Treatment of Recractory Myoclonus with Perampanel in Lance Adams Syndrome- A Report of two cases
Lance-Adams syndrome (LAS) is a rare complication of anoxic brain injury and characterized by uncontrolled myoclonic jerks/ action myoclonus. Less than 200 cases of Lance Adams Syndrome have been reported in worldwide literature since its first definition in 1960s. It is thought to be due to disinhibition of GABAergic systems. Patients usually have good recovery of cognition but physically disabled due to severe myoclonic jerks which may be resistant to treatment with anti-myoclonic medications. 
Here we report two cases of Lance Adams syndrome patients who were resistant to treatment with triple high-dose antiepileptic regime (levetiracetam, clonazepam and sodium valproate) but responded to Perampanel. Both patients had significant improvement of myoclonic jerks and their functional abilities. We also describe specialist therapy techniques used during their rehabilitation.
Case-1 was a 69 year old man who suffered from hypoxic brain injury following severe hospital-acquired pneumonia. His past medical history included paranoid schizophrenia, leg length discrepancy of 10cm and vertigo. At the time of admission to our rehabilitation unit he was 3 months post-hypoxic brain injury and was on high doses of Levetiracetam, Sodium valproate and clonazepam. He was on Aripiprazole for his schizophrenia. He had severe daytime somnolence which prevent him participating in his rehabilitation program. He presented with severe cognitive and communication difficulties. It is likely that the premorbid diagnosis of schizophrenia was additionally impacting his cognition. 
His Unified Myoclonus Rating Scale (UMRS) on admission showed severe functional disability with score of 27 out of 28 and global disability score of 3 out of 4. Following the start of Perampanel we were able to stop daytime doses of clonazepam which led to resolution of daytime somnolence. Although still unable to walk, his UMRS scores improved greatly. UMRS Functional score 19/28 and global disability score was 2/4. On discharge he was able to self-propel in his wheelchair, and feed and drink himself more efficiently. Therapeutic techniques included a combination of isolated and paced movements within repeated reach and grasp tasks. This was extended by using distraction to divide attention from the intentional movement and give opportunity for more automatic movements.
Case-2 was 37 year old female who suffered from anoxic brain injury due to accidental decannulation of tracheostomy tube which was difficult to re-insert. She was admitted to our rehabilitation unit 6 months post brain injury and was on treatment medication of sodium valproate, clonazepam and Levetiracetam for treatment of myoclonic jerks. Her past medical history included obstructive sleep apnoea, obesity and anxiety disorder. On admission she had a tracheostomy tube in situ. Her myoclonic jerks were severe putting het at risk of falls and even effecting her speech. She was able to perform sara steady transfers and mobilize two lengths of parallel bars with assistance of two. Her motor functions showed great variability and at her best she was able to mobilize 5 meters with assistance of 1 and supervision of two therapists. She has BERG balance score of 18/56. She was keen to stop clonazepam. We managed to wean the clonazepam off without no increase of myoclonic jerks. She was commenced on Perampanel which led to increased fluidity of stepping, ability to mobilize 30 meters with supervision of one person, climbing up and down about 20 steps and a much clearer speech. Her BERG balance score increased to 32/56. As the dose of Perampanel increased, valproate was weaned off and stopped too without any worsening of myoclonus. She was also supported with mindfulness approach, cognitive-behavioural therapy and music &singing as a distraction during mobilization.  
Conclusion: Although rare, Lance Adams Syndrome is a very disabling condition and may be difficult to treat. Perampanel should be considered for refractory cases. In our two cases Perampanel led to increased function and mobility and aided to wean off other anti-epileptic medications without any worsening of myoclonus. 







(SUBMITTED VERSION-449 words)
Treatment of Recractory Myoclonus with Perampanel in Lance Adams Syndrome- A Report of two cases

Lance-Adams syndrome (LAS) is a rare complication of anoxic brain injury (ABI) and characterized by uncontrolled myoclonic jerks/ action myoclonus. Patients usually have good cognition but physically disabled due to severe myoclonic jerks.

Here we report two cases of LAS who were resistant to treatment with high-doses of triple antiepileptics (levetiracetam, clonazepam and valproate) but responded well to Perampanel with improvement of myoclonic jerks and their functional abilities. 

Case-1 was a 69 year old man who suffered from ABI following severe pneumonia. His past medical history included paranoid schizophrenia, leg length discrepancy of 10cm and vertigo. He was admitted to our unit 3 months post-ABI. He had severe daytime somnolence which prevented him participating in his rehabilitation program. He also had severe cognitive and communication difficulties. 
His Unified Myoclonus Rating Scale (UMRS) on admission showed severe functional disability score of 27/28 and global disability score of 3/ 4. Following the start of Perampanel we stopped the daytime doses of clonazepam which resolved daytime somnolence. With Perampanel his UMRS scores improved greatly (Functional score 19/28 and global disability score 2/4). On discharge he was able to self-propel in his wheelchair, and feed and drink himself more efficiently. Therapeutic techniques included a combination of isolated and paced movements within repeated reach and grasp tasks. This was extended by using distraction to divide attention from the intentional movement and give opportunity for more automatic movements.
Case-2 was 37 year old female who suffered from ABI due to accidental decannulation of tracheostomy tube. She was admitted to our rehabilitation unit 6 months post ABI. Her past medical history included obstructive sleep apnoea, obesity and anxiety disorder. Her myoclonic jerks were severe putting het at risk of falls and even effecting her speech. She was able to mobilize two lengths of parallel bars with assistance of two. Her motor functions showed great variability and at her best she was able to mobilize 5 meters with assistance of one. Her BERG balance score was 18/56. We managed to wean the clonazepam off without  increase of myoclonic jerks. She was commenced on Perampanel which led to increased fluidity of stepping, ability to mobilize 30 meters with supervision of one person, climbing up and down 20 steps and a much clearer speech. Her BERG balance score increased to 32/56. Moreover, were able to wean off Valproate. She was also supported with mindfulness approach, cognitive-behavioural therapy and music &singing as a distraction during mobilization. 
 
Conclusion: Lance Adams Syndrome is a very disabling condition and may be difficult to treat. Perampanel should be considered for refractory cases. In our two cases Perampanel led to increased function and aided to wean off other anti-epileptic medications without any worsening of myoclonus.


Treatment of Recractory Myoclonus with Perampanel in Lance Adams Syndrome- A report of two cases