M. Aramideh

Brainstem reflexes: Electrodiagnostic techniques, physiology, normative data, and clinical applications

An overview is provided on the physiological aspects of the brainstem reflexes as they can be examined by use of clinically applicable neurophysiological tests. Brainstem reflex studies provide important information about the afferent and efferent pathways and are excellent physiological tools for the assessment of cranial nerve nuclei and the functional integrity of suprasegmental structures. In this review, the blink reflex after trigeminal and nontrigeminal inputs, corneal reflex, levator palpebrae inhibitory reflex, jaw jerk, masseter inhibitory reflex, and corneomandibular reflex are discussed. Following description of the recording technique, physiology, central pathways, and normative data of these reflexes, including an account of the recording of recovery curves, the application of these reflexes is reviewed in patients with various neurological abnormalities, including trigeminal pain and neuralgia, facial neuropathy, and brainstem and hemispherical lesions. Finally, simultaneous electromyographic recording from the orbicularis oculi and the levator palpebrae muscles is discussed briefly in different eyelid movement disorders.

Blink reflex recovery curves in blepharospasm, torticollis spasmodica, and hemifacial spasm.

R1 and R2 blink reflex responses to single and paired stimuli were investigated in 23 control subjects: 21 patients with blepharospasm (BSP), 20 patients with torticollis spasmodica (TS), and 23 with hemifacial spasm (HFS). For paired stimuli, we compared measurements of area and peak responses at two and three times R2 threshold. R1 and R2 indices were calculated as the average of the recovery values at 0.5‐, 0.3‐, and 0.21‐s interstimulus intervals to test individual patients. Peak amplitude measurements at three times R2 threshold were optimal. The R2 index was abnormal in 67% of BSP patients, 37% of TS patients, and 50% of HFS patients on the affected side and 20% on the unaffected side. A normal R2 index in one third of patients with BSP may indicate that different pathophysiological mechanisms are involved in this type of focal dystonia.

DYT6 dystonia: Mutation screening, phenotype, and response to deep brain stimulation†

Mutations in THAP1, a gene encoding a nuclear pro‐apoptotic protein, have been associated with DYT6 dystonia. First reports on the phenotype of DYT6 dystonia show an early onset dystonia with predominant cranio‐cervical and laryngeal involvement. Here we assessed the frequency and phenotype of THAP1 mutation carriers in a large Dutch cohort of adult‐onset (≥26 years) dystonia (n = 388) and early‐onset dystonia (n = 67) patients. We describe the phenotype of DYT6 dystonia patients and their response on GPi DBS. Overall, 3 nonsynonymous heterozygous mutations were detected in the early‐onset group (4.5%). Two DYT6 families were identified, showing a heterozygous phenotype. All patients had segmental or generalized dystonia, often associated with profound oromandibular and laryngeal involvement. No nonsynonymous mutations were found in patients with adult‐onset focal dystonia. Rare synonymous variants were identified in conserved regions of THAP1, two in the adult‐onset cervical dystonia group and one in the control group. Four DYT6 dystonia patients were treated with GPi DBS with moderate to good response on motor function but marginal benefit on speech.

Botulinum toxin in cervical dystonia: low dosage with electromyographic guidance

Sixty patients with idiopathic cervical dystonia were treated a total of 240 times with botulinum toxin type A (BTA). Selected muscles were injected with BTA under electromyographic (EMG) guidance. The clinical effect was measured on the Tsui scale and a 10-point anchored visual analogue scale. A dosage of 150–300 mouse units was used in 77% of the treatments (mean 204 mouse units). Based on the Tsui scale, 45% of 240 treatments were still effective at the moment of reinjection (median improvement 2 points). Based on the 10-point anchored visual analogue scale, 73% of treatments were successful (median improvement 3 points). Forty-eight patients (80%) responded favourably to the treatment. Side-effects were mild and transient. Dysphagia occurred in 9% of treatments. Antibody production was investigated in 41 patients and was negative in all. A striking difference from previous reports is the lower dosage used in this study. The clinical response, however, was similar to that of other studies. We conclude that a dosage of 200–400 mouse units BTA (Dysport) may also be effective in the treatment of cervical dystonia, but with fewer side effects. EMG guidance and application of BTA into deep cervical muscles may further improve the clinical effect.

Pretarsal application of botulinum toxin for treatment of blepharospasm.

The response to botulinum toxin type A was compared after two injection techniques in 45 patients with blepharospasm. Initially, patients were treated according to a triple injection technique; two injections into the upper eyelid and one injection into the lower eyelid. Subsequently, without altering the dose, the same patient group received two further injections into the pretarsal portion of the orbicularis oculi muscle of the upper lid. Triple injections were given in 227 treatments, of which 81% were successful. Mean duration of benefit was 8.5 weeks. Additional pretarsal injections were given in 183 treatment sessions. The number of successful treatments significantly increased, to 95% (P < 0.001), and the mean duration of benefit increased to 12.5 weeks (P < 0.001). Ptosis occurred significantly less often after pretarsal injections (P < 0.01). Patients with combined blepharospasm and involuntary levator palpebrae inhibition responded better to the pretarsal injection technique.

Long-term effect of botulinum toxin on impairment and functional health in cervical dystonia

We investigated the long-term effect of botulinum toxin type A (BTA) on impairment as well as functional health in terms of disability, handicap, and quality of life in 64 patients with cervical dystonia. These patients, who first participated in a double-blind trial, were followed for another 12 months. Fifty-four patients continued treatment after 12 months of follow-up and showed improvement on all scales. Furthermore, this effectiveness appeared to increase during follow-up, which suggests a cumulative clinical effect of BTA.

Motor persistence of orbicularis oculi muscle in eyelid‐opening disorders

Article abstract—We describe clinical and EMG findings in three patients with an inability to reopen the eyes after voluntary closure of the eyelids. Synchronous EMG recording from the levator palpebrae (LP) and orbicularis oculi (OrbOc) muscles revealed that after voluntary closure of the eyelids and upon the command to open the eyes, all three patients were unable to inhibit the “voluntary” contraction of the OrbOc muscles, while on clinical examination there was no evidence of ongoing OrbOc muscle contraction. This “motor persistence” was restricted predominantly to the pretarsal portion of the OrbOc. In one patient, it occurred as an isolated abnormality of the eyelid movement and was recorded as an additional EMG abnormality in two patients with blepharospasm and involuntary LP inhibition. Clinical examination alone cannot differentiate this type of disorder of supranuclear control of eyelid movement from involuntary LP inhibition; simultaneous EMG recording from the LP and OrbOc muscles is required. Injection of botulinum toxin into the pretarsal portion of OrbOc muscles is helpful.

Electromyography and recovery of the blink reflex in involuntary eyelid closure: a comparative study.

Electromyographic (EMG) activity of orbicularis oculi and levator palpebrae muscles was recorded to study the origin of involuntary eyelid closure in 33 patients. The evoked blink reflex in all patients and in 23 controls was also studied. To examine the excitability of facial motoneurons and bulbar interneurons in individual patients and to compare the results with EMG findings, R1 and R2 recovery indices were calculated in all subjects, as the average of recovery values at 0.5, 0.3, and 0.21 second interstimulus intervals. Based on EMG patterns, the patients were divided into three subclasses: EMG subclass 1, 10 patients with involuntary discharges solely in orbicularis oculi muscle; EMG subclass 2, 20 patients with involuntary discharges in orbicularis oculi and either involuntary levator palpebrae inhibition or a disturbed reciprocal innervation between orbicularis oculi and levator palpebrae; EMG subclass 3, three patients who did not have blepharospasm, but had involuntary levator palpebrae inhibition in association with a basal ganglia disease. The total patient group showed an enhanced recovery of both R1 and R2 components compared with controls. Although 30 out of 33 patients had blepharospasm (EMG subclasses 1 and 2), R1 recovery index was normal in 64% and R2 recovery index was normal in 54%. Patients with an abnormal R2 recovery index had an abnormal R1 recovery index significantly more often. All patients from EMG subclass 1 had an abnormal R2 recovery index, whereas all patients from EMG subclass 3 had normal recovery indices for both R1 and R2 responses. Seventy five per cent of the patients from EMG subclass 2 had normal recovery indices. The results provide further evidence that physiologically blepharospasm is not a homogeneous disease entity, and indicate that different pathophysiological mechanisms at the suprasegmental, or segmental level, or both are involved.

Blink Reflexes and Lateral Spreading in Patients with Synkinesia after Bell’s Palsy and in Hemifacial Spasm

We compared various electrodiagnostical tests in patients with hemifacial spasm and in patients who developed synkinesia after Bell’s palsy. We examined the evoked blink reflexes in the orbicularis oculi (o. oculi) and orbicularis oris (o. oris) muscles in 23 patients with hemifacial spasm (HFS), in 10 patients with synkinesia after Bell’s palsy (BPS) and in 22 control subjects. In the patient groups, we recorded synkinesia, latency and amplitude of compound muscle action potential (CMAP) in the mental muscle after stimulation of the facial nerve and we examined electromyographic activity of the o. oculi and mental muscles synchronously. Furthermore, we studied the phenomenon of lateral spreading, also known as ephaptic transmission, between the different facial nerve branches. Patients with BPS had a prolonged R1 latency on the affected side in o. oculi and smaller mental CMAP amplitude as an indication of facial nerve damage and nerve fiber loss. This was not found in patients with HFS, who showed an increased amplitude of the R1 and R2 responses in o. oris. Patients with BPS showed only an increased R1 amplitude in o. oris. All patients had signs of synkinesia. Lateral spreading with different patterns was present in all patients with HFS and in half of the patients with BPS. Latencies of early and late responses showed no differences between HFS and BPS. In addition to alterations in facial nucleus excitability in both conditions, ectopic re-excitation of facial nerve axons in HFS may explain the differences in neurophysiological findings between HFS and BPS patients. A loss of control following synaptic stripping may also be a contributing factor.

A retrograde double fluorescent tracing study of the levator palpebrae superioris muscle in the cynomolgus monkey

In the cynomolgus monkey, motoneurons innervating the levator palpebrae superioris muscle form a nucleus within the oculomotor nuclei called the central caudal nucleus. After double fluorescent neuronal retrograde tracing experiments, using fast blue and diamidino yellow as tracers in the levator palpebrae superior muscles, labelled motoneurons (30%) were found in an unpaired central caudal nucleus. Approximately 2% of the labelled motoneurons were double-labelled. The labelled and double-labelled neurons were distributed randomly over the central caudal nucleus, lateralization of populations of levator motoneurons within this nucleus was not observed. The afferent innervation of the levator palpebrae superioris muscle was restricted to the ophthalmic branch area of the gasserian ganglion. Primary afferent labelled neurons were absent from mesencephalic nucleus of the fifth nerve. Surprisingly, fast blue was also found in the ophthalmic branch area of the contralateral ganglion of Gasser, while diamidino yellow was present only ipsilaterally. About 1% of the afferent labelled neurons were double-labelled. The results reveal that in the cynomolgus monkey the central caudal nucleus is not only topographically but also functionally one nucleus. Afferent innervation of the levator palpebrae superioris muscle is probably bilaterally organized.