Pathology-CNS Flashcards
What will the structures indicated in the developing embryo become?
Neural crest cells = PNS. Neural tube wall = CNS. Cavity of Neural tube = ventricles.
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?
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.
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?
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.
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?
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.
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?
Cerebral aqueduct stenosis
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?
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.
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?
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.
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?
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)
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?
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.
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?
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.
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?
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.
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?
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.
What part of the CNS is affected in meningitis?
Leptomeninges (arachnoid & pia mater)
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?
Most common causes of bacterial meningitis in neonates are 1) Group B Strep (vaginal canal) 2) E. Coli (vaginal canal) and 3) Listeria monocytogenes
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?
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.
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?
Strep pneumoniae is the most common cause of bacterial meningitis in adults and elderly
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?
H. Influenzae
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?
Fungi
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?
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.
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?
L4-L5. You will go through the skin, ligaments, dura and will not pierce through the pia mater.
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?
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).
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?
~60mg/dL. CSF glucose is usually 2/3 serum glucose.
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?
Bacterial meningitis is the most common cause of serious complications due to the amount of inflammation and swelling bacterial infections cause in the brain.
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?
Hydrocephalus, hearing loss, seizures etc.
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?
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).
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?
1) Mild Global Ischemia 2) Severe Global Ischemia 3) Moderate Global Ischemia
What areas of the brain are at highest risk for ischemia in patients with moderate global ischemia?
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).
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?
Transient ischemic attack < 24 hours. Ischemic stroke > 24 hours.
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?
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.
What artery to the lenticulostriate blood vessels branch off of?
Middle cerebral artery.
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?
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).
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?
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.
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?
Xanthochromia. This gives the CSF a yellow tinge due to breakdown of biliruben products.
Rupture of what blood vessel most likely caused the hemorrhage seen in the image below?
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.
What genetic conditions are most commonly associated with the condition seen below?
Note the rupture of the saccular out pouching (berry aneurism). Marfan and ADPKD.
What event is usually needed to create an epidural hematoma?
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.
What is “talk and die” syndrome?
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.
What would you expect to see on CT of a patient with an epidural hematoma?
Lens-shaped lesion because the hematoma is confined to the sutures.
What are the most common causes of the condition seen below? Why?
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.
How do clinical symptoms of a subdural hematoma compare with an epidural hematoma?
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.
What type of brain herniation leads to cardio-pulmonary arrest?
Tonsillar. The cerebellar tonsils compress the inferior portion of the medulla in the foramen magnum.
What type of brain herniation leads to compression of the anterior cerebral artery and infarction?
Sub-falcine herniation
What are the three complications associated with the type of herniation shown below?
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
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?
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.
What region of the brain seen below gives you a hint that this patient may have had multiple sclerosis?
Regions of gray mater where is should be white due to demyelination.
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?
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)
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?
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.
What causes formation of the neurofibrillary tangles seen below in patients with Alzheimer’s disease?
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.
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?
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.
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?
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.
What structures form the striatum of the basal ganglia?
Caudate nucleus and the putamen
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?
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)
What protein causes the intracellular vacuolations to appear in the brain biopsy below?
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.
Where do gliobastoma multiforme brain tumors typically arise?
Cerebral hemispheres. Note that it crosses the corpus callosum.
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?
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.
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?
Meningiomas have a whirled appearance with psammoma bodies (microscopic calcifications)
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?
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.
A young child presents with the brain tumor shown below. What are the histological characteristics of this tumor?
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.
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?
This patient has a malignant ependymoma. Histology would reveal perivascular pseudo rosettes (pink material between the tumor cells surrounding the blood vessel)
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?
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.
