Exam 2: CNS Pt3 Flashcards
What is the MC form of CNS malformations? What do they involve?
Neural Tube Defects; involve incomplete closure of neural tube during embryogenesis
What Neural Tube Defects have a wide range of clinical presentations that may involve abnormalities in what areas?
- spinal cord or brain
- meninges
- bones or spine of cranium
- tissues overlying spine or cranium
What is a well-known risk factor for Neural Tube Defects? Esp. during what time frame?
maternal folic acid (folate) deficiency; esp. during 1st tri of gestation
If a mother takes in adequate amounts of folic acid how much is the neural tube defect risk reduced by?
70%
What are the four Neural Tube Defects of our focus?
- Spina bifida occulta
- Myelomeningocele
- Encephalocele
- Anencephaly
What involves failure of the posterior segment of the vertebral bodies and is the mildest neural tube defect?
Spina bifida occulta
Where is spina bifida occulta most commonly discovered?
upper cervical spine (C1) or lumbosacral region of spine
may have normal skin or tuft of hair or may be ass. with cafe au lait spot or “dimpling”
What is a more severe form of neural tube defect that involves failed bone formation in posterior elements of lumbosacral spine along with extension of CNS tissue through the bony defect?
Myelomeningocele (sometimes called a “severe form of spina bifida”)
What will Myelomeningocele commonly cause?
- severe disability
- interfers with inds. lower extremity motor and sensory fxns
- bowel and bladder dysfunction
- overlying skin may be ulcerated and is prone to inf.
What is a neural tube defect that involves a diverticulum (blind-ended pouching) and where is this occur?
Encephalocele; usually occurs at midline of occipital region of skull
How does an Encephalocele manifest?
Depends:
- involve very little neurological involvement and be filled w/ fluid or fibrotic tissues
- involve larger amounts of brain tissues–> disability (quad or ataxia) or DEATH
- -craniofacial abnormalities
What is a severe neural tube defect involving failure of anterior end of CNS (telencephalon) to fully develop?
Anencephaly
- involves absent formation of forebrain and superior aspects of skull
What typically occurs with Anencephaly?
stillbirth; not compatible w/ post-natal life
–or are blind, deaf, and unable to feel pain, and unaware of surroundings
What is an “abnormal widening of the central canal of the spinal cord that creates a cavity” where CSF accumulates? Where does CSF come from?
Hydromyelia
- connected to 4th ventricle of brain
What may Hydromyelia cause?
damage to midbrain and cervical spine cord and/ or elevated nerve roots
What other malformation is Hydromyelia associated with?
infants who have a Type II Chiari Malformation (Arnold-Chiari) and communicating hydrocephalus
Smaller dilations ass. with Hydromyelia may be asymptomatic, but what may large dilations cause?
- neck or arm pain
- upper extremity weakness
- loss of sensations in hands or arms
What is a cyst (fluid-filled cavity) w/in the spinal cord and is most likely to develop in young adult males (~ age 30)?
Syringomyelia (“syrinx”)
Where are Syringomyelia most frequently discovered? How many on average does this affect?
cervical spine cord
~ 8 in 100,000
What are the cysts of Syringomyelia (“syrinx”) also associated with?
Type 1 Chiari malformations
and thought to be ass. with spinal trauma
What condition creates reduced pain and temperature sensation in a “shawl-like” distribution over one or both arms as well as ant. and post. upper thorax?
Syringomyelia (“syrinx”)
- due to disrupting spinothalamic fibers that mediate pain and temp sensation
How does one evaluate for Hydromyelia and Syringomyelia?
MRI
What are three Perinatal Brain injuries?
- Intraparenchymal Hemorrhage
- Infarct
- Cerebral Palsy
What puts one at risk for Intraparenchymal Hemorrhage and where does it occur and what does it possibly cause?
prematurity*
- deep (near ventricles) and may cause hydrocephalus
What can cause chalky plaques/ necrosis or cysts in the supratentorial white matter, that is ass. with prematurity?
Infarct
What is a non-progressive motor defect and is due to fetal injury of hypoxia or infection and causes spasticity, dystonia, ataxia, or tremors and is a Perinatal brain injury ass. with prematurity?
Cerebral Palsy
What do 1/3 of individuals with Cerebral Palsy have?
decrease cognition or seizures
What is an autoimmune conditions involving episodes of CNS demyelination and produces multiple “white matter lesions” described as “plaques”?
Multiple Sclerosis (MS)
What is the MC demyelinating disorder?
Multiple Sclerosis (MS)
~ 1 in 1,000
What is described as a “multifocal white matter disease”?
Multiple sclerosis (MS)
Who is more common to develop Multiple Sclerosis and at what age?
Females are 2x as likely, and Dx around reproductive time frame of adulthood
T/F. Multiple Sclerosis has a weak genetic component.
False- MS has a STRONG genetic component
Describe the genetic component associated with Multiple Sclerosis.
Risk increase of:
- 150x if monozygotic (identical) twin has it
- 15x if 1st degree relative has it
- 3x if have HLA-DR2 allele
What is Multiple Sclerosis classified as?
A type IV hypersensitivity
What do the white matter plaques of Multiple Sclerosis contain?
abundant T cells (CD4+ and CD8+ T cells) and macrophages
Compare and contrast the Active vs Inactive Plaques of Multiple Sclerosis.
Active Plaques –> inflam and myelin debris
Inactive Plaques–> past autoimmune injury and minimal or dormant inflam.
What demyelinating disease features motor and sensory abnormalities, fatigue, diplopia, nystagmus, dysarthria, dysphagia, weakness/clumbsiness, ataxia, muscle spams, pain, numbness, paranesthesia, bladder incontinence, or sexual dysfunction, and maybe cognitive dysfxn ass. with unstable mood, depression, or seizures?
Multiple Sclerosis (MS)
T/F. Brain is susceptible to periods of too little or too much glucose or other nutrient deficiencies.
True
What are two types of Thiamine Deficiency?
- Wernicke-Korsakoff syndrome
- Beriberi
(vit B1 deficiency)
What syndrome causes CNS injury from thiamine deficiency and is characterized by an acute onset of extreme confusion, amnesia, confabulation, and ataxia?
Wernicke-Korsakoff syndrome
vit. B1 deficiency
What type of individuals does Wernicke-Korsakoff syndrome typically affect?
inds. suffering from chronic alcoholism
What syndrome characteristically manifests in inds. suffering from chronic alcoholism, but also could be inds. with chronic gastritis, gastric bypass surgery, or persistent vomiting?
Wernicke-Korsakoff syndrome
What develops from CNS injury caused by thiamine deficiency (vit B1) and causes lower extremity paresthesia and eventual paralysis, along with nystagmus of eyes?
Beriberi
this form = “Dry Beriberi”
What type of Beriberi involves cardiovascular system and increase HR (tachycardia), vasodilation, peripheral edema, and dilated cardiomyopathy?
“wet beriberi”
What type of vitamin deficiency injures that spinal cord and causes
“subacute combined degeneration of the spinal cord”?
Cobalamin deficiency (B12)
What destroys ascending AND descending tracts of spinal cord, slowly and causes lower extremity ataxia, paresthesia, spastic weakness, and possible paraplegia?
Cobalamin (B12) Deficiency
What are two types of Metabolic Glucose Disorders that will affect the CNS?
- Hypoglycemia
2. Hyperglycemia
What is most likely to occur due to inappropriate/excessive insulin use? What does this mimic in the brain and what areas are brain are most susceptible ?
Hypoglycemia; mimics global cerebral ischemia; injury deep areas of brain–> like hippocampus
What is most likely to occur in the setting of inadequately controlled type I or type II diabetes mellitus?
Hyperglycemia
How does prolonged hyperglycemia cause injury to the brain?
causing a hyperosmolar state and intracellular dehydration
What effects to patients mimic that are experiencing prolonged hyperglycemia to the brain? How does it manifest?
mimics effects of acute alcohol intoxication and manifests with confusion, stupor, and possible coma or death
T/F. Neurodegenerative disease are characterized by the destruction of CNS neurons.
True
What will virtually all neurodegenerative conditions involve the onset of?
Dementia = “a chronic or persistent disorder of the mental processes caused by brain disease or injury and marked by memory disorders, personality changes, and impaired reasoning”
What is defined as: “a chronic or persistent disorder of the mental processes caused by brain disease or injury and marked by memory disorders, personality changes, and impaired reasoning” ?
dementia
What are the 5 neurodegenerative disease we are addressing?
- Alzheimer disease
- Parkinson disease
- Lewy Body dementia
- Huntington disease
- ALS (Amyotrophic lateral sclerosis)
What is the most common form of dementia?
Alzheimer disease
What is the age group affected by Alzheimer disease?
older adults
- 3% ppl age 65-74
- 47% (nearly half) of those over 85 years
Death from Alzheimer disease is most likely to occur due to what?
lethal pneumonia
What type of onset does Alzheimer Disease have?
insidious–> disorientation, aphasia, personality change–> eventually complete loss of “executive functioning”
When is the more advanced stage of Alzheimers disease likely to occur? How does it manifest?
5-10 years after Dx
- severe disability
- immobility
- inability to talk
What condition are beta-amyloid plaques known to accumulate in the brain of?
Alzheimer disease
- known to have neurotoxic effect
What will the beta-amyloid plaques cause in the brain of inds with Alzheimer disease?
neurotoxic effect and breakdown cerebral neurons–> forming “neurofibrillary tangles” involving clusters of tau proteins
What condition is characterized by beta-amyloid plaques forming neurofibrillary tangles involving clusters of tau proteins?
ALZHEIMER DISEASE
What are Tau proteins?
a microtubule-ass. axonal protein that helps form the structure of neurons–> when neurons break down these accumulate
(therefore ass. with a lot of neurodegenerative diseases)
What is a neurodegenerative disease that causes sever motor disturbances due to injury to dopaminergic CNS neurons?
Parkinson Disease
What conditions has motor movements described as bradykinesia, involving tremor, skeletal muscle rigidity, and instability while standing, and a “stooped” posture?
Parkinson Disease
–often refer to these altered motor movements as “Parkinsonism”
T/F. Parkinsonism only develops from Parkinson Disease.
False– yes, most often it does develop from Parkinson Disease, BUT it can also develop from CNS trauma, toxic exposure that impact dopaminergic neurons, CNS tumors, ADRs
What area is characteristically involved in neurodegeneration of Parkinson Disease?
substantia nigra of the midbrain
- causes “pallor” (paleness) of this normally pigmented area
Besides the substantia nigra, what other dopaminergic neuron areas can be destroyed with Parkinson Disease?
- cerebral cortex
- medulla
- pons
What condition has the characteristic neuronal inclusion called “Lewey Body” composed of alpha-synuclein?
Parkinson Disease
When are most inds. Dx with Parkinson Disease? How long until they are unable to safely walk?
middle-to-older adulthood (45-65)
w/in about 10-15 years
What condition has the common features of a tremor, a “festinating” gait involving short “shuffling” steps, stooped posture, pill-rolling tremor in hands, and generalized skeletal rigidity?
Parkinson Disease
What medication can be given to inds with Parkinson Disease?
L-DOPA and deep brain stimulation to help improve motor dysfunction, but DO NOT alter progressive nature of it
In the later stages of Parkinson Disease, what do about 1/3 of individuals exerpeince?
anxiety and depression
What is the most likely cause of death in individuals with Parkinson Disease?
lethal pneumonia or following a traumatic fall (head injury and form subdural hematoma)
What is a neurodegenerative condition that is very similar to Parkinson Disease, but the onset of cognitive dysfunction onsets within a year of the motor defects?
Lewy Body Dementia
mainly same features as Parkinson Disease
What is discovered in the brain of inds with Lewy Body Dementia?
Lewy bodies
What is a neurodegenerative disease that develops following an autosomal dominant mutation in the Huntington (HHT) gene on chromosome 4, which codes for Huntington protein? What does this mutation result in?
Huntington disease
– unstable trinucleotide repeats of CAG nucleotides
T/F. Huntington Disease will increase in severity as it is passed down the germline.
True– due to being a trinucleotide mutation (autosomal dominant)
How does one get Huntington Disease?
an autosomal dominant mutation in Huntington (HHT) gene–> is a genetic anticipation (b/c is a trinucleotide repeat that worsens as gets passed down germline)
What does Huntington Disease manifest with?
- dementia
- neuropsychiatric instability
- hallucinations
- chorea (jerky movements)
When does Huntington Disease manifest?
young adulthood 30-40 years–> therefore is an inherited condition that is NOT congenital
Degeneration of the caudate and putamen nuceli of the striatum are characteristic of what condition?
Huntington Disease
–but there is widespread cerebral atrophy
How soon will Huntington Disease results in death? What do patients MC die from?
death w/in about 15 years of Dx
- lethal pneumonia
- chocking
- unintentional injuries
- suicide
T/F. Huntington Disease has strong ass. with suicide due to guilt of potentially passing it onto children and the severe dementia and hallucinations.
true
What is a neurodegeneration that causes destruction of BOTH upper motor neurons and lower motor neurons?
Amyotropic lateral sclerosis (ALS or Lou Gehrig’s Disease)
What are the upper motor neurons involves in ALS?
Betz cells of motor cortex on posterior aspect of frontal lobe
What are the lower motor neurons involved in ALS?
- cortiocospinal and corticobulbar tracts of spina lcord
- anterior horn cells of spinal cord
- ventral nerve roots
When is ALS most likely to occur? In what sex?
sporadically during 5th decade of life (during 40’s)
males
What manifests gradually with subtle weakness in distal extremities and muscle fasciculations and is extremely aggressive in worsening symptoms and w/in a year or two from onset one will be in a wheelchair?
ALS (Amyotropic lateral sclerosis)
What area muscles/area is uniquely NOT affected in ALS?
extraocular muscles
also cognition and dementia
Is ALS a fatal disease? How soon? How?
Yes, most die of lethal pneumonia or choking w/in 3 years from onset of weakness
Is there any genetic factor with ALS?
10% of ALS patients, it is genetic–> irregularity in superoxide dismutase gene (SOD1) –> promote apoptosis of motor neurons
autosomal dominant
T/F. Indviduals that inherit the SOD1 gene mutation are more likely to have a later onset of their ALS condition.
False– it is an early onset at about 20-40 years
non-inherited ALS– during 40s
T/F. Intracranial CNS tumors are more common than intraspinal tumors.
true
intracranial–> 15 per 100,000
intraspinal–> 2 per 100,000
T/F. Most CNS tumors are due to metastasis.
False– most (75%) of CNS tumors are primary CNS tumors, arising form w/in CNS
What are clinical features of CNS tumors, regardless the type?
- unexplained HAs
- seizures
- focal neurological deficits
- increased ICP
What are the three main forms of Gliomas? What age groups ass?
(transformed glial cells)
- astrocytomas (adults/diffuse)
- oligodendrogliomas (adults/diffuse)
- ependymomas (pediatrics/localized)
Most adults who develop a glioma will develop which type?
astrocytoma
What age and where are astrocytomas most likely to manifest?
age 30-60 and in cerebral hemispheres, like frontal lobe
Astrocytomas are categroized based on grades. Describe them: Grade I Grade II Grade III Grade IV
Grade I –> well-differentiated
Grade II –> diffuse astrocytomas
Grade III –> anaplastic astrocytomas
Grade IV –> “glioblastomas”
What is the survival rate of astrocytomas?
1-5 years and 5 years at the best
What is the most aggressive and most lethal tumor in adults?
glioblastomas (Grade IV Astrocytoma)
–15 month survival
What is a benign astrocytoma that has a characteristic cystic appearance and develops in children or young adults, and MC develop in cerebellum or spinal cord?
Pilocytic astrocytoma
–well-demarcated boarder and greater likelihood of being resected when compared to other astrocytomas
What is a CNS tumor that is a glioma type and is about 10% all adult gliomas, and can be benign or malignant?
Oligodendroglioma
What is the survival rate of oligodendrogliomas?
well-differentiated (low grade) –> 10-20 years survival
more anaplastic (high grade)–> 5-10 years survival (only high grade = malignant)
Where are oligodendrogliomas most likely to manifest and what age?
cerebral hemispheres, esp. frontal or temporal lobes
aduts 30-50
What is a malignant glioma that most likely develops in periventricular locations and near central canal of spinal cord or next to 4th ventricle within first two decades of life?
ependymoma
What age do ependymoma most likely manifest? What may they cause?
first two decades of life
obstruct CSF flow and cause hydrocephalus
Adults who develop ependymomas are likely to have what other condition?
(NF2) Neurofibromatosis type 2
What can be detected due to presence of ependymal rosettes, or “fibrillary” appearance, or “spoke-wheel” arrangement?
ependymomas
What are malignant embryonal neoplasms that develop within pediatrics exclusively in cerebellum, frequently at midline of infratentorial cerebellum?
Medulloblastoma
How do Medulloblastoma manifest at cellular level?
contain “small round cells”
Homer-wright rosettes
well-circumscribed
When are Medulloblastomas MC Dx?
What is their survival rate?
age 9
75% for children who undergo surgical excision and radiation
What is the most common CNS neoplasm among immunocompromised individuals, as in AIDS?
Primary central nervous system lymphoma
What is Primary central nervous system lymphoma?
a rare form of lymphoma or CNS cancer (1-2%) and is characteristic of AIDS
Individuals with Primary central nervous system lymphoma, uniquely test positive for what infection?
Epstein-Barr Virus (EBV) —mono
T/F. Primary central nervous system lymphoma is almost always of the “diffuse large B cell lymphona”.
true
What CNS tumor arises from tranformed arachnoid cells? Where are they located?
Meningiomas
- any surface of CNS
- w/in ventricular system
T/F. Meningiomas can be benign or malignant, and about 90% are malignant.
False– about 90% are BENIGN
What CNS tumor will present as “whorled” or “syncytial” cellular cluster histologically?
Meningiomas
Who and what age are most likely to have meningiomas?
females 2x likely
middle to older adulthood
What other condition are Meningiomas associated with?
(NF2) Neurofibromatosis type 2
What percent of CNS tumors does Secondary metastasis into the CNS constitute for?
25%
What are the most common tissue types to metastasis into CNS?
- lung cancer (MC)
- breast cancer
- melanoma
- kidney cancer
- cancer of GI tract
(these make up 80% of all cancers that mets to CNS)
T/F. Mets to CNS will manifest usually as an isolated tumor.
False– they manifest with multiple metastatic lesions
come onnnnnnn
What appearance does metastasis cancer to the CNS have?
well-demarcated boarders and “polka dot” appearance
manifest at junction b/w grey and white matter
What are the two familial tumors syndromes that have mutations in tumor suppressor genes that are of our focus on how they affect the CNS?
- Tuberous Sclerosis
2. Von Hippel-Lindau Disease
What autosomal dominant familial tumor syndrome develops following mutated TSC1 or TSC2 tumor suppressor gene?
Tuberous Sclerosis
What familial tumor syndrome allows for multiple benign tumors and cysts to develop throughout the body?
Tuberou Sclerosis
What are the CNS-related features of Tuberous Sclerosis?
cortical hamartomas–> sometimes called “tubers” along the subependymal hamartomas
- seizures
- cognitive impairment
- obstructive hydrocephalus
What features does Tuberous sclerosis have on other body features?
benign tumor or cysts in multiple organ systems
angiofibromas = cutaneous nodules across nasal bridge and cheeks
What is an autosomal dominant familial tumor syndrome that develops following mutated VHL tumor suppressor gene?
Von Hippel-Lindau Disease
What does mutations in VHL tumor suppressor genes allow?
(ass. with Von Hippel-Lindau Disease)
- multiple hemangioblastomas to develop
What are hemangioblastomas?
highly-vascular tumors of of small thin-walled vessels
ass. with Von Hippel-Lindau Disease
What are the CNS related features of Von Hippel-Lindau Disease?
formation of multiple CEREBELLAR hemangioblastomas
possible hemangioblastomas in brainstem, spinal cord, or spinal nerve roots
What is a characteristic feature of Von Hippel-Lindau Disease?
Retinal involvement
Produces:
- diplopia
- blindness
