Apraxia of eyelid closure in a patient with progressive supranuclear palsy]

We reported a 68-year-old man with progressive supranuclear palsy who present with apraxia of eyelid closure. He showed horizontal and vertical supranuclear ophthalmoplegia, neck dystonic posture, pseudobulbar palsy and subcortical dementia. He opened his eyes almost all day long except for sleeping. His spontaneous blinking was noted at less than 1 per a minute. Although he closed his eyes reflexively, he could not close his eyes by verbal command. He occasionally closed his eyelids by using both hands. The surface electromyographic (EMG) findings revealed that the frequency of frontal muscle contraction did not decrease, and rather increased during verbal command to close his eyes. The contraction frequency of orbicularis oculi muscle did not increase by the command of voluntary eyelid closure. It is suggested that abnormal contractions of frontalis and orbicularis oculi muscles which are correlated in eyelid closing and opening might contribute to the apraxia of eyelid closure.     

Eyelid movement abnormalities in progressive supranuclear palsy

We systematically videotaped eyelid movements in a community-based series of 38 patients with progressive supranuclear palsy (PSP). Ten patients (26%) had blepharospasm, "apraxia" of lid opening and/or "apraxia" of lid closing. These patients as a group had more severe upgaze paresis but no greater disease duration than the patients without supranuclear lid dysfunction. Patients used a variety of synkinetic movements to overcome lid-movement abnormalities. One patient displayed "slow blinks," a phenomenon not previously described in PSP. Blink rate in PSP, 3.0/min, was markedly lower than that in patients with Parkinson's disease (PD), 12.5/min, and patients with PSP but not PD increased their blink rate during command versional eye movements.     

A 62-year-old woman presenting with progressive nonfluent aphasia, apraxia of eyelid opening, supranuclear gaze palsy, and asymmetric rigidity

A 62-year-old woman presented with difficulty in speaking and difficulty in opening her eyes. A neurological examination revealed progressive nonfluent aphasia (PNFA), apraxia of eyelid opening, supranuclear vertical gaze palsy, and mild asymmetric rigidity. The diagnosis was difficult to establish because of unusual clinical features, and progressive supranuclear palsy (PSP) was considered. The results from recent studies suggest a positive association between PNFA and a diagnosis of corticobasal degeneration (CBD) or PSP, even in mild parkinsonism cases. The overlapping clinical, genetic, and pathological features of CBD and PSP have also been recently recognized. However, in Japan, there have been few reports evaluating the clinical features of CBD or PSP accompanied by primary progressive aphasia. We report the case of our patient and compare the clinical features of our patient with those of Japanese patients with CBD or PSP accompanied by primary progressive aphasia; moreover we discuss clues that can lead to the correct clinical diagnosis of patients with primary progressive aphasia and parkinsonism comorbidities.     

Progressive supranuclear palsy: what's new?

Progressive supranuclear palsy (PSP) has been described as a clinical syndrome characterized by an impairment of voluntary control of gaze (supranuclear palsy), postural and gait instability, and behavioral and cognitive deficits including a frontal syndrome and psychic retardation. However, in the recent years, at least four other clinical forms of PSP have been recognized: PSP-Parkinsonism, "pure akinesia with gait freezing", PSP with cortico-basal syndrome, and PSP with speech apraxia. PSP-Parkinsonism mimics the signs and symptoms of idiopathic Parkinson's disease, including a significant reactivity to levodopa. "Pure akinesia with gait freezing" is characterized by a difficulty of self-initiation of motor programs, usually walking program. PSP with cortico-basal syndrome mimics cortico-basal degeneration (CBD) in that unilateral or asymmetric limb dystonia and apraxia are prominent signs. PSP with speech apraxia is an isolated syndrome of progressive anarthria. All these clinical syndromes are due to brain accumulation of phosphorylated tau protein. The differences in clinical expression within the framework of PSP can be explained by the differences in the topographical distribution of the lesions. PSP is considered as a primary tau disease ("tauopathy") such as CBD and some forms of fronto-temporal lobar degeneration. At the level of neuropathology, the pattern of tau abnormal inclusions differentiates PSP from other tau diseases, but some overlaps are reported. Moreover, several of the clinical forms of PSP partially or fully overlap with the other tauopathies. As a whole, the emergence of new clinical forms of PSP challenges the nosology of tauopathies and our understanding of these diseases.     

Eyelid movements in health and disease. The supranuclear impairment of the palpebral motility.

The eyelid movements are mediated mainly by the orbicularis oculi (OO) and the levator palpebrae superioris (LPS) muscles. Dissociated upper lid functions exhibit different counterbalanced action of these muscles, and in blinking they show a strictly reciprocal innervation. The disturbance of this close LPS-OO relationship likely leads to many of the central lid movement disorders. Three groups of supranuclear motor impairment of lid movements are considered: the disorders of the lid-eye movements' coordination, the disturbances of blinking and lid "postural" maintenance, and the alteration of voluntary lid movements. Nuclei of the posterior commissure control the inhibitory modulation of LPS motor-neuronal activity and they are involved in the lid-eye coordination disorders such as lid retraction, which is observed in the Parinaud's syndrome and also in parkinsonism and progressive supranuclear palsy. Spontaneous (SB) and reflex blinking consist of two components: the inhibition of the basal tonic LPS activity, which keeps the eyes open, and the concurrent activation of the OO muscles. LPS inhibition precedes and outlasts the OO activation. This normal configuration is impaired in parkinsonism and blepharospasm (BSP). SB shows a highly interindividual rate variation (among 10-20 per minute in adults) and abnormal blink rates occur in neurological diseases related to dopaminergic transmission impairments. Lid postural abnormalities include involuntary eyelid closure, which is usually associated with inability to open the eyes. Two major disorders share these two aspects: BSP and blepharocolysis (BCO). BSP consists of an involuntary overactivity of the OO, with LPS co-contraction activity, and is expressed as frequent and prolonged blinks, clonic bursts, prolonged tonic contraction or a blend of all of them. BCO (commonly named "so-called lid opening apraxia") is an overinhibition of the LPS with no evidence of ongoing OO activity. BSP and BCO occur in many instances of idiopathic dystonias and basal ganglia diseases and, less frequently, in rostral brainstem lesions. Both may coincide in the same patient. Voluntary lid movement disorders comprise the impairment of Bell's phenomenon, the voluntary eyelid closure palsy and the so-called cerebral ptosis, all related to lesions of frontal cortical areas and/or the corticospinal system.     

"Apraxia" of eyelid opening: an involuntary levator inhibition

Apraxia of lid opening was described by Goldstein and Cogan as "a non paralytic motor abnormality characterized by the patient's difficulty in initiating the act of lid elevation." We studied six such patients with this finding accompanied by vigorous frontalis contraction and no evidence of ongoing orbicularis oculi contraction, dysfunction of the oculomotor nerve, or loss of ocular sympathetic innervation. Four patients had Parkinson's disease or atypical parkinsonism, one had progressive supranuclear palsy, and one had Shy-Drager syndrome. At onset of ocular symptoms, mean age was 64 years, and the mean duration of extrapyramidal symptoms was 9.7 years. By definition, the motor system must be intact in any apraxia. Therefore, this disorder of lid opening in patients with extrapyramidal motor dysfunction is not an apraxia, but rather involuntary levator palpebrae inhibition of supranuclear origin.     

Treatment of progressive supranuclear palsy with tricyclic antidepressants

After a single patient with progressive supranuclear palsy (PSP) improved when given amitriptyline, we compared the effects of amitriptyline, desipramine, and placebo on the symptoms and signs of four patients with PSP in a double-blind, double-crossover manner. There was good correlation between the use of tricyclic agents and symptomatic improvement, although all patients remained disabled. Amitriptyline produced better overall improvement, whereas desipramine preferentially improved apraxia of eyelid opening.     

A case of bilateral ptosis associated with cerebral hemispheric lesions

Ptosis occurs in a variety of disorders including myasthenia gravis, oculomotor palsy, Horner's syndrome and brain stem disorders. There are also supranuclear lesions causing blepharoptosis. The latter disorders are reflex blepharospasm, apraxia of eyelid opening and Meige's syndrome. Since the total number of bilateral ptosis associated with cerebral hemispheric lesions is very few, whether the responsible lesions are located in the nondominant hemisphere or bilateral hemispheres are still controversial. We report here a case of bilateral cerebral ptosis that occurred in association with cerebral infarction of the nondominant hemisphere.     

Chronic progressive spinobulbar spasticity with disturbance of voluntary eyelid closure. Report of a case with special reference to MRI and electrophysiological findings

We describe a 56-year-old man who had a progressive pseudobulbar palsy, spastic tetraparesis, forced laughing and disturbance of voluntary eyelid closure, and was clinically compatible with chronic progressive spinobulbar spasticity. Magnetic resonance images (MRI) revealed atrophy of the bilateral motor cortices and single photon emission tomography after intravenous injection of N-isopropyl-p-iodoamphetamine iodine-123 (IMP-SPECT) showed hyporadioactivity in the same regions. Electrophysiological studies on supranuclear paralysis of eyelid closure demonstrated that so-called apraxia and motor impersistence coexisted and that in attempts to keep the eyelid closed the inhibition of basal activity of the levator palpebrae superioris muscle and activation of the orbicularis oculi muscle were insufficient, indicating the impaired reciprocity of these ocular muscles. The corresponding lesion of these eyelid symptoms was considered to be the bilateral motor cortices.     

A Case of Bilateral Ptosis Associated with Cerebral Hemispheric Lesions

Abstract: Ptosis occurs in a variety of disorders including myasthenia gravis, oculomotor palsy, Horner's syndrome and brain stem disorders. There are also supranuclear lesions causing blepharoptosis. The latter disorders are reflex blepharospasm, apraxia of eyelid opening and Meige's syndrome. Since the total number of bilateral ptosis associated with cerebral hemispheric lesions is very few, whether the responsible lesions are located in the nondominant hemisphere or bilateral hemispheres are still controversial. We report here a case of bilateral cerebral ptosis that occurred in association with cerebral infarction of the nondominant hemisphere.     

Combination of blepharospasm and apraxia of eyelid opening: a condition resistant to treatment

Blepharospasm is seen in many cases of Parkinsonism including progressive supranuclear palsy. These patients usually respond well to botulinum toxin, however some patients subsequently fail to respond to even higher doses of botulinum toxin after an initial good response. They should not be considered failure of treatment with botulinum toxin, as a significant number of these patients have underlying apraxia of eyelid opening in addition to blepharospasm, which may be the cause of failure to respond to botulinum toxin. Combination of eyelid crutches or myomectomy with botulinum toxin is more effective in these patients as compared to an individual treatment modality. In this report, we present two patients with progressive supranuclear palsy who failed to respond to botulinum toxin because they had underlying apraxia of lid opening. Partial myomectomy in one patient and eyelid crutches in the other in combination with botulinum toxin lead to a much better response to botulinum toxin.     

建立人工面神经反射弧恢复失神经支配眼轮匝肌的闭眼功能

目的：建立人工面神经反射弧,恢复面瘫兔的闭眼功能。 方法：试验动物为新西兰兔12只。采用手术切断面神经制备单侧周围性面瘫模型,患侧行肌电图检查确诊。术后第5天患侧植入刺激电极,健侧植入采集电极并留置1月。患侧分别于术后第7天、第28天给予电流刺激;而健侧采集电极则连续采集2周的肌电信号。建立健侧眼轮匝肌肌电信号采集、中枢信号处理模式识别、患侧电流刺激眼轮匝肌系统。当健侧眼轮匝肌采集的肌电信号经信号识别、提取以及电脑分析判断,符合其闭眼刺激阈值时,即对人工电刺激器发出指令,由刺激电极直接作用于患侧眼轮匝肌,引起眼睑完全闭合。结果：刺激方式为正负方向矩形波,电流强度为0.40—0.70mA之间可引起患侧眼轮匝肌收缩,眼睑完全闭合。当健侧眼睑闭合时,其肌电信号电压大于50uV,触发电刺激器,电流刺激即引发患侧眼轮匝肌收缩,完成眼睑闭合。结论：利用MEMS技术,在面瘫兔模型建立“人工面神经反射弧”,恢复患侧眼轮匝肌闭眼功能。     

Concurrence of multiple types of eyelid synkinesia in a patient with congenital anomalies

We report the case of a 5-year-old boy with multiple congenital anomalies, including ptosis, polydactyly, ventricular septal defect, epilepsy, and intellectual deficits. The patient presented with synkinetic eyelid movements accompanying jaw and ocular movements, including Marcus-Gunn phenomenon (eyelid elevation at mouth opening) in the right eye, inverse Marcus-Gunn phenomenon (aggravation of ptosis at mouth opening) in the left eye, and unilateral eyelid elevation on each side during ipsilateral abduction. This suggests that the different types of synkinesia may represent a common etiology of aberrant innervations and/or reflex phenomena of the cranial nerves caused by a specific genetic defect.     

Clinical effectiveness of tandospirone citrate (5-HT1A agonist) on patients with progressive supranuclear palsy]

BACKGROUND: Serotonin activity has been shown to be increased in the basal ganglia of patients with progressive supranuclear palsy (PSP), and may be responsible for its extrapyramidal features that do not respond to 1-dopa. OBJECTIVE: To investigate clinical effectiveness of 5-HT1A agonist, tandospirone citrate (TC), on various clinical features of PSP. METHOD: Clinical signs of eight patients (2 women and 6 men) who fulfilled NINDS-SPSP criteria of PSP were studied before and after administration of TC. Each of vertical gaze palsy, apraxia of eyelid opening, neck dystonia, bradykinesia, postural instability, gait disturbances, dysarthria, dysphagia, and bladder disturbances was graded, and evaluated before, and two and four weeks after oral administration of TC 30 mg/day. RESULTS: TC was well tolerated in six patients for four weeks. The other two patients developed dizziness or liver dysfunction in the second week, and dropped out. Neck dystonia, postural instability, and bradykinesia were improved significantly in the fourth week. On the contrary, vertical gaze palsy, dysarthria, and dysphagia responded poorly to TC. Apraxia of eyelid opening was present in three patients, and was improved in two. Bladder disturbances were present in three patients, and did not respond to TC. CONCLUSION: Among various clinical features in PSP, TC was effective preferentially on extrapyramidal ones. Suppression of serotonergic activities in the basal ganglia of PSP may be underlying in the effectiveness of this 5-HT1A agonist.     

Modified Lundie loops improve apraxia of eyelid opening.

BACKGROUND: Current treatments are unsatisfactory for improving apraxia of eyelid opening, defined as a delay or inability to open closed eyelids voluntarily in the presence of intact motor pathways. METHODS: Improvement in functional health was assessed using the Blepharospasm Disability Scale (BDS) in five consecutive patients with apraxia of eyelid opening treated with wire loops affixed behind ordinary spectacles (Lundie loops) and modified to provide pressure on the brow as a stimulus to keep the eyelids elevated. RESULTS: All five patients showed improvement in BDS scores. The mean percentage of normal activity of the study population improved from 25% to 37.6%. Outdoor activities were not significantly altered with the use of the device. CONCLUSIONS: Modified Lundie loops appear to be helpful in improving the functional health of patients with eyelid apraxia. These results will need to be verified in larger trials.     

Limb apraxia and cognitive impairment in progressive supranuclear palsy

Limb apraxia occurs in progressive supranuclear palsy (PSP); however, its characteristics and relation to dementia are unclear. We compared 25 probable PSP patients on cognitive and ideomotor apraxia tests with 19 healthy controls. Eleven PSP patients were demented (D-PSP) and 14 not (ND-PSP). D-PSP patients did worse than controls and ND-PSP patients in all cognitive tests; and ND-PSP patients did worse than controls in all except the memory test. In the apraxia test, PSP patients committed mainly sequence errors and executed complex gestures badly. Apraxia correlated strongly with dementia. In PSP, limb apraxia seems mainly due to frontal deafferentation and lesions, but only when these are severe enough to cause dementia.     

Atypical presentation of progressive supranuclear palsy

Four pathologically documented cases of progressive supranuclear palsy are reported. Two patients exhibited severe dementia and 2 parkinsonism; none had the classic ophthalmoplegia. On retrospective analysis, clues to the diagnosis included early prominent gait disturbance, apraxia of eyelid opening in 1 patient, lack of tremor, poor response to levodopa-carbidopa, and severe rigidity with a posture of neck extension terminally in 1 patient. The clinical presentation of progressive supranuclear palsy, therefore, is not as stereotyped as previously thought, and the diagnosis can be overlooked if one adheres rigidly to the classic diagnostic criteria.