| Eligibility |
Inclusion Criteria:
1. Age between 22-75 years.
2. Clinical diagnosis of chronic Locked-In Syndrome (LIS) certified by an independent
board-certified neurologist, defined here as impairments of voluntary motor control
that are widespread and severe enough to prevent independent initiation and
maintenance of communication, spoken or otherwise, without the assistance of a
caregiver. Diagnosis of LIS requires exclusion of cognitive impairments as a cause for
impaired communication (see Exclusion Criteria). For inclusion in this study,
participants may have one of the following clinical variants of LIS:
a. "Classic" Locked-In Syndrome, with the following signs documented on neurological
examination i. Quadriplegia ii. Bulbar palsy iii. Anarthria iv. Partial or complete
preservation of vertical eye movements and upper eyelid movements, or b. "Incomplete"
Locked-In Syndrome, with the aforementioned signs of "Classic" LIS, documented on
neurological examination, except that voluntary movements other than upper eyelid and
vertical eye movement may be preserved, albeit still severe enough to prevent
independent initiation and maintenance of communication, without the assistance of a
caregiver. Preserved voluntary movements may include: i. Horizontal eye movements ii.
Facial movements iii. Movements of the extremities not sufficient to reliably operate
a joystick or mouse
3. Clinical diagnosis of, and confirmatory/exclusionary testing consistent with, one of
the following irreversible or progressive neurological disorders as the cause for
chronic Locked-In Syndrome, as defined above:
a. Permanent lesion of corticospinal and corticobulbar tracts in the ventral pons
(basis pontis) due to ischemic stroke, hemorrhage, or trauma, based on the following:
i. Documented history of acute ischemic or hemorrhagic brainstem stroke or traumatic
brainstem injury at onset of LIS ii. Ancillary testing including the following:
1. Brain MRI confirming a chronic lesion of the ventral pons, with no change on serial
images at least 1 month apart, consistent with findings on neurological examination,
involving at least 50% of the cross-sectional area on both sides of the basis pontis on at
least one axial section 2. Absence of lesions on brain MRI that could contribute to
communication impairment, including lesions of Broca's or Wernicke's areas, or sensorimotor
cortex 3. EEG demonstrating posterior basic rhythm reactive to eye opening and closing iii.
No clinical evidence of improving communication ability for at least 1 year prior to
recruitment, confirming chronic LIS b. Diagnosis of Amyotrophic Lateral Sclerosis (ALS),
certified by an independent board-certified neurologist with expertise in neuromuscular
disorders, satisfying the following El Escorial World Federation of Neurology diagnostic
criteria for probable, laboratory supported, or definite ALS: i. Signs of lower motor
neuron (LMN) degeneration by neurological examination (weakness, atrophy, and
fasciculations), electrophysiological (electromyographic findings of denervation), or
neuropathological determination (muscle biopsy) in bulbar and at least two of three spinal
regions (cervical, thoracic, lumbosacral), or in all three spinal regions ii. Signs of
upper motor neuron (UMN) degeneration by clinical examination (spasticity, hyperreflexia,
pseudobulbar affect, pathological reflexes) in bulbar and at least two of three spinal
regions (cervical, thoracic, lumbosacral), or in all three spinal regions iii. Progressive
spread of signs within a region or to other regions, together with the absence of
electrophysiological or neuroimaging evidence of other disease processes that might explain
clinical and electrophysiological signs of LMN and/or UMN degeneration (see below) iv.
Confirmatory testing including:
1. Electrophysiological Studies
1. Electromyographic findings of denervation (reduced recruitment, large motor unit
action potentials, and fibrillation potentials) in clinically involved regions,
including 3 of the following 4 muscle regions: bulbar, cervical, thoracic, and
lumbosacral
2. Nerve conduction studies confirming absence of demyelination as an explanation
for aforementioned LMN signs
2. Neuroimaging, including brain and spine MRI, ruling out brain or spinal lesions
(spinal cord or root compression) that could explain aforementioned LMN or UMN signs
3. Clinical laboratory examinations, determined by clinical judgment, to ascertain
possible ALS-related syndromes v. History, physical, and laboratory examinations
ruling out alternative diagnoses as cause of aforementioned clinical syndrome,
including monoclonal gammopathy, autoimmune motor system degeneration,
hyperthyroidism, hyperparathyroidism, paraneoplastic syndrome, infections of the
central nervous system, toxic-metabolic disorders, or spinal cord injury due to
trauma, electric shock, radiation therapy, vasculitis, ischemia, hemorrhage, or
spondylotic myelopathy vi. No clinical evidence for improving communication ability
for at least 6 months, confirming chronic LIS
4. Reliable means of communicating with caregiver(s) before entering the study, for
example using vertical eye movements or eye blinking. Assessment of communication
capabilities may be made by a physiatrist, a speech therapist, and/or an occupational
therapist.
5. Residence within a reasonable driving distance from the JHU research team
6. Medically stable, including stable respiratory function, with or without artificial
ventilation (see Section 12.2.3, Section 12.2.6, and Section 12.2.11).
7. Surgical clearance by the participant's primary healthcare provider, study physicians,
and any necessary consultants
8. Stable psychosocial support system with caregiver(s) capable of monitoring the
participant throughout the study. Caregivers must be willing and able to be present
and provide routine care during all study activities except during hospitalization for
device implantation.
9. Ability to understand and comply with study session instructions determined through
the regular administration of simple study questionnaires.
Exclusion Criteria:
1. Strong and frequent muscle spasms not controlled by medication
2. Recent or remote history of brain tumor or tumor resection in any location
3. Cognitive impairments, according to neurological examination and neuropsychological
testing, that contribute to impaired communication, or that could interfere with
informed consent or participation in study activities
4. "Complete" Locked-In Syndrome without any voluntary movement, including vertical eye
movements or blinking, without any reliable means of communicating with caregivers or
others.
5. Known allergy to implanted materials
6. Contraindications to MRI prior to implantation (inability to lie flat in the scanner,
MRI-incompatible metal objects in or attached to the body, claustrophobia)
7. Brain lesions that involve potential targets for implantation of BCI electrodes in
sensorimotor cortical areas
8. No clearly identifiable targets for implantation of BCI electrodes after two
pre-implantation functional magnetic resonance imaging (fMRI) localizer scans. Targets
are identified as cortical areas of activation during attempted movements and/or
speech.
9. Severe psychiatric illness that could interfere with informed consent or participation
in study activities
10. Persistent suicidal ideation within the past 12 months or prior suicide attempt
11. Medical conditions contraindicating surgery or chronic device implantation
12. Treatment with immunosuppressive drugs
13. Chronic or acute medical condition that is anticipated to require surgery,
radiotherapy, chemotherapy, immunosuppression, and/or MRI
14. Pregnant (confirmation through blood test), planning to become pregnant (sexually
active without using effective birth control), or nursing an infant.
15. Visual impairment that would prevent use of computer monitor
16. Active cancer within the past year
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