A rare case report of Lance-Adams Syndrome

Lance-Adams syndrome or chronic post-hypoxic myoclonus, is a rare complication of post-cardiopulmonary resuscitation, accompanied by action myoclonus and cerebellar ataxia. It manifests as diffuse action-triggered jerking movements resulting in significant morbidity. A case of Lance-Adams syndrome is presented here in a 60-year-old farmer admitted to the intensive care unit with history of cobra bite, in coma and respiratory failure, revived elsewhere. His EEG and CT brain was unremarkable. This patients myoclonus was poorly controlled by a variety of anti-epileptic medications. Over 75 days of rehabilitation there was improvement in ambulation and there were no cognitive deficits.


Introduction
With improvements in emergency medical services, the number of survivors of any hypoxic event (respiratory or cardiac) damaging brain has increased. These survivors may develop neurological complications, such as epilepsy, memory disturbances, depression, parkinsonism, dystonia, chorea, athetosis, tremor, akinetic-rigid syndromes and chronic post hypoxic myoclonus(PHM). 1 The latter is also known as Lance-Adams syndrome. 2 This is predominantly characterized by action myoclonus starting in days to weeks after cardiorespiratory resuscitation (CPR) in survivors . Here we present one case of LAS in a patient during snake bite management.

Case report
A 60 year old farmer was brought to emergency room on 4-9-2012, with a reference letter of cardiac resuscitation. 6hours earlier he was bitten by a cobra over foot in his field, which was initially followed by breathing difficulty and blurring of vision in about 30min. He was given one antisnake venom injection in a local hospital, was intubated endotracheally before shifting to our hospital. There was no history of nausea, vomiting, paraesthesia, dizziness, sweating, diplopia, weakness of limbs and bleeding manifestations. There was no relevant past medical history and patient had no ill habits.

Results
Patient had multiple ventricular ectopic, self-limited, without hemodynamic disturbance. During next 36 hours patient continued to be comatosed GCS-3/15, (not sedated), severe myoclonic jerks appeared involving face, tongue, neck and limbs. Brain stem reflexes were intact (pupilary reflex, deglutition reflex, cough reflex). Clonazepam (0.5mg twice daily), sodium valproate (1.5gm/day in divided doses), infusion of propofol and midazolam temporarily were useful. Serial coagulation profile improved, haemoglobin level improved, platelets and renal function were normal. CT brain was normal.
Course in the hospital-5 days later brain stem reflexes were found to be preserved , generalised hypotonia, areflexic, unprovoked myoclonic jerks persisted , these were severe whenever patient voluntarily opened eyes and moved limbs. Ventilator support was stopped on 12 th day as the patient had adequate respiratory efforts and GCS was 6/15. Temperature was 99-100 0 F, profuse sweating was noted in between the episodes. Myoclonic jerks varied from time to time, completely absent for 1-2 days and often continuously present during awake hours. His sensorium improved, he gestured of difficulty in swallowing, esophagogastroduodenoscopy showed normal mucosa. Adding phenobarbitone (120mg/day) and piracetam (400mg thrice daily) helped him little. Rehabilitation started with passive limb exercises, ambulation and oral feeds. His blood pressure was high throughout hospital stay and needed antihypertensive drug. Patient started walking with support, over 75 days; he was able to swallow liquids and dysarthria improved. At the time of discharge MMSE score was 23, there were no sensory deficits, bowel and bladder function was normal, clonazepam, sodium valproate, phenobarbitone, piracetam and phenytoin sodium continued.

Discussion
Initially, post-hypoxic myoclonic status epilepticus (brainstem origin-and coma is a pre-requisite for the diagnosis), was thought of, since the patient was in deep coma. As he recovered, Lance Adams syndrome (LAS) was considered. The syndrome of intention or action myoclonus as a sequel to hypoxic encephalopathy was originally described by Lance JW and Adams RD in 1963, in the course of primary respiratory failure. 3 it is characterized mainly by action myoclonus, associated cerebellar ataxia and very mild intellectual deficit. It was described in four patients after surviving cardiac arrest. These patients initially developed a generalized myoclonus accompanied by dysmetria, dysarthria, and ataxia. Over time, the myoclonus persisted but its character changed to a predominantly action myoclonus involving the limbs. It was hypothesized that this particular constellation of symptoms was due to cerebral hypoxia. Dysfunction of various parts of the central nervous system, including the basal ganglia, thalamus, midbrain, and cerebellum, is implicated in the pathogenesis. The neurotransmitters related to LAS are known to be serotonin and gamma-aminobutyric acid (GABA).Purkinje cells of cerebellum probably being susceptible to anoxic injury, may play a key role. 4 Purkinje cells are deficient in aldolase C and Excitatory amino-acid transporter 4 (EAAT4) that allow them to survive pathologically intense synaptic input from the inferior olive after the restoration of blood flow, they have reduced capability to sequester glutamate and reduced ability to generate energy during anoxia. LAS has diverse clinical, electrophysiological, and neurochemical abnormalities and the loss of serotonin within the inferior olive nucleus has been thought to play a certain role and GABA may interact with th e serotonin system to suppress posthypoxic myoclonus. 3,5 This patient's myoclonus was poorly controlled by a variety of anti-epileptic medications, i.e. valproate sodium, piracetam, clonazepam, phenobarbitone and phenytoin sodium. Levetiracetam is said to be useful in patients with chronic myoclonus. 6,7,8 Cranial single photon emission computed tomography (SPECT) and, 18F-fluorodeoxyglucose positron emission tomographic (PET) scan, cranial magnetic resonance spectroscopy (MRS) may show perfusion abnormalities(these tests were not available in our institute).
The probable factors that promoted susceptibility to the development of posthypoxic myoclonus in our patient, were severe anemia, old age, under nutrition and unrecognised hypertension, though snake bite complications were managed adequately. 9 Over 75 days of rehabilitation there was improvement in ambulation. Deep brain stimulation is tried in severe PHM to interrupt connections of ventrolateral thalamus and pontinetegmentum. 10

Conclusion
Worldwide so far about 150 cases of LAS are reported, in various causes like hanging 3 , myocardial infarction 11 , bronchial asthma 12,13,14 , and post surgical recovery. 15 Early recognition and rehabilitation carries long term good prognosis. 16 On thorough search we could not get any case report of LAS from India in journals and we presume that this is the first LAS case report from India.