3.2. Treatment, recovery of command following and
improvement of frontal reactivity
Considering the dysconnectivity pattern, involving the bilateral mesial
frontal cortex and the basal ganglia (Figure 6) and consistent with a
mesocircuit hypothesis, a treatment with amantadine, a pro-dopaminergic
drug with antiglutamatergic and anticholinergic properties, was
attempted (Kraus & Maki, 1997; Thibaut et al. , 2019). Amantadine
was administered according to the following schedule: 50mg once daily in
week 13, 100 mg once daily in week 14, 100 mg twice daily in week 15,
150 mg twice daily up to the discharge (week 20) (Figure 1).
Increasing doses of amantadine were paralleled by a gradual recovery of
responsiveness from a fluctuating low-level MCS- to a stable
high-behavioral MCS “plus” (MCS+) diagnosis (week 17), due to the
appearance of subtle but reproducible movement to command with CRS- R
assessments (Figure 1). Notably, motor execution was finally achieved by
the recovery of voluntary motility of the right hand, corresponding to
the side where MEP, EMG and fMRI findings previously converged in
predicting a residual preservation of the central and peripheral motor
pathway.
Before IRU discharge (week 20), the patient underwent a final TMS-EEG
exam (week 19) to reassess the state of cortical circuits. TEP revealed
an increase of brain complexity not only when targeting the left
parietal site (PCI from 0.40 to 0.47, Figure 4 panel B, green circle;
panel C”, green TEP) but notably also over the right superior frontal
gyrus; here, the recovery of fast oscillations and late component both
locally and bilaterally, far from the stimulation site resulted in
higher complexity responses (PCI from 0.27 to 0.32, Figure 4 panel B,
green diamond; panel C’, green TEP), This change paralleled the recovery
of executive functions suggesting that TMS-EEG may represent an
interesting read-out of regional changes in cortical circuits that are
relevant for functional recovery during the IRU stay.