LOCKED in SYNDROME: a Case Report

LOCKED IN SYNDROME: A Case Report

Jalellah B. Noor, MD1, Marietta Olaiver, MD, FPCP, FPNA2, Alexander Abe MD, FPNA3, Jonathan Bernanrdo, MD, FPCP, FPCC4

Ospital ng Makati

Philippines

Abstract

Background

Locked In Syndrome (LIS) is a rare neurological condition characterized by complete paralysis of voluntary muscles in all parts of the body except control of eye movement, preserved cognitive functioning and a primary code of communication that uses vertical eye movements or blinking. This condition leaves the individual completely mute and paralyzed. Prevalence is unknown. Their only means of communication is by blinking or vertical eye movements because of sparing of the midbrain tectum, which allows communication.

Case Presentation

We report a case of a 53-year-old male, newly diagnosed with hypertension, presented to an emergency room with left-sided body weakness and numbness and decreased verbal output. Over 10 days, patient had been experiencing intermittent rotatory dizziness, no history of trauma nor loss of consciousness. After presentation, patient became quadriplegic, anarthric and presented an initial period of coma, requiring intubation and ventilatory assistance.

Investigations

History, physical and neurological examinations, CT scan, electroencephalogram, functional MRI studies, ultrasound techniques such as transcranial doppler and carotid duplex scan and 2D-echochardiography.

Treatment and Outcome:

Medical management started on neuroprotection, antiplatelet, low molecular weight heparin, maintaining an airway and adequate oxygenation, tracheostomy, gastrostomy, early intensive rehabilitation, and family counselling. While admitted, patient developed ventilatory acquired pneumonia as caused of demise of patient.

Conclusion:

Locked-in syndrome can be difficult to diagnose because some patients emerge from coma into locked-in state after a variable delay. It can be missed if voluntary vertical eye movement is not assessed in patients who seem unresponsive, hence a thorough investigation was clearly of utmost importance.

Keywords: Locked-in Syndrome, Cerebrovascular Disease, Vertical Nystagmus

Introduction:

Locked In Syndrome (LIS) is a rare neurological condition defined in 1966 and redefined in 1986 as quadriplegia and anarthria with preservation of consciousness1. It is caused by an insult to the ventral pons, most commonly an infarct, haemorrhage, or trauma2. Dizziness or vertigo, hemiparesis, and headache were the most frequently reported initial symptoms. In most patients these symptoms occurred during the day prior to the onset of the "locked-in" state, but in a few patients the symptoms were present for days to even months prior to onset3. The actual prevalence rate of LIS is not specifically documented in the literatures. Diagnosis is not always reported as some individuals die during acute phase while some recover. Pulmonary complications represented the leading cause of death after the first week post onset of locked-in state, hence, high risk of develoing significant respiratory problems4.

Case Report

A 78 year old, male, right handed, Filipino, presented with left-sided body weakness and numbness. Patient was apparently well until 10 days prior to admission, patient experienced intermittent rotatory dizziness with slurring of speech relieved by rest. One day prior to admission, with recurrence of dizziness described as rotatory, but still with slurred speech, he sought consult in a private Clinic with BP of 190/100 where he was diagnosed with Beningn Paroxysmal Positional Vertigo and Hypertension Stage II. He was given Betahistine 16mg 1 tab 3x a day as needed for dizziness and Losartan 50mg, 1 tab once a day respectively. 5 hours prior to admission, at around 10am, patient complained of left-sided body numbness with weakness and was noted to have decreased verbal output but can comprehend and follow some commands. He sought consult at Ospital ng Makati Emergency Room and subsequently admitted at 1pm.

Patient is recently diagnosed with Hypertension Stage II on Losartan 50mg, 1 tab once a day, not known diabetes, no previous hospitalizations nor previous operations, nor exposure to radiation. He has prostatic enlargement maintained on Tamsulosin 200mcg, 1 tab once at bedtime with good compliance. Patient's father has hypertension, siblings has type 2 diabetes mellitus and heart disease on maternal side. He was nonsmoker, occasional alcoholic beverage drinker, denies illicit drug use, no known allergies to food and drugs, fond of eating spicy and fatty foods. He was a retired seaman residing in USA, and a volunteer employee at Home of Aged in USA.

The clinical examination revealed average built male, weighing 75kg, BMI of 27.5 kg/m2 (overwight) with blood pressure of 170/90 (mean arterial pressure 117 mmHg), heart rate of 62 beats per minute, respiratory rate of 20 cycles per minute, afebrile at 37degrees with 02 saturation of 98%. The rest of the physical examination were unremarkable. On neurological examination at the emergency room, his initial glasgow coma scale was 11 (E4V2M5), National Institutes of Health (NIH) Stroke Scale of 19, slurred speech and responds to queries, 2-3 mm pupils sluggishly reactive to light, AVR ratio 2:3, no signs of hypertensive retinopathy, preferential gaze to right with full extraocular muscle movement, left central facial palsy, bilateral weak gag reflex, cannot shrug left shoulder because of left sided weakness, left hemiplegia of 2/5 upper and 1/5 lower extrimities. With the same degree of painful stimulation, there is a delay in the response over the left upper and lower extemities.

Work-ups such as Complete blood count, electrolytes, kidney and liver functions tests, chest xray and urinalysis were normal. Initial Plain Cranial CT (Figure 1) showed chronic infarct, right subinsular region with mild microvascular ischemic disease and atherosclerotic intracranial vessel disease. He was admitted as a case of Cerebrovascular Disease Infarct, Moderate, Right Frontoparietal Area. He was started on Citicoline 2g TIV q8, Aspirin 100mg OD, Atorvastatin 80mg OD, Mannitol 150cc q4, and MAP maintained at 110 to 130 mmHg.

On his 12th hour of hospital stay, he presented with vertical nystagmus, quadriplegia, broca's aphasia, glasgow coma scale of 8 (E3V2M3), NIHS Score of 19 progresssed to 24, absent extraocular muscle movement. He had endotracheal intubation. Cranial MRI (Figure 2) done revealed acute to subacute infarct at anterior two-thirds of the pons, chronic infarct at periphery of the left pons and right lentiform nucleus; atherosclerrotic internal carotid arteries; occlusion or very slow flow in the distal vertebral arteries and proximal basilar artery. Patient then started on Enoxaparin 6000u SC OD and the rest of medications were continued. On his 4th hospital day, with stable vital signs, still with the same presentation, transcranial doppler ultrasound done revealed normal peak systolic doppler velocity in bilateral opthalmic arteries, terminal internal carotid arteries, middle cerebral arteries, anterior communicating arteries and posterior circulation. Carotid Duplex Scan showed <50% stenosis at right common carotid artery, 50-59% stenosis right internal carotid artery, <50% (1-15%) stenosis left internal carotid artery, high resistance waveform pattern in the left vertebral artery (vertabral – 0 – vertebral 2) and left vertebral artery (vertebral 0 – vertebral 1) may be indicative of a more distal occlusive in the posterior circulation, normal antegrade flow in bilateral vertebral arteries. Echocardiography revealed concentric left ventricular hypertrophy with adequate wall motion and contractility, aortic annular calcification, mild to moderate aortic regurgitation and reversed mitral inflow pattern indicative of Grade 1 left ventricular diastolic dysfunction. Patient also underwent tracheostomy and gastrostomy. Low molecular weight heparin maintained as DVT prophylaxis and on antiembolic stocking. Early intensive rehabilitation and family counselling were done. While admitted and maintained on mechanical ventilatory support, patient developed ventilator acquired pneumonia and eventually expired on his 30th day of hospitalization.

Discussion

Locked in syndrome defines in 1966 as quadriplegia, lower cranial nerve paralysis, and mutism with preservation of consciousness, vertical gaze and upper eyelid movement. It was was redefined in 1986 as quadriplegia and anarthria with preservation of consciousness. This redefinition served to clarify that mutism could imply unwillingness to speak1. Ischemic strokes are the most common cause. They most commonly occur following a basilar artery thrombosis with secondary occlusion of the perforating arteries2. Individuals affected in this manner probably represent less than 1% of all strokes, though the incidence rate is probably underestimated4.

Dizziness or vertigo, hemiparesis, and headache were the most frequently reported initial symptoms. The symptoms in most cases occurred during the day prior to the onset of the "locked-in" state, but in a few patients the symptoms were present for days to even months prior to onset. The sensory findings in LIS were found to vary from normal to absent which may reflect the difficulty in performing an adequate sensory examination. Consciousness and awareness of the environment are reinforced by their ability to communicate using their residual motor function. Anarthria causes dysphagia and limits the use of facial expression in communication. Although medial and lateral gaze palsies are typical, patients usually retain upper eyelid control and vertical eye movement because of sparing of the midbrain tectum, which allows communication4.

Most patients requires assistance in the form of assisted ventilation and secretion management. Pulmonary complications represented the leading cause of death after the first week post onset of the locked-in sate. It is apparent that the “locked-in state” patient is at high risk of developing significant respiratory problems, hence, needs to be monitored closely. Since sensory testing is difficult, other tests such as brainstem auditory evoked response is best to perform accurately in the "locked-in" patient, and somatosensory evoked responses provide a valuable means of evaluating the integrity of the afferent pathways as well as localizing the extent of the lesion4.

Locked-in syndrome has been classified into three categories: Classic (quadriplegia and anarthria with preserved consciousness and vertical eye movement), Incomplete (the same as classic but with remnants of voluntary movement other than vertical eye movement) and total (total immobility and inability to communicate, with full consciousness.)2

The diagnosis of Locked-in syndrome is based on clinical features and is dependent upon physical and neurological examination. A complete coma exam including cranial nerves and volitional eye/eyelid movements should be performed. Locked- in syndrome may be mistaken for coma (eyes closed and does not follow commands) or a vegetative state (eyes may open and move but not command). It can be difficult to diagnose because some patient emerge from coma into a locked-in state after a variable delay. It can be missed if voluntary vertical eye movement is not assessed in patients who seem unresponsive. Cranial imaging is performed to elucidate the diagnosis. When magnetic resonance imaging, as the preferred modality, shows a ventral pontine insult in an otherwise unresponsive patient, the assessor should re-examine vertical eye movement5. Conventional x-ray cerebral angiography is the gold standard for identifying and quantifying stenoses of cerebral arteries. Transcranial doppler will help detect stenotic lesions in the large intracranial arteries in MCA, ACA and PCA such lesions increase systolic flow velocity. Carotid duplex and transcranial ultrasound studies eliminates the need for conventional x-ray angiography in evaluating vascualr stenosis. EEG cannot definitely identify such awareness, a normal EEG in an unresponsive patient helps to distinguish LIS from othe forms of coma6.

The acute management of patients with locked-in syndrome is similar to that for patients with other acute brain stem insults. The initial emphasis is on maintaining an airway and adequate oxygenation. Managing reversible medical causes and reducing risk factors are essential while preventing the complications of immobility, dysphagia, and incontinence. Thrombolysis protocol is similar to that of other ischemic strokes. Intra-arterial thrombolysis is therapeutic strategy but further studies are needed to establish its routine use7. Chest physiotherapy, frequent positional changes, postural drainage, and suctioning, may limit pulmonary complications. Corneal ulceration, due to impaired eye closure, can be treated by lateral tarsorrhaphy or botulinum therapy. Avoiding full eye closure is important because it will prevent communication. Pathological crying can respond to selective serotonin reuptake inhibitors2.

Prognosis is poor as some patients do not survive the acute phase, or experience very limited recovery. During the acute phase, infections (commonly pneumonia) are the most common cause of death. Life expectancy is severely reduced. Early rehabilitation is favorable prognostic factor to reduce mortality from acute locked-in syndrome. Although most survivors remain either in a chronic locked-in state or severely impaired, early signs of recovery can be exploited through multidisciplinary rehabilitation5.

Conclusion

Locked-in syndrome present as a great challenge to internists, hence, thorough investigation is needed in arriving at diagnosis. Internists should do the complete neurological examination and assessment. To our knowledge, there is no known documented incidence in the local setting of Makati, and other parts of Philippines. It can be difficult to diagnose and it can be missed if voluntary vertical eye movement is not assessed. With the various new modalities to diagnose LIS, there now exists the possibility to unlock sufferers from this devastating neurological condition.

Figure 1

Figure 2

Authors:

1. Resident, Department of Internal Medicine, Ospital ng Makati, Makati City, Philippines

2. Internal Medicine-Neurology Consultant, Department of Internal Medicine, Ospital ng Makati, Makati City, Philippines

3. Neurology Consultant, Department of Internal Medicine, Ospital ng Makati, Makati City, Philippines

4. Internal Medicine – Adult Cardiology/Vascular Medicine, Department of Internal Medicine, Ospital ng Makati, Makati City, Philippines

References:

1. Haig AJ, Katz RT, Sahgal V. Mortality and complications of the locked-in syndrome. Arch Phys Med Rehabil1987;68: 24-7
2. Smith, E, Delargy M., Locked-in Syndrome. BMJ: British Medical Journal. 2005; 330 (7488): 406-409
3. Doble, J.E., Haig, A.L., Anderson, C., and Katz, R. (2 Impairment, Activity, Participation, Life Satisfaction, Survival in persons with Locked-in Syndrome for over decade: Follow-up on a previously reported cohort. Journal of Head Trauma Rehabilitation, 18, 435-444
4. Patterson, James MD, Grabois, Marin MD; Locked-In Syndrome: A Review of 139 Cases, Stroke Vol 17, No 4, 1986; 17:758-764
5. Bruno, Marie-Aurelie MD, Locked-in syndrome; December 2012 Ver4.16.0
6. Harrison's Principle of Internal Medicine, 19th Edition, Volume 2, page 2580-2581
7. Khanna, Kunal MBBCh, Ajit Verma MMS, MD, MRCP, MRCPE, Bella Richard MMBS, FRCP, Msc, Journal of Clinical Gerontology and Geriatrics, The Locked In Syndrome: Can it be unlocked?, December 2011, Vol.2 (4): 96-99, doi:10.1.16/j.jcgg.2011