Medical Neuropsychology
Chapter 3 – neuropsychological problems in neuro-oncology
Incidence rate
Brain and other CNS tumors occur more in men than women. The most pronounced groups are:
European-Americans, Latnos, African-Americans.
Survival rate 5 years afer tumor = conventonal metric for “cure”. Brain tumors are the second most
common malignancy of childhood and accounts for 20% of all childhood cancers.
Brain tumors are solid neoplastc masses of genetcally dysregulated cells that divide at elevated rates,
have lost their diferentated cellular functon, and rapidly transform surrounding cells and tssues.
Normally, tumor suppressor genes inhibit cell proliferaton and growth, so that cells have a normal life
span. Oncogenes are abnormally actvated versions of normal genes that promote cellular proliferaton
and growth, so that the cells has an exaggerated tendency to grow and divide.
Other diseases that are associated with brain tumor:
1. Gliomatosis cerebri: individual neoplastc cells that difusely permeate the brain (instead of
forming a tumor mass). Glial tumors originate in the white mater. ost patents experience
over tme severe cognitve loss (executve dysfuncton, memory impairments, psychiatric
features, sensorimotor impairments).
2. etastases from other cancers: most common in brain, lungs, bones and liver. Cancers that most
ofen disseminate to the brain via blood or CSF:: small cell lung cancer, breast cancer, melanoma,
renal cancer, colon cancer. In childhood, cancers that may metastse to the brain are: sof tssue
and bone sarcomas. The improved prognosis for cancer patents leads to higher incidences of
metastases.
3. Neurofbromatosis : occurs as autosomal trait disorder and as spontaneous mutaton.
NF: 1: also called von Recklingshausen neurofbromatosis and commonly associated with optc
gliomas and chromosome 17. Cog. Impairments vary widely (reasoning, visuoconstructve skills,
memory, logical abstracton).
NF:2: associated with chromosome 22, progressive fatal disease
NF: 1 and 2 are both associated with a higher risk for brain tumors.
4. Paraneoplastc syndrome: can occur as immunological responses to neurons in the presence of
oncogenes that are rapidly dividing and cause neurological syndromes
5. Tuberous sclerosis: rare genetc disease that causes benign brain tumors to grow on the cerebral
cortcal surface and on the walls of the ventricles. Also results in seiuures, skin growth, autsm
and mental retardaton. Treatment is limited to symptom management (incl. antepileptc
medicaton). A newly discovered possible treatment might be rapamycin.
6. Radiotherapy-induced brain tumors: has a risk of causing brain tumors decades afer treatment,
risk for other cancers is even higher. The most common lesions are DNA double-strand breaks,
, repair systems, that are stmulated by radiated are error prone and may lead to mutatons
tumor suppressor gene inactvaton.
Diagnosis of brain neoplasm
Risk factors:
- Serious head injury decades before diagnosis (meningioma)
- Prior radiaton exposure decades before diagnosis
- Immune suppression leading to lymphomas
- Genetc disorder
- Possibly: environmental carcinogens and viruses
Classifcaton:
Tumors are defned by the cells from which they were generated. ost common forms are:
- In adults: difuse, fbrillary astrocytoma
- In children: low-grade astrocytoma (benign) and medulloblastoma (malign)
Tumors are graded based on a four-level system, which determines the degree of malignancy and
classifes cells in terms of abnormal characteristcs.
General classifcaton:
1. Well diferentated and low-grade
2. oderately diferentated and intermediate
3. Poorly diferentated and high-grade
4. Undiferentated and high-grade
Abnormalites that are considered include:
Pleomorphism = change in the structure of a neural cell
Nuclear atypical: abnormalites in the nuclei of brain cells
Gliomas are classifed as:
- Low-grade / I: well diferentated and without other signs of abnormalites in cell nuclei
- Low-grade/ II: moderately diferentated but stll benign. Grad II tumors have a higher risk of
transformaton into more malignant forms and spreading into surrounding tssue
- Anaplastc/ III: poorly diferentated and spread
- High grade, undiferentated and highly malignant and aggressive/ VI
Tumor grade seems to be associated with the severity of neuropsychological defcit. High grade tumors
grow faster and are more disruptve of neural connectons. A problem in cognitve assessment is that
pre-tumor scores are rarely available. Tumors can masquerade as dementa or psychiatric disturbances.
Brain tumors seem to result in less injury as expected based solely on neuroimaging. Rapidly acquired
brain injury also results in secondary mechanisms of neural injury and death, which is not the case for
,brain tumors. Cognitve consequences afer brain injury like stroke is much more predictable than for a
brain tumor. Seeing as tumors rather infltrate than destroy tssue, RI scans do not reveal the degree of
necrosis and hypoxia. PET can measure hypoxia.
Regional cognitve efects of tumors are only possible in a broad generaliued manner: verbal functons
are associated with lef hemisphere tumor lesions, while visuospatal functons are associated with right
hemisphere tumor lesions. Patents with small tumors could compensate for their defcits by for example
an increased reacton tme. Defcits might therefore be covered and not clearly associable to a brain
region. In conclusion: in neuropsychological assessment reacton tme measurements are ofen more
sensitve to brain tumor efects than accuracy rates.
In non-progressive brain tumors, cognitve decline is rather rare. If it occurs, it is cause for concern.
However, cognitve stability can be dramatcally disturbed by resecton. Signifcantly improvements have
been reported two years afer resecton including neural plastcity and morphologic adjustments.
Diagnosis of neurocognitve impairments focuses on the consistencies and inconsistencies with the
examiner’s expectatons with the functons associated with the tumor region.
A patent-specifc method (based on the individual tumor locaton) to predict the growth and recurrence
seems to be superior to a brief but generally sensitve model in predictng tumor growth prior to
scheduled RI scans. Studies show that only the tumor-specifc variables change immediately prior to
recurrence.
Neurosurgery
Patents with surgical resecton ofen have sudden-onset disrupton of speech, motor functons,
cogniton and afect immediately afer resecton. Cognitve functoning takes at least 2 years to recover,
based on contnuous improvements.
Neuropsychiatric disturbances
Depression and fatige: depression is twice as prevalent in cancer patent than in all other medical
conditons combined. However, newly diagnosed patents usually report only low levels of depression
(might be due to repression and denial). Seeing as the treatment period for brain tumors is shorter than
for other forms of cancer, it produces less stress. Depression starts of low during frst symptoms and
diagnosis, but are likely to increase in the course due to treatment side-efects, fear of relapse etc.
Increasing depression seems to be unrelated to fatgue levels.
Predictors for poor quality of life in in tumor patents:
- Being female
- Being divorced
- Bilateral tumor involvement
- Having received chemotherapy
- Having a poor performance status
- Possibly: fnancial risks, marital stress, loss of work status
, Brain tumors in the frontal lobes have the highest regional associaton with depression. Brain tumors can
therefore ofen be misdiagnosed as depression or other neuropsychiatric disturbances. SSRIs are the
most common used drug to treat tumor-related depression and anxiety. Efects of methylphenidate are
mixed. Another drug, odafnil, is used to treat fatgue and cognitve impairments such as processing
speed, memory etc.
Anxiety: PTSS has been shown to be more prevalent in parents of children brain tumor survivors than in
the children themselves. RI studies show that all anxious patents had tumors either in the right cortex,
ofen temporal lobe, or in the lef cerebellar hemisphere.
Asperier’s syndrome/mild agtsm: Children with brain tumors sometmes present with a pre-existng
diagnose of ASD. Children with ASD behavior (1. social cognitonn 2. Distress when environmental
structure is alteresn 3. Hyperfocus on limited personal interestsn 4. Stereotypical body or speech
expressions) ofen have lesions in the cerebellar hemispheres and/or the temporal lobes. There seems to
be an elevated rate for autsm in NF:1 and the other way around, seeing as both are associated with the
same brain regions (also associated with spongiform dysplasia). It should be made clear that terms are
only used descriptvely, and that the syndrome is probably not fully present.
Coinitve afeetve syndrome: defned by signifcant defcits in executve functon (planning and set
shifing), spatal cogniton, language, abstract reasoning, atenton regulaton, memory and personality is
characteriued by bilateral or large unilateral lesions in the posterior cerebellar lobes, vermis and in pan
cerebellar disorders. The co-occurrence of the cognitve and afectve symptoms is thought to arise from
the disrupton of the cerebello-thalamo-cortcal and cortcal-pontne-cerebellar tracts. There are no
medicatons for this syndrome, however behavioral techniques applied from the feld of autsm, such as
the constructon of daily routnes, can help.
OCD: OCD can be a consequence of brain tumor. Studies found higher rates of OCD 3 month afer
surgery in the frontal lobes and women. OCD resultng from a brain tumor may have atypical
characteristcs that make is difcult to treat. Treatment focuses on identfying the sources of anxiety,
that lead to OCD and using behavioral and psychopharmacological treaments to reduce sensitvity to the
anxiety-causing thoughts.
Hypothalamie syndromes: Tumors in the hypothalamus are, frst, associated with disorders of eatng
behavior (hyperphagia, symptoms of anorexia). However, they also produce symptoms such as
hyperactvity, anxiety atacks, euphoria, aggressiveness, sleep disturbances and headaches. Gelastc
seiuures are rather rare (inappropriate smiling, giggling). Patents are usually troubled with constant
irritability and mild hyperactvity. No treatment optons available.
Adjuvant treatment efects
Radiation therapy
1. Stereotactc radiotherapy: multple small fractons of ioniuing radiaton given over tme to a highly
focal area
Chapter 3 – neuropsychological problems in neuro-oncology
Incidence rate
Brain and other CNS tumors occur more in men than women. The most pronounced groups are:
European-Americans, Latnos, African-Americans.
Survival rate 5 years afer tumor = conventonal metric for “cure”. Brain tumors are the second most
common malignancy of childhood and accounts for 20% of all childhood cancers.
Brain tumors are solid neoplastc masses of genetcally dysregulated cells that divide at elevated rates,
have lost their diferentated cellular functon, and rapidly transform surrounding cells and tssues.
Normally, tumor suppressor genes inhibit cell proliferaton and growth, so that cells have a normal life
span. Oncogenes are abnormally actvated versions of normal genes that promote cellular proliferaton
and growth, so that the cells has an exaggerated tendency to grow and divide.
Other diseases that are associated with brain tumor:
1. Gliomatosis cerebri: individual neoplastc cells that difusely permeate the brain (instead of
forming a tumor mass). Glial tumors originate in the white mater. ost patents experience
over tme severe cognitve loss (executve dysfuncton, memory impairments, psychiatric
features, sensorimotor impairments).
2. etastases from other cancers: most common in brain, lungs, bones and liver. Cancers that most
ofen disseminate to the brain via blood or CSF:: small cell lung cancer, breast cancer, melanoma,
renal cancer, colon cancer. In childhood, cancers that may metastse to the brain are: sof tssue
and bone sarcomas. The improved prognosis for cancer patents leads to higher incidences of
metastases.
3. Neurofbromatosis : occurs as autosomal trait disorder and as spontaneous mutaton.
NF: 1: also called von Recklingshausen neurofbromatosis and commonly associated with optc
gliomas and chromosome 17. Cog. Impairments vary widely (reasoning, visuoconstructve skills,
memory, logical abstracton).
NF:2: associated with chromosome 22, progressive fatal disease
NF: 1 and 2 are both associated with a higher risk for brain tumors.
4. Paraneoplastc syndrome: can occur as immunological responses to neurons in the presence of
oncogenes that are rapidly dividing and cause neurological syndromes
5. Tuberous sclerosis: rare genetc disease that causes benign brain tumors to grow on the cerebral
cortcal surface and on the walls of the ventricles. Also results in seiuures, skin growth, autsm
and mental retardaton. Treatment is limited to symptom management (incl. antepileptc
medicaton). A newly discovered possible treatment might be rapamycin.
6. Radiotherapy-induced brain tumors: has a risk of causing brain tumors decades afer treatment,
risk for other cancers is even higher. The most common lesions are DNA double-strand breaks,
, repair systems, that are stmulated by radiated are error prone and may lead to mutatons
tumor suppressor gene inactvaton.
Diagnosis of brain neoplasm
Risk factors:
- Serious head injury decades before diagnosis (meningioma)
- Prior radiaton exposure decades before diagnosis
- Immune suppression leading to lymphomas
- Genetc disorder
- Possibly: environmental carcinogens and viruses
Classifcaton:
Tumors are defned by the cells from which they were generated. ost common forms are:
- In adults: difuse, fbrillary astrocytoma
- In children: low-grade astrocytoma (benign) and medulloblastoma (malign)
Tumors are graded based on a four-level system, which determines the degree of malignancy and
classifes cells in terms of abnormal characteristcs.
General classifcaton:
1. Well diferentated and low-grade
2. oderately diferentated and intermediate
3. Poorly diferentated and high-grade
4. Undiferentated and high-grade
Abnormalites that are considered include:
Pleomorphism = change in the structure of a neural cell
Nuclear atypical: abnormalites in the nuclei of brain cells
Gliomas are classifed as:
- Low-grade / I: well diferentated and without other signs of abnormalites in cell nuclei
- Low-grade/ II: moderately diferentated but stll benign. Grad II tumors have a higher risk of
transformaton into more malignant forms and spreading into surrounding tssue
- Anaplastc/ III: poorly diferentated and spread
- High grade, undiferentated and highly malignant and aggressive/ VI
Tumor grade seems to be associated with the severity of neuropsychological defcit. High grade tumors
grow faster and are more disruptve of neural connectons. A problem in cognitve assessment is that
pre-tumor scores are rarely available. Tumors can masquerade as dementa or psychiatric disturbances.
Brain tumors seem to result in less injury as expected based solely on neuroimaging. Rapidly acquired
brain injury also results in secondary mechanisms of neural injury and death, which is not the case for
,brain tumors. Cognitve consequences afer brain injury like stroke is much more predictable than for a
brain tumor. Seeing as tumors rather infltrate than destroy tssue, RI scans do not reveal the degree of
necrosis and hypoxia. PET can measure hypoxia.
Regional cognitve efects of tumors are only possible in a broad generaliued manner: verbal functons
are associated with lef hemisphere tumor lesions, while visuospatal functons are associated with right
hemisphere tumor lesions. Patents with small tumors could compensate for their defcits by for example
an increased reacton tme. Defcits might therefore be covered and not clearly associable to a brain
region. In conclusion: in neuropsychological assessment reacton tme measurements are ofen more
sensitve to brain tumor efects than accuracy rates.
In non-progressive brain tumors, cognitve decline is rather rare. If it occurs, it is cause for concern.
However, cognitve stability can be dramatcally disturbed by resecton. Signifcantly improvements have
been reported two years afer resecton including neural plastcity and morphologic adjustments.
Diagnosis of neurocognitve impairments focuses on the consistencies and inconsistencies with the
examiner’s expectatons with the functons associated with the tumor region.
A patent-specifc method (based on the individual tumor locaton) to predict the growth and recurrence
seems to be superior to a brief but generally sensitve model in predictng tumor growth prior to
scheduled RI scans. Studies show that only the tumor-specifc variables change immediately prior to
recurrence.
Neurosurgery
Patents with surgical resecton ofen have sudden-onset disrupton of speech, motor functons,
cogniton and afect immediately afer resecton. Cognitve functoning takes at least 2 years to recover,
based on contnuous improvements.
Neuropsychiatric disturbances
Depression and fatige: depression is twice as prevalent in cancer patent than in all other medical
conditons combined. However, newly diagnosed patents usually report only low levels of depression
(might be due to repression and denial). Seeing as the treatment period for brain tumors is shorter than
for other forms of cancer, it produces less stress. Depression starts of low during frst symptoms and
diagnosis, but are likely to increase in the course due to treatment side-efects, fear of relapse etc.
Increasing depression seems to be unrelated to fatgue levels.
Predictors for poor quality of life in in tumor patents:
- Being female
- Being divorced
- Bilateral tumor involvement
- Having received chemotherapy
- Having a poor performance status
- Possibly: fnancial risks, marital stress, loss of work status
, Brain tumors in the frontal lobes have the highest regional associaton with depression. Brain tumors can
therefore ofen be misdiagnosed as depression or other neuropsychiatric disturbances. SSRIs are the
most common used drug to treat tumor-related depression and anxiety. Efects of methylphenidate are
mixed. Another drug, odafnil, is used to treat fatgue and cognitve impairments such as processing
speed, memory etc.
Anxiety: PTSS has been shown to be more prevalent in parents of children brain tumor survivors than in
the children themselves. RI studies show that all anxious patents had tumors either in the right cortex,
ofen temporal lobe, or in the lef cerebellar hemisphere.
Asperier’s syndrome/mild agtsm: Children with brain tumors sometmes present with a pre-existng
diagnose of ASD. Children with ASD behavior (1. social cognitonn 2. Distress when environmental
structure is alteresn 3. Hyperfocus on limited personal interestsn 4. Stereotypical body or speech
expressions) ofen have lesions in the cerebellar hemispheres and/or the temporal lobes. There seems to
be an elevated rate for autsm in NF:1 and the other way around, seeing as both are associated with the
same brain regions (also associated with spongiform dysplasia). It should be made clear that terms are
only used descriptvely, and that the syndrome is probably not fully present.
Coinitve afeetve syndrome: defned by signifcant defcits in executve functon (planning and set
shifing), spatal cogniton, language, abstract reasoning, atenton regulaton, memory and personality is
characteriued by bilateral or large unilateral lesions in the posterior cerebellar lobes, vermis and in pan
cerebellar disorders. The co-occurrence of the cognitve and afectve symptoms is thought to arise from
the disrupton of the cerebello-thalamo-cortcal and cortcal-pontne-cerebellar tracts. There are no
medicatons for this syndrome, however behavioral techniques applied from the feld of autsm, such as
the constructon of daily routnes, can help.
OCD: OCD can be a consequence of brain tumor. Studies found higher rates of OCD 3 month afer
surgery in the frontal lobes and women. OCD resultng from a brain tumor may have atypical
characteristcs that make is difcult to treat. Treatment focuses on identfying the sources of anxiety,
that lead to OCD and using behavioral and psychopharmacological treaments to reduce sensitvity to the
anxiety-causing thoughts.
Hypothalamie syndromes: Tumors in the hypothalamus are, frst, associated with disorders of eatng
behavior (hyperphagia, symptoms of anorexia). However, they also produce symptoms such as
hyperactvity, anxiety atacks, euphoria, aggressiveness, sleep disturbances and headaches. Gelastc
seiuures are rather rare (inappropriate smiling, giggling). Patents are usually troubled with constant
irritability and mild hyperactvity. No treatment optons available.
Adjuvant treatment efects
Radiation therapy
1. Stereotactc radiotherapy: multple small fractons of ioniuing radiaton given over tme to a highly
focal area
