Deep brain stimulation for treatment patients in vegetative state and minimally conscious state

36.1

Introduction

Persistent vegetative state (VS) (PVS) was first described as wakefulness without awareness . VS, a clinical entity known as a coma vigile , apallic syndrome , or PVS , includes complete unawareness of the self and environment, usually accompanied by variable sleep–awake cycles, with preserved spontaneous respirations, digestion, and thermoregulation. Giacino et al. proposed the concept of the minimally conscious state (MCS) that is characterized by inconsistent but clearly discernible behavioral evidence of consciousness and can be distinguished from VS . Patients in MCS may follow, from time to time, specific commands, gestural or verbal yes/no responses, and some degree of purposeful movements.

The incidence of VS continuing for at least 6 months is at a rate of between 5 and 25 per million population, while the prevalence in adults is between 40 and 168 per million population . According to Beaumont and Kenealy, the incidence and prevalence of MCS have yet to be established .

Patients in the MCS and/or VS require special care, increased involvement of caregivers, health-care personnel, and the entire society. Unfortunately, there is no standardized and efficient treatment for those two conditions.

The treatment of this entity is controversial and ethically troublesome . Johnson gives one extreme view of this ethical quandary in his paper The right to die in the minimally conscious state where he wrote, “Life prolonging care may have negative value for some persons in a permanent MCS, who experience some minimal awareness, but have little to no hope of further recovery and little prospect of escaping a condition that is profoundly disabling and socially isolating” .

The Multi-Society Task Force defines the criteria for the diagnosis of VS as (1) no evidence of awareness of self or environment and inability to interact with others; (2) no evidence of sustained, reproducible, purposeful, or voluntary behavioral responses to visual, auditory, tactile, or noxious stimuli; (3) no evidence of language comprehension or expression; (4) intermittent wakefulness manifested by the presence of sleep–wake cycles; (5) sufficiently preserved hypothalamic and brainstem autonomic functions to permit survival with medical and nursing care; (6) bowel and bladder incontinence; and (7) cranial nerve reflexes (pupillary, oculocephalic, corneal, vestibulo–ocular, and gag) as well as spinal reflexes preserved to various extents . The task force also reported that recovery of consciousness from a posttraumatic PVS is unlikely after 12 months, while recovery from a nontraumatic PVS after 3 months is exceedingly rare .

36.2

A short history of deep brain stimulation for vegetative state and minimally conscious state

One of the first groups that tried to aggressively treat VS and MCS using chronic deep brain stimulation (DBS) was Hassler et al. . According to their report, chronic electrical stimulation started 21 weeks after the initial trauma in a patient with apallic syndrome, using electrodes positioned in the left rostral part of the thalamus and right internal pallidum. Over a period of 19 days of stimulation, a strong arousal reaction was noted, along with some other improvements, such as spontaneous movements; however, no substantial changes in the level of consciousness were achieved.

McLardy et al. reported, in a 1964 case study, on a patient who was comatose after neurotrauma, treated with chronic DBS . They explored a broad range of stimulation parameters at the upper pontine reticular formation but reported no improvement in the level of consciousness.

Sturm et al. delivered chronic DBS to one patient who continued to have MCS signs 3 weeks after the clipping of a basilar tip aneurysm . Bilateral stimulation was initially tried with one electrode placed in the left rostral part of the lamella medialis thalami and another on the right side. The right-side electrode was removed because its stimulation had no effect. However, the effect of the left electrode, through which stimulation was delivered for a period of 7 weeks, consisted of a rise in the level of clinical responsiveness and the patient’s ability to follow simple commands; in addition, there were even some periods of verbal interactions.

Cohadon and Richer stimulated the centromedian–parafascicular (CM–pf) nuclei unilaterally in 25 patients in VS after neurotrauma . In 12 of the patients, no changes in neurological status occurred, and all 12 remained in VS during the 1–10-year follow-up period. In the remaining 13 patients, recovery of some degree of consciousness was obtained. They concluded that DBS likely accelerated recovery and possibly improves ultimate level of performance. In addition, the authors suggest that failure of DBS is a predictor of the irreversibility of posttraumatic VS.

The most extensive studies of DBS for VS and MCS were published over several papers by Tsubokawa, Yamamoto, et al. . They described selection criteria and the results of DBS implants in 21 VS patients and 5 MCS patients. In the VS cohort, they targeted the mesencephalic reticular formation ( Nucleus cuneiformis ) in two patients and the CM–pf complex in 19 patients, while the CM–pf complex was targeted in all patients in MCS. Patients for DBS were selected according to their neurophysiological evaluation. Eight of the 21 VS patients recovered from VS and were able to communicate through speech or other responses, but they continued to require assistance with their activities of daily living and remained bedridden with severe disability. Four of the five MCS patients emerged from the bedridden state. All eight patients who recovered from VS before DBS implantation demonstrated periods of desynchronization on their electroencephalography (EEG). Wave V of the brainstem auditory evoked response (BAER) and the N20 of the somatosensory evoked potential (SEP) were present yet had an abnormally increased latency. The pain related P250 response was greater than 7 μV .

Schiff et al. assessed DBS in a single MCS patient following a 6-month double-blind alternating crossover study and reported positive results .

Magrassi et al. reported beneficial effects on spasticity and myoclonus from bilateral thalamic stimulation in three patients with different disorders of consciousness (two patients in VS and one in MCS), including some evidence of conscious behavior .

Latest, Chudy et al. in 2018 reported long-term results of DBS in the CM–pf nuclei in VS and MCS patients . After evaluation and screening of 46 patients, 14 of them underwent DBS (10 patients VS and 4 patients in MCS). The authors showed improvement in consciousness in four patients (three patients in MCS and one in VS).

36.3

Patients and methods

The neurophysiologic, clinical, and imaging criteria were fulfilled by 10 of 45 VS candidates and by all 4 of the MCS patients. In the VS group the patient’s ages ranged from 16 to 59 years (mean of 35 years). 6 of the 10 patients were male, 3 were in VS related to trauma and 7 were in VS following an anoxic brain lesion due to cardiac arrest. The length of time from the injury to initiation of DBS ranged from 2.5 to 21.5 months. Patients in the MCS group age ranged from 16 to 28 years (mean of 20 years). This group included three male patients who had sustained cardiac arrest and cerebral hypoxia and one female patient who suffered a brain injury in a car accident. The length of time from the injury to initiation of DBS ranged from 65 days to 11.5 years in this group. Clinical and demographic data of the patients included in study are presented in Table 36.1 .

Patients in VS and MCS were selected based on multiple tests as follows: (1) neurophysiologic evaluations that consisted of SEPs, motor evoked potentials (MEPs), brainstem auditory evoked potentials (BAEPs), and 12/24 hour EEG; and (2) neuroimaging that consisted of positron emission tomography (PET) and magnetic resonance imaging (MRI).

Neurophysiological testing was performed under propofol sedation to avoid muscle contamination.