Research on the mechanism of cognitive decline in patients after cerebellar pontine angle tumour surgery

Vestibular schwannoma (VS) is a benign and rare tumour localized in the
cerebellopontine angle (CPA), accounting for 5-10% of all intracranial tumours
(1). In the Netherlands, around 600 patients each year are diagnosed with a
tumour in the cerebellopontine angle region, of whom 250 patients end up at
Radboud University Medical Center (UMC)(2,3,4). Most often surgery is not
indicated and other treatment options like watchful waiting and radiosurgery is
sufficient.

However in larger tumours, often accompanied by severe clinical symptoms due to
their location close to vital anatomical structures, i.e., the
cranial nerves and/or the brainstem, surgery is the first choice of treatment
(Koos classification grade 4)(5). In Radboud UMC, this surgery is done on 15-20
patients per year. Symptoms include, amongst others, impaired facial nerve
function, progressive unilateral hearing loss, tinnitus and vertigo (6).

Resection of a CPA tumour involves major risks. For example, approximately
10-25% of patients report cognitive complaints postoperatively, which they
consider very disabling to their quality of life and may lead to lifelong
residual symptoms. Since this is not routinely included in the follow up, this
percentage is only a rough estimate.

To date, there are few reports on whether a CPA tumour itself can cause
cognitive dysfunction, and the number of reported cases is small. Goebel et al.
(2018) included 45 patients with an untreated CPA tumour and found that 69%
reported neurocognitive problems (7). To date, there are no studies available
concerning cognitive dysfunction after CPA surgery.

More importantly, little is known about the underlying mechanism. Deng et al.
(2022) demonstrated that cognitive decline in patients with an untreated VS was
correlated to changes in white matter pathways relative to healthy control
patients. The authors found that in patients with VS decline of general
cognitive function, attention, memory, executive control, and visuospatial and
visuoperceptual abilities was related to white matte damage in the minor
forceps of the corpus callosum compared to control patients (8).

To our knowledge, no previous studies interested in cognitive decline and white
matter fiber tracts after CPA surgery are available. At present, there are few
studies on the white matter fiber tracts of cerebellar systems in paediatric
tumours. Emotional, cognitive, and behavioural disturbances have been described
in children after surgery for tumours in the posterior cranial fossa using
various overlapping terms like cerebellar mutism syndrome (CMS), posterior
fossa syndrome (PFS) and cerebellar cognitive affective syndrome (CCAS) (9,
10). Recent investigations have led to new insights that damage to the
cerebellar peduncles, seen in tractography correlates with decline in cognitive
function. The current hypothesis is that CCAS arises from damage to the tractus
cerebello-dento-thalamo-corticalis which causes interruption of important
circuits and leads to hypofunction of supratentorial cortical areas (9, 10). In
our opinion, there could possibly be a similar explanation for cognitive
dysfunction after CPA surgery.

Our aim is to identify cognitive dysfunction in patients with a cerebellar
pontine angle tumour (koos classification grade 4 schwannoma) that have been
operated in order to prevent cognitive decline in future patients.
For this purpose, we want to subject a group of patients who underwent
resection of a CPA tumour and the control group (diagnosed with a Koos
classification grade 1-4, however without indication for surgery) to extensive
neuropsychological testing in combination with a comprehensive MRI scan to
answer the following primary questions:

1. How common is cognitive dysfunction (as detectable by neuropsychological
testing and the CCAS/Schmahmann scale) in patients after CPA surgery compared
to control patients?

2. Is there a correlation between cognitive dysfunction of patients after
resection of a CPA tumour (Koos classification grade 4) and abnormalities on
the MRI scan (both anatomical (T1/T2/Flair) and tractographic (DWI; fractional
anisotropy or ADC)) compared to control patients?

This is the first study concerning patients with cognitive dysfunction after
CPA tumour surgery. Due to the low annual incidence of VS, this explorative
study has a cross sectional study design.

The nature and extent of the burden and risks associated with participation in
this study are low and will have no therapeutic consequences for participants.
As mentioned before, this study consists of a comprehensive neuropsychological
examination and the CCAS/Schmahmann scale, both in which various cognitive
domains are measured including attention and concentration, executive
functions, memory, language, visual-spatial skills, abstraction ability and
neuropsychiatric symptoms. The test takes about 1-1.5h and a visit to the
Radboud UMC in Nijmegen is necessary.

In addition, participation includes a comprehensive MRI without contrast with a
duration of up to 1h at the Donders institute. If there is a contra-indication
for MRI, the patient is not eligible for the study and will be excluded. The
burden and risks of MRI are estimated to be low.