Atypical Presentation of the Classical Form of Locked-In Syndrome in a Young Patient

Abstract

Locked-in syndrome (LIS) is an uncommon neurologic disorder that manifests in quadriplegia and anarthria with preserved cognition and self-awareness. Generally, patients with LIS may live for years with preserved quality of life and cognitive function, but with severe disability. There are 3 types of LIS: classic, partial, and total. The classical form is defined by total immobility, with preservation of the ability to perform vertical eye movements, blink, and maintain a normal level of consciousness. We present an unusual case of classical LIS in a 54-year-old man who presented initially with acute-onset left lower extremity weakness and dysarthria with radiographic evidence of extensive, acute right paramedian pontine infarction and high-grade vertebral artery stenosis. However, a week later, the patient developed sudden-onset aphonia, bilateral facial palsy, and quadriplegia with repeat magnetic resonance imaging of the brain showing expansion of right paramedian pontine stroke to also involve the left paramedian pons, without significant change to the vertebral stenosis and basilar artery patency.

Introduction

Locked-in syndrome (LIS) is a rare neurological disorder characterized by quadriplegia, aphonia, and sustained vertical eye movements. Patients with LIS have preserved cognitive function and the ability to communicate through vertical or lateral eye movement or blinking the upper eyelid. ¹ The prevalence and incidence of LIS is unknown partly because the disease has high mortality rate in an acute setting; but also, only a handful of cases are reported each year. ² The etiologies of LIS involve damage to the paramedian base of the pons due to ischemic stroke, pontine hemorrhage, brain tumors, infection/abscess of the pons, central pontine myelinolysis, and trauma.^3,4 Locked-in syndrome has 3 main subtypes: classical, partial, and total. The classical form is defined by total immobility, with the preservation of the ability to perform vertical eye movements, blink, and maintain a normal level of consciousness. ³ In the acute setting, computed tomography (CT) or magnetic resonance imaging (MRI) of the brain helps characterize the causative agent to establish a treatment earlier. Physical examinations analyzing motor function, sensation, and reflexes are often reassessed to rule out other potential conditions and estimate the rate of recovery in patients. Due to the rare nature of LIS, recovery and management have been a topic of debate. Still, an increasing amount of literature has demonstrated efficacy in traditional supportive management and rehabilitation.

Case Presentation

A right-handed Hispanic male in his 50s with hypertension, hyperlipidemia, and type II diabetes mellitus presented with acute onset of left upper extremity weakness, left facial asymmetry, and dysarthria. Patient stated that 5 days prior to presentation, he noticed left lower extremity weakness after playing soccer for 2 hours. He attributed symptoms to the moderate activity from earlier in the day. The leg weakness persisted, to the point that he tripped and lost his balance the following day. The day before presenting to the emergency department (ED), the patient noticed that his left facial side was weak and his left arm was now showing signs of weakness, accompanied with difficulty grasping objects. This prompted him to come to the ED for evaluation. In the ED, his vital signs were significant for hypertension to as high as 200/114. The rest of his vital signs were within normal range. The National Institutes of Health Stroke Scale (NIHSS) score was 7 corresponding to the left facial droop, left upper and lower extremity drift, and mild-moderate dysarthria. Patient was moved from emergency room to the stroke unit (Table 1).

Table 1.

Showing Each of 11 Items on the NIHSS Deficit Scale Including Item Number, Item Name, and Total Score (Out of 31).

Significant neurological findings at admission and discharge
Admission	National Institutes of Health Stroke Scale/Score (NIHSS)	Level of consciousness (1a): Alert, keenly responsive LOC questions (1b): Answers both questions correctly LOC commands (1c): Performs both tasks correctly Best gaze (2): Normal Visual (3): No visual loss Facial palsy (4): Partial paralysis (left) Motor arm, left (5a): Drift Motor arm, right (5b): No drift Motor leg, left (6a): Drift Motor leg, right (6b): No drift Limb ataxia (7): Present in 2 limbs Sensory (8): Normal, no sensory loss Best language (9): No aphasia Dysarthria (10): Mild-to-moderate dysarthria, patient slurs at least some words and, at worst, can be understood with some difficulty Extinction and Inattention (11) (Formerly Neglect): No abnormality NIH Stroke Scale: 7
Discharge	NIHSS	Level of consciousness (1a): Opens eyes, unresponsive LOC questions (1b): Aphasic LOC commands (1c): Performs 0 tasks Best gaze (2): Normal Visual (3): No visual loss Facial palsy (4): Partial paralysis (left) Motor arm, left (5a): Drift but doesn’t hit bed Motor arm, right (5b): No movement Motor leg, left (6a): No movement Motor leg, right (6b): No movement Limb ataxia (7): Paralyzed Sensory (8): No response, quadriplegic Best language (9): Mute Dysarthria (10): Mute Extinction and inattention (11) Extinction to > 1 modality NIH Stroke Scale: 30

Abbreviations: NIHSS, National Institutes of Health Stroke Scale/Score; NIH, National Institutes of Health.

The bold text in Table 1 is to highlight specific positive neurological changes.

Investigations

Laboratory evaluation revealed hemoglobin A1c 9%, low-density lipoprotein (LDL) 172, and triglyceride level 245. Hypercoagulable workup, including lupus anticoagulant, anticardiolipin, b2 glycoprotein, and phosphatidylserine antibodies, was unrevealing. Vitamin B12, folic acid, and homocysteine serum levels were normal. Patient was SARS-Cov-2 negative. Computed tomography of the head without contrast showed hypodensity in central pons suggestive of an acute infarct (Figure 1). Computed tomography angiography revealed severe left intracranial vertebral artery stenosis as well as moderate right cervical internal carotid artery (ICA) stenosis (Figure 2A). Magnetic resonance imaging of the brain showed an extensive, irregularly shaped acute infarct of the right paramedian, in addition to chronic moderate small-vessel ischemic disease, a chronic left caudate head infarct with petechial hemorrhage as well as a few scattered cerebral microhemorrhages (Figure 3A). Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) were both unremarkable. On the eighth day after admission, the patient woke up complaining of worsening left-sided hemiparesis and now right lower extremity heaviness, and intermittent hiccups. Neurological examination revealed absent upper and lower extremities motor movement bilaterally with left facial palsy. Patient was anarthric and only able to move eyes vertically and laterally in both directions. Repeat CT angiography showed no change in the high-grade left vertebral artery stenosis and patent basilar artery (Figure 2B). However, the repeat MRI of the brain now showed expansion of pontine stroke to now involving the left paracentral pons in addition to the previous right paracentral pons (Figure 3B). Speech and language pathology evaluated the patient with video fluoroscopy, which revealed severe oropharyngeal dysphagia characterized by minimal tongue motion resulting in posterior escape of liquids as well as anterior labial spillage. In addition, it was observed that the patient had impaired initiation of the pharyngeal swallow, impaired laryngeal elevation, no anterior hyoid excursion, absent epiglottic inversion, absent laryngeal vestibular closure, impaired base of tongue to posterior pharyngeal wall, and minimal distention/duration of pharyngoesophageal segment.

Figure 1.

Computed tomography (CT) of the head without contrast showing hypodensity in the right side of pons, not crossing the midline (highlighted within the red circle).

Figure 2.

(A) Volumetric reconstruction of the initial CT angiogram demonstrates severe stenosis of the left intradural vertebral artery (arrowhead). (B) Volumetric reconstruction of the subsequent CT angiogram reveals no significant change.

Figure 3.

Axial diffusion-weighted image at the level of the brainstem from (A) the initial MRI examination demonstrates acute right paracentral pontine infarct; (B) subsequent MRI examination demonstrates larger acute right pontine infarct as well as new acute infarct of the left paracentral pons.

Management

Initially, the patient was loaded with clopidogrel 300 mg (P2Y12 platelet function test was normal), aspirin 325 mg, and started on atorvastatin 80 mg on the first day. Then, he was continued on low-dose aspirin 81 mg daily, clopidogrel 75 mg daily, and atorvastatin 80 mg daily. Hemodynamically, the patient was kept at permissive hypertension with systolic blood pressure between 130 and 160. Neurological and vital signs checks were conducted every 4 hours. The patient was being monitored on telemetry 24 hours a day. Finger stick monitoring was initiated with the goal of fingerstick blood glucose of less than 150 given his history of diabetes mellitus. Given worsening symptoms of left extremity weakness, anarthria, and paresthesia, neurosurgery was consulted for digital subtraction angiography. However, on the eighth day after admission, the nurse activated a rapid response team when patient was unable to follow commands or move any of his limbs. When the neurology and the intensive care outreach teams reached bedside, physical examination confirmed the absence of motor movement in the bilateral upper and lower extremities and bilateral facial palsy. However, patient was able to protect his airway and only able to move his eyes vertically and laterally in both directions. Patient was diagnosed with LIS, classical type. Over the next 5 days, discussions between the patient’s health care proxy agent and palliative care team regarding percutaneous endoscopic gastrostomy (PEG) tube and code status were held. It was determined that the patient should receive a PEG tube and remain full code. On the morning of the 16th day after admission, he was found to be in severe respiratory distress, taking frequent shallow breaths, with oxygen saturations in the mid to high 80s. Medical intensive care unit (MICU) team was consulted and recommended immediate endotracheal intubation. Patient was transferred to the MICU service for further management. Computed tomography of the head was obtained and revealed small conversion to hemorrhagic stroke. Aspirin and plavix were stopped. Repeat CT of the head 6 hours later did not show changes from prior CT, and duo-antiplatelet therapy was deemed safe to restart by neurocritical attending. Patient likely had aspiration pneumonia in the setting of acute pontine infarction. After 1 week in the MICU, the patient underwent tracheostomy for long-term airway management. Patient was transferred to skilled nursing facility with a private neurology team.

Discussion

Locked-in syndrome is a manifestation of brainstem infarct in the pons characterized by quadriplegia, paresthesia, bulbar palsy and preserved vertical eye movement, blinking, and level of consciousness. Thrombosis of the upper segment of the basilar artery resulting in infarction, hemorrhage, trauma (brain stem contusion or vertebro-basilar axis dissection), viral brainstem encephalitis, central pontine myelinolysis, demyelinating disease, and brain tumors are the usual causes of LIS.^3,5 Pontine infarction can also result from large-vessel occlusion of the vertebral artery and its branches from either dissection or atherosclerosis. ⁶ There are also reports of severe Guillain Barre syndrome and snake bites that may have caused LIS.^7-9 Risk factors include hypertension, hyperlipidemia, fibromuscular dysplasia, trauma, and spinal manipulation. Patients with the LIS may have various involuntary motor phenomena, including ocular bobbing, crying, trismus, oral automatisms, groaning, facial grimacing, yawning, palatal myoclonus, sighing, coughing, bruxism, and laughing.

Our case highlights a rare occurrence of progressive classical LIS due to right-sided pontine paramedian branch infarction followed by contralateral paramedian branch infarction occurring 8 days later despite treatment with maximum medical therapy. Cerebrovascular imaging revealed high-grade left vertebral artery stenosis in the setting of right vertebral artery and basilar artery complete patency.

Our understanding is that the likely etiology of our patient’s classical LIS was due to bilateral small-vessel disease of the pontine paramedian perforators in the setting of uncontrolled vascular risk factors including diabetes mellitus with hgA1c 9% and hyperlipidemia with LDL 172. We aren’t certain to why it took 8 days for the acute symptoms to progress to LIS. However, it is highly likely that the patient’s initial symptoms that brought him to the hospital were secondary to embolus/emboli from the diseased vertebral artery. However, the progression to LIS was due to the small-vessel disease of the pontine paramedian perforators in a patient with significant risk factor.

The progressive nature of our patient’s symptoms is the key factor we want publish this case so that physicians are aware that LIS can manifest in such a stepwise progressive fashion. It is imperative that the medical community is familiar with such unusual presentation of classical LIS so that they can remain vigilant for worsening acute changes. Most importantly, aggressive modification of vascular risk factors is imperative to reduce the risk of subsequent strokes and other vascular events that may lead to cerebral small-vessel disease and possible LIS.

Conclusion

We present a case of LIS that presented in an unusual manner, given the progression of neurologic symptoms resulting in a “locked-in” state, without obvious evidence of re-injury or trauma that may have caused progression of stenosis or dissection in the affected vertebral artery. In our patient, it was even more important to remain vigilant in serial neurologic examinations given the almost stepwise progression of his motor and bulbar weakness, which eventually required intubation, mechanical ventilation, and tracheostomy placement prior to discharge to skilled nursing facility.