Summary:
The last decades has been observed an increase in incidence of the brain
tumors.
There is a peak of cerebellar medulloblastomas in childhood.
The posterior fossa tumors represent the 85% of brain tumors in children
aged between 2 and 12 years.
Some of the children who had been operated on for cerebellar tumor, that
infiltrated the inferior vermis, the dental nucleus or the floor of the 4th
ventricle developed mutism, cognitive and behavioral disturbances.
These symptoms helped in understanding that the cerebellum is implicated in
the cognitive and the behavioral (affective) functions and for their
development are responsible the neuronal closed loops between the
cerebellum, the basal ganglia and the cerebral cortex in frontal,
subfrontal, prefrontal, parietal and temporal area.
The aim of this study was 1) Τo investigate the presurgical
neuropsychological and behavioral impairment in children aged between 5
and 16 years with posterior fossa tumors. The following neuropsychological
and neurobehavioral examinations were performed:
1)The children’s executive functions were assessed using the short form
of Wechsler Intelligence Scale for Children (WISC).
2) For the assessment of visuospatial functions, spatial memory and visuomotoρ
integration skills, the Bender- Gestalt Test (BGT) was used.
3)For the assessment of the visual perception and and visual memory the Benton
Visual Retention Test (BVRT) was used.
4)Furthermore, parents or caregivers completed the Child Behavior Checlist of
Achenbach (CBCL) for their children’s behavior for the last 6 months.
The neuropsychological tests (WISC, BGT, and BVRT) revealed no significant
differences between patients and the controls of A group. These findings
suggest that children with posterior fossa tumors were not affected by brain
dysfunction.
This information is very important because it could serve as a baseline
before therapy induction, document changes from baseline after
therapy, evaluate cognitive effects of surgery, and assessment of
rehabilitation potential.
The CBCL revealed significant somatic concerns compared with measure
norms. Furthemore, the patients differed in aggressiveness, anxiety symptoms,
internalizing problems, attention and total problems. Perhaps the closed loops
between the cerebellum, the basal gaglia and the areas of brain cortex play a
role for the development of these affective problems.
2) Νext step of this study was to be obtained a sample of ventricular CSF
during the operation for shunt placement, or during the tumor removal from
the 4th ventricle. This CSF sample was used for the assessment of the
concentration of monoamine metabolites : for the norepinephrine the
3-methoxy-4-hydroxy-phenylgycol (MHPG), for the dopamine the homovanillic acid
(HVA), and for the serotonine the 5-hydroxyindoloacetic acid (5-HIAA).
Simultaneously, a blood sample was also obtained for assessment of the
same metabolites in the serum. For the norepinephrine the concentration
of vanillylmandelic acid (VMA) was evaluated in 24-hour urine samples.
During the same time period the levels of the above metabolites
were measured in the CSF of B group of controls.
Τhe aim of the study was to investigate the role of biogenic amines in
the ventricular CSF of children suffering from posterior fossa tumors and
their possible correlation with tumor histology and cognitive functioning.
Τhe biogenic amines (dopamine, epinephrine, norepinephrine, and serotonine)
are produced by a biological process and are involved in the
regulation of multiple neuronal functions such as regulation of motor
coordination, reward-driven learning, arousal, processing of sensory
input, memory, appetite, emotional stability, sleep, mood, vomiting,
social behavior, and the secretion of anterior pituitary and other hormones.
The measured values of monoamine metabolites in CSF reflect the average of
concentrations accumulated from all brain regions.
Ιn this study was found a negative relationship between the concentration
of MHPG and the verbal scale of the WISC of the patients with tumors
(r=-0.67, p=0,009). There was also a negative relationship between the
concentration of MHPG and the total W.I.S.C. (r=-0.49, p=0.0073).
Perhaps the tumor of the posterior fossa influences the noradrenergic
system through the closed neuronal loops between the the cerebellum, the basal
gagglia and the brain cortex, as previously mentioned.
Αlso in this study there was a positive correlation between the
performance scale of the W.I.S.C. (with wich the function of the right
brain hemisphere is assessed) and the HVA levels in the CSF (r= 0.55, p=0.041).
It is well known that there is a intercorrelation between the different
neurotrasmitters in the neuronal systems. So in the case of biogenic amines
each monoaminergic system can affect the others. In this study were assessed:
a) the concentrations of monoamine metabolites in the CSF and blood (serum),
and b) the 24-hour urine concentrations of VMA in the patients with posterior
fossa tumors.
The concentration of each metabolite was compared to the others. So there
was a significant correlation between MHPG and HVA concentrations in CSF
(r=0.62, p=0.002).
The concentration of 5-HIAA in the CSF was correlated significantly with the
HVA concentration from the samples obtained from the serum (r=0.046,
p=0.03). The urine concentration of VMA were correlated significantly with
HVA in CSF, MHPG in CSF , HVA in serum, and 5-HIAA in serum.
In this study the concentration of MHPG in the CSF of patients who
suffered from astrocytomas were found increased compared whith those who
suffered from medulloblastomas.
There was also a trend toward increased HVA in concentration in
ventricular CSF of patients with posterior fossa tumors compared to controls.
These tumors were neuroectodermal and glial in histology (p=0.06).
There was also a positive correlation between the HVA concentration in both
the CSF and serum samples. Ιt is possible that the tumor
influences the secretion of the neurotransmitters as a result of
neuronal dysfunction, or the tumor itself is producing neurotransmitters.
In this study the concentration of 5-HIAA in the CSF of patients was
increased in 70.6% , compared with 29.4% of the B group of the controls
(Fisher exact test p= 0.031) .
Some of the patients with tumor of posterior fossa demonstrated the presence
of anxiety, aggressiveness, internalizing, and self concern symptoms compared
with controls. These symptoms perhaps produce alteration in activity of
the central serotonergic system, and as a result the increased 5- HIAA in the
CSF of the patients.
On the other hand that icreased 5-HIAA levels were found in B group
of controls might be explained by the anxiety that hospitalization produces.
This condition may increase the activity of monoaminergic neurons in the CNS
and might explain the increase of 5-HIAA in the CSF concentration.
