summarizes the demographic and clinical data of the seven subjects included in this study. In male subjects, dystonia first became manifest in their fourth or early fifth decade (44–52 years of age). In contrast, dystonia onset was 60 and 65 years, respectively, in the two female patients. At the time of this report, dystonia duration was between 7 and 15 years in all subjects. No subject showed clinical evidence of Parkinsonism, ataxia, spasticity, or posterior cervical (extensor) myopathy. Four patients had other sites of involvement, all within the craniocervical region. During the course of their disease, all subjects were given trials of oral agents for their dystonia and AEO. Treatments included benzodiazepines, tetrabenazine, anticholinergic agents, an analeptic (modafinil), a dopamine agonist (pramipexole), levodopa, and muscle relaxants. In aggregate, oral pharmacotherapy was only mildly beneficial in our cohort. Injections of onabotulinumtoxin A were employed to relieve the symptoms of blepharospasm (range: 47–110 units) and cervical dystonia (100–255 units). All patients received injections into the pretarsal portions of the OO muscles. Although complemented by the effects of botulinum toxin injections, all subjects required surgical intervention in the form of OO myectomy or blepharoplasty for adequate control of blepharospasm.
Subject #1 () is a Caucasian male with type II diabetes and hyperlipidemia. Blepharospasm onset was mildly asymmetrical, initially presenting in the left eye, followed by right eye involvement a few months later. Cervical dystonia, manifest as isolated anterocollis, appeared 5 years later. The severity of both blepharospasm and anterocollis has progressed slowly over time. Neither blepharospasm nor anterocollis has responded to trials of clonazepam (maximum dosage: 1 mg t.i.d.), tetrabenazine (maximum dosage: 25 mg t.i.d.), or trihexyphenidyl (maximum dosage: 5 mg t.i.d.). Baclofen (10 mg b.i.d.) has been associated with mild improvement in neck discomfort. This patient did not obtain satisfactory clinical improvement with injections of onabotulinumtoxin A and underwent limited OO myectomy at age 50 and, more extensive, integrated upper eyelid myectomy25
at age 56. Bilateral electromyographically (EMG)-guided injections of onabotulinumtoxin A (178–255 units) into the sternocleidomastoid, scalene, levator scapulae, longus colli, and longus capitis muscles were performed on three occasions, but provided only minimal benefit. In contrast, since his second myectomy procedure, this patient's blepharospasm and AEO have responded well to injections of onabotulinumtoxin A (8 units each upper eyelid pretarsal OO muscle, 47 units total).
Photographs of Three Subjects with Blepharospasm and Anterocollis
Subject #2 (), a Caucasian male, has had dry eye symptoms that were treated with punctal plugs and, eventually, tear duct cauterization. Mild but non-sustained improvements in both blepharospasm and cervical dystonia were noted with benzodiazepines (clonazepam and alprazolam) and trihexyphenidyl. AEO showed no reliable response to amphetamines. A bedtime dose of cyclobenzaprine has helped to reduce nocturnal neck discomfort. Slight improvement in AEO and blepharospasm was noted after a limited bilateral OO myectomy and frontalis muscle sling procedure. Over the past 4 years, this patient's bilateral blepharospasm and AEO have responded satisfactorily to injections of onabotulinumtoxinA (20 units each upper eyelid pretarsal OO muscle, 94 units total). In contrast, cervical dystonia with severe anterocollis has shown only modest improvements with EMG-guided injections of onabotulinumtoxin A. Current medical problems include hyperlipidemia, hypertension, and type II diabetes mellitus. The patient's sister had a single episode of bilateral eyelid closure suggestive of blepharospasm that lasted approximately 3 months and resolved without specific treatment.
Subject #3, a Caucasian female with long-standing type I diabetes mellitus, noticed the simultaneous onset of segmental craniocervical dystonia (blepharospasm and cervical dystonia) at the age of 60, 2 weeks after the loss of her spouse. Blepharospasm and AEO did not improve with clonazepam or modafinil, but have responded well to injections of onabotulinumtoxin A (10 units each upper eyelid pretarsal OO muscle, 73 units total). Peri-oral dystonia has been well controlled with injections of onabotulinumtoxin A. Bilateral dermatochalasis was treated with blepharoplasty. In general, better clinical results were obtained with injections of onabotulinumtoxin A after blepharoplasty. Cervical dystonia manifest as anterocollis with minimal left rotational torticollis has responded well to EMG-guided injections of onabotulinumtoxinA (up to 220 units).
Subject #4, an African-American male, gets limited relief of both blepharospasm and cervical dystonia symptoms when he touches his left lateral brow. He was treated with limited OO myectomy at 47 years of age. His blepharospasm and AEO have been successfully managed with injections of onabotulinumtoxin A (16 units each upper eyelid pretarsal OO muscle, 100 units total) and low-dose trihexyphenidyl (2–4 mg daily). He has declined injections of botulinum toxin for treatment of his cervical dystonia, although it has become more severe over the past several years. A younger sister has isolated blepharospasm, reportedly responsive to injections of onabotulinumtoxin A.
Subject #5 (), a Caucasian female, did not benefit from various combinations of medications including trihexyphenidyl, clonazepam, modafanil, pramipexole, levodopa, and cyclobenzaprine. Injections of onabotulinumtoxin A were moderately beneficial for blepharospasm, but produced minimal improvement in cervical dystonia. Additional reductions in blepharospasm severity and improved responses to injections of onabotulinumtoxin A were apparent after extensive integrated OO myectomy.25
However, owing to progression of anterocollis and persistent need for onabotulinumtoxin A injections to control blepharospasm, the subject underwent bilateral microelectrode-guided placement of bilateral globus pallidus pars interna (GPi) electrodes (Medtronic Kinetra). The benefits of surgery were apparent within weeks, and with her current settings (right GPi: case +, contact zero −, 2.5 V, 90 µs pulse width, 130 Hz; left GPi: case +, contact five −, 2.4 V, 60 µs pulse width, 130 Hz), there has been marked improvement of blepharospasm, AEO, and cervical dystonia. She no longer requires injections of onabotulinumtoxin A for blepharospasm/AEO, and her cervical dystonia is much improved with only slight anterocollis and minimal residual pain. Concomitant medical problems include restless legs syndrome, well controlled with pramipexole, and gastroesophageal reflux disease.
Subject #6 is a Caucasian male who underwent bilateral limited OO myectomy and frontalis muscle suspension owing to marginal benefits of onabotulinumtoxinA injections. Subsequently, an integrated upper eyelid myectomy25
was required to control blepharospasm and AEO. Since the more extensive myectomy, blepharospasm and AEO have responded well to injections (onabotulinumtoxin A: 10 units each upper eyelid pretarsal OO muscle, 62 units total). This patient has also obtained consistently good results with EMG-guided injections of onabotulinumtoxin A (up to 238 units) for treatment of cervical dystonia. At age 53, this subject began to exhibit episodic air hunger due to inspiratory laryngeal dystonia, a diagnosis confirmed by a neurolaryngologist via historical information in combination with videostroboscopy, direct laryngoscopy, and laryngeal EMG. Modest improvements in laryngeal dystonia were noted with EMG-guided injections of onabotulinumtoxin A into the thyroarytenoid muscles. Ultimately, however, a tracheostomy was required for symptom control. This patient's father, now deceased, was treated by the senior author for segmental craniocervical dystonia with severe jaw-opening, cervical dystonia with rotational torticollis and mild anterocollis, and very mild blepharospasm. Of note, subject #6's father did not show evidence of AEO or require injections for treatment of blepharospasm.
Subject #7, a Caucasian male, has blepharospasm and cervical dystonia manifest as isolated anterocollis. This patient has also exhibited mild lower facial dystonia and AEO. Sensory tricks for cervical dystonia (touching the side or back of the neck or chin) and blepharospasm (touching a lateral eyebrow) provide limited relief. He first underwent limited OO myectomy, which was followed by an integrated upper eyelid myectomy,25
and then by lower eyelid myectomy. More recently, he underwent OO myo-osseous fixation with titanium screws,26
which has been associated with marked subjective improvement in blepharospasm (~90%). For cervical dystonia, he has obtained mild benefit from injections of onabotulinumtoxin A, performed without the use of EMG guidance. Family history of dystonia includes multiple individuals in four consecutive generations. The patient's mother and one of three brothers have blepharospasm. The patient's maternal grandmother (deceased) and one of two sisters (deceased) were reported to have had manifestations of blepharospasm and lower facial dystonia.