Accepted Manuscript Locked-in syndrome responding to thrombolytic therapy
Thomas M. Johnson, Cynthia S. Romero, Austin T. Smith PII: DOI: Reference:
S0735-6757(18)30559-X doi:10.1016/j.ajem.2018.07.003 YAJEM 57657
To appear in:
American Journal of Emergency Medicine
Received date: Accepted date:
28 June 2018 2 July 2018
Please cite this article as: Thomas M. Johnson, Cynthia S. Romero, Austin T. Smith , Locked-in syndrome responding to thrombolytic therapy. Yajem (2018), doi:10.1016/ j.ajem.2018.07.003
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Thomas M. Johnson, M.D. Cynthia S. Romero, M.D. Austin T. Smith, M.D. Department of Emergency Medicine Vanderbilt University Medical Center 1313 21st Ave, South 703 Oxford House Nashville, TN 37232-4700 Phone: 615-936-1160 Fax: 615-936-1316
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Locked-In Syndrome Responding to Thrombolytic Therapy
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Authors report no relevant funding or conflicts of interest
ACCEPTED MANUSCRIPT ABSTRACT Locked-in syndrome (LIS) is an exceedingly rare condition that has been described as a fate worse than death. Unfortunately, exam findings can be subtle and imaging is poorly sensitive, often leading to a delay in diagnosis. We present a case of a 70-
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year-old female who presented to our emergency department after developing
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respiratory distress followed by sudden unresponsiveness. She was diagnosed with
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LIS and had an immediate and remarkable improvement after administration of
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tissue plasminogen activator (TPA). Patients presenting with sudden onset altered mental status require a very careful physical exam, even if deemed comatose, and
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should be considered for emergent imaging for stroke. Fortunately, our patient
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recovered well and was discharged home in good condition.
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INTRODUCTION
Locked-in syndrome (LIS) is defined as complete paralysis of all voluntary muscles
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except for vertical eye movements and blinking in addition to retained
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consciousness with inability to speak 1. Diagnosis of LIS is largely clinical as imaging has poor sensitivity 2,3. Given the diagnostic difficulty, diagnosis of LIS is often delayed, with one study demonstrating a mean time of diagnosis of 78.8 days 4. We present a case of a patient who presented with acute onset of altered mental status and was found to have LIS. She was given tissue plasminogen activator (TPA) and improved within minutes and was ultimately discharged home several days later.
ACCEPTED MANUSCRIPT CASE REPORT
A 70-year-old female presented to our emergency department (ED) by helicopter after an episode of shortness of breath followed by sudden unresponsiveness.
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History was obtained by air EMS who was told by family that the patient was seen
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two hours prior to their arrival in her usual state. She then developed respiratory
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distress and then suddenly collapsed to the ground. She had a reported past medical
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history of congestive heart failure but no further medical history could be obtained. On EMS arrival, she was noted to have agonal breathing with a Glasgow Coma Scale
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(GCS) of 3 and was successfully intubated by ground EMS using intravenous succinylcholine and versed. She was transferred by air EMS to our emergency
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hours prior to arrival in the ED.
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department and received intravenous rocuronium approximately one and a half
Upon arrival to the ED, the patient was intubated, with a GCS of 3T. Her vital signs
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were within normal limits except for mild hypotension, though her mean arterial
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pressure was greater than 65. Her endotracheal tube position was confirmed with end-tidal capnography and bilateral lung auscultation. Physical exam was significant for a GCS of 3T, 2mm bilateral nonreactive pupils, no motor response to pain, no motor response to verbal stimuli, flaccid quadriparesis, no corneal reflex, and no gag reflex. Given the unclear etiology of the patient’s sudden onset altered mental status, a non-contrasted computed tomography (CT) scan of the head along with a CT
ACCEPTED MANUSCRIPT angiogram of the head and neck was ordered. The stroke team was alerted as well given the unclear history and concern for potential basilar artery stroke.
Imaging revealed no acute intracranial hemorrhage, but did show severe stenosis of
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the proximal bilateral internal carotid arteries (ICAs) (Figures 1,2) and greater than
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50% stenosis of the left vertebral artery along with a narrow caliber basilar artery
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(Figure 3). Upon careful reassessment with the stroke team, the patient was able to
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answer questions by moving her eyes upward to commands. She endorsed having intact sensation. In consultation with the stroke team, we elected to administer
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tissue plasminogen activator (TPA) given the physical exam findings and absence of any sedatives or paralytics in over 2 hours. No family was available, but the patient
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was able consent for TPA using eye movements. Within minutes of the infusion, the
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patient was noted to have minimal spontaneous movements of her right arm
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followed by movements of all four extremities. The patient was admitted to the neurologic intensive care unit and was successfully extubated later that morning.
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She was discharged home six days later with preserved cranial nerve functions and
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moving all 4 extremities.
DISCUSSION
Locked-in syndrome (LIS) is defined as complete paralysis of all voluntary muscles except for vertical eye movement and blinking in addition to retained consciousness with inability to speak 1. It is an exceedingly rare condition, so much so that no
ACCEPTED MANUSCRIPT reported incidence exists in the literature. It arises from damage to the ventral pons that is usually caused by ischemia or hemorrhage 4 but can also occur from trauma, brainstem malignancies, infections (pontine abscess or brainstem encephalitis), central pontine myelinolysis, demyelination such as in multiple sclerosis, or
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drugs/toxins 5.
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Symptoms arise due to the numerous neuronal tracts that run through the pons.
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Loss of voluntary limb movement is due to bilateral lesions of cerebrals peduncles in the midbrain, base of the pons, and medullary pyramids. Eye movement and
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consciousness mediation are located in the dorsal portion of the tegmentum in the midbrain and pons and are therefore spared. Bilateral lesions in this area, though,
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can cause loss of horizontal eye movement and coma; however consciousness is
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preserved if medial tegmentum lesions are unilateral.
This ultimately causes a constellation of symptoms, classically taught as
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quadriplegia and anarthria with preservation of consciousness 5,6. Interestingly, our
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patient reportedly presented initially with respiratory distress. While not classic for LIS, the medial and lateral reticular formation control the respiratory, cardiac, and vasomotor functions. Injury to this region could potentially explain her atypical presentation.
Diagnosis of LIS is largely clinical as initial imaging such as computed tomography (CT) can be poorly sensitive 2. Magnetic resonance imaging (MRI) has a higher
ACCEPTED MANUSCRIPT sensitivity but can still result in false negatives within the first 24 hours 3. Additionally, many patients have contraindications to MRI. Standard stroke evaluation tools such as the commonly used pre-hospital FAST (face, arm, speech) are also poor at predicting a posterior circulation stroke 7. Given the diagnostic
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difficulty, diagnosis of LIS is often delayed, with one study demonstrating a mean
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time of diagnosis of 78.8 days 4.
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Rapid identification of the syndrome is critical to reduce morbidity and mortality. In thromboembolic causes, several treatments exist such as thrombolytic therapy and
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and endovascular treatment. Further, early identification improves long-term treatment as these patients have preserved consciousness, which is important for
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caregivers to understand. In a psychological analysis of LIS survivors, their quality
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of life was found to be worse than that of cancer patients with many having
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considered euthanasia at some point during their illness 5 8.
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Prognosis for patients diagnosed with locked-in syndrome varies. Numerous case
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studies have been done regarding prognosis for this grave illness, the largest of which showed a mortality of 60%. Moreover, functional recovery was good in those with a vascular etiology who survived past 4 months 9.
Fortunately, in our case, the diagnosis was recognized quickly and the patient was started on tissue plasminogen activator (t-PA) within three hours of symptom onset, and subsequently had a dramatic improvement in her neurologic exam within
ACCEPTED MANUSCRIPT several minutes. Her CT and CT angiogram imaging demonstrated severe stenosis of the proximal bilateral internal carotid arteries (ICAs) (Figures 1,2) and greater than 50% stenosis of the left vertebral artery along with a narrow caliber basilar artery (Figure 3). To our knowledge, only one other case of locked-in syndrome that has
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demonstrated a significant neurological improvement after administration of t-PA,
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and in that case, the patient had also received heparin and medication-induced
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hypertension 10. In another case report, brief improvement occurred though
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symptoms subsequently recurred 11.
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Although our patient received t-PA early in the course of the illness, there is evidence for use of intravenous or endovascular treatment up to 24 hours after
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onset of symptoms for basilar artery occlusions 12. In regards to selection of therapy,
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intravenous thrombolysis or intra-arterial thrombolysis appear to be similar in
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terms of survival and good neurologic outcomes 13 14.
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Our patient was discharged from the hospital home six days after therapy, with
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ability to move all four extremities and with preserved cranial nerve functions.
This case highlights the need for high index of suspicion for syndromes of massive posterior circulation disruption, despite the lack of definitive findings on imaging. Reassessment of the critically ill and unresponsive patient is necessary, and making sure to only deem a patient unresponsive once vertical gaze and upper eyelid movement has been carefully assessed.
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ACCEPTED MANUSCRIPT Figure 1: A computed tomography angiogram of the neck showing severe stenosis of the right internal carotid artery. Figure 2: A computed tomography angiogram of the neck showing severe stenosis of the left internal carotid artery.
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Figure 3: A non-contrasted computed tomography scan of the head showing a small caliber basilar artery
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