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Botulinum toxin treatment of apraxia of eyelid opening in progressive supranuclear palsy: Report of two cases
525
CLINICAL NOTES
Botulinum Toxin Treatment of Apraxia of Eyelid Opening in Progressive Supranuclear Palsy: Report of Two Cases Francesco Piccione, MD, Elena Mancini, MD, Paolo Tonin, MD, Massimo Bizzarini, MD ABSTRACT. Piccione F, Mancini E, Tonin P, Bizzarini M. Botulinum toxin treatment of apraxia of eyelid opening in progressive supranuclear palsy: report of two cases. Arch Phys Med Rehabil 1997;78:525-9. We report two patients, with postural instability and dystonic parkinsonism whose adjunctive disabling feature was blindness due to an inability to reopen the eyes after voluntary closure of the eyelids, as in apraxia of lid opening (ALO). Supranuclear downgaze paresis permitted the diagnosis of progressive supranuclear palsy (PSP) in one case. Electromyographic studies showed a loss of normal reciprocal inhibition between the levator palpebrae and the pretarsal portion of the orbicularis oculi, with a cocontraction of these two antagonist muscles. The evoked blink reflex, tested with the paired shock technique, showed enhanced recovery of R2 response. Botulinum toxin A injections directed toward the junction of the preseptal and pretarsal parts of the palpebral orbicularis oculi muscle improved eyelid motility in both patients. Successive static and dynamic balance training and development of compensatory strategies for visual scanning deficits reduced gait imbalance, the number of falls, and the disability level as measured on the Northwestern University Disability Scale.
© 1997 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation
oculi muscle"), in spite of phasic or tonic activities of the LP. Recently Krack and Marion 1 presumed that isolated spasm of the pretarsal portion of OO results in ALO, while the involvement of the orbital portion of the OO muscle produces typical blepharospasm. We report clinical and electromyographic evidence for considering ALO an eyelid dystonia in patients with PSP. Appreciation that dystonia is the pathophysiologic mechanism underlying ALO provided therapeutic guidance and favored the patient's rehabilitative management. PATIENTS AND METHODS
Two patients with dystonic parkinsonism and blindness due to an inability to reopen the eyes after voluntary closure of the eyelids, as in ALO, were clinically examined. A pretreatment electrophysiological examination was carried out to investigate the origin of the eyelid movement disorder of the patients and to gain therapeutic guidance. Immediately after this examination, single botulinum toxin treatment was given. Subsequently, it was possible to perform a rehabilitation program lasting 4 weeks. Disability level of patients was assessed before and after rehabilitative treatment using the gait score of the NorthWestern University Disability Scale. 6
PRAXIA OF LID OPENING (ALO) is a disorder of eyelid motility, more prominent in idiopathic blepharospasm, progressive supranuclear palsy (PSP), and other dystonic parkinsonian syndromes, characterized by the patient's inability to reopen the eyes after voluntary closure of the eyelids. 1 On clinical observation, there was no overt spasm of the orbicularis oculi muscle (OO) and the eyes appeared to be passively shut with frontalis muscle overaction causing elevation of the brows. Disorders of eyelid motility may be found in more than one third of patients with PSP and include decreased blink rate, eyelid retraction, apraxia of eyelid opening and closure, and blepharospasm. 2 Lepore and Duvoisin~ suggested that ALO is due to involuntary levator palpebrae muscle (LP) inhibition of supranuclear origin. Elston4judged this disorder as a variant of blepharospasm due to abnormal contraction in the pretarsal portion of OO. Aramideh et al5 considered inability to reopen the eyes after voluntary closure of the eyelids as an incapacity to inhibit the contraction of the OO ("motor persistence of orbicularis
A
From the Departmentof Neurorehabilitation,OspedaleS. Camillo,AlberoniVenezia (Drs. Piccione, Mancini,Tonin);and the Department of Neurology, Ospedali CiviliRiuniti,Venezia(Dr. Bizzarini),Italy. Submittedfor publicationMay 13, 1996.Acceptedin revisedform September 17, 1996. No commercialparty having a direct financialinterestin the results of the research supportingthis articlehas or will confer a benefituponthe authors or upon any organizationwith whichthe authorsare associated. Reprints requests to Dr. FranceseoPiccione, Ospedale San Camillo,30011, Alberoni-Venezia,Italy. © 1997by the AmericanCongressof RehabilitationMedicineandthe American Academyof PhysicalMedicineand Rehabilitation 0003-9993/97/7805-402153.00/0
Fig 1. MRI in patient 1 showing pronounced brain stem atrophy in a picture of a mild diffuse cerebral atrophy without lateral ventricular dilatation.
Arch Phys Med Rehabil Vol 78, May 1997
526
TREATMENT OF APRAXIA OF EYELID OPENING IN PSP, Piccione
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Patient 1. A 61-year-old man with no history of neurological disease experienced increasing difficulty with ambulation leading to frequent falls, stiffness in voluntary axial movements of the body, and progressive slurring of speech: On neurological examination he showed downgaze paresis, bradykinesia, axial rigidity, and dysarthria; his gait was slow and wide-based, with postural instability and sitting "en bloc." L-DOPA therapy produced no improvement. Three years after the onset of the disease, the symptoms progressed and the patient clinically presented an inability to open the eyes after voluntary closure of the eyelids. On clinical observation, there was no clear spasm of the OO and the eyes appeared to be passively shut with frontalis muscle overaction causing elevation of the brows on attempt to open the eyes. The patient also suffered from episodes of involuntary eyelid closure, always without any evidence of clinically visible lowering of the brows beneath the superior orbital rim, worsening in bright light or while walking. The eyes could be opened by stroking or massaging the inferior lids. On follow-up, the patient developed apraxia of eyelid closure and subsequently had trouble swallowing solid foods and liquids, as well as cognitive impairment in short-term memory and spatial orientation. Magnetic resonance imaging (MRI) showed pronounced midbrain atrophy in a picture of a diffuse cerebral atrophy (fig 1). Patient 2. A 68-year-old woman had been in good health until age 62 when she noted clumsiness in walking and postural
Arch Phys Med Rehabil Vol 78, May 1997
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Case Reports
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Fig 2. EMG recording in patient 1, showing that following the command to close the eyes, the pretarsal portion of OO showed dense bursts of action potentials accompanied by inhibition of the LP, whereas on the command to open the eyes, contraction of the OO persisted, despite the activity of the LP, and the eyes remained closed.
instability with abrupt falls. Subsequently, she developed extreme slowness in motion, apathy with loss of initiative, and stiffness in voluntary axial movements. At the age of 63, the clinical features were characterized by bradykinesia, disorder of postural reflexes, neck rigidity in extension, and mild dysarthria. Parkinsonism was considered as a clinical diagnosis. Treatment with levodopa did not improve her neurological symptoms. Four years after the onset of the disease she complained of transient inability to open her eyes and difficulty in swallowing. On admission, neurological examination revealed stiff and broadbased gait with a tendency to fall. She showed neck dystonia, dysarthria, and dysphagia. A lower limb dystonia was present, with tonic extension of the big toe. She fell heavily when sitting down and had difficulty getting up from a chair unless she pushed off with her hands. Cognitive evaluation revealed mild cognitive impairment of short memory and mental slowing. She clinically presented a transitory inability to initiate lid opening, without any obvious spasms of the OO. The effort to open the eyes was demonstrated by forceful frontalis contraction. The eyes could be opened by touching the inferior lids. All examinations, including computed tomography (CT) of the brain, were normal. Investigation with MRI revealed a puntiform left-sided hyperintense white matter lesion of uncertain aetiology. Because of defects in route-finding and inability to visually scan the environment, both patients required close supervision for daily living activities such as transfers and ambulation. Both patients never walked alone and needed considerable help, even
TREATMENT OF APRAXIA OF EYELID OPENING IN PSP, Piccione
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for short distances, to avoid falls. Rehabilitative activities, including limb coordination, static and dynamic balance training, and ambulation activities with assistive devices, were useless. Electrophysiological Investigation Synchronus electromyogram (EMG) recording was performed from LP and the CO with the subjects in supine position, as reported by Aramideh et al. 7 A bipolar needle electrode (0.3mm) was inserted through the middle portion of the closed upperlid, to record from LP. Patients were then asked to open their eyes and EMG activity of the LP increased. This muscle was differentiated from the superior rectus by the antagonistic activity during voluntary eye opening and closure. A further bipolar needle electrode was also inserted into the pretarsal portion of OO. Patients were asked to close their eyes and EMG activity of the CO increased. The two EMG signals were displayed simultaneously on a Nicolet Viking IP with a high pass filter set at 300Hz (to minimize movement artifact), and low pass filter at 10KHz. 6 Patients were instructed to close their eyes and open their eyes, at first in darkness and then in bright light. Blink reflex study was performed by using the paired shock technique suggested by Kimura8 to investigate the state of excitability of the facial motoneurons and bulbar interneurons rather than the integrity of the blink reflex circuit. A pair of cutaneous recording electrodes (0.5cm) were placed on both OO, the active one on the middle part of the lower eyelid. The stimuli, of
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0.1msec duration, were applied to the supra orbital nerve, at the supraorbital foramen, at an intensity adjusted to three times the threshold of the R2 response. The low pass filter was set at 3KHz and the high pass filter at 30Hz. The sweep time was kept at 100msec. Paired (conditioning and test) stimuli were given at variable interstimuli interval between 166 and 500msec. Amplitude of rectified responses to pair stimuli were analyzed and compared offtine. Treatment The botulinum toxin treatment consisted of four injections per eye9 of botulinum toxin type A (Botoxb), into the components of the OO. Injections were directed toward the junction of the preseptal and pretarsal portions, laterally and medially in the upper and lowerlid. Doses were expressed in units of botulinum toxin. The dose of botulinum toxin was 12.5U per eye. Successive rehabilitative treatment consisted of limb coordination activity and fine motor activities, with visual, auditory, spatial, and tactile cues, static and dynamic balance training, ambulation activities with assistive devices, trying to incorporate trunk flexion and rotation. Botulinum toxin treatment was not repeated. RESULTS EMG recording in patient 1 revealed that following the command to close the eyes, the pretarsal portion of CO showed dense bursts of action potentials accompanied by inhibition of
Arch Phys Med Rehabil Vol 78, May 1997
528
TREATMENT OF APRAXIA OF EYELID OPENING IN PSP, Piccione
Fig 4. Recovery cycle of the R2 component of the blink reflex in patient 1, at interval of 200 and of 165msec between test and conditioning stimuli. For each session the upper traces are the rectified EMG activity from left OO (LOO) and the lower traces are from right OO (ROO). The stimuli were applied to the right supraorbital nerve at the start of the sweep. The amplitude of the R2 was decreased to about 30% of unconditioned values when the interval between the conditioning and the test stimuli was 165msec, while the response was unaffected (or only moderately decreased) when interstimuli interval was 200msec.
the LP, whereas on the command to open the eyes, contraction of the OO persisted, despite the activity of the LP, and the eyes remained closed (fig 2). Involuntary discharges in the pretarsal portion of OO determined also involuntary eyelid closure, in bright light. EMG recording in patient 2 revealed that following the command to open the eyes, activity of LP increased, but the OO remained active for 2 to 3 seconds, resulting in episodes of cocontractions of the LP and OO, during which the eyelids remained closed. Delayed inhibition of OO discharges, accompanied by a further increase in LP activity, permitted eyelid opening (fig 3). Blink reflex study, performed by using the paired shock technique, showed an enhanced recovery cycle of the R2 component in both patients. In fact, the amplitude of the R2 was decreased to about 30% of unconditioned values, when the interval between the conditioning and the test stimuli was 165msec (patient 1) or 200msec (patient 2). The response was unaffected (or only moderately decreased) when the interstimuli interval was between 250 and 500msec (fig 4). Botulinum toxin injections directed toward the junction of the preseptal and pretarsal parts of the palpebral OO improved eyelid motility in both patients. The duration of benefit was 4 to 5 weeks. During this period better eyelid motility and visual scanning permitted rehabilitative activities. Rehabilitation reduced gait imbalance, the number of falls, and the disability level as measured by the Northwestern University Disability Scale. Before the treatment both patients never walked alone and needed moderate help indoors and outdoors (gait score, 3). Following the rehabilitation program of 4 weeks, both patients ambulated independently (gait score, 7).
Arch Phys Med Rehabil Vol 78, May 1997
DISCUSSION Adult-onset dystonia-parkinsonism syndrome may occur in untreated patients with a clinical diagnosis of idiopathic Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). 1° Nevertheless, importance of dystonia in the pathophysiology of PSP has been emphasized by many authors with regard to both the axial dystonia that is a cardinal feature of the disease, and with regard to the frequent occurrence of focal dystonias, including limb dystonia and blepharospasm. 11 Characteristic features of patient 1, including supranuclear downgaze paresis, prominent early postural instability with frequent fails, axial rigidity, bradykinesia, pseudobulbar signs, and cognitive impairment of frontal type, permitted the clinical diagnosis of PSP. 12 The presence of axial dystonia and focal dystonias may be a key finding in considering the diagnosis of PSP in patient 2, with postural instability and atypical parkinsonism but lacking ophthalmoplegia. Absence of tremor and autonomic dysfunction, rapid progression of disease, and no benefit from levodopa therapy excluded the clinical diagnosis of PD and of MSA. 1314 ' In both patients, the distinctive disabling feature was blindness due to an inability to reopen the eyes after voluntary closure of the eyelids, as in ALO. We presented clinical and electromyographic evidence for considering ALO an eyelid dystonia. Both patients showed an inability to reopen the eyes after voluntary closure of the eyelids, due to inability to inhibit the contraction of the OO, in spite of phasic or tonic activities of the LP, as in "motor persistence of orbicularis oculi muscle" described by Aramideh et al. 5 In patient 1, involuntary discharges in the pretarsal portion of OO also determined involuntary eyelid closure, as in ' 'pretarsal blepharospasm". 4 Our patients did not show drooping of the eyelids, as in "involuntary levator palpebrae inhibition",3 because the tonic activity of the LP was intact. On follow-up,
TREATMENT OF APRAXIA OF EYELID OPENING IN PSP, Piccione
patient 1 developed apraxia of eyelid closure and was unable to close the eyelids on command. Therefore, our patient was unable to inhibit a voluntary contracted m u s c l e - - L P in apraxia of eyelid closure and OO in apraxia of eyelid opening. Our study showed a loss of normal reciprocal inhibition between LP and the pretarsal portion of OO, with a cocontraction of these two antagonistic muscles. This EMG pattern is common to the different types of dystonia. In fact, dystonic movements produce continous or semicontinous involuntary electromyographic activity, characterized by contraction of the agonist and antagonist muscles that increases during the execution of voluntary movements. An increased R2 recovery curve has been found in patients with parkinsonism, blepharospasm and various focal dystonias. 7'15'16Our blink reflex studies confirmed an increased excitability of brain stem interneurons in dystonic parkinsonian syndrome. Blindness due to ALO associated with postural instability may have contributed to incapacity to walk or stand unassisted in our patients. Botulinum toxin injections directed toward the junction of the preseptal and pretarsal parts of the palpebral OO improved eyelid motility in both patients, probably eliminating the trigger mechanism for inability to initiate lid opening. ~7'18 Better eyelid motility and improved visual scanning obtained with botulinum toxin injections permitted rehabilitative training, which reduced gait imbalance, number of falls, and disability level as measured by the Northwestern University Disability Scale. 19,2° Our patient's gait improvement probably resulted from rehabilitative treatment of postural instability and from botulinum toxin resolution of visual complaints due to ALO. These results confirm that botulinum toxin may be useful for symptomatic treatment of focal dystonias in PSP, including both blepharospasm and limb dystonia, ~'2'2a and favor the rehabilitative management of patients. References 1. Krack P, Marion MH. "Apraxia of lid opening", a focal eyelid dystonia: clinical study of 32 patients. Mov Disord 1994; 6:610-5. 2. Friedman DI, Jankovic J, McCrary III JA. Neuro-ophthalmic findings in progressive supranuclear palsy. J Clin Neuroophthalmol 1992; 12:104-9. 3. Lepore FE, Duvoisin RC. "Apraxia" of eyelid opening: an involuntary levator inhibition. Neurology 1985; 35:423-7. 4. Elston JS. A new variant of blepharospasm. J Neurol Neurosurg Psychiatry 1992;55:369-71. 5. Aramideh M, Ongerboer de Visser BW, Koelman JHTM, Speelman JD. Motor persistence of orbicularis oculi muscle in eyelid-opening disorders. Neurology 1995;45:897-902.
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6. Canter CJ, De La Torre R, Mier M. A method for evaluating disability in patients with Parkinson's disease. J Nerv Mental Disord 1961; 133:143-7. 7. Aramideh M, Ongerboer de Visser BW, Devriese PP, Bour LJ, Speelman JD. Electromyographic features of levator palpebrae superioris and orbicularis oculi muscles in blepharospasm. Brain 1994; 117:27-38. 8. Kimura J. Disorder of interneurons in parkinsonism. The orbicularis oculi reflex to paired stimuli. Brain 1973;96:87-96. 9. Eleopra R, Tugnoli V, Caniatti L, De Grandis D. Botulinum toxin treatment in the facial muscles of humans: evidence of an action in untreated near muscles by peripheral local diffusion. Neurology 1996;46:1158-60. 10. Rivest J, Quinn N, Mardsen CD. Dystonia in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy. Neurology 1990;40:1571-8. 11. Rafal RD, Friedman JH. Limb dystonia in progressive supranuclear palsy. Neurology 1987;37:1546-9. 12. Collins SJ, Ahlskog JE, Parisi JE, Maraganore DM. Progressive supranuclear palsy: neuropathologically based diagnostic clinical criteria. J Neurol Neurosurg Psychiatry 1995;58:167-73. 13. Daniel SE, de Bruin VMS, Lees AJ. The clinical and pathological spectrum of Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy): a reappraisal. Brain 1995; 118:759-70. 14. Colosimo C, Albanese A, Hughes AJ, de Bruin VMS, Lees AJ. Some specific clinical features differentiate multiple system atrophy (striatonigral variety) from Parkinson's disease. Arch Neurol 1995; 52:294-8. 15. Berardelli A, Rothwell JC, Day BL, Marsden CD. Pathophysiology of blepharospasm and oromandibular dystonia. Brain 1985; 108: 593-608. 16. Eekhof JLA, Aramideh M, Bour LJ, Hilgevoord AAJ, Speelman HD, Ongerboer de Visser BW. Blink reflex recovery curves in blepharospasm, torticollis spasmodica, and hemifacial spasm. Muscle Nerve 1995; 19:10-5. 17. Vails-Sole J, Tolosa ES, Ribera G. Neurophysiological observations on the effects of botulinum toxin treatment in patients with dystonic blepharospasm. J Neurol Neurosurg Psychiatry 1991;54:310-3. 18. Aramideh M, Ongerboer de Visser BW, Brans JWM, Koelman JHTM, Speelman JD. Pretarsal application of botulinum toxin for treatment of blepharospasm. J Neurol Neurosurg Psychiatry 1995; 59:309-11. 19. Dam M, Tonin P, Casson S, Bracco F, Piron L, Pizzolato G, et al. Effects of conventional and sensory-enhanced physiotherapy on disability of Parkinson's disease patients. Adv Nenrol 1996;69:5515. 20. Sosner J, Wall GC, Sznajder J. Progressive supranuclear palsy: clinical presentation and rehabilitation of two patients. Arch Phys Med Rehabil 1993;74:537-9. 21. Polo KB, Jabbari B. Botulinum toxin-A improves the rigidity of progressive supranuclear palsy. Ann Nenrol 1994; 35:237-9. Suppliers a. Mortara Rangoni Europe SRL, Via Oradour N. 7, 40016 S. Giorgio Di Piano (BO), Italy. b. Allergan SPA, Via Costarica 20/22, 00040 Pomezia (RM), Italy.
Arch Phys Med Rehabil Vol 78, May 1997
CLINICAL NOTES
Botulinum Toxin Treatment of Apraxia of Eyelid Opening in Progressive Supranuclear Palsy: Report of Two Cases Francesco Piccione, MD, Elena Mancini, MD, Paolo Tonin, MD, Massimo Bizzarini, MD ABSTRACT. Piccione F, Mancini E, Tonin P, Bizzarini M. Botulinum toxin treatment of apraxia of eyelid opening in progressive supranuclear palsy: report of two cases. Arch Phys Med Rehabil 1997;78:525-9. We report two patients, with postural instability and dystonic parkinsonism whose adjunctive disabling feature was blindness due to an inability to reopen the eyes after voluntary closure of the eyelids, as in apraxia of lid opening (ALO). Supranuclear downgaze paresis permitted the diagnosis of progressive supranuclear palsy (PSP) in one case. Electromyographic studies showed a loss of normal reciprocal inhibition between the levator palpebrae and the pretarsal portion of the orbicularis oculi, with a cocontraction of these two antagonist muscles. The evoked blink reflex, tested with the paired shock technique, showed enhanced recovery of R2 response. Botulinum toxin A injections directed toward the junction of the preseptal and pretarsal parts of the palpebral orbicularis oculi muscle improved eyelid motility in both patients. Successive static and dynamic balance training and development of compensatory strategies for visual scanning deficits reduced gait imbalance, the number of falls, and the disability level as measured on the Northwestern University Disability Scale.
© 1997 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation
oculi muscle"), in spite of phasic or tonic activities of the LP. Recently Krack and Marion 1 presumed that isolated spasm of the pretarsal portion of OO results in ALO, while the involvement of the orbital portion of the OO muscle produces typical blepharospasm. We report clinical and electromyographic evidence for considering ALO an eyelid dystonia in patients with PSP. Appreciation that dystonia is the pathophysiologic mechanism underlying ALO provided therapeutic guidance and favored the patient's rehabilitative management. PATIENTS AND METHODS
Two patients with dystonic parkinsonism and blindness due to an inability to reopen the eyes after voluntary closure of the eyelids, as in ALO, were clinically examined. A pretreatment electrophysiological examination was carried out to investigate the origin of the eyelid movement disorder of the patients and to gain therapeutic guidance. Immediately after this examination, single botulinum toxin treatment was given. Subsequently, it was possible to perform a rehabilitation program lasting 4 weeks. Disability level of patients was assessed before and after rehabilitative treatment using the gait score of the NorthWestern University Disability Scale. 6
PRAXIA OF LID OPENING (ALO) is a disorder of eyelid motility, more prominent in idiopathic blepharospasm, progressive supranuclear palsy (PSP), and other dystonic parkinsonian syndromes, characterized by the patient's inability to reopen the eyes after voluntary closure of the eyelids. 1 On clinical observation, there was no overt spasm of the orbicularis oculi muscle (OO) and the eyes appeared to be passively shut with frontalis muscle overaction causing elevation of the brows. Disorders of eyelid motility may be found in more than one third of patients with PSP and include decreased blink rate, eyelid retraction, apraxia of eyelid opening and closure, and blepharospasm. 2 Lepore and Duvoisin~ suggested that ALO is due to involuntary levator palpebrae muscle (LP) inhibition of supranuclear origin. Elston4judged this disorder as a variant of blepharospasm due to abnormal contraction in the pretarsal portion of OO. Aramideh et al5 considered inability to reopen the eyes after voluntary closure of the eyelids as an incapacity to inhibit the contraction of the OO ("motor persistence of orbicularis
A
From the Departmentof Neurorehabilitation,OspedaleS. Camillo,AlberoniVenezia (Drs. Piccione, Mancini,Tonin);and the Department of Neurology, Ospedali CiviliRiuniti,Venezia(Dr. Bizzarini),Italy. Submittedfor publicationMay 13, 1996.Acceptedin revisedform September 17, 1996. No commercialparty having a direct financialinterestin the results of the research supportingthis articlehas or will confer a benefituponthe authors or upon any organizationwith whichthe authorsare associated. Reprints requests to Dr. FranceseoPiccione, Ospedale San Camillo,30011, Alberoni-Venezia,Italy. © 1997by the AmericanCongressof RehabilitationMedicineandthe American Academyof PhysicalMedicineand Rehabilitation 0003-9993/97/7805-402153.00/0
Fig 1. MRI in patient 1 showing pronounced brain stem atrophy in a picture of a mild diffuse cerebral atrophy without lateral ventricular dilatation.
Arch Phys Med Rehabil Vol 78, May 1997
526
TREATMENT OF APRAXIA OF EYELID OPENING IN PSP, Piccione
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Patient 1. A 61-year-old man with no history of neurological disease experienced increasing difficulty with ambulation leading to frequent falls, stiffness in voluntary axial movements of the body, and progressive slurring of speech: On neurological examination he showed downgaze paresis, bradykinesia, axial rigidity, and dysarthria; his gait was slow and wide-based, with postural instability and sitting "en bloc." L-DOPA therapy produced no improvement. Three years after the onset of the disease, the symptoms progressed and the patient clinically presented an inability to open the eyes after voluntary closure of the eyelids. On clinical observation, there was no clear spasm of the OO and the eyes appeared to be passively shut with frontalis muscle overaction causing elevation of the brows on attempt to open the eyes. The patient also suffered from episodes of involuntary eyelid closure, always without any evidence of clinically visible lowering of the brows beneath the superior orbital rim, worsening in bright light or while walking. The eyes could be opened by stroking or massaging the inferior lids. On follow-up, the patient developed apraxia of eyelid closure and subsequently had trouble swallowing solid foods and liquids, as well as cognitive impairment in short-term memory and spatial orientation. Magnetic resonance imaging (MRI) showed pronounced midbrain atrophy in a picture of a diffuse cerebral atrophy (fig 1). Patient 2. A 68-year-old woman had been in good health until age 62 when she noted clumsiness in walking and postural
Arch Phys Med Rehabil Vol 78, May 1997
260 ~U 'R~t~ rl
IHtlJll.~9OL~lllLlilFllree
~ 'r Irt" I'1,~1 m~f'r l"I1;'le'~"d"r~'F~l~
Case Reports
2
1
Fig 2. EMG recording in patient 1, showing that following the command to close the eyes, the pretarsal portion of OO showed dense bursts of action potentials accompanied by inhibition of the LP, whereas on the command to open the eyes, contraction of the OO persisted, despite the activity of the LP, and the eyes remained closed.
instability with abrupt falls. Subsequently, she developed extreme slowness in motion, apathy with loss of initiative, and stiffness in voluntary axial movements. At the age of 63, the clinical features were characterized by bradykinesia, disorder of postural reflexes, neck rigidity in extension, and mild dysarthria. Parkinsonism was considered as a clinical diagnosis. Treatment with levodopa did not improve her neurological symptoms. Four years after the onset of the disease she complained of transient inability to open her eyes and difficulty in swallowing. On admission, neurological examination revealed stiff and broadbased gait with a tendency to fall. She showed neck dystonia, dysarthria, and dysphagia. A lower limb dystonia was present, with tonic extension of the big toe. She fell heavily when sitting down and had difficulty getting up from a chair unless she pushed off with her hands. Cognitive evaluation revealed mild cognitive impairment of short memory and mental slowing. She clinically presented a transitory inability to initiate lid opening, without any obvious spasms of the OO. The effort to open the eyes was demonstrated by forceful frontalis contraction. The eyes could be opened by touching the inferior lids. All examinations, including computed tomography (CT) of the brain, were normal. Investigation with MRI revealed a puntiform left-sided hyperintense white matter lesion of uncertain aetiology. Because of defects in route-finding and inability to visually scan the environment, both patients required close supervision for daily living activities such as transfers and ambulation. Both patients never walked alone and needed considerable help, even
TREATMENT OF APRAXIA OF EYELID OPENING IN PSP, Piccione
527
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for short distances, to avoid falls. Rehabilitative activities, including limb coordination, static and dynamic balance training, and ambulation activities with assistive devices, were useless. Electrophysiological Investigation Synchronus electromyogram (EMG) recording was performed from LP and the CO with the subjects in supine position, as reported by Aramideh et al. 7 A bipolar needle electrode (0.3mm) was inserted through the middle portion of the closed upperlid, to record from LP. Patients were then asked to open their eyes and EMG activity of the LP increased. This muscle was differentiated from the superior rectus by the antagonistic activity during voluntary eye opening and closure. A further bipolar needle electrode was also inserted into the pretarsal portion of OO. Patients were asked to close their eyes and EMG activity of the CO increased. The two EMG signals were displayed simultaneously on a Nicolet Viking IP with a high pass filter set at 300Hz (to minimize movement artifact), and low pass filter at 10KHz. 6 Patients were instructed to close their eyes and open their eyes, at first in darkness and then in bright light. Blink reflex study was performed by using the paired shock technique suggested by Kimura8 to investigate the state of excitability of the facial motoneurons and bulbar interneurons rather than the integrity of the blink reflex circuit. A pair of cutaneous recording electrodes (0.5cm) were placed on both OO, the active one on the middle part of the lower eyelid. The stimuli, of
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0.1msec duration, were applied to the supra orbital nerve, at the supraorbital foramen, at an intensity adjusted to three times the threshold of the R2 response. The low pass filter was set at 3KHz and the high pass filter at 30Hz. The sweep time was kept at 100msec. Paired (conditioning and test) stimuli were given at variable interstimuli interval between 166 and 500msec. Amplitude of rectified responses to pair stimuli were analyzed and compared offtine. Treatment The botulinum toxin treatment consisted of four injections per eye9 of botulinum toxin type A (Botoxb), into the components of the OO. Injections were directed toward the junction of the preseptal and pretarsal portions, laterally and medially in the upper and lowerlid. Doses were expressed in units of botulinum toxin. The dose of botulinum toxin was 12.5U per eye. Successive rehabilitative treatment consisted of limb coordination activity and fine motor activities, with visual, auditory, spatial, and tactile cues, static and dynamic balance training, ambulation activities with assistive devices, trying to incorporate trunk flexion and rotation. Botulinum toxin treatment was not repeated. RESULTS EMG recording in patient 1 revealed that following the command to close the eyes, the pretarsal portion of CO showed dense bursts of action potentials accompanied by inhibition of
Arch Phys Med Rehabil Vol 78, May 1997
528
TREATMENT OF APRAXIA OF EYELID OPENING IN PSP, Piccione
Fig 4. Recovery cycle of the R2 component of the blink reflex in patient 1, at interval of 200 and of 165msec between test and conditioning stimuli. For each session the upper traces are the rectified EMG activity from left OO (LOO) and the lower traces are from right OO (ROO). The stimuli were applied to the right supraorbital nerve at the start of the sweep. The amplitude of the R2 was decreased to about 30% of unconditioned values when the interval between the conditioning and the test stimuli was 165msec, while the response was unaffected (or only moderately decreased) when interstimuli interval was 200msec.
the LP, whereas on the command to open the eyes, contraction of the OO persisted, despite the activity of the LP, and the eyes remained closed (fig 2). Involuntary discharges in the pretarsal portion of OO determined also involuntary eyelid closure, in bright light. EMG recording in patient 2 revealed that following the command to open the eyes, activity of LP increased, but the OO remained active for 2 to 3 seconds, resulting in episodes of cocontractions of the LP and OO, during which the eyelids remained closed. Delayed inhibition of OO discharges, accompanied by a further increase in LP activity, permitted eyelid opening (fig 3). Blink reflex study, performed by using the paired shock technique, showed an enhanced recovery cycle of the R2 component in both patients. In fact, the amplitude of the R2 was decreased to about 30% of unconditioned values, when the interval between the conditioning and the test stimuli was 165msec (patient 1) or 200msec (patient 2). The response was unaffected (or only moderately decreased) when the interstimuli interval was between 250 and 500msec (fig 4). Botulinum toxin injections directed toward the junction of the preseptal and pretarsal parts of the palpebral OO improved eyelid motility in both patients. The duration of benefit was 4 to 5 weeks. During this period better eyelid motility and visual scanning permitted rehabilitative activities. Rehabilitation reduced gait imbalance, the number of falls, and the disability level as measured by the Northwestern University Disability Scale. Before the treatment both patients never walked alone and needed moderate help indoors and outdoors (gait score, 3). Following the rehabilitation program of 4 weeks, both patients ambulated independently (gait score, 7).
Arch Phys Med Rehabil Vol 78, May 1997
DISCUSSION Adult-onset dystonia-parkinsonism syndrome may occur in untreated patients with a clinical diagnosis of idiopathic Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). 1° Nevertheless, importance of dystonia in the pathophysiology of PSP has been emphasized by many authors with regard to both the axial dystonia that is a cardinal feature of the disease, and with regard to the frequent occurrence of focal dystonias, including limb dystonia and blepharospasm. 11 Characteristic features of patient 1, including supranuclear downgaze paresis, prominent early postural instability with frequent fails, axial rigidity, bradykinesia, pseudobulbar signs, and cognitive impairment of frontal type, permitted the clinical diagnosis of PSP. 12 The presence of axial dystonia and focal dystonias may be a key finding in considering the diagnosis of PSP in patient 2, with postural instability and atypical parkinsonism but lacking ophthalmoplegia. Absence of tremor and autonomic dysfunction, rapid progression of disease, and no benefit from levodopa therapy excluded the clinical diagnosis of PD and of MSA. 1314 ' In both patients, the distinctive disabling feature was blindness due to an inability to reopen the eyes after voluntary closure of the eyelids, as in ALO. We presented clinical and electromyographic evidence for considering ALO an eyelid dystonia. Both patients showed an inability to reopen the eyes after voluntary closure of the eyelids, due to inability to inhibit the contraction of the OO, in spite of phasic or tonic activities of the LP, as in "motor persistence of orbicularis oculi muscle" described by Aramideh et al. 5 In patient 1, involuntary discharges in the pretarsal portion of OO also determined involuntary eyelid closure, as in ' 'pretarsal blepharospasm". 4 Our patients did not show drooping of the eyelids, as in "involuntary levator palpebrae inhibition",3 because the tonic activity of the LP was intact. On follow-up,
TREATMENT OF APRAXIA OF EYELID OPENING IN PSP, Piccione
patient 1 developed apraxia of eyelid closure and was unable to close the eyelids on command. Therefore, our patient was unable to inhibit a voluntary contracted m u s c l e - - L P in apraxia of eyelid closure and OO in apraxia of eyelid opening. Our study showed a loss of normal reciprocal inhibition between LP and the pretarsal portion of OO, with a cocontraction of these two antagonistic muscles. This EMG pattern is common to the different types of dystonia. In fact, dystonic movements produce continous or semicontinous involuntary electromyographic activity, characterized by contraction of the agonist and antagonist muscles that increases during the execution of voluntary movements. An increased R2 recovery curve has been found in patients with parkinsonism, blepharospasm and various focal dystonias. 7'15'16Our blink reflex studies confirmed an increased excitability of brain stem interneurons in dystonic parkinsonian syndrome. Blindness due to ALO associated with postural instability may have contributed to incapacity to walk or stand unassisted in our patients. Botulinum toxin injections directed toward the junction of the preseptal and pretarsal parts of the palpebral OO improved eyelid motility in both patients, probably eliminating the trigger mechanism for inability to initiate lid opening. ~7'18 Better eyelid motility and improved visual scanning obtained with botulinum toxin injections permitted rehabilitative training, which reduced gait imbalance, number of falls, and disability level as measured by the Northwestern University Disability Scale. 19,2° Our patient's gait improvement probably resulted from rehabilitative treatment of postural instability and from botulinum toxin resolution of visual complaints due to ALO. These results confirm that botulinum toxin may be useful for symptomatic treatment of focal dystonias in PSP, including both blepharospasm and limb dystonia, ~'2'2a and favor the rehabilitative management of patients. References 1. Krack P, Marion MH. "Apraxia of lid opening", a focal eyelid dystonia: clinical study of 32 patients. Mov Disord 1994; 6:610-5. 2. Friedman DI, Jankovic J, McCrary III JA. Neuro-ophthalmic findings in progressive supranuclear palsy. J Clin Neuroophthalmol 1992; 12:104-9. 3. Lepore FE, Duvoisin RC. "Apraxia" of eyelid opening: an involuntary levator inhibition. Neurology 1985; 35:423-7. 4. Elston JS. A new variant of blepharospasm. J Neurol Neurosurg Psychiatry 1992;55:369-71. 5. Aramideh M, Ongerboer de Visser BW, Koelman JHTM, Speelman JD. Motor persistence of orbicularis oculi muscle in eyelid-opening disorders. Neurology 1995;45:897-902.
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6. Canter CJ, De La Torre R, Mier M. A method for evaluating disability in patients with Parkinson's disease. J Nerv Mental Disord 1961; 133:143-7. 7. Aramideh M, Ongerboer de Visser BW, Devriese PP, Bour LJ, Speelman JD. Electromyographic features of levator palpebrae superioris and orbicularis oculi muscles in blepharospasm. Brain 1994; 117:27-38. 8. Kimura J. Disorder of interneurons in parkinsonism. The orbicularis oculi reflex to paired stimuli. Brain 1973;96:87-96. 9. Eleopra R, Tugnoli V, Caniatti L, De Grandis D. Botulinum toxin treatment in the facial muscles of humans: evidence of an action in untreated near muscles by peripheral local diffusion. Neurology 1996;46:1158-60. 10. Rivest J, Quinn N, Mardsen CD. Dystonia in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy. Neurology 1990;40:1571-8. 11. Rafal RD, Friedman JH. Limb dystonia in progressive supranuclear palsy. Neurology 1987;37:1546-9. 12. Collins SJ, Ahlskog JE, Parisi JE, Maraganore DM. Progressive supranuclear palsy: neuropathologically based diagnostic clinical criteria. J Neurol Neurosurg Psychiatry 1995;58:167-73. 13. Daniel SE, de Bruin VMS, Lees AJ. The clinical and pathological spectrum of Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy): a reappraisal. Brain 1995; 118:759-70. 14. Colosimo C, Albanese A, Hughes AJ, de Bruin VMS, Lees AJ. Some specific clinical features differentiate multiple system atrophy (striatonigral variety) from Parkinson's disease. Arch Neurol 1995; 52:294-8. 15. Berardelli A, Rothwell JC, Day BL, Marsden CD. Pathophysiology of blepharospasm and oromandibular dystonia. Brain 1985; 108: 593-608. 16. Eekhof JLA, Aramideh M, Bour LJ, Hilgevoord AAJ, Speelman HD, Ongerboer de Visser BW. Blink reflex recovery curves in blepharospasm, torticollis spasmodica, and hemifacial spasm. Muscle Nerve 1995; 19:10-5. 17. Vails-Sole J, Tolosa ES, Ribera G. Neurophysiological observations on the effects of botulinum toxin treatment in patients with dystonic blepharospasm. J Neurol Neurosurg Psychiatry 1991;54:310-3. 18. Aramideh M, Ongerboer de Visser BW, Brans JWM, Koelman JHTM, Speelman JD. Pretarsal application of botulinum toxin for treatment of blepharospasm. J Neurol Neurosurg Psychiatry 1995; 59:309-11. 19. Dam M, Tonin P, Casson S, Bracco F, Piron L, Pizzolato G, et al. Effects of conventional and sensory-enhanced physiotherapy on disability of Parkinson's disease patients. Adv Nenrol 1996;69:5515. 20. Sosner J, Wall GC, Sznajder J. Progressive supranuclear palsy: clinical presentation and rehabilitation of two patients. Arch Phys Med Rehabil 1993;74:537-9. 21. Polo KB, Jabbari B. Botulinum toxin-A improves the rigidity of progressive supranuclear palsy. Ann Nenrol 1994; 35:237-9. Suppliers a. Mortara Rangoni Europe SRL, Via Oradour N. 7, 40016 S. Giorgio Di Piano (BO), Italy. b. Allergan SPA, Via Costarica 20/22, 00040 Pomezia (RM), Italy.
Arch Phys Med Rehabil Vol 78, May 1997