Opsoclonus-myoclonus syndrome in patients with locked-in syndrome: a therapeutic porthole with gabapentin

Abstract

Patients with locked-in syndrome, although fully conscious, have quadriplegia, mutism, and lower cranial nerve paralysis. The preservation of vertical gaze and upper eyelid movements usually enables them to interact with the environment through an eye-coded communication. However, locked-in syndrome may be complicated by the development of an opsoclonus-myoclonus syndrome that may represent an additional impediment to communication. We evaluated whether off-label treatment with gabapentin could help patients with locked-in syndrome and opsoclonus-myoclonus symptoms regain voluntary control of full eye movements. A mechanism responsible for gabapentin-induced improvement has been also hypothesized. In this study, 4 patients presenting with locked-in syndrome complicated by opsoclonus-myoclonus syndrome were continuously treated with gabapentin up to 1200 mg/d. The treatment resulted in a rapid and long-lasting resolution of opsoclonus-myoclonus symptoms without adverse effects. After 2 weeks, patients showed voluntary attempts to communicate through eye blinking and thereafter regained voluntary control of full eye movements. This event enabled them to regain a communication channel with relatives and physicians and to start using eye-controlled brain-computer interfaces. Because of its effectiveness in restoring eye movement control, gabapentin opened a communicative porthole in the patients' lives. Since opsoclonus may be related to disorders of the inhibitory control of saccadic burst neurons by pontine pause cells, we hypothesize that gabapentin acts as a regulator of saccadic circuits.

FIGURE 1.

Brain magnetic resonance images for patients 1 and 2 showing the pontine ischemic lesion (A and B) and for patient 3 showing the pontine hemorrhage (C). Computed tomogram for patient 4 showing the central pontine myelinolysis (D).

FIGURE 2.

Physical Component Summary (PCS) and Mental Component Summary (MCS) scores for each patient as obtained by the 36-Item Short Form Health Survey. Locked-in syndrome was affected more on the PCS than on the MCS.

FIGURE 3.

Neural network that subserves the ipsilateral horizontal conjugate gaze. From the abducent nucleus (VI), both axons that innervate the lateral rectus (LR) and axons that cross the midline arise; the last ascend into the medial longitudinal fasciculus (MLF) and innervate the medial rectus (MR) motoneurons located at the oculomotor nucleus (III). Excitatory burst neurons (EBN) and pause neurons (PN) are located within the pontine paramedian reticular formation (PPRF). Saccadic accuracy is supported by a balance between the EBN and PN and their effect on ipsilateral tonic neurons (TN) and contra lateral inhibitory burst neurons (IBN). Full and empty arrows indicate excitatory and inhibitory synapses, respectively.