Music and musicality in brain surgery: The effect on delirium and language

Delirium is a neuropsychiatric clinical syndrome with overlapping symptoms with
the neurologic primary disease. This is why delirium is such a difficult and underexposed
topic in neurosurgical literature. Delirium is a complication which might
affect recovery after brain surgery, hence we describe in Chapter 2 a systematic
review which focuses on how delirium is defined in the neurosurgical literature.
We included twenty-four studies (5589 patients) and found no validation studies
of screening instruments in neurosurgical papers. Delirium screening instruments,
validated in other cohorts, were used in 70% of the studies, consisting of the
Confusion Assessment Method (- Intensive Care Unit) (45%), Delirium Observation
Screening Scale (5%), Intensive Care Delirium Screening Checklist (10%), Neelon
and Champagne Confusion Scale (5%), and Nursing Delirium Screening Scale (5%).
Incidence of post-operative delirium after intracranial surgery was 19%, ranging from
12 – 26% caused by variation in clinical features and delirium assessment methods.
Our review highlighted the need of future research on delirium in neurosurgery,
which should focus on optimizing diagnosis, and assessing prognostic significance
and management.

It is unclear what the impact of delirium is on the recovery after brain surgery,
as delirium is often a self-limiting and temporary complication. In Chapter 3 we
therefore investigated the impact of delirium, by means of incidence and health
outcomes, and identified independent risk factors by including 2901 intracranial
surgical procedures. We found that delirium was present in 19.4% with an average
onset (mean/SD) within 2.62/1.22 days and associated with more Intensive Care
Unit (ICU) admissions and more discharge towards residential care. These numbers
confirm the impact of delirium with its incidence rates, which were in line with our
previous systematic review, and significant health-related outcomes. We identified
several independent non-modifiable risk factors such as age, pre-existing memory
problems, emergency operations, and modifiable risk factors such as low preoperative
potassium and opioid and dexamethasone administration, which shed light
on the pathophysiologic mechanisms of POD in this cohort and could be targeted
for future intervention studies.
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As listening to recorded music has been proven to lower delirium-eliciting factors in
the surgical population, such as pain, we were interested in the size of analgesic effect
and its underlying mechanism before applying this into our clinical setting. In Chapter
4 we describe the results of a two-armed experimental randomized controlled trial in
which 70 participants received increasing electric stimuli through their non-dominant
index finger. This study was conducted within a unique pain model as participants
were blinded for the outcome. Participants in the music group received a 20-minute
music intervention and participants in the control group a 20-minute resting period.
Although the effect of the music intervention on pain endurance was not statistically
significant in our intention-to-treat analysis (p = 0.482, CI -0.85; 1.79), the subgroup
analyses revealed an increase in pain endurance in the music group after correcting for
technical uncertainties (p = 0.013, CI 0.35; 2.85). This effect on pain endurance could
be attributed to increased parasympathetic activation, as an increased Heart Rate
Variability (HRV) was observed in the music vs. the control group (p=0.008;0.032).
As our prior chapters increased our knowledge on the significance of delirium on the
post-operative recovery after brain surgery and the possible beneficial effects of music,
we decided to design a randomized controlled trial. In Chapter 5 we describe the
protocol and in Chapter 6 we describe the results of this single-centered randomized
controlled trial. In this trial we included 189 patients undergoing craniotomy and
compared the effects of music administered before, during and after craniotomy with
standard of clinical care. The primary endpoint delirium was assessed by the delirium
observation screening scale (DOSS) and confirmed by a psychiatrist according
to DSM-5 criteria. A variety of secondary outcomes were assessed to substantiate
the effects of music on delirium and its clinical implications. Our results support
the efficacy of music in preventing delirium after craniotomy, as found with DOSS
(OR:0.49, p=0.048) but not after DSM-5 confirmation (OR:0.47, p=0.342). This
possible beneficial effect is substantiated by the effect of music on pre-operative
autonomic tone, measured with HRV (p=0.021;0.025), and depth of anesthesia
(p=<0.001;0.022). Our results fit well within the current literature and support the
implementation of music for the prevention of delirium within the neurosurgical
population. However, delirium screening tools should be validated and the long-term
implications should be evaluated after craniotomy to assess the true impact of music
after brain surgery.


Musicality and language in awake brain surgery
In the second part of this thesis, the focus swifts towards maintaining musicality and
language functions around awake craniotomy. Intra-operative mapping of language
does not ensure complete maintenance which mostly deteriorates after tumor resection.
Most patients recover to their baseline whereas other remain to suffer from aphasia
affecting their quality of life. The level of musical training might affect the speed and
extend of postoperative language recovery, as increased white matter connectivity in
the corpus callosum is described in musicians compared to non-musicians. Hence,
in Chapter 7 we evaluate the effect of musicality on language recovery after awake
glioma surgery in a cohort study of forty-six patients. We divided the patients into
three groups based on the musicality and compared the language scores between these
groups. With the first study on this topic, we support that musicality protects against
language decline after awake glioma surgery, as a trend towards less deterioration of
language was observed within the first three months on the phonological domain (p
= 0.04). This seemed plausible as phonology shares a common hierarchical structure
between language and singing. Moreover, our results support the hypothesis of
musicality induced contralateral compensation in the (sub-) acute phase through the
corpus callosum as the largest difference of size was found in the anterior corpus
callosum in non- musicians compared to trained musicians (p = 0.02).
In Chapter 8 we addressed musicality as a sole brain function and whether it can
be protected during awake craniotomy in a systematic review consisting of ten
studies and fourteen patients. Isolated music disruption, defined as disruption during
music tasks with intact language/speech and/or motor functions, was identified in
two patients in the right superior temporal gyrus, one patient in the right and one
patient in the left middle frontal gyrus and one patient in the left medial temporal
gyrus. Pre-operative functional MRI confirmed these localizations in three patients.
Assessment of post-operative musical function, only conducted in seven patients by
means of standardized (57%) and non-standardized (43%) tools, report no loss of
musical function. With these results we concluded that mapping music is feasible
during awake craniotomy. Moreover, we identified certain brain regions relevant for
music production and detected no decline during follow-up, suggesting an added
value of mapping musicality during awake craniotomy. A systematic approach to map
musicality should be implemented, to improve current knowledge on the added value
of mapping musicality during awake craniotomy.