Dear Sir, A 60-year-old right-handed female presented with an insidious onset and gradually progressive, asymmetric parkinsonism with left upper limb dystonia and apraxia over 2 years. Initially, she had eye-opening difficulty, which later progressed to eye-closure difficulty over the past 9 months. She was born to nonconsanguineous parents, with an uneventful past and family history. Her general examination was normal. Her eye movements showed slow saccades with a reduced blink rate. Spontaneous and reflexive eye closure was normal, but she had difficulty closing her eyes on command Video 1. On passive eyelid closure, she was unable to maintain eye closure, clinically suggesting motor impersistence (MI) Video 1. She had normal power, with exaggerated deep tendon reflexes and bilateral extensor plantar responses. No primitive reflexes were elicited. She had dystonic posturing and ideomotor apraxia of the left upper limb. Her sensory and cerebellar examinations were normal. Other systemic examination was also normal. Initial investigations for asymmetric parkinsonism with apraxia revealed normal blood parameters, and brain magnetic resonance imaging showed bilateral parietal lobe atrophy, more pronounced on left Figure 1. Autoimmune and paraneoplastic antibody testing results were negative, and electroneuromyography findings were normal. She was diagnosed with probable corticobasal syndrome based on established criteria by Armstrong J et al. (akinesia and dystonia with limb apraxia). She was started on levodopa-carbidopa, baclofen, and other supportive measures, following which she did not show any noticeable response. "href": "Single Video Player", "role": "media-player-id", "content-type": "play-in-place", "position": "float", "orientation": "portrait", "label": "Video 1", "caption": "", "object-id": {"pub-id-type": "doi", "id": "", "pub-id-type": "other", "content-type": "media-stream-id", "id": "1fc65zcnu", "pub-id-type": "other", "content-type": "media-source", "id": "Kaltura"} Figure 1: Magnetic resonance imaging of the brain: (A, B) axial; (C) coronal; and (D) sagittal sections showing atrophy in the bilateral parietal regions (left greater than right) Eyelid opening and closure, though seemingly simple functions, are a complex process involving the inactivation of the levator palpebrae superioris (LPS) and activation of the orbicularis oculi (OOc). They can be categorised into spontaneous (involuntary, independent of stimulus), reflexive (in response to a stimulus), and voluntary (intentional) types. This intricate process is centrally regulated by the brainstem (including the superior colliculus, reticular formation, pons, and substantia nigra), the cerebellum, and the bilateral cortex. 1, 2 For voluntary eyelid movement, a verbal command is sent to the auditory association cortex in the dominant hemisphere, where it is deciphered. The final decision, after interpretation, is then transmitted to the motor association cortices via the arcuate fasciculus (ipsilateral) and the corpus callosum (contralateral). 3 Supranuclear centres, with right-hemisphere dominance, are known to control these volitional eyelid movements. Therefore, impaired voluntary eyelid closure may result from 1) failure to understand the command, 2) unwillingness to comply, 3) lesions in the facial nerve, central cranial nuclei, or oculomotor muscles, or 4) lesions in the cortex and its projections. 3 The first two possibilities were ruled out in our patient, as she was cooperative and able to follow other commands well. Intact blink and corneal reflexes ruled out local and brainstem pathology. However, the patient’s poor response to levodopa raised concerns about basal ganglia involvement. Given the left-sided apraxia, we hypothesized that cortical pathology or callosal disconnection might have contributed to her apraxia of eyelid closure (AEC). Eyelid movement abnormalities associated with neurodegenerative conditions include eyelid retraction, increased or decreased blink rate, apraxia of eyelid opening (AEO), and blepharospasm. AEC is a relatively rare condition that is defined as difficulty in voluntary eye closure, with normal spontaneous and reflexive eye closure and normal eye closure during sleep. Patients have normal comprehension and can carry out simple commands, with no attentional or language abnormalities. Roth first described this condition in 1901, and Lewandowski designated it as AEC in 1907, noting normal blinking in these cases with disturbance only of the motor-intentional process. 4 Studies have shown lesions in the frontal (premotor and supplementary motor areas SMA), parietal (posterior parietal area or praxis centre of the parietal cortex), corticobulbar tracts, opercular regions, centrum semiovale, corona radiata, or corpus callosum can cause AEC. 5 The condition can be unilateral or bilateral, with right nondominant hemisphere involvement being predominantly reported. Typically, subcortical structures are known to have a role in eye opening and AEO, but not in eye closure or AEC. However, a report by Ragasudha et al. showed that subcortical lesions produced AEC, which responded to dopaminergic medications. 6 Another related entity is motor impersistence (MI), which can co-occur with or follow AEC and is defined as the inability to maintain voluntary eye closure for more than a few seconds. It is a sign of supranuclear involvement with nondominant hemisphere localisation. AEC and MI were once considered the same entity, but differ in severity, with MI occurring at any time during the illness. This co-occurrence indicates a failure of both the initiation and sustained execution of voluntary eye closure. Although both AEO and AEC are disruptions of voluntary eyelid function, AEC is much less common than AEO. One possible explanation for this rarity could be underreporting of the defect, as it causes less disability and may often go unnoticed. 7 In AEO, there is a disruption of basal ganglia connections, resulting in eyelid dystonia, which is commonly reported in neurodegenerative conditions. In contrast, AEC represents a true apraxia—an elusive and underexplored entity. Another possibility might involve the engagement of distinctive brain areas beyond those affected in AEO; however, further exploration is needed for a clearer understanding. 8-12 Thus far, AEC has been reported in conditions such as Parkinson’s disease, progressive supranuclear palsy (PSP), postencephalitic parkinsonism, Creutzfeldt–Jakob disease (CJD), Huntington’s disease, amyotrophic lateral sclerosis, autopsy-confirmed vascular PSP, Biswanger’s disease, cortical angioma, chronic progressive spinobulbar spasticity, multiple sclerosis, mental retardation, subarachnoid haemorrhage, Balo’s concentric sclerosis, and stroke. 13, 14 In a systematic review by Nicoletti et al. , among 34 patients, 32 had significant right-hemispheric dominance, and 19 had bilateral cortical involvement. 12 Functional studies of normal volitional blinking have shown bilateral activation of the middle precentral gyrus and the SMA, whereas in AEC, impairments have been noted in the frontal (frontal eye fields, supplementary eye fields) and parietal (parietal eye fields) lobes, either bilaterally or in the nondominant hemisphere. This pattern is distinct from that seen in AEO, which shows predominant involvement of subcortical and insular structures. 5, 8, 12, 15, 16 Electrophysiological studies revealed incomplete inhibition of the LPS and a return to the basal tonic state of the LPS during OOc activation, which occurred abruptly and briefly, with impaired reciprocity between the LPS and OOc. The blink reflex was normal, with no clinical evidence of muscle spasm or dystonia and increased frontalis muscle contraction was noted. 15, 17, 18 The main limitation was that surface electromyography could not be performed in our study, which might have aided in the diagnosis. Histopathological studies by Russel et al. in patients with CJD and AEC showed predominant cortical neuronal involvement rather than involvement of the descending motor tracts. 9 AEC is distinct from AEO and should be considered in routine clinical practice Table 1. A comprehensive history, along with clinical examination and electrophysiological studies, can aid in differentiating it from other eyelid abnormalities. Recognition of this uncommon, subtle sign can help in localising the lesion and refining the differential diagnoses. Table 1: Differentiating features between apraxia of eyelid opening and apraxia of eyelid closureAcknowledgements We thank the patient and patient’s family for their cooperation and time. Author contributions A. Research project: Conception: Karri Madhavi, Sai D. Yaranagula, Rukmini M. Kandadai, Rupam Borgohain, Sruthi Kola Organization: Karri Madhavi, Rukmini M. Kandadai Execution: Karri Madhavi, Rukmini M. Kandadai B. Statistical analysis: Karri Madhavi, Sai D. Yaranagula, Rukmini M. Kandadai Design: Karri Madhavi, Rukmini M. Kandadai Execution: Karri Madhavi, Rukmini M. Kandadai Review and Critique: Karri Madhavi, Sai D. Yaranagula, Rukmini M. Kandadai, Rupam Borgohain C. Manuscript preparation: Writing of the first draft: Karri Madhavi Review and Critique: Karri Madhavi, Sai D. Yaranagula, Rukmini M. Kandadai, Rupam Borgohain, Sruthi Kola Ethical compliance statement All procedures performed involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards. The authors confirm that this work did not require ethical approval from the institutional review board. Verbal and written consent was obtained from the patient for publication of this case study. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Madhavi et al. (Thu,) studied this question.