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Show Journal of Clinical Neuro- ophthalmology 9( 4); 281- 284. 1989. Blepharospasm Associated with Olivopontocerebellar Atrophy Abdorasool Janati, M, D., W. Steven Metzer, M. D., Robert L. Archer, M. D., Jess Nickols, M. D., and Jugalkishor Raval, M. D. © 1989 Raven Press, Ltd., New York We report two cases of cranial dystonia ( blepharospasm) associated with olivopontocerebellar atrophy ( OrCA). The pathophysiology of blepharospasm appears to involve an increased excitability of the interneurons of the blink and corneal reflexes. It is hypothesized that blepharospasm associated with OrCA might be due to rostral brainstem lesions disrupting central dopaminergic and cholinergic pathways, resulting in disinhibition of brainstem reflexes or denervation supersensitivity of the facial nuclear complex. Key Words: Blepharospasm- Meige's syndromeDystonia- Movement disorders- Olivopontocerebellar atrophy- Cerebellar degeneration. From the Neurology Service of the McClellan Memorial Veterans Administration Medical Center ( A. J., W. s. M., J. N.), and the Departments of Neurology ( A. J., W. S. M., R. L. A., J. N., J. R) and Psychiatry ( W. s. M.), University of Arkansas for Medical Sciences, Little Rock, Arkansas. Address correspondence and reprint requests to Dr. A. Janati at Neurology Service ( 127/ LR), McClellan MemonaI Veterans Administration Medical Center, 4300 West Seventh Street, Little Rock, AR 72205, U. S. A. 281 Olivopontocerebellar atrophy ( OrCA) was described by Dejerine and Thomas in 1900, who distinguished the entity from Freidreich's ataxia and the " hereditary cerebellar ataxia" of Marie, while noting a similarity to the familial ataxia reported by Menzel in 1891 ( 1). Until recently, OrCA has been considered a rare pathological entity, with only 117 anatomically confirmed cases reported until 1980 ( 2). Many now consider OrCA to be a clinical syndrome comprising a large heterogenous group of disorders that share clinical features of the hereditary ataxias, parkinsonism, and the hereditary choreas. Some cases are dominantly or recessively inherited, whereas others appear to be sporadic ( 1). There is controversy regarding the utility of this concept of such a heterogenous clinical entity as OrCA, with some arguing that cases of OrCA should simply be considered variants of multiple system degeneration ( 3). Blepharospasm is a relatively uncommon condition that has been estimated to have a prevalence of 1 in 10,000. Onset is usually between the ages of 50 and 70 years, and women are more commonly afflicted than men. Only occasionally is there a family history of the disorder ( 4). Blepharospasm consists of repeated, involuntary, bilateral contractions of the orbicularis oculi muscles. It often begins as an increase in the spontaneous blink rate and may gradually progress to occupational and social disability and functional blindness ( 4- 6). Idiopathic blepharospasm alone is commonly referred to as essential blepharospasm. Idiopathic blepharospasm combined with orofacial dystonia has been referred to as orofacial- cervical dystonia, blepharospasm- oromandibular dystonia syndrome, Meige's syndrome, and Brueghel's syndrome. Some consider blepharospasm alone or oromandibular dystonia alone to be formes frustes 282 A. ] ANATI ET AL. of the complete syndrome ( 4). It is commonly accepted that the syndrome was first described by Henry Meige, a French neurologist, in 1910, who termed it " spasme facial median," although Marsden has pointed out that the syndrome was recognized by rieter Brueghel, the Elder in the 16th century ( 7). We report two cases of OrCA, one sporadic and one familial, associated with blepharospasm and orofacial dystonia. CASE REPORTS Case 1 A 56- year- old man noted the onset, at age 44, of unsteadiness, gait disturbance, slurred speech, dysphagia, and urinary incontinence. These symptoms insidiously progressed, and he became wheelchair bound at age 53. The onset of involuntary blinking and facial movements was noted about that time. Neurological evaluation at another institution included computed tomography ( CT) of the head, which revealed cerebellar and pontine atrophy. A diagnosis of OrCA was made. Further evaluation at age 54 years included electrodiagnostic testing, which indicated a sensorimotor axonopathy. Laboratory studies included , hemogram, serum electrolytes, calcium, blood urea nitrogen, creatine, T4' and arterial blood . gases, which were unremarkable. The symptoms noted continued to progress insidiously. No change in mentation occurred. There is no history of exposure to dopaminergic receptor- blocking drugs until age 56, when metoclopramide was prescribed for a few weeks for dyspepsia. There was no family history of any neurological disorders. He was readmitted at age 56. General physical examination revealed a wellnourished white man who was wheelchair bound, and was otherwise unremarkable. Neurological examination revealed normal mental status. Speech was scanning and dysarthric. Cranial nerves were intact. There was no evidence of a Kayser- Fleischer ring. Optokinetic nystagmus was intact. Ocular dysmetria and hypometric saccades were evident. Frequent involuntary contraction of the orbicularis oculi muscles was noted, with a blink rate of 40/ min. Involuntary orofacial dystonic movements were present. Bilateral intention tremor and dysmetria were present with attempted trajectory movements of the upper extremities. Severe truncal ataxia prevented standing without assistance. Mild distal muscular atnll, hv and weakness were present, with minimal diffuse rigidity. Myotatic re- J Clin Neuro- ophthIJlmol, Vol. 9, No. 4, 1989 flexes were slightly, diffusely hyperactive, and plantar reflexes were extensor bilaterally. A repeat head CT scan demonstrated severe cerebellar and pontine atrophy ( Fig. 1). Case 2 A 52- year- old woman noted the onset of gait disturbance and lower extremity weakness in her 20s, which progressed insidiously. At about age 45, she noted the insidious onset of slurred speech, and she began to experience involuntary, forceful eye closure at about age 49, particularly in response to bright light. Five of her seven siblings were similarly afflicted, but with no history of involuntary eye closure. No change in mentation was noted, and there was no history of exposure to dopaminergic receptor- blocking drugs. General physical examination was unremarkable. A neurological examination revealed normal mental status. Scanning, dysarthric speech was present. Cranial nerves were intact. There was no evidence of a Kayser- Fleischer ring. Frequent involuntary contraction of the orbicularis oculi muscles was noted. Involuntary orofacial dystonia was present. Trajectory movements of the upper extremities were normal, but severe lower extremity and truncal ataxia was present. Myotatic reflexes were slightly, diffusely hyperactive, and plantar reflexes were extensor bilaterally. Nerve conduction testing and head CT were normal. FIG. 1. Computed tomography of the head in case 1 demonstrates severe cerebellar and pontine atrophy. BLEPHAROSPASM- OPCA 283 DISCUSSION Clinical features reportedly associated with OPCA are diverse. Duvoisin considers cerebellar dysfunction and extrapyramidal dysfunction to be essential features. Other features often present include corticospinal tract manifestations and cerebellar eye signs. Features of variable occurrence include supranuclear ophthalmoplegia, optic nerve atrophy, retinal degeneration, orthostatic hypotension, incontinence, impotence, anhidrosis, myoclonus, amyotrophy, and dementia ( 1). Extrapyramidal dysfunction is most commonly manifest as bradykinesia and rigidity, with these parkinsonian features being present in most patients. Generalized and focal dystonias have been recognized, with torticollis probably being the most common focal dystonia associated with OPCA ( 2,8- 10). Ocular dysfunction reported in OrCA has included nystagmus, jerky pursuit, fixation instability, ocular dysmetria, hypometric saccades, loss of optokinetic nystagmus, slowing of saccades, and supranuclear ophthalmoplegia ( 1). We are aware of only four previously reported cases of blepharospasm associated with OrCA ( 11- 15). orCA has been characterized pathologically by atrophy due to neuronal loss in the cerebellar cortex, basis pontis, and inferior olivary nuclei. There also may be neuronal loss in the spinal cord, cerebral cortex, and basal ganglia ( 16). Anatomical pathological studies of the brainstern of OrCA patients have revealed gliosis or neuronal loss of the arcuate, pontine, inferior olivary and pontobulbar nuclei. Purkinje cell loss reportedly results from an anterograde transsynaptic degenerative phenomenon. Atrophy or gliosis has been reported to involve multiple areas of the reticular formation. The central tegmental fasciculus and various cranial nerve nuclei have also been involved in various cases ( 2). Neurophysiological investigations have frequently detected abnormal brainstem auditory evoked potential latencies in patients with OrCA ( 1). Phenomenologically, blepharospasm is considered to be a focal dystonia ( 4,7,11,15). Electromyographic recording of facial muscles with blepharospasm indicates irregular bursts of cocontraction activity in these muscles lasting 200- 300 ms to many seconds. These burst durations are much longer than those seen with myoclonus, tics, and chorea; they resemble spasms seen with generalized torsion dystonia ( 17). Blepharospasm is commonly accompanied by oromandibular dystonia and sometimes by spasmodic dysphonia or axial dystonia, such as torticollis ( 7,11). A detailed electrophysiological study found a number of abnormalities in patients with blepharospasm. Electromyographic activity was noted to be similar to that seen in other dystonic muscles. Amplitude and duration of the Rl and R2 components of the blink reflex were both increased, and some patients exhibited Rl on the side contralateral to the stimulus. The excitability cycle of recovery of the blink reflex was enhanced. Unlike voluntary blinking, electroencephalographic backaveraging failed to reveal any Bereitschafts potential ( readiness potential) preceding blepharospasm. These collective observations have led to the conclusion that there is an increased excitability of the interneurons of the blink and corneal reflexes with blepharospasm, and that this is probably due to drive from pathways from the basal ganglia ( 17). There have been few pathological studies of idiopathic blepharospasm. One recent postmortem examination of a patient with Meige's syndrome revealed neuronal loss in the substantia nigra, locus ceruleus, midbrain tectum and dentate nuclei, as well as Lewy bodies in the brainstem pigmented nuclei ( 18). Another recent pathological investigation found a small angioma in the dorsal pons at the site of the central tegmental tract in a patient who had been diagnosed as having essential blepharospasm. In three other cases of idiopathic cranial dystonia, no significant brainstem abnormalities were detected ( 19). Blepharospasm clinically similar to essential blepharospasm has been reported in patients with multiple sclerosis plaques of the rostral brainstem, and with infarctions of rostral brainstem, diencephalon, and basal ganglia bilaterally ( 12,14,20- 22). Neurophysiological and pathological findings thus provide some evidence of brainstem pathology or enhancement of basal ganglia brainstem " drive" playing a role in the genesis of blepharospasm. Delayed onset of dystonia in a patient with static encephalopathy has been attributed to " sprouting" of surviving neurons ( 23). Similarly, disruption of central dopaminergic and cholinergic pathways due to rostral brainstem lesions, as seen with OrCA, might result in disinhibition of brainstem reflexes or denervation supersensitivity of the facial nuclear complex, resulting in cranial dystonia, such as blepharospasm ( 12,13,24). This pathophysiological model is supported by the observation that another movement disorder, palatal myoclonus, possibly results from delayed denervation supersensitivity after a lesion of the inferior olive ( 25). Interestingly, a case of blepharospasm , Clill Neuro- ophthalmol, Vol. 9, No. 4, 1989 284 A. JANATI ET AL. associated with palatal myoclonus has been reported ( 13). REFERENCES 1. Duvoisin RC. The olivopontocerebellar atrophies. In: Marsden CD, Fahn 5, eds. Mopement disorders 2. London: Butterworth, 1987: 249- 69. 2. Berciano J. Olivopontocerebellar atrophy. I Neurol Sci 1982; 53: 253-- 72. 3. Harding AE. Commentary: olivopontocerebelJar atrophy is not a useful concept. In: Marsden CD, Fahn 5, eds. Mopement disorders 2. London: Butterworth, 1987: 269- 71. 4. Metzer WS, Nazarian SM. Blepharospasm: overview and update. In: Smith JL, Katz RS, eds. Neuro- ophthalmology enters the nineties. Miami, Florida: Dutton Press, 1988: 343-- 53. 5. Dening TR. 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