Pathology-CNS

Question 1

What will the structures indicated in the developing embryo become?

Answer 1

Neural crest cells = PNS. Neural tube wall = CNS. Cavity of Neural tube = ventricles.

Question 2

A mother comes to see you in clinic for her follow up prenatal care visit. Her history reveals a previous miscarriage, where the fetus had a frog-like appearance (shown below). Today her lab values reveal an elevated AFP. What can you do to decrease the chances that this birth defect does not happen again?

Answer 2

The image shows anencephaly, a neural tube defect where the skull and brain fail to form. Neural tube defects can be detected by elevated AFP levels during pregnancy. Incidence of neural tube defects can be decreased by ensuring the pregnant mother has adequate folate intake.

Question 3

A pregnant mother comes to see you for her prenatal check up. Labs reveal an elevated AFP. Physical exam reveals an increase in amniotic fluid. What neural tube defect is associated with this increase in amniotic fluid?

Answer 3

Anencephaly. When the brain and skull fail to develop in the fetus, the swallowing centers do not fire in the fetus and it does not swallow the amniotic fluid. This causes development of maternal polyhydramnios.

Question 4

You are working in the labor and deliver department when a mother gives birth to a child with a little dimple and patch of hair over the region of the posterior vertebral arch. What is the spectrum of the neural tube defect in this child?

Answer 4

This child has spina bifida occulta. In some cases the posterior vertebral arch fails to close so much that the meninges (meningocele) and spinal cord (meningomyeleocele) are exposed, which is defined as true spina bifida.

Question 5

A mother brings her 2 week old infant to the pediatric unit because of an enlarging head. Imaging studies reveal a hydrocephalus in the lateral and 3rd ventricles. What is your diagnosis?

Answer 5

Cerebral aqueduct stenosis

Question 6

A mother of a young child comes to the pediatric unit complaining that her child’s head is enlarged and impaired motor function. Imaging of the child’s brain is shown below. What structure failed to develop in this child?

Answer 6

This child has Dandy Walker Syndrome. This is characterized by a massively dilated 4th ventricle (hydrocephalus) and near absence of the cerebellum due to failure of the cerebellar vermis to develop.

Question 7

A mother brings her young child to the pediatric unit complaining of motor impairment and headaches in her child. Imaging studies of the child’s brain reveals extension of the cerebellar tonsils through the foramen magnum. What other symptoms are associated with this congenital malformation?

Answer 7

This child has Arnold-Chiari malformation. The herniation of the cerebellar tonsils through the foramen magnum can also cause hydrocephalus from CSF blockade in the 4th ventricle. This condition is also associated with meningomyelocele and syringomyelia.

Question 8

A mother brings her child in to see you complaining of headaches and loss of pain and temperature sensation in the upper extremities. The child has maintains fine touch and position sense. Imaging studies reveal extension of the cerebellar tonsils through the foramen magnum. What future symptoms may manifest in this child if the disease process expands?

Answer 8

This child has syringomyelia associated with Arnold-Chiari malformation. Note that syringomyelia can also occur with trauma. Syringomyelia is characterized by cystic degeneration of the anterior commissure at C8- T1. Since this is where the pain and temperature sensory signals cross before going to the thalamus, the child has lost those sensations. The syrinx can further expand to hit the anterior horns (affecting lower motor neurons: UE muscle atrophy & weakness) and the lateral horns (affecting facial sympathetic input and causing Horner’s syndrome: ptosis, meiosis & anhydrosis)

Question 9

You get your summer experience all lined up and finally get to your program in India. The first patient you see comes to you complaining of fever, sore throat, nausea, vomiting and abdominal pain.You tell him that he probably has a viral infection and send him home. A few weeks later he comes back complaining of flaccid paralysis in the extremities, muscle atrophy, impaired reflexes and a negative Babinski sign. What autosomal recessive disorder will present with the same conditions as the patient you are seeing?

Answer 9

This patient has symptoms consistent with poliovirus. The virus attacks the anterior horn and destroys the lower motor neurons. There is an autosomal recessive disorder, Werdnig-Hoffman Disease, that is an inherited degeneration of the anterior motor horn. This disease presents as floppy baby syndrome and death will occur a few years after birth.

Question 10

A 47 year old woman comes to see you complaining of flaccid paralysis of her legs, decreased reflexes and muscle atrophy. She has a negative Babinski sign. In a later appointment she presents with spastic paralysis, increased muscle tone and a positive Babinski sign. What physical exam finding will help you distinguish this patient’s condition from syringomyelia?

Answer 10

This patient has lower motor neuron signs (anterior motor horn) and upper motor neuron signs (lateral corticospinal tract) that indicate Amyotrophic Lateral Sclerosis. The key physical exam finding that differentiates ALS from syringomyelia is preserved sensory and pain function.

Question 11

A 27 year old man came to your clinic concerned because his grandmother just died of ALS. What genetic mutation would you test for to see if this patient is at risk for the same disease?

Answer 11

Some familial cases of Amyotrophic Lateral Sclerosis are associated with zinc-copper superoxide dismutase mutations. Decreased function of superoxide dismutase causes an increase in ROS because the body cannot convert it to hydrogen peroxide. ROS can damage neurons.

Question 12

A 3 year old boy comes to see you in clinic complaining of increased difficulty with coordination while walking. Physical exam reveals loss of deep tendon reflexes, lower extremity muscle weakness, a mid systolic ejection murmur and loss of vibratory sense and proprioception. How would a genetic mutation cause the symptoms seen in this child?

Answer 12

This patient has Friedreich Ataxia. This is an autosomal recessive disorder due to an unstable trinucleotide repeat (GAA) in the frataxin gene. The frataxin gene is essential for mitochondrial Fe regulation. Mutation of this gene cause increased ROS production via the fentin reaction. Increased ROS cause degeneration of the spinal cord and cerebellum.

Question 13

What part of the CNS is affected in meningitis?

Answer 13

Leptomeninges (arachnoid & pia mater)

Question 14

You are doing your rotation in pediatrics, checking on the new babies. You notice that one child has a high fever and order labs which reveal bacterial meningitis. What are the most suspected microbes in this baby?

Answer 14

Most common causes of bacterial meningitis in neonates are 1) Group B Strep (vaginal canal) 2) E. Coli (vaginal canal) and 3) Listeria monocytogenes

Question 15

You are working at a community family health clinic and start seeing a lot of kids and teenagers coming back from band camp with bacterial meningitis. What is the most suspected microbe causing meningitis in these kids? How does this bug get to the meninges?

Answer 15

Neisseria meningitidis is the most common cause of bacterial meningitis in children and teenagers. It infects in the nasopharynx, gets in the blood, then goes to the meninges.

Question 16

You are working at a retirement home when an older gentleman presents with headache, neck stiffness, fever, vomiting and altered mental status. Labs reveal increased neutrophils in his CSF. What is the most suspected microbe causing his meningitis?

Answer 16

Strep pneumoniae is the most common cause of bacterial meningitis in adults and elderly

Question 17

You are working at a family health clinic in California when a hippie mom brings her infant to see you because of a high fever and vomiting. Physical exam and labs reveal bacterial meningitis. What is the most common cause of bacterial meningitis in non vaccinated infants?

Answer 17

H. Influenzae

Question 18

A 29 year old woman comes to your clinic with headache, neck stiffness, fever, vomiting and altered mental status. She has a history of HIV. What is the most common cause of meningitis in patients with HIV?

Answer 18

Fungi

Question 19

A patient comes to your clinic with headache, neck stiffness, fever and photophobia. Labs do not reveal any bacterial or fungal offenders. What is the most common cause of this type of meningitis and how is it transmitted?

Answer 19

Coxsackievirus is the most common cause of viral meningitis. It is transmitted via the fecal-oral route. Also note that photophobia is much more common in viral infections.

Question 20

A patient comes to see you complaining of headache, neck stiffness, nausea, vomiting and altered mental status. You suspect meningitis and decide to do a lumbar puncture. Where do you do the puncture and what layers will you go through?

Answer 20

L4-L5. You will go through the skin, ligaments, dura and will not pierce through the pia mater.

Question 21

A patient comes to see you complaining of headache, neck stiffness, nausea, vomiting and altered mental status. You suspect meningitis and decide to do a lumbar puncture. What things in the fluid would point you towards bacterial, viral or fungal meningitis?

Answer 21

Bacterial = PMNs w/ low glucose content (bacteria consume glucose) and a positive gram stain/culture. Viral = lymphocytes w/ normal glucose. Fungal = lymphocytes w/ low CSF glucose (fungi consume glucose).

Question 22

If a patient has a serum blood glucose of 90mg/dL, what will be defined as low CSF glucose when you do his lumbar puncture?

Answer 22

~60mg/dL. CSF glucose is usually 2/3 serum glucose.

Question 23

A patient comes to the hospital complaining of headache, neck stiffness, nausea, vomiting and altered mental status. Physical exam reveals a fever of 105 degrees. On his third day in the hospital he dies. What type of meningitis did this patient most likely have?

Answer 23

Bacterial meningitis is the most common cause of serious complications due to the amount of inflammation and swelling bacterial infections cause in the brain.

Question 24

A 31 year old man survived bacterial meningitis, but has had persistent CNS symptoms after the infection resolved due to healing and scarring of the infected tissue. What residual symptoms might he have?

Answer 24

Hydrocephalus, hearing loss, seizures etc.

Question 25

A 77 year old man is brought to the ED because of rapid onset symptoms of blindness and diffuse muscle weakness. Past medical history reveals diabetes and hypertension. Imaging reveals occlusion of the watershed areas of the brain. What other conditions could cause a patient to present in this manner?

Answer 25

This patient has moderate global cerebral ischemia. This is caused by low perfusion to the brain (atherosclerosis), acute decreased blood flow (shock), chronic hypoxemia (anemia) and repeated episodes of hypoglycemia (insulinoma).

Question 26

Three patients come to the ED on a Sunday afternoon. One had a few hours of confusion that was fixed after glucose infusion in the ED. The second patient had diffuse necrosis of his brain and is now in a vegetative state. The third patient had a brain CT scan that showed cortical laminar necrosis. What is your diagnosis in these patients?

Answer 26

1) Mild Global Ischemia 2) Severe Global Ischemia 3) Moderate Global Ischemia

Question 27

What areas of the brain are at highest risk for ischemia in patients with moderate global ischemia?

Answer 27

Watershed areas (very ends of the anterior and middle cerebral arteries), the pyramidal neurons of the cortex in cortical layers III, V & VI (presents as a cortical laminar necrosis), the pyramidal neurons of the hippocampus (impairs long-term memory) and the Purkinje layer of the cerebellum (cerebellar signs).

Question 28

A patient comes to the ED complaining of focal neurological symptoms consistent with regional cerebral ischemia. What determines if he had an ischemic stroke or a transient ischemic attack?

Answer 28

Transient ischemic attack \< 24 hours. Ischemic stroke \> 24 hours.

Question 29

A 77 year old man is brought to the ED because of rapid onset symptoms of blindness in one eye and left arm muscle weakness. What are the different ways this patient could have developed an ischemic stroke and how would the infarction appear in each way?

Answer 29

1) Thrombosis atherosclerotic plaque = pale infarct in periphery of cortex 2) Embolus, usually from left heart to middle cerebral artery = red infarct 3) Lacunar stroke from hyaline arteriolosclerosis, most often in lenticulostriate vessels which go to the deep structures of the brain.

Question 30

What artery to the lenticulostriate blood vessels branch off of?

Answer 30

Middle cerebral artery.

Question 31

A 77 year old man is brought to the ED because of rapid onset symptoms of blindness in one eye and left arm muscle weakness. CT scan reveals cortical laminar necrosis. What would be the earliest detectable histological findings of ischemic stroke in this patient? What signs follow this?

Answer 31

Red neurons appear 12 hours after the stroke. After 24 hours neutrophils will infiltrate and liquefactive necrosis will ensue. Microglial cells come and clear out the dead cells and granulation tissue appears after about a week. After a month, fluid-filled cystic spaces surrounded by astrocytes appear (gliosis).

Question 32

A 63 year old woman comes to the emergency department complaining of nausea, vomiting and a debilitating headache. She has a history of hypertension and after a few hours she goes into a coma. She dies the next day and an image of her autopsy is shown below. Why is the location of the lesion seen in her brain classic for the condition that resulted in her death?

Answer 32

This woman had an intracerebral hemorrhage. Her long history of hypertension contributed to weakening of the lenticulostriate blood vessel walls, which feed the basal ganglia and deep structures of the brain. Rupture of Charcot-Bouchard micro aneurysms in the lenticulostriate vessels is what caused the intracerebral hemorrhage and ultimately her death.

Question 33

A 42 year old male comes to the ED after falling of off his mountain bike complaining of a sudden headache that is the worst he has ever had in his life. Physical exam reveals stiffness when moving his neck downward. If this patient has a subarachnoid hemorrhage, what would you be looking for when you perform a lumbar puncture?

Answer 33

Xanthochromia. This gives the CSF a yellow tinge due to breakdown of biliruben products.

Question 34

Rupture of what blood vessel most likely caused the hemorrhage seen in the image below?

Answer 34

This patient had a subarachnoid hemorrhage. This is the only thing that will cause hemorrhage at the base of the brain. The most common cause of subarachnoid hemorrhage is rupture of the branch point of the anterior communicating artery in the Circle of Willis. This is because the branch point lacks a tunica media and is more prone to saccular outpouchings.

Question 35

What genetic conditions are most commonly associated with the condition seen below?

Answer 35

Note the rupture of the saccular out pouching (berry aneurism). Marfan and ADPKD.

Question 36

What event is usually needed to create an epidural hematoma?

Answer 36

Fracture (most often temporal bone). The dura tightly adheres to the skull and you need a high pressure artery, like the middle meningial artery, to rupture to create a separation in that potential space.

Question 37

What is “talk and die” syndrome?

Answer 37

When you have an epidural hematoma, the dura tightly adheres to the sutures of the skull. Often, when the hematoma is confined to the sutures patients are asymptomatic. Once the pressure in the hematoma builds up significantly, it can rupture through the dura and the suture, expand and suddenly cause life-threatening herniation.

Question 38

What would you expect to see on CT of a patient with an epidural hematoma?

Answer 38

Lens-shaped lesion because the hematoma is confined to the sutures.

Question 39

What are the most common causes of the condition seen below? Why?

Answer 39

Trauma and CNS atrophy. This is a subdural hematoma (note the dura on the right side of the picture). Subdural hematomas are most often caused by rupture of bridging veins between the dura and arachnoid space from trauma or stretch when the brain atrophies.

Question 40

How do clinical symptoms of a subdural hematoma compare with an epidural hematoma?

Answer 40

Subdural hematomas are more slowly progressing because the bridging veins are a low pressure system and it takes longer for the brain to herniated from intracranial pressure.

Question 41

What type of brain herniation leads to cardio-pulmonary arrest?

Answer 41

Tonsillar. The cerebellar tonsils compress the inferior portion of the medulla in the foramen magnum.

Question 42

What type of brain herniation leads to compression of the anterior cerebral artery and infarction?

Answer 42

Sub-falcine herniation

Question 43

What are the three complications associated with the type of herniation shown below?

Answer 43

This is an uncal herniation, where the uncus of the temporal lobe herniates through the tentorum cerebelli. It is associated with: 1) CN III compression and the eyes move down and out w/ a dilated pupil 2) Compression of the posterior cerebral artery and infarction of the occipital lobe and 3) Hemorrhage on the brainstem from the herniation pulling on the paramedian artery

Question 44

What type of demyelinating disorders are associated with mutations in enzymes responsible for the production or maintenance of the myelin sheaths in the CNS?

Answer 44

Leukodystrophies

Question 45

A patient comes to see you because he has a genetic demyelinating disorder. Brain tissue biopsy reveals an accumulation of myelin in the lysosomes. What enzyme is most likely deficient in this patient?

Answer 45

He has metachromatic leukodystrophy which is characterized by a deficiency in arylsulfatase. This makes it so myelin cannot be degraded and is the most common leukodystrophy.

Question 46

A patient comes to see you because he has a genetic demyelinating disorder. Brain tissue biopsy reveals an accumulation of galactocerebroside in macrophages. What enzyme is most likely deficient in this patient?

Answer 46

This patient has Krabbe disease, characterized by a deficiency in galactocerebroside beta-galactosidase.

Question 47

A patient comes to see you because he has a genetic demyelinating disorder. Brain tissue biopsy reveals fatty acid accumulation in the white matter. Later he dies and autopsy reveals fatty acid accumulation in the adrenal glands. What enzyme is most likely deficient in this patient?

Answer 47

This patient has adrenoleukodystrophy. This is characterized by an inability to add coenzyme A to long-chain fatty acids.

Question 48

A patient comes to see you because he has a genetic demyelinating disorder. Brain tissue biopsy reveals autoimmune destruction of CNS myelin and oligodendrocytes. What puts people at risk for this condition?

Answer 48

This patient has multiple sclerosis. This is associated the HLA-DR2 gene and living in regions away from the equator.

Question 49

You are doing your rotation in the neurology clinic and see six patients that day with the same diagnosis, but different complaints. One patient has blurred vision in one eye, another has vertigo and scanning speech (like he’s drunk) the 3rd has difficulty looking with both eyes from one side to another (shown below), the 4th has hemiparesis & unilateral loss of sensation, the 5th has lower extremity loss of sensation & weakness and the las has bowel/bladder incontinence and sexual dysfunction. What is causing the symptoms to present this way in each patient?

Answer 49

These patients all have multiple sclerosis, but different regions of the brain are involved. The first patient has involvement of the optic nerve, the second the brainstem, the third the medial longitudinal folliculus (MLS), causing internuclear ophthalmoplegia (lesions on the MLF prevent CN VI from lighting up CN III to drag the MR in the same direction as the LF), the 4th cerebral white matter, the 5th the spinal cord and the 6th the autonomic nervous system.

Question 50

You are seeing a patient in the neurology clinic who is 28 years old and complains of vertigo, bladder incontinence and slurred speech. Physical exam reveals decreased lower extremity sensation and muscle weakness. Several members of his family have this same condition. What diagnostic tests might you run on this patient?

Answer 50

This patient has suspected multiple sclerosis. MRI = plaques. Lumbar puncture = increased lymphocytes, increased Ig with Oligoclonal IgG bands and myelin basic protein (because it is being destroyed).

Question 51

What region of the brain seen below gives you a hint that this patient may have had multiple sclerosis?

Answer 51

Regions of gray mater where is should be white due to demyelination.

Question 52

You are seeing a patient in the neurology clinic who is 28 years old and complains of vertigo, bladder incontinence and slurred speech. Physical exam reveals decreased lower extremity sensation and muscle weakness. Several members of his family have this same condition. How do you treat this patient?

Answer 52

Acute treatment: high dose steroids. Long term: IF-beta to slow disease progression

Question 53

You are consulting with a mother in the family clinic about vaccinating her child for measles. She asks you if her kids get sick, but survive, won’t they be fine for the rest of their lives now? You say that they actually aren’t off the hook for the rest of their lives. Why is this?

Answer 53

Measles can cause subacute sclerosing panencephalitis years after the primary infection. This is because the virus causes viral inclusions to form in the neurons (gray matter) and oligodendrocytes (white matter) making it a panencephalitis.

Question 54

A 44 year old man comes to the ED with rapidly progressive neurological deficits. A few days later he dies. History reveals that he had AIDS. Autopsy of his brain reveals demyelination in multiple regions of the brain. How did this patient’s development of AIDS ultimately contribute to the rapid neurological degradation?

Answer 54

This is a case of Progressive Multifocal Leukoencephalopathy. This is characterized by a latent JC virus infection of oligodendrocytes that gets activated when people become immunosuppressed.

Question 55

A 48 year old woman is brought to the ED because of complete paralysis. Physical examination reveals complete paralysis except for her eyes. Her family said that she has been an alcoholic for decades. Labs reveal thiamine deficiency. What is your diagnosis and how could hospital staff cause this condition to manifest in a patient?

Answer 55

Central pontine myelinolysis. This is characterized by focal demyelination of the pons and can also be caused by rapid IV correction of hyponatremia.

Question 56

What clinical symptoms are associated with degenerative CNS disorders?

Answer 56

Degenerative disorders refer to degeneration of the neurons in the CNS (gray matter). This can be in the cortex, which causes dementia, or in the basal ganglia, which causes movement disorders.

Question 57

A 68 year old woman comes to see you in the neurology clinic complaining of difficulty remembering things short term. You assess her and determine it is just senile memory loss and send her home. A few years later she comes back with her daughter. She now cannot speak, has personality changes and has lost many of her learned motor skills. Imaging reveals degeneration of the gray matter in the cortex of the patient’s brain. What protein is being deposited in the cortex?

Answer 57

AB Amyloid. In Alzheimer’s disease, you see slow-onset memory loss without focal neurological deficit because amyloid precursor protein (APP) is cleaved to its beta form (AB amyloid) which slowly deposits in the cortex over time

Question 58

What genetic factor will increase patient risk for the sporadic form of Alzheimer’s disease?

Answer 58

The #1 risk factor for the sporadic form is age. Risk is increased if patients have the epsilon-4 allele of APO-E because this allele increases conversion of APP to the beta form.

Question 59

What genetic factor will decrease patient risk for the sporadic form of Alzheimer’s disease?

Answer 59

Epsilon-2 allele of APO-E.

Question 60

What genetic factors cause the early onset form of Alzheimer’s disease?

Answer 60

The presenilin 1 gene causes the familial form and trisomy 21 (APP is on chromosome 21)

Question 61

An 88 year old man passed away in the nursing home yesterday. He was bedridden with severe dementia. Autopsy of his brain is shown below. What characteristics of this patient’s brain make you think he had Alzheimer’s disease?

Answer 61

Diffuse cerebral atrophy, narrowing of the gyri and widening of the sulci. Not seen here, but most likely present is hydrocephalus ex vacuo (hydrocephalus due to cerebral atrophy)

Question 62

A 68 year old woman comes to see you in the neurology clinic complaining of difficulty remembering things short term. You assess her and determine it is just senile memory loss and send her home. A few years later she comes back with her daughter. She now cannot speak, has personality changes and has lost many of her learned motor skills. A few weeks later she passes away and biopsy of her brain is shown below. What is your diagnosis?

Answer 62

Alzheimer’s disease. Note the A-beta amyloid pink deposit with neuritic processes (neuritic plaque) in the top image. Note the neurofibrillary tangles in the bottom image.

Question 63

Why are patients with Alzheimer’s disease at increased risk for cerebral hemorrhage?

Answer 63

Cerebral amyloid angiopathy. The A-beta amyloid deposits around the blood vessel walls of the brain and weakens them.

Question 64

What causes formation of the neurofibrillary tangles seen below in patients with Alzheimer’s disease?

Answer 64

Tau protein within the neuron normal helps with microtubule reorganization. In Alzheimer’s disease it gets hyperphosphorylated, can no longer help in reorganization of the microtubules and forms these neurofibrillary tangles.

Question 65

How is Alzheimer’s disease diagnosed?

Answer 65

By exclusion and confirmed by autopsy after the patient dies.

Question 66

A 77 year old man comes to the ED with moderate global ischemia. History reveals hypertension, microscopic polyangiitis and one coronary bypass surgery. If this patient develops dementia, what regions of the brain were most likely affected by the global ischemia?

Answer 66

Global ischemia typically affects the hippocampal layer of the temporal lobe and layers 3,5 and 6 of the cortex, which is gray matter. Damage to these regions causes dementia.

Question 67

How do you treat the second most common cause of dementia?

Answer 67

The second most common cause is vascular dementia. You treat the vasculidity (HTN, atherosclerosis or vasculitis)

Question 68

A 70 year old woman is brought to the neurology clinic complaining of progressive dementia. Her daughter states that it all started when her behavior started to change and then she had difficulty understanding many of the things people would say to her. What would microscopic analysis of the patient’s brain reveal?

Answer 68

This patient has Pick Disease. This is characterized by degeneration of the frontal and temporal cortexes only (hence the behavioral and language problems early on). Microscopically you would see round aggregates of tau protein in cortical neurons.

Question 69

Where is the brain are neurons lost in patients with Parkinson Disease? Why does this loss cause the movement disorder seen in Parkinson Disease?

Answer 69

You see degenerative loss of dopaminergic neurons in the substantia nigra pars compacta of the basal ganglia. The dopaminergic neurons secrete dopamine which normally binds to D1 and D2 receptors in the basal ganglia striatum. Normally, this increases cortical stimulation (D1 receptor) and decreases cortical inhibition (D2 receptor) with an overall increase in cortical stimulation. Loss of dopaminergic neurons disrupts this pathway.

Question 70

What is the main risk factor for Parkinson’s disease? How is the disease related to drug use?

Answer 70

#1 risk factor is age. Associated with MPTP in elicit drugs.

Question 71

What are the clinical features of Parkinson’s disease?

Answer 71

Degeneration of the substantia nigra causes movement disorders “TRAP”: Tremor, Rigidity, Akinesia/bradykinesia (expressionless face), Postural instability and a shuffling gait.

Question 72

An 80 year old man comes to see you in clinic because of a tremor. Physical exam reveals a shuffling gait, postural instability, rigidity and akinesia. A few years later the patient dies and a biopsy of his brain compared to another brain is shown below. What would you expect to see on microscopic analysis of his brain?

Answer 72

Note the degeneration of the substantia nigra. This is indicative of Parkinson Disease. On microscopic analysis you would see Lewy bodies (round eosinophilic inclusions within the neuron) composed of alpha-synuclein.

Question 73

A 70 year old man comes to see you in clinic because of a tremor and hallucinations. Physical exam reveals a shuffling gait, postural instability, rigidity and akinesia. 6 months later he develops dementia. Where was the brain biopsy seen below most likely taken from in the patient’s brain?

Answer 73

In normal Parkinson’s disease, dementia is a late-onset symptom. If dementia is early onset after diagnosis of Parkinsonian-like symptoms, then they have Lewy body dementia. In Lewy body dementia, Lewy bodies are found in the cortical region of the brain, hence the dementia and hallucinations.

Question 74

What structures form the striatum of the basal ganglia?

Answer 74

Caudate nucleus and the putamen

Question 75

A 47 year old man died an autopsy of his brain is shown below. Several other members of his family had the same condition. What would have been the key physical exam finding in this patient that would relate to his condition?

Answer 75

Note degeneration of the caudate nucleus in the section. GABAergic neurons are in the caudate nucleus. They send inhibitory signals to the cortex. In Huntington’s disease, these neurons degenerate and patients have chorea (random sporadic movements) and athetosis (slow involuntary snake-like movements of the fingers)

Question 76

A 45 year old man comes to see you in clinic complaining of inability to control random sporadic movements, dementia and depression. MRI reveals degeneration of the caudate nucleus. Why is this man’s offspring more likely to develop this condition earlier in life?

Answer 76

This man has Huntingtin’s disease, caused by expanded trinucleotide repeats (CAG) in the huntingtin gene. The repeats get longer and longer with every generation and the expansion occurs during spermatogenesis.

Question 77

What is a common cause of death in patient’s with Huntingtin’s disease?

Answer 77

Suicide

Question 78

A 52 year old woman comes to see you complaining of urinary incontinence, gait instability and dementia. Her symptoms are improved with lumbar puncture. What is causing this patient’s dementia? How would you treat this patient long-term?

Answer 78

The triad of urinary incontinence, gait instability and dementia is typical of normal pressure hydrocephalus. These symptoms come from increased CSF stretching the corona radiata. Long term treatment is to shunt CSF from ventricles into peritoneum with a VP shunt.

Question 79

A 52 year old woman comes to see you complaining of urinary incontinence, gait instability and dementia. Her symptoms are improved with lumbar puncture. What is the pathophysiology of this patient’s condition?

Answer 79

In normal pressure hydrocephalus, the arachnoid granulation exchange of CSF into the sinuses is impaired and CSF accumulates, expanding the ventricles and the corona radiata. This makes the patient wet, wacky and wobbly (urinary incontinence, dementia and gait instability).

Question 80

What protein causes the intracellular vacuolations to appear in the brain biopsy below?

Answer 80

Prion Protein C (PrPc) in its alpha-conformation is the normal protein in our brain. In patients with spongiform encephalopathy, that protein is converted to its beta form (PrPsc). PrPsc cannot be degraded which causes it to accumulate in neurons & glial cells and cause intracellular vacuolations. It also goes back to PrPc and converts more of it to the pathological form, PrPsc.

Question 81

What 3 ways can normal alpha prion protein (PrPc) be converted to beta prion protein (PrPsc)?

Answer 81

Sporadically, Inherited and Transmitted (exposure to the beta-pleated protein will turn your alpha prions to beta prions)

Question 82

A 47 year old woman is brought to the neurology clinic by his wife. She complains that he has developed dementia in the last two weeks. History reveals recent corneal transplant and use of HGH for body building. Physical exam reveals ataxia and startle myoclonus (muscular contraction with minimal stimulation). What are you likely to see on EEG of this patient?

Answer 82

This patient has CJD. Although rare, transmission of the beta prion can happen with transplantation and HGH use. On EEG you would see spike-wave complexes.

Question 83

What are the three types of spongiform encephalopathy?

Answer 83

CJD. vCJD (mad cow disease). Familial fatal insomnia (characterized by insomnia & exaggerated startle response)

Question 84

How do lung cancers, kidney cancers and breast cancers typically present in the brain?

Answer 84

Multiple well-circumscribed tumors at the junction of the gray and white matter.

Question 85

Where do primary brain tumors like to metastasize to?

Answer 85

Nowhere. They are typically locally destructive and rarely metastatic.

Question 86

From what 5 cells do most primary brain tumors originate from?

Answer 86

Astrocytes, oligodendrocytes, ependymal cells, neurons and meningiothelial cells.

Question 87

What is the most common astrocyte tumor in kids?

Answer 87

Pilocytic Astrocytoma (most common benign CNS tumor in kids)

Question 88

What is the most common astrocyte tumor in adults?

Answer 88

Gliobastoma Multiforme (most common malignant CNS tumor in adults)

Question 89

What is the most common form oligodendrocyte tumors?

Answer 89

Oligodendroglioma (typically in adults)

Question 90

What is the most common form of ependymal tumors?

Answer 90

Ependymoma (typically in children)

Question 91

What is the most common form of neuron tumors?

Answer 91

Medulloblastoma (in kids, derived from neuroectoderm)

Question 92

What is the most common form of meningothelial tumors?

Answer 92

Meningioma (most common benign CNS tumor, mostly in adult females)

Question 93

How does the location of most adult tumors compare to that in most childhood tumors?

Answer 93

Adult tumors: above tentorium cerebelli, childhood tumors: below tentorium cerebelli.

Question 94

Where do gliobastoma multiforme brain tumors typically arise?

Answer 94

Cerebral hemispheres. Note that it crosses the corpus callosum.

Question 95

A 34 year old woman has a brain tumor and her biopsy is shown below. What intermediate filament is most likely present in the cells seen below?

Answer 95

Note the pseudopalisading cells around the necrotic area of cells. This is characteristic of gliobastoma multiforme. The tumor arises from glial cells which have the intermediate filament GFAP.

Question 96

A 37 year old woman comes to the neurology clinic because of a recent onset of seizures. Imaging reveals a benign round mass attached to the dura. Why is this tumor more common in females than males?

Answer 96

This patient has a meningioma derived from arachnoid cells. These cells have estrogen receptors and women have more estrogen than men.

Question 97

A 37 year old woman comes to the neurology clinic because of a recent onset of seizures. Imaging reveals a benign round mass attached to the dura. What would histological analysis of this patient’s mass reveal?

Answer 97

Meningiomas have a whirled appearance with psammoma bodies (microscopic calcifications)

Question 98

A 48 year old man comes to the neurology clinic complaining of a loss of hearing and ringing in his ears. What benign CNS tumor commonly causes these symptoms?

Answer 98

Schwannomas commonly present at the cerebellar-pontine angle (CPA) and involve CN VIII.

Question 99

A 48 year old man comes to the neurology clinic complaining of a loss of hearing and ringing in his ears. Imaging reveals bilateral tumors at the cerebellar-pontine angle. What other condition is this patient’s condition commonly associated with? What could you stain for histologically to confirm your diagnosis?

Answer 99

This patient has a schwannoma. Bilateral tumors are commonly associated with NF2 (neurofibromatosis type II). You could stain for S-100 expressed by these tumors.

Question 100

A 62 year old man presents with seizures and a CNS tumor. Biopsy is shown below. What are the classic gross characteristics of this tumor?

Answer 100

Note the “fried egg” appearance of the cells below. This is indicative of an Oligodendroglioma. These present as calcified tumors in the white matter, usually in the frontal lobe.

Question 101

A young child presents with the brain tumor shown below. What are the histological characteristics of this tumor?

Answer 101

Note the cystic lesion in the cerebellum with a mural nodule growing off it, this is typical of Pilocytic astrocytomas. Histological characteristics include eosinophilic infiltrates into the astrocytes (Rosenthal fibers) and GFAP + because they are glial cells.

Question 102

What cells are medulloblastomas derived from?

Answer 102

Granular cells of the cerebellum which come from neuroectodermal tissue.

Question 103

A child presents with a tumor in his cerebellum. The tumor has grown rapidly over the past few months and has spread via the CSF to the spinal cord. What would you expect to see histologically in a biopsy of this tumor?

Answer 103

This child has a medulloblastoma with a “drop metastasis” through the 4th ventricle to the spinal cord. Histological examination would reveal Homer-Wright rosettes.

Question 104

A young child present with a tumor beneath the tentorum cerebelli in the 4th ventricle. Imaging reveals hydrocephalus in the lateral ventricles. What would you expect to see on histological analysis of this tumor?

Answer 104

This patient has a malignant ependymoma. Histology would reveal perivascular pseudo rosettes (pink material between the tumor cells surrounding the blood vessel)

Question 105

A 13 year old boy comes to see you with the vision problems shown below. Imaging reveals a calcified supratentorial mass. What embryological origin is the source of this tumor?

Answer 105

This patient has a craniopharyngioma. These typically arise from the epithelial remnants of Rathke’s pouch, which is the remnant of the anterior pituitary gland from when it ascended from the roof of the mouth into the sella turcica. This tumor can compress the optic chiasm and cause the bitemporal hemianopsia (missing the outer half of both optic fields) seen in this boy.

Question 106

What is the prognosis for a child with a craniopharyngioma?

Answer 106

They are benign and can be resected but typically recur.