that homosynaptic metaplasticity might operate in the brainstem circuitry of the blink reflex.

Somatosensory eye blink reflex in peripheral facial palsy

To investigate the association between somatosensory blink reflex (SBR) and peripheral facial palsy (PFP) severity and trigeminal blink reflex (BR) changes in cases with PFP and subsequent postparalytic facial syndrome development (PFS). One hundred and twenty subjects with peripheral facial palsy and post-facial syndrome and 44 age and gender matched healthy volunteers were enrolled to this study. Blink reflexes and somatosensory blink reflex were studied in all. The association between R1 and R2 responses of the BR and SBR positivity was investigated. SBR was elicited in 36.3% of normal subjects, in 18.3% of PFP and in 65.3% of PFS patients. In the paralytic side, the frequency of SBR positivity was significantly lower in PFP group compared to controls and SBR was most frequently observed in patients with PFS. Compared to PFP and control groups, SBR positivity on the non-paralytic side significantly revealed a higher rate in PFS patients. SBR positivity of patients in whom R1 or R2 were absent, was significantly lower than those subjects with prolonged or normal R1 or R2 responses. PFP and successive PFS are good models for the sensory motor gate mechanisms and/or excitability enhancement of brainstem neurons responsible for SBR.

Impaired long‐term potentiation–like plasticity of the trigeminal blink reflex circuit in Parkinson's disease

We investigated the hypothesis that Parkinsons's disease (PD) is associated with abnormal plasticity of the neuronal circuits mediating blink reflex. We induced long-term potentiation (LTP)-like plasticity in trigeminal wide dynamic range neurons of the blink reflex circuit by pairing an high-frequency train of electrical stimuli over the right supraorbital nerve (SO) coincident with the R2 response elicited by a preceding SO stimulus. The facilitation of the R2 response after the induction protocol was markedly decreased in patients relative to controls. Treatment with dopaminergic drugs normalized the LTP-like plasticity of the R2 response. We conclude that nigrostriatal denervation disrupts LTP-like plasticity in the trigeminal reflex circuit.

Effects of Caffeine on the Trigeminal Blink Reflex

The acoustic startle and trigeminal blink reflexes share the same motor output. Since caffeine has been shown to augment the startle reflex, it was proposed that caffeine would also increase the trigeminal blink reflex. In 6 humans, the effects of caffeine (100 mg) on the trigeminal blink reflex were investigated. Reflex blinks were elicited by stimulation of the supraorbital branch of the trigeminal nerve. Following ingestion of caffeinated coffee, reflex blinks increased in amplitude and duration and occurred at a shorter latency than reflex blinks following ingestion of decaffeinated coffee. Since the blink reflex is a brainstem reflex, these results suggest that the psychomotor effects of caffeine facilitate brainstem processing.

Blink effect on slow vergence.

Blinks are known to change the kinematic properties of fast eye movements, probably by changes in the brain stem circuits. To determine whether slow disconjugate (slow vergence) eye movements are affected by blinks under natural viewing conditions, we elicited airpuff-evoked trigeminal blinks randomly during ongoing steady slow vergence eye movements. Lid and binocular eye movements were recorded by the scleral search coil method. Slow vergence eye movements showed a peak of vergence velocity during the final part of the blink, which depends on the stimulus direction. We propose that the direction-specific blink effect on slow vergence may be caused by changes in brain stem premotor circuits.

Aging of the trigeminal blink system.

This study characterizes trigeminal blinks in normal human subjects between 20 and 80 years of age, 60-year-old Parkinson's disease patients, and young and old guinea pigs. In normal humans over 60 years of age, lid-closing duration, and the excitability and latency of the trigeminal reflex blink increase significantly relative to younger subjects. Aged guinea pigs appear to display similar increases in reflex blink duration and latency. Reflex blink amplitude, however, does not change consistently with age. For subjects less than 70 years of age, a unilateral trigeminal stimulus evokes a 37% larger blink in the eyelid ipsilateral to the stimulus than in the contralateral eyelid, but 70-year-olds exhibit blinks of equal amplitude. In all cases, blink duration is identical for the two eyelids. If normal, age-related loss of dopamine neurons explains these trigeminal blink modifications, then Parkinson's disease should exaggerate age-related changes in these blink parameters. Preliminary data show that Parkinson's disease increases blink duration and excitability relative to age-matched control subjects. Thus, it seems likely that normal, age-related loss of dopamine neurons accounts for increases in trigeminal blink excitability and duration. A previously uncharacterized type of trigeminally evoked blink appears after age 40 in humans and in aged guinea pigs. In subjects less than 40 years old, a single trigeminal stimulus elicits a single reflex blink. In subjects over age 40, however, a single stimulus frequently evokes a reflex blink and additional blinks that occur at a fixed interval relative to the preceding blink. These "blink oscillations" may arise from oscillatory processes within trigeminal reflex blink circuits. The presence of exaggerated blink oscillations in subjects with dry eye and benign essential blepharospasm suggests that an alteration of blink oscillation mechanisms plays a critical role in these disorders.

Influence of the superior colliculus on the primate blink reflex

In this study we used microstimulation to investigate the influence of the superior colliculus on the trigeminal blink reflex. We report that stimulation in the intermediate to deep layers of the tectum produced inhibition of reflex blinks at a latency of approximately 26 ms. We considered the hypothesis that the blink inhibition was mediated via the omnipause neurons (OPNs) of the eye movement control system in the brainstem. Our results show that the least effective sites for suppression were in the rostral colliculus. This is inconsistent with the prediction that OPNs should be maximally recruited from the rostral tectum near the "fixation zone." From these points and other considerations, we conclude that the reflex blink suppression from the superior colliculus is not directly mediated by the OPNs or the saccadic eye movement circuits.

Animal model explains the origins of the cranial dystonia benign essential blepharospasm.

The current study demonstrates that combining two mild alterations to the rat trigeminal reflex blink system reproduces the symptoms of benign essential blepharospasm, a cranial dystonia characterized by uncontrollable spasms of blinking. The first modification, a small striatal dopamine depletion, reduces the tonic inhibition of trigeminal reflex blink circuits. The second alteration, a slight weakening of the lid-closing orbicularis oculi muscle, begins an adaptive increase in the drive on trigeminal sensory-motor blink circuits that initiates blepharospasm. By themselves, neither of these modifications causes spasms of lid closure, but combined, they induce bilateral forceful blinking and spasms of lid closure. A two-factor model based on these rodent experiments may explain the development of benign essential blepharospasm in humans. The first factor, a subclinical loss of striatal dopamine, creates a permissive environment within the trigeminal blink circuits. The second factor, an external ophthalmic insult, precipitates benign essential blepharospasm. This two-factor model may also be applicable to the genesis of other cranial dystonias.

The trigeminally evoked blink reflex. I. Neuronal circuits.

In this study, we characterized the pathways that generate the trigeminal blink reflex in the guinea pig. Blinks were evoked by stimulation of the supraorbital branch of the trigeminal nerve and measured by recording electromyographic activity in the lid-closing orbicularis oculi muscle (OOemg) and, in one case, lid position. Blinks evoked by stimulation of the supraorbital nerve consisted of two bursts of muscle activity ipsilateral to the side of stimulation. The first, R1, had a latency of 6.9 ms and the second, R2, had a latency of 17.25 ms. Increasing stimulus intensity to 3 times threshold for evoking an ipsilateral blink elicited an R1 and R2 response contralaterally, with latencies of 9.2 ms and 19.25 ms, respectively. We investigated the causes for this bipartite response that is seen in the guinea pig, as well as other mammals including humans. The two-component response could arise from different populations of afferents, or from different central circuits, or a combination of these two causes. Multiunit recording in the trigeminal ganglion and simultaneous measurement of the OOemg showed that activation of A beta afferents alone was sufficient to elicit both the R1 and the R2 responses, but that activation of A delta afferents could enhance both responses. Different neural circuits, however, produce the R1 and R2 responses. Transganglionic tracing with wheatgerm agglutin or choleragenoid subunit of cholera toxin bound to HRP revealed that primary afferents from the supraorbital branch of the trigeminal nerve terminated densely in the dorsal horn of spinal cord segment C1 and in the caudalis-interpolaris border region of the spinal trigeminal nucleus. Injections of HRP into the orbicularis oculi motoneuron region of the facial nucleus showed that both of these regions projected to the facial nucleus. Hemisections at the level of C1 eliminated the R2 blink response, but not the R1 response, evoked by stimulation of the supraorbital branch of the trigeminal nerve. Subsequent hemisections at the level of the obex eliminated the R1 response. Microinjections of the GABAB agonist baclofen into the spinal trigeminal nucleus at the level of the obex abolished the R1 but not the R2 response. Thus, the spinal trigeminal nucleus produces the R1 component, whereas the R2 component originates in the C1 region of the spinal cord.

Differential sensitivity of trigeminal blink reflex responses to hypoxia and hypercapnia in the cat

Differential sensitivity of trigeminal blink reflex responses to hypoxia and hypercapnia in the cat

Differential sensitivity of trigeminal blink reflex responses to hypoxia and hypercapnia in the cat

Differential sensitivity of trigeminal blink reflex responses to hypoxia and hypercapnia in the cat