Video.
Alcohol-responsive movement disorders—a unifying hypothesis? We present video examples of robust responses to EtOH or Xyrem in thirteen selected patients treated by the senior author in IRB-approved clinical trials or clinical practice over the last fifteen years. We specifically selected video segments that illustrated a robust response. Patient #1, a 37-year-old woman, underwent a routine gynecological surgery complicated by an unrecognized esophageal intubation leading to refractory severe PHM [47]. Despite treatment with clonazepam, valproic acid, phenobarbital, topiramate, zonisamide and levetiracetam, paroxysms of myoclonus affecting the trunk, head and limbs, are triggered by any attempt to move. Twenty minutes after ingesting two eight-ounce glasses of wine in the office, her myoclonus improved for the first time in three and a half years, enough for her to gesture fluidly (telling her husband to “shut up”). Her husband was deeply moved, stating that “the gesture has returned”. She was even able to walk with only mild support from her home aide while the EtOH effect lasted. She participated in a single patient, IRB-approved, add-on clinical trial of Xyrem, and brief clips of her attempts to pour water are shown before and one hour after ingesting 4 gm of Xyrem (although she tolerated this dose without sedation, in subsequent trials lower doses of Xyrem were employed), After the trial concluded, she was treated with Xyrem in open label fashion for a decade at doses of 1.5 gm every three hours, until her demise from medical illness. Patient #2 sustained an asthmatic arrest leading to PHM fifteen years before this video was taken. Despite treatment with clonazepam and levetiracetam, action and intention myoclonus and negative myoclonus on standing were significant. The video segment illustrates myoclonus before and one hour after ingestion of 2.5 gm of Xyrem [48]. Patient #3 developed severe PHM after a spontaneous bilateral pneumothorax leading to cardiopulmonary arrest. Despite treatment with valproic acid, levetiracetam and zolpidem, severe action and intention myoclonus were disabling. He was admitted to hospital in order to titrate increasing doses of Xyrem in an observed setting (he did not receive an EtOh challenge as he was only 19 years old). One hour after administration of 1.5 gm of Xyrem, action and intention myoclonus were reduced, allowing him to perform tasks such as brushing his hair for the first time. He has remained on Xyrem for the last three years with clear awareness of kinetics of the drug, and no evidence of tachyphylaxis [51]; bilateral DBS of the GPi was performed two years after this video was taken, with additional functional benefit. Patient #4 developed severe PHM after a cardiac arrest triggered by a pulmonary embolus. Despite treatment with clonazepam, valproic acid, zonisamide and levetiracetam, severe myoclonic jerks of his arms and torso left him completely functionally dependent. In this home video before and one hour after ingestion of six ounces of 80 proof vodka, significant improvement in myoclonus at rest and with action is evident. He did not tolerate Xyrem due to worsening depression, and he subsequently underwent bilateral DBS of the GPI, with surgical results pending at the time of this writing.
Patients #5–8 demonstrate the response of VT and ET to treatment with Xyrem in IRB-approved clinical trials [18,43]. Patient #5, a 61-year-old woman with VT, is shown speaking and phonating before and one hour after ingesting one gram of Xyrem. A moderate-amplitude vocal tremor is evident before treatment, with modest reduction in the amplitude of tremor (without change in frequency). Patients #6–8, all with ET, are shown in brief video clips before and after treatment with Xyrem [36]. Patient #6 attempts to draw an Archimedes spiral with disastrous results; one hour after ingesting two grams of Xyrem he is able to perform the task. Patient #7 is shown before and one hour after administration of 1.5 gm of Xyrem. Interestingly, the video shows that after treatment she was aware that she could pour water with her left hand before she attempts to perform the task. Patient #8 was videotaped in fifteen-minute intervals after ingesting 1.5 gm of Xyrem to assess the pharmacokinetics of the improvement. Before treatment, action tremor of the right hand interferes with her attempt to pour water. Forty-five minutes after ingesting 1.5 gm of Xyrem, a significant reduction of tremor is seen, and tremor disappears at sixty minutes, surprising the patient and her husband. Despite this robust response, she did not continue treatment due to the sedative side effects of the drug.
The following three patients with SCGE-MD (#s 9, 10 and 11) are shown in brief clips taken during their participation in a clinical trial [36]. Patient #9 is shown pouring water before and one hour after administration of 2.5 gm of Xyrem. Patient #10 is more severely affected, with myoclonus affecting walking and pouring. Myoclonus was moderately improved at relatively high doses of Xyrem (video shown one hour after administration of four grams). The final patient was afflicted with predominant axial jerks triggered by actions such as pouring. One hour after administration of two gm of Xyrem, myoclonus was improved.
The final two patients, #s 12 and 13, participated in a study of the effects of Xyrem on SD with functional MRI [72]. Patient #12 is afflicted with ADSD and is usually treated successfully with botulinum toxin injections bilaterally to the thyroarytenoid muscles. Her ADSD was exquisitely responsive to EtOH, and she is shown before and one hour after administration of 1.5 gm of Xyrem with near resolution of vocal breaks. The final patient, patient #13, is afflicted with ABSD, and is shown before and one hour after administration of one gram of Xyrem, with resolution of his abductor breaks.