Pathology Flashcards
Rhinitis
Inflammation of the nasal mucosa
Allergic rhinitis
- subtype of rhinitis due to type I hypersensitivity (immediate hypersensitivity)
- characterized by inflammatory infiltrate with eosinophils
- associated with other atopic disorders (asthma and eczema)
What cells type I hypersensitivity reactions associated with?
early phase: sensitized mast cells and basophils
late phase: eosinophils
Mechanism of type 1 hypersensitivity
Sensitization:
- antigen is presented to CD4+ Th2 cells specific to the antigen
- TH2 cells stimulate B-cell produce of IgE antibodies to that antigen
- IgE binds to Fcε receptors on the surface of tissue mast cells and blood basophils
Hypersensitivity
- later exposure to antigen crosslinks the bound IgE on sensitized cells –> degranulation
- release of initial mediators pre-formed mediators
- histamine (bronchoconstriction, mucus secretion, vasodilation, vascular permeability)
- tryptase (proteolysis)
- kininogenase (kinins and vasodilation, vascular permeability, edema)
- ECF-A (attact eosinophil and neutrophils)
- Formation and release of late stage mediators
- leukotriene B4 (basophil attractant)
- leukotriene C4, D4 (same as histamine but 1000x more potent)
- prostaglandins D2 (edema and pain)
- PAF (platelet aggregation and heparin release –> microthrombi)
What are patients who have repeated bouts of rhinitis at risk for?
Development of nasal polyps
Nasal polyp
Protrusion of edematous, inflamed nasal mucosa usually secondary to repeated bouts of rhinitis
- Child with nasal polyps –> think cystic fibrosis
- Also occurs in patients with aspirin-intolerant asthma
Aspirin intolerant asthma
Characterized by a triad of
- asthma
- aspirin-induced bronchospasms
- nasal polyps (~10% of asthmatic adults)
2 conditions associated w/ nasal polyps
- aspirin intolerant asthma
- cystic fibrosis (children typically)
Angiofibroma
- Benign tumor of nasal mucosa composed of large blood vessels and fibrous tissue
- classically seen in adolescent males (very very rarely seen in female)
- presents with profuse epistaxis (nose bleed)
Nasopharyngeal carcinoma
- Malignant tumor of nasopharyngeal epithelium
- associated with EBV
- Classically seen in African children and Chinese adults
- Often presents with involvement of cervical lymph nodes
- Biopsy usually reveals pleomorphic keratin-positive epithelial cells (poorly differentiated squamous cell carcinoma) in the background of lymphocytes
Intermediate filament that can be stained for in epithelial cells? What type of cancers is it associated with?
Keratin – carcinomas
Acute epiglottitis
Inflammation of the epiglottis
H influenza type B is most common cause (immunized or nonimmunized)
Acute epiglottitis presentation
- High fever, sore throat (due to inflammation in that region)
- drooling with dysphagia (swollen epiglottis –> compromised airway –> dysphagia (difficulty swalling))
- muffled voice, inspiratory stridor (compromised airway)
Risk of acute airway obstruction
Laryngotracheobronchitis
Inflammation of the upper airway
Parainfluenza virus is the most common cause
Presents with a hoarse, “barking” cough and inspiratory stridor
Patient presents with a hoarse, “barking” cough and inspiratory stridor
laryngotracheobronchitis
laryngotracheobronchitis most common cause
parainfluenza virus (RNA virus)
vocal cord nodule
Nodule that arises on vocal cord.
Most often due to excessive use –> bilateral presentation
Nodule is composed of degenerative (myxoid) connective tissue
Presents with hoarseness; resolves with rest
vocal cord nodule - most common cause
wear and tear – excessive use
resolves with rest
Laryngeal papilloma
- Benign papillary tumor of vocal cord
- Due to HPV 6 and 11 (b/c its HPV, you would expect koilocytic change on biopsy)
- Single mass in adults and multiple in children
- Presents with hoarseness
Laryngeal papilloma causes
HPV 6 and 11 –> will cause koilocytic change
Laryngeal carcinoma
Squamous cell carcinoma arising from epithelial lining of vocal cord
Risk factors: alcohol and tobacco
Possible to get larygneal carcinoma that evolves from laryngeal papilloma (as it is due to a HPV virus)
Presents with hoarseness; other signs include cough and stridor
Laryngeal carcinoma risk factors
Biggest ones: alcohol and tobacco
Rare, but can occur: laryngeal papilloma —> laryngeal carcinoma
Pneumonia
Infection of the lung parenchyma
occurs when normal defenses are impaired
- cough reflex (not able to remove organisms/particles that we normally would cough up
- dmg to mucociliary escalator
- mucous plugging
What normal defenses are typically damaged to allow for pneumonia?
- cough reflex (not able to remove organisms/particles that we normally would cough up
- dmg to mucociliary escalator
- mucous plugging
Pneumonia clinical features
- fever and chills (due to organism leaking out into the blood)
- cough with yellow-green and rusty sputum (yellow green = pus, rusty = blood)
- tachypnea with pleuritic chest pain (pain when you breathe in due to stretching of the pleura)
- decreased breath sounds with dullness to percussion (dullness due to the exudates from inflammation)
- elevated WBC count
Diagnosing pneumonia clinically
chest x-ray
sputum gram stain and culture
blood cultures
pneumonia patterns on chest x-ray
- Lobar pneumonia – consolidation to an entire lobe
- bronchopneumonia – consolidation that runs along the small airways
- interstitial pneumonia – no consolidation but infection of the intersitium of the lung (the connective tissue of the alveolar air sacs). xray will show diffuse lung markings
1 & 2 are typically associated with bacterial infections
3 is considered atypical pneumonia and is more often associated with viral infections
What types of pneumonia patterns on chest x-ray are associated with bacterial infections?
Lobar pneumonia
bronchopneumonia
What types of pneumonia patterns on chest x-ray are associated with viral infections?
interstitial pneumonia
Lobar pneumonia
Consolidation of infection to an entire lobe
Usually bacterial
Most common causes:
- S pneumoniae (95%)
- Klebsiella pneumoniae
Most common cause of community-acquired pneumonia
Streptococcus pneumoniae – ~95% of all pneumonia
Usually in middle-aged adults and elderly
Klebsiella pneumoniae
Causes ~5% of pneumonia via aspiration of enteric flora.
Affects mostly (people most at risk for aspiration):
- elderly in nursing homes
- alcoholics
- diabetics
This bug has a thick mucoid capsule. When coughed up, it will give the sputum a gelatinous (currant jelly) sputum.
Often complicated by an abscess.
4 classic phases of lobar pneumonia
- Congestion (infection –> dilation of vessels and increased permeability –> edema = congestion)
- Red hepatization (exudate, neutrophils, and hemorrhage filling the alveolar air sacs)
- grey hepatization (breakdown of the RBCs within the exudate from the red hepatization step)
- resolution (via regeneration by the type II pneumocyte)
hepatization refers to the lung becoming solid instead of spongy (like the liver) due to the exudate and blood.
What occurs in the recovery process after a pneumonia infection? What cell type is predominantly responsible for this?
Patient regenerates the part of the lung that was infected.
This is done by the type II pneumocyte (stem cell of the lung)
Secondary pneumonia
- Bacterial pneumonia superimposed on a viral upper respiratory tract infection
- Idea is that the initial viral infection knocks out the mucociliary escalator and increases the risk of developing pneumonia
Most common cause of secondary pneumonia
Staphylococcus aureus
Complications of S. aureus infection
abscess or empyema (pus in the pleural space)
Haemophilus influenzae
Commonly causes secondary pneumonia or pneumonia superimposed on COPD (leads to exacerbation of COPD)
Pseudomonas aeruginosa
commonly associated with pneumonia in cystic fibrosis patients
Moraxella catarrhalis
Commonly associated with community-acquired pneumonia and penumonia superimposed on COPD (leads to exacerbation of COPD)
Legionella pnemophilia
Commonly associated with:
- community-acquired pneumonia
- pneumonia superimposed on COPD
- pneumonia in immunocompromised states
transmitted from water source
intracellular organism best visualized by silver stain
Most common causes of bronchopneumonia
- S. aureus
- H. influenzae
- P. aeruginosa
- M. catarrhalis
- L. pneumophila
Interstitial pneumonia
Aka atypical pneumonia – diffuse interstitial infiltrates of the lung
Symptoms are more atypical – presents with relativley mild upper respiratory symptoms
- minimal sputum
- cough
- low fever
Interstitial pneumonia symptoms
“atypical”
Presents with relativley mild upper respiratory symptoms
- minimal sputum
- cough
- low fever
Bugs associated with interstitial pneumonia
“atypical”
- Mycoplasma pneumoniae
- Chlamydia pneumoniae
- Respiratory syncytial virus (RSV)
- Cytomegalovirus (CMV)
- Influenza virus
- Coxiella burnetii
Mycoplasma pneumoniae
Most common cause of atypical pneumonia
Usually affect young adults (military recruits or college students living in a dormitory)
Complications:
- autoimmune hemolytic anemia (IgM against I antigen on RBCs causes cold hemolytic anemia)
- erthema multiforme
Chlamydia pneumoniae
Second most common cause of atypical pneumonia in young adults
Respiratory syncytial virus (RSV)
Most common cause of atypical pneumonia in infants
Cytomegalovirus (CMV)
Commonly associated with atypical pneumonia with posttransplant immunosuppressive therapy
Influenza virus
Commonly associated with atypical pneumonia in:
- elderly
- immunocompromised
- those with preexisting lung disease
Increases risk for superimposed S aureus or H influenzae bacterial pneumonia
- most deaths are not associated with virus infection but rather the secondary bacterial pneumonia that follows due to the weakening of the defense mechanisms
Coxiella burnetii
- Associated with atypical pneumonia with high fever (Q fever)
- normal atypical pneumonia causes low fever
- Seen in farmers and veterinarians (Coxiella spores are deposited on cattle by ticks or are present in cattle placentas)
-
Coxiella is a rickettsial organism, but it is distinct from most rickettsiae because:
- it causes pneumonia
- does not require arthropod vector for transmission (survives as highly heat-resistant endospores)
- does not produce a skin rash
Why is Coxiella burnetii distinct from most rickettsiae?
- it causes pneumonia
- does not require arthropod vector for transmission (survives as highly heat-resistant endospores)
- does not produce a skin rash
Aspiration pneumonia
Seen in patients at risk for aspiration (ie alcoholics and comatose patients)
Due to anaerobic bacteria in oropharynx
- Bacteroides
- Fusobacterium
- Peptococcus
Classically results in right lower lobe abscess
Most common anaerobic bacteria in oropharynx
- Bacteroides
- Fusobacterium
- Peptococcus
Aspiration pneumonia - where does it classically present and why?
Right lower lobe abscess because the right main stem bronchus branches at a less acute angle than the left –> more easier for the bacteria to go down the right than the left –> right lower lob abscess
Tuberculosis - bug responsible
Mycobacterium tuberculosis
Typically from inhalation –> results in primary TB
Primary TB
Arises with initial exposure
Results in focal caseating necrosis in the lower lobe of lung and hilar lymph nodes
Foci undergo fibrosis and calcification forming Ghon complex.
Primary TB is generally asymptomatic but leads to a positive PPD
Ghon complex
a lesion seen in the lung that is caused by tuberculosis. The lesions consist of a calcified focus of infection and an associated lymph node.
i.e. a foci that has undergone fibrosis and calcification
Primary TB - clinical features
Usually asymptomatic.
X-ray/biopsy (after death) will show the formation of Ghon complexes (areas of calcification and fibrosis due to bacterial presence)
PPD +
Secondary TB
Arises with the reactivation of TB
Commonly due to AIDS, may also be seen with aging
Occurs at apex of lung – b/c oxygen tension is the highest at the apex of the lung
Forms cavitary foci of caseous necrosis –> may lead to miliary pulmonary TB or tuberculous bronchopneumonia
What causes secondary TB?
Reactivation of the ghon complex (ie primary TB)
Where does secondary TB most often occur? and why?
Apex of the lung because that is where the oxygen tension is the highest
Secondary TB - clinical features
- Fevers and night sweats
- cough with hemoptysis
- weight loss
- biopsy reveals caseating granulomas
- AFB stain reveals acid-fast bacilli
TB - where can it spread?
Can involve any tissue, but most high yield places:
- Meninges (meningitis) – w/ granulomas at the base of the brain
- Cervical lymph nodes
- Kidney (sterile pyuria) – most common
- Lumbar vertebrae (Pott disease)
Cleft lip and palate
- Full-thickness defect of lip or palate
- Due to failure of facial prominences to fuse
- Cleft lip and palate usually occur together
Aphthous Ulcer
- Painful, superifical ulceration of oral mucosa
- arises in relation ot stress and resolves spontaneously, but often recurs
- characterized by grayish base surrounded by erythema
Behcet Syndrome
Presents as a triad
- recurrent aphthous ulcers
- genital ulcers
- uveitis
Due to immune complex vasculitis involving small vessles.
Can be seen after viral infection, but etiology is unknown
Triad associated with Behcet Syndrome
- recurrent aphthous ulcers
- genital ulcers
- uveitis
Oral Herpes
Vesicles involving oral mucosa that rupture resulting in shallow, painful, red ulcers
Usually due to HSV-1
- Primary infection occurs in childhood. Lesions heal, but virus remains dormant in ganglia of trigeminal nerve.
- Stress and sunlight cause reactivation of virus
- Leads to vesciles that often arise on lips (cold sore)
Most common cause of oral herpes
HSV-1
Where does herpes simple viruses lay dormant in oral herpes?
ganglia of trigeminal nerve
Oral herpes
Squamous cell carcinoma of the oral mucosa
Malignant neoplasm of squamous cells lining oral mucosa
Major risk factors
- tobacco
- alcohol
Floor of mouth is most common location
Major risk factors for squamous cell carcinoma of the oral mucosa
tobacco
alcohol
Most common location for squamous cell carcinoma of the oral mucosa
floor of the mouth
Squamous dysplasia of the oral mucosa
Often presents as luekoplakia (white plaques) and erythroplakia (red plaque)
often biopsied to rule out carcinoma
Patient presents with oral leukoplakia, what 3 things come to mind?
Have to distinguish between 3 things:
- squamous cell dysplasia – presents as a white plaque that cannot be scraped away
- oral candidiasis (thrush) – white deposit on the tongue that is easily scraped away. Usually seen in immunocompromised states
- Hairy luekoplakia – white, rough (‘hairy’) patch that arises on the lateral tongue. Usually seen in immunocompromised individuals (AIDS) and is due to EBV-induced squamous cell hyperplasia. NOT premalignant
Erythoplakia of oral mucosa
‘Red plaque’
Represents vascularized luekoplakia, ie a lot of new growth that includes angiogenesis
Highly suggestive of squamous cell dysplasia
What is suggestive of squamous dysplasia of oral mucosa?
Erythoplakia and leukoplakia.
Erythoplakia is more much indicative that there is dysplasia. Leukoplakia needs to rule out candidiasis and hairy luekoplakia
Major Salivary Glands (3)
- Parotid
- Submandibular
- Sublingual
Mumps
Infection with mumps virus
results in bilateral inflamed parotid glands
Can also cause
- orchitis (infection of testicles) –> risk of sterility (teenagers)
- pancreatitis – will result in increased serum amylase (but need to becareful, because both the gland and the pancreas produce amylase)
- aseptic meningitis
Mumps - complications (3)
- orchitis (infection of testicles) –> risk of sterility (teenagers)
- pancreatitis – will result in increased serum amylase (but need to becareful, because both the gland and the pancreas produce amylase)
- aseptic meningitis
Mumps - why is there an increase in serum amylase?
Both overactivity of the infected glands (bilateral parotid) and possible pancreatitis.
Sialadenitis
Inflammation of the salivary gland
Most commonly due to an obstruction stone (sialolithiasis) leading to S aureus infection.
- whenever you block a tube, you increase the likelihood of an infection behind the tube
usually unilateral
sialolithiasis
Also termed salivary calculi or salivary stone
A condition where a calcified mass or sialolith forms within a salivary gland, usually in the duct of the submandibular gland
What is the biggest issue associated w/ sialadenitis?
sialolithiasis leading to an S. aureus infection
Pleomorphic adenoma
- Most common tumor of salivary gland
- Benign tumor composed of stromal (ie cartilage) AND epithelial tissue (ie glands)
- whenever a tumor comprises of 2 tissues, it is called a biphasic tumor
- Usually arises in parotid
- Presents as a mobile, painless, circumscribed mass at angle of jaw
- all the key characteristics of being benign
- mobile = did not invade tissue
- painless = has not invaded the facial nerve (runs right through parotid gland)
- circumscribed = different from all the tissue surrounding it (hence foreign, but benign)
- all the key characteristics of being benign
- High rate of recurrence
- mostly due to the fact that this tumor has irregular margins and inexperienced surgeons are more likely to leave a little bit of tissue behind that allows to regrowth
- Rarely may transform into carcinoma
- presents with signs of facial nerve damage
Pleomorphic adenoma - most common location and presentation
Arises in parotid.
Presents as a mobile, painless, circumscribed mass at angle of jaw
- all the key characteristics of being benign
- mobile = did not invade tissue
- painless = has not invaded the facial nerve (runs right through parotid gland)
- circumscribed = different from all the tissue surrounding it (hence foreign, but benign)
Why is there a high rate of recurrent of pleomorphic adenomas?
mostly due to the fact that this tumor has irregular margins and inexperienced surgeons are more likely to leave a little bit of tissue behind that allows to regrowth
Pleomorphic adenoma - what happens when this tumor transforms into a carcinoma? How do you tell?
Patients will likely present with pain (invasion/destruction of the facial nerve in the parotid gland)
Warthin tumor
Benign cystic tumor with abundant lymphocytes and germinal centers
- cystic tumor with lymph node tissue
2nd most common tumor of salivary gland
almost always arises in parotid – common for LN tissue to be associated with parotid
Warthin tumor - where does it most commonly arise?
Parotid gland – this gland is one of the last glands to embryologically separate out and is not uncommon for it to be associated with lymphoid tissue
Mucoepidermoid carcinoma
Malignant tumor composed of mucinous and squamous cells
Usually arises in parotid; commonly involves the facial nerve (dmg to this nerve is common in malignancies)
TE fistula
Congenital defect resulting in connection between the esophagus and trachea
multiple different variants, most common: atresia of the proximal esophagus w/ connection of the distal esophagus (other end) to the trachea.
Presents with:
- vomiting – food goes into esophagus, but b/c it is closed, it will come right back up
- excess amniotic fluid (polyhydramnios) – during gestation, baby will “eat” some of the amniotic fluid. Since the esophagus is blocked, baby can’t so will be left with excess amniotic fluid in the sac
- abdominal distension – air into the stomach (via fistula)
- aspiration – stomach contents coming back up
Esophageal web
Thin protrusion of esophageal mucosa, most often in upper mucosa
Presents with dysphagia for poorly chewed food
Increased risk for esophageal squamous cell carcinoma
Plummer-Vinson Syndrome
Severe iron deficiency anemia
esophageal web
beefy-red tongue due to atrophic glossitis
- due to atrophy of the mucosa. Redness due to exposure of the underlying vasculature
Zenker diverticulum
Outpouching of pharyngeal mucosa through acquired defect in the muscular wall
- typically due to some abnormal pressure in the pharynx when you are swallowing
Arises above upper esophageal sphincter at junction of esophagus and pharynx
Presents with dysphagia, obstruction and halitosis (bad breathe – food trapped can rot)
Also known referred to sometimes as a “false” diverticulum
- means you only protruded one part of the wall and it does not include the muscularis layer
False diverticulum
A diverticulum that does not include the muscularis or adventitia. Typically very superifical diverticulum.
Most of the GI diverticulums (including Zenker’s) are false diverticulums
Mallory-Weiss Syndrome
Longitudinal laceration of mucosa at GE junction
Caused by severe vomiting –> which causes a longitudinal laceration of the GE mucosa as the vomit comes up each time.
- Usually due to alcoholism or bulimia
Presents with painful hematemesis (laceration bleeds into the vomit)
Risk of Boerhaave syndrome
Boerhaave syndrome
Rupture of esophagus, typically occuring after forceful emesis. Associated with but also different than Mallory-Weiss syndrome (which is a nontransmural esophageal tear)
Rupture of esophagus –> air in the mediastinum –> air track up through the facial planes and get into the subcutaneous tissue (esp in region of neck) –> subcutaneous emphysema (air beneath the skin); will get crackling when you press the skin
Esophageal varices
Dilated submucosal veins in lower esophagus
Arise secondary to portal HTN (a portion of the blood supply to the esophagus drains into the portal system (the majority going via azygous vein into the SVC))
Asymptomatic, but risk fo rupture exists (painless hematemesis if ruptured)
most common type of death in patients with cirrhosis (who all have portal hypertension, and reduce coagulation factors –> massive bleeding)
What is the most common cause of death in patients with cirrhosis? and why?
Esophageal varices.
Patients with cirrhosis have malfunctional liver alongside portal hypertension. The portal hypertension predisposes them to esophageal varices that can rupture and the malfunctional liver reduces the production of coagulation factors so any kind of bleed will be amplified with an inability to clot.
Achalasia
A = without, chalasia = relaxation
Disordered esophageal motility with inability to relax LES
Due to damaged ganglion cells in myenteric plexus
- dmg can be idiopathic or secondary to known insult (ie Chagas disease – trypanosome infection)
2 factors associated with achalasia
- inability to relax the LES
- dysfunctional esophageal motility
Achalasia - clinical features
3, 4 – Inability to relax the LES –> buildup of food at the LES = increased LES pressure –> expansion of the esophageal walls to accomodate the buildup == bird beak sign
- Dysphagia for solids and liquids – both solids and liquids require the peristalsis of the esophageal wall
- Putrid breathe - solids accumulates in the esophagus and will rot creating the bad breathe
- High LES pressure on esophageal manometry
- “bird-beak” sign on barium swallow
- Increased risk for esophageal squamous cell carcinoma
GERD
Gastroesophageal reflux disease
reflux of acid from the stomach due to reduced LES tone
Risk factors:
- alcohol
- tabacco
- obesity
- fat-rich diet
- caffeine
- hiatal hernia (hernia of the stomach into the esophagus which bypasses the LES. W/o the LES, the changes of reflux are significantly higher)
Clinical features
- heartburn (mimics cardiac chest pain)
- asthma (adult-onset) and cough
- damage to enamel of teeth
- ulceration with stricture and Barrett esophagus are late complications
Normal cellular lining of the esophagus
Non-keratinizing squamous epithelium
What does the lining of the esophagus change into due to GERD?
Non-ciliated columnar cells with goblet cells
GERD risk factors
- alcohol
- tabacco
- obesity
- fat-rich diet
- caffeine
- hiatal hernia (hernia of the stomach into the esophagus which bypasses the LES. W/o the LES, the changes of reflux are significantly higher)
Sliding hiatal hernia
hernia of the stomach into the esophagus which bypasses the LES.
W/o the LES, the changes of reflux are significantly higher –> increased risk for GERD
Paraesophageal hernia
hernia of the stomach through the diaphram alongside the esophagus.
Distinguished by having bowel sounds in the lower lung fields.
Doesn’t necessarily result in GERD.
GERD - clinical features
All having to do with shooting acid up the esophagus
- heartburn (mimics cardiac chest pain)
- asthma (adult-onset) and cough
- acid reaching the airway and causing adult-onset asthma
- damage to enamel of teeth – acid reaching the teeth
- ulceration with stricture and Barrett esophagus are late complications
- too much acid == dmg to the mucosa such that it ulcerates (ulceration is the complete knockout of the mucosa) –> if you knockout the mucosa, you also knockout the stem cells –> healing of the ulcers will be via fibrosis == stricture
Barrett esophagus
Most commonly associated with GERD
Metaplasia from a non-keratinizing squamous epithelium (NKSE) to a non-ciliated columnar epithelium with goblet cells in the lower 1/3 of the esophagus
- this is a response of the stem cells to stress
- b/c it is a metaplasia, it can progress to dysplasia and then henceforth to adenocarcinoma
Esophageal carcinoma
Adenocarcinoma - malignant proliferation of glands
- normally do not have glands in the esophagus. Requires the metaplasia associated with Barrett’s esophagus that progresses into the adenocarcinoma.
- This metaplasia only occurs in the lower 1/3 of the esophagus
- most common type of esophageal carcinoma in the west
Squamous cell carcinoma
- most common esophageal cancer worldwide
- usually arises in upper or middle third of the esophagus
- Risk factors: anything that causes irritation to the esophagus
- alcohol and tobacco
- very hot tea (southern china and iran)
- achalasia (rotting of the food that builds up irritates the mucosa)
- esophageal web (ie plummer-vinson syndrome) – also via the rotting of food that gets lodged
- esophageal injury (ie lye ingestion)
Esophageal squamous cell carcinoma - risk factors
anything that causes irritation to the esophagus
- alcohol and tobacco
- very hot tea (southern china and iran)
- achalasia (rotting of the food that builds up irritates the mucosa)
- esophageal web (ie plummer-vinson syndrome) – also via the rotting of food that gets lodged
- esophageal injury (ie lye ingestion)
Why is there a high rate of incidence of esophageal carcinoma in southern china and iran? What type of cancer is it?
Squamous cell carcinoma.
Due to their habits of drinking hot tea. Hot tea irritates the esophagus and increases the risk of carcinoma
Esophageal carcinoma - presentation
Presents late
- Progressive dysphagia (starts as a dysphagia for solids and progresses to dysphagia for solids + liquids as the tumor gets bigger)
- weight loss
- pain
- hematemesis (as the cancer grows, it will expand the mucosa which can result in bleeding and pain)
- squamous cell carcinoma may additionally present with hoarse voice (invasion into the recurrent laryngeal nerve) and cough (invasion into trachea)
Esophageal squamous cell carcinoma - additional symptoms
Located in the upper 2/3 of the eosphagus (typically).
may additionally present with hoarse voice (invasion into the recurrent laryngeal nerve) and cough (invasion into trachea)
Regional lymph node spreading of esophageal carcinoma
Upper 1/3 – cervical nodes
Middle 1/3 – mediastinal or tracheobronchial nodes
Lower 1/3 – celiac and gastric nodes
If an esophageal carcinoma arises in the upper 1/3 of the esophagus, which lymph node(s) will the cancer likely spread to?
Cervical nodes
If an esophageal carcinoma arises in the middle 1/3 of the esophagus, which lymph node(s) will the cancer likely spread to?
mediastinal or tracheobronchial nodes
If an esophageal carcinoma arises in the lower 1/3 of the esophagus, which lymph node(s) will the cancer likely spread to?
celiac and gastric nodes
Neural tube defects - cause and association
Arise from incomplete closure of neural tube
Associated with low folate levels prior to conception
Dandy-Walker Malformation
Congenital failure of the cerebellar vermis to develop
Presents as a massively dilated 4th ventricle with an absent cerebellum; often accompanied by hydrocephalus
How are neural tube defects detected?
Elevated AFP in amniotic fluid and maternal blood
What do the neural crest cells go on to develop into?
PNS
What do the wall of the neural tube cells go on to develop into?
CNS
What does the lumen of the neural tube go on to develop into?
Ventricles and the spinal cord canal
Anencephaly
Failure of closure at the cranial aspect of the neural tube ==> anencephaly
Absence of skull and brain
“Frog-like” appearance of the fetus
Results in maternal polyhydramnios (increase in AF)
- lack of brain ==> lack of CNS control over swallowing ==> no swallowing of AF –> increased AF
maternal polyhydramnios - how does is come about in anencephaly?
lack of brain ==> lack of CNS control over swallowing ==> no swallowing of AF –> increased AF
Spina bifida
Failure of closure at the caudal end of the neural tube
Failure of posterior vertebral arch to close
- Spina bifida occulta (mild version) – leads to a dimple or patch of hair overlying the vertebral defect
- Spina bifida (severe version) – leads to meningocele (only meninges) or menignomyeleocele (meninges + spinal cord)
Spina bifida - mild vs severe?
- Spina bifida occulta (mild version) – leads to a dimple or patch of hair overlying the vertebral defect
- Spina bifida (severe version) – leads to meningocele (only meninges) or menignomyeleocele (meninges + spinal cord)
Spina bifida - severe form – what are the 2 ways it can present?
Meninges protruding out or meninges & spinal cord protruding
meningocele (only meninges herniates) or menignomyeleocele (meninges + spinal cord herniation)
Cerebral aqueduct stenosis
Congenital stenosis of the channel that drains CSF from the 3rd to 4th ventricles
Leads to accumulation of CSF in the ventricles
Presents with enlarging head circumference
What structure produces CSF?
Choroid plexus
Flow of CSF in the brain
choroid plexus –> lateral ventricle –> 3rd ventricle (via foramen of monroe) –> 4th ventricle (via the cerebral aqueduct)
What structure lies between the lateral ventricle and the 3rd ventricle?
foramen of monroe
What structures lies between the 3rd and 4th ventricle?
Cerebral aqueduct
cerebral aqueduct stenosis - presentation
Since there is an accumulation of CSF in the ventricles –> pts typically present with enlarging head circumference
Dandy-Walker Malformation
Congenital failure of the cerebellar vermis to develop
Presents as a massively dilated 4th ventricle with an absent cerebellum; often accompanied by hydrocephalus
What often accompanies a Dandy-Walker malformation?
hydrocephalus - considering you have a massively dilated 4th ventricle, one would assume they would have a buildup of fluid in the brain (definition of hydrocephalus)
Arnold-Chiari Malformation
Congenital extension of cerebellar tonsils through foramen magnum –> increased pressure which may obstruct CSF flow –> possible hydrocephalus
May occur in association with meningomyelocele and syringomyelia (Syrinx = fluid filled cavity)
Syrinx
fluid filled cavity
A syrinx is a fluid-filled cavity within the spinal cord (syringomyelia) or brain stem (syringobulbia)
meningocele
protrusion of meninges
meningomyelocele
protrusion of meninges and spinal cord
Syringomyelia
- cystic degeneration of the spinal cord
- arises with trauma or in association with a type 1 Arnold-Chiari malformation
- usually occurs at C8-T1
- presents as sensory loss of pain and temperature with sparing of fine touch and position sense in upper extremities – due to involvement of the anterior white commissure of the spinothalamic tract with sparing of the dorsal column
- Syrinx expansion results in involvement of other spinal tracts leading to
- muscle atrophy and weakness w/ impaired reflexes (dmg to LMNs of the anterior horn)
- Horner syndrome - ptosis, miosis and anhidrosis (disruption of the lateral horn of the hypothalamospinal tract)
Syringomyelia - which sections of spine does it normally present in?
C8 to T1
presents as sensory loss of pain and temperature with sparing of fine touch and position sense in upper extremities – due to involvement of the anterior white commissure of the spinothalamic tract with sparing of the dorsal column
Syringomyelia - what happens when the syrinx expands?
- muscle atrophy and weakness w/ impaired reflexes (dmg to LMNs of the anterior horn)
- Horner syndrome - ptosis, miosis and anhidrosis (disruption of the lateral horn of the hypothalamospinal tract)
Horner Syndrome
Triad of ptosis (droopy eyelid), miosis (constricted pupil), and anhidrosis (decreased sweating)
Results from an interruption of sympathetic nerve supply to the eye
Poliomyelitis
Damage to the anterior motor horn due to poliovirus infection
Presents with LMN signs – flaccid paralysis w/ muscle atrophy, fasciculations, weakness with decreased muscle tone, impaired reflexes, and negative Babinski sign (downgoing toes)
Poliomyelitis - what is it due to?
poliovirus infection
poliomyelitis - presentation
Presents with LMN signs – flaccid paralysis w/ muscle atrophy, fasciculations, weakness with decreased muscle tone, impaired reflexes, and negative Babinski sign (downgoing toes)
Lower motor neuron failure - signs
- Flaccid paralysis w/ muscle atrophy
- fasciculations - muscle undergoes this when it is dying
- weakness with decreased muscle tone
- impaired reflexes
- negative Babinski sign
Werdnig-Hoffman Disease
Inherited degeneration of the anterior motor horn
autosomal recessive
Presents as a “floppy baby” – death occurs within a few years after birth
ALS (Lou Gehrig’s Disease)
- amyotrophic lateral sclerlosis
- Degenerative disorder of upper AND lower motor neurons of the corticospinal tract
- Anterior motor horn degeneration –> LMN signs – flaccid paralysis w/ muscle atrophy, fasciculations, weakness w/ decreased muscle tone, impaired reflexes, and negative Babinski sign
- Lateral corticospinal tract degeneration leads to UMN signs – spastic paralysis with hyperreflexia, increased muscle tone, and positive Babinski sign.
Upper motor neuron failure - signs
- spastic paralysis with hyperreflexia
- increased muscle tone
- positive Babinski sign.
ALS - early signs
atrophy and weakness of hand
How to distinguish ALS from syringomyelia?
lack of sensory impairment in ALS
ALS - causes
Mostly sporadic
Some familial cases caused by SOD1 mutation (Zinc-copper superoxide dismutase mutation) –> leads to free radical injury in neurons
Friedreich ataxia
Degeneration disorder of the cerebellum and spinal cord
- degeneration of cerebellum –> ataxia
- degeneration of multiple spinal cord tracts –> loss of vibratory sense and proprioception, muscle weakness in lower extremities, and loss of deep tendon reflexes
Autosomal recessive – due to expansion of GAA trinucleotide repeat in the frataxin gene
- Frataxin is essential for mitochondrial iron regulation
- loss results in iron buildup with free radical damage
Presents in early childhood –> wheelchair bound within a few years
associated with hypertrophic cardiomyopathy
Friedreich ataxia - what trinucleotide repeat is it associated with? What gene does it involve?
GAA trinucleotide repeat in the frataxin gene
frataxin
- gene involved in Friedreich ataxia.
- Frataxin is essential for mitochondrial iron regulation
- Loss results in iron buildup –> increased hydroxide ions via increased fenton reactions –> free radical damage
Friedreich ataxia - genetics - how is it inherited?
Autosomal recessive
Friedreich ataxia - presentation
Presents in early childhood with muscle weakness –> wheelchair bound within a few years
Associated with hypertrophic cardiomyopathy
Meningitis
Inflammation of the leptomeninges
Pia and arachnoid together are termed leptomeninges
Leptomeninges
Term refers to both the pia and the arachnoid
Layers of the meninges
PAD
Outside
D - dura
A - arachnoid
P - pia
Brain
Diagnosis of meningitis
Spinal tap (samples CSF) - needle between L4 and L5 (level of the iliac crest)
This can be done b/c spinal cord ends at L2 but subarachnoid space and cauda equina continue to S2.
Bacterial meningitis CSF findings
increased neutrophils
decreased CSF glucose
Viral meningitis CSF findings
lymphocytes w/ normal CSF glucose
Fungal meningitis CSF findings
lymphocytes with decreased CSF glucose
Bacterial meningitis - complications
Death - herniation secondary to cerebral edema
hydrocephalus, hearing loss, and seizures – sequelae related to fibrosis
Cerebrovascular disease
neurologic deficit due to cerebrovascular compromise
85% due to ischemia
15% due to hemorrhage
Why are neurons very susceptible to ischemia?
Neurons are dependent on serum glucose as an essential energy source and will undergo necrosis within 3-5 minutes of ischemia (blockage of blood flow = blockage of both oxygen and blood that is carryng the vital glucose)
Global cerebral ischemia - major etiologies (causes)
- Low perfusion (ie atherosclerosis)
- Acute decrease in blood flow (ie cardiogenic shock)
- chronic hypoxia (ie anemia)
- repeated episodes of hypoglycemia (ie insulinoma)
Global cerebral ischemia- clinical features
Depends on the duration and magnitude of insults
Mild
- results in transient confusion w/ prompt recovery
Severe
- diffuse necrosis
- survival leads to a ‘vegetative state’
Moderate
- leads to infarcts in watershed areas (area lying between regions fed by the ACA and MCA) and damage to highly vulernable regions such as
- pyramidal neurons of cerebral cortex (layers 3, 5, and 6) –> laminar necrosis
- pyramidal neurons of hippocampus (temporal lobe) –> dmg to long term memory
- Purkinje layer of the cerebellum – responsible for integrating sensory perception w/ motor control
Ischemic stroke
Regional ischemia to the brain that results in focal neurologic deficits lasting >24
If symptoms lasts < 24 hours, event is termed transient ischemic attack (TIA)
subtypes of ischemic stroke
thrombotic – due to rupture of an atherosclerotic plaque
embolic – due to thromboemboli
lacunar – secondary to hyaline arteriolosclerosis, a complication of hypertension
Thrombotic stroke
Due to rupture of an atherosclerotic plaque
Atherosclerosis usually develops at branch points (ie bifurcation of internal carotid and MCA in the circle of willis)
Results in a pale infarct at the periphery of the cortex
Where does atherosclerosis typically develop?
Atherosclerosis usually develops at branch points (ie bifurcation of internal carotid and MCA in the circle of willis)
Embotic stroke
due to thromboemboli (most common source of emboli is left side of heart)
usually involves the MCA
results in a hemorrhagic infarct at the periphery of the cortex
Embotic stroke - most common source of emboli?
left side of heart – very intuitive – left side of heart pumps to systemic circulation (which includes the brain). the emboli must originate from left side. Right sided emboli will lodge in pulmonary circulation.
Lacunar stroke
Secondary to hyaline arteriolosclerosis, a complication of hypertension
Most commonly involves lenticulostriate vessels –> resulting in small cystic areas of infarction
- Involvement of internal capsule –> pure motor stroke
- involvement of the thalamus –> pure sensory stroke
Lacunar stroke - internal capsule involvment
results in a pure motor stroke
Lacunar stroke - involvement of thalamus
results in a pure sensory stroke
What type of necrosis is associated with ischemic stroke?
Liquefactive necrosis
Ischemic stroke - timeline
- Necrosis (24 hours)
- infiltration by neutrophils (days 1-3)
- microglial cells (days 4-7)
- gliosis (weeks 2-3)
intracerebral hemorrhage
- bleeding into brain parenchyma
- classically due to rupture of Charcot-Bouchard microaneurysms of the lenticulostriate vessels
- complication of hypertension (treatment of HTN reduces incidence by half)
- basal ganglia most common site
- Presents as severe headache, N&V, and eventual coma
Charcot-Bouchard microaneurysms
- aneurysms of the brain vasculature which occur in small blood vessels (less than 300micrometre diameter).
- Charcot–Bouchard aneurysms are most often located in the lenticulostriate vessels of the basal ganglia and are associated with chronic hypertension.
- Charcot–Bouchard aneurysms are a common cause of cerebral hemorrhage.
intracerebral hemorrhage - presentation
severe headache
N&V
eventual coma
subarachnoid hemorrhage
- bleeding into subarachnoid space
- presents as a sudden headache (“worst headache of my life”) with nuchal rigidity (inability to flex neck forward due to stiffness of neck muscles)
- Lumbar puncture shows xanthochromia (yellow hue due to bilirubin)
- Most frequently (85%) due to rupture of a berry aneurysm
- Other causes include AV malformations and an anticoagulated state
- most frequently located in the anterior circle of Willis at branch points of the anterior communicating artery
- associated with Marfan syndrome and autosomal ominant polycystic kidney disease
subarachnoid hemorrhage - presentation
presents as a sudden headache (“worst headache of my life”) with nuchal rigidity (inability to flex neck forward due to stiffness of neck muscles)
subarachnoid hemorrhage - distinct findings on lumbar puncture
xanthochromia (Yellow hue due to bilirubin)
subarachnoid hemorrhage - most common location
most frequently located in the anterior circle of Willis at branch points of the anterior communicating artery
subarachnoid hemorrhage - diseases associated
- Marfan syndrome
- autosomal dominant polycystic kidney disease
Berry aneurysms
Thin-walled saccular outpouchings that lack a media layer thus increasing the risk for rupture
Epidural hematoma
Collection of blood between the dura and the skull
Classically due to a fracture of the temporal bone w/ rupture of the middle meningeal artery –> bleeding separates the dura from the skull
- results in a lens-shaped lesion on CT
- lucid interval may preced neurologic signs
Herniation is a lethal complication
epidural hematoma - classic cause
Classically due to a fracture of the temporal bone w/ rupture of the middle meningeal artery –> bleeding separates the dura from the skull
results in a lens-shaped lesion on CT
lucid interval may preced neurologic signs
subdural hematoma
Collection of blood underneath the dura; blood covers the surface of the brain
Due to tearing of bridging veins that lie between the dura and arachnoid; usually arises w/ trauma
- crescent-shaped lesion on CT
- Presents w/ progressive neurologic signs
- increased rate of occurence in the elderly due to age-related cerebral atrophy (decrease size of brain increases the space that the bridging veins need to cross –> stretching –> increased chance of tearing)
Herniation is a lethal complication
Why does the chances of subdural hematoma’s increase in the elderly?
increased rate of occurence in the elderly due to age-related cerebral atrophy (decrease size of brain increases the space that the bridging veins need to cross –> stretching –> increased chance of tearing)
Herniation - types
- Tonsillar herniation – displacement of the cerebellar tonsils into the foramin magnum
- Subfalcine herniation – displacement of the cingulate gyrus under the falx cerebri
- Uncal herniation – displacement of the temporal lobe uncus under the tentorium cerebelli
Tonsillar herniation
displacement of the cerebellar tonsils into the foramin magnum
compression of the brain stem leads to cardiopulmonary arrest
Subfalcine herniation
displacement of the cingulate gyrus under the falx cerebri
compression of the anterior cerebral artery leads to infarction
Uncal herniation – displacement of the temporal lobe uncus under the tentorium cerebelli
Subfalcine herniation - biggest concern
compressin of the anterior cerebral artery that can lead to infarction
Uncal herniation
displacement of the temporal lobe uncus under the tentorium cerebelli
- Compression of CN3 (oculomotor) leads to eye moving “down and out” and a dilated pupil
- Compression of PCA –> infarction of occipital lobe (contralateral homonymous hemianopsia)
- Rupture of paramedia artery –> Duret (brainstem) hemorrhage)
3 main concerns associated with uncal herniations
- Compression of CN3 (oculomotor) leads to eye moving “down and out” and a dilated pupil
- Compression of PCA –> infarction of occipital lobe (contralateral homonymous hemianopsia)
- Rupture of paramedia artery –> Duret (brainstem) hemorrhage)
Cells responsible of myelination
Oligodendrocytes –> CNS
Schwann cells –> PNS
defining characteristic of demyelinating disorders
destruction of myelin or oligodendrocytes; axons are generally preserved
Leukodystrophies
Inherited mutations in enzymes necessary for production or maintenance of myelin
Examples:
- Metachromatic leukodystrophy
- Krabbe disease
- Adrenoleukodystrophy
Metachromatic leukodystrophy
deficiency of arylsulfatase (autosomal recessive)
- sulfatides cannot be degraded and accumulate in the lysosomes of oligodendrocytes (lysosomal storage disease)
Most common leukodystrophy
Most common leukodystrophy
Metachromatic leukodystrophy
deficiency of arylsulfatase (autosomal recessive)
- sulfatides cannot be degraded and accumulate in the lysosomes of oligodendrocytes (lysosomal storage disease)
arylsulfatase
responsible for degrading sulfatides
deficiency in this enzyme will result in storage of sulfatides accumulating in the lysosomes of oligodendrocytes (lysosomal storage disease) resulting in their dysfunction/death
Deficiency results in metachromatic leukodystrophy
Krabbe disease
deficiency of galactocerebrosidase (autosomal recessive)
- galactocerebroside accumulates in macrophages
Adrenoleukodystrophy
impaired addition of CoA to long-chain fatty acids (X-linked defect)
accumulation of fatty acids damages adrenal glands and white matter of the brain
Multiple Sclerosis (MS)
Autoimmune destruction of CNS myelin and oligodendrocytes
Most common chronic disease of young adults (20-30); more commonly seen in women
Associated iwth HLA-DR2
More commonly seen in regions away from the equator
Multiple Sclerosis (MS) - presentation
Relapsing neurologic deficits with periods of remission (multiple lesions in time and space). Clincial features include
- Blurred vision in one eye (optic nerve)
- vertigo and scanning speech mimicking alcohol intoxication (brainstem)
- internuclear ophthalmoplegia (medial longitudinal fasciculus)
- Hemiparesis or unilateral loss of sensation (cerebral white matter, usualy periventricular)
- lower extremity loss of sensation or weakness (spinal cord)
- bowel, bladder, and sexual dysfunction (ANS)
Multiple Sclerosis (MS) - diagnosis
Dx using MRI and lumbar puncture
- MRI reveals plaques (areas of white matter demyelination)
- lumbar puncture shows increased lymphocytes, increased immunoglobulins with oligoclonal IgG bands and myelin basic protein
Multiple Sclerosis (MS) - treatment
Long term – interferon beta slows proression of disease
Acute attacks treated w/ high-dose steroids
Subacute sclerosing panencephalitis
Progressive, debilitating encephalitis leading to death
Due to slowly progressing, persistent infection of the brain stem by measles virus
- infection occurs in infancy; neurologic signs arise years later (during childhood)
characterized by viral inclusions within neurons (gray matter) and oligodendrocytes (white matter)
What disease is associated with measles infection?
Subacute sclerosing panencephalitis
Infections occurs in infancy, neurologic signs arise years later
Progressive multifocal leukoencephalopathy
JC virus infection of oligodendrocytes (white matter)
- immunosuppression (ie AIDS or leukemia) leads to reactivation of the latent virus
presents with rapidly progressive neurologic signs (visual loss, weakness, dementia) leading to death
What disease is associated with JC virus?
Progressive multifocal leukoencephalopathy
- JC virus infection of oligodendrocytes (white matter)
- immunosuppression (ie AIDS or leukemia) leads to reactivation of the latent virus
- presents with rapidly progressive neurologic signs (visual loss, weakness, dementia) leading to death
Central Pontine Myelinolysis
Focal demyelination of the pons (anterior brain stem)
due to rapid intravenous correction of hyponatremia
- occurs in severely malnourished patients (ie alcoholics and patients with liver disease)
classically presents with acute bilateral paralysis (“locked in” syndrome)
Degeneration of brain cortex results in…?
dementia
Degeneration of brainstem and basal ganglia results in…?
movement disorders
Alzheimer Disease
Degenerative disease of cortex – most common cause of dementia
most cases (95%) are sporadic and seen in elderly
- risk increases with age (doubles every 5 years after the age of 60)
- E4 allele of apolipoprotein E (APOE) associated with increased risk. E2 associated with decreased
Most common cause of dementia
Alzheimer disease – degenerative disease of cortex
Alzheimer Disease - what gene is associated with increased risk
E4 allele for apolipoprotein E. E2 allele associated with decreased risk.
Alzheimer Disease - early onset seen in…
- Familial cases – associated with presenilin 1 and presenilin 2 mutations
- Down syndrome – commonly occurs by age 40
Alzheimer Disease - clinical features
- Slow-onset memory loss (begins with short-term memory loss and progresses to long-term memory loss)
- Progressive disorientation
- Loss of learned motor skills and language
- Changes in behavior and personality
- Patients become mute and bedridden; infection is a common cause of death
- focal neurologic deficits are not seen in early disease
Alzheimer Disease - morphologic features
- Cerebral atrophy with narrowing of the gyri, widening of the sulci and dilation of the ventricles
- neuritic plaques - extracellular core comprised of Aß amyloid with entangled neuritic processes
- Aß amyloid is derived from amyloid precursor protein (APP). APP normally undergoes alpha cleavage. Beta cleavage results in Aß amyloid
- neurofibrillary tangles - intracellular aggregates of fibers composed of hyperphosphorylated tau protein
- tau is a microtubule-associated protein
- loss of cholinergic neurons in the nucleus basalis of Meynert
Alzheimer Disease - diagnosis
made by clinical and pathological correation
- presumptive diagnosis is made clinical after excluding other causes
- confirmed by histology at autopsy (when possible)
Vascular dementia
Multifocal infarction and injury due to hypertension, atherosclerosis, or vasculitis
2nd most common cause of dementia
Pick Disease
Degenerative disease of the frontal and temporal cortex; spares the patietal and occipital lobes
characterized by round aggregates of tau protein (Pick bodies) in neurons of the cortex
Behavioral and language symptoms arise early; eventually progresses to dementia
Pick bodies
aggregates of tau protein
Parkinson disease
Degenerative loss of dopaminergic neurons in the substantia nigra of the basal ganglia
- nigrostriatal pathway of basal ganglia uses dopamine to initiate movement
Common disorder related to aging – seen in 2% of older adults
unknown etiology
Clinical features (TRAP)
- Tremor - pill rolling tremor at rest; disappears with movemet
- Rigidity - cogwheel rigidity in the extremeties
- Akinesia/bradykinesia - slowing of voluntary movement; expressionless face
- Postural instability and shuffling gait
Parkingson Disease - Clinical Features
“TRAP”
Tremor - pill rolling tremor at rest; disappears with movemet
Rigidity - cogwheel rigidity in the extremeties
Akinesia/bradykinesia - slowing of voluntary movement; expressionless face
Postural instability and shuffling gait
Parkinson disease - histology
- loss of pigmented neurons in substantia nigra
- round eosinophilic inclusions of α-synuclein (Lewy bodies) in affected neurons
Parkingson disease - late disease
Dementia
Early onset dementia is suggestive of Lewy body dementia, which is characterized by dementia, hallucinations and parkinsonian features
- histology reveals cortical Lewy bodies
Lewy bodies aka α-synuclein
characteristic in Parkinson disease
Loss of dopaminergic cells in the substantia nigra
Characteristic in Parkinson Disease
Huntington Disease
Degeneration of GABAergic neurons in the caudate nucleus of the basal ganglia
Autosomal dominant disorder (chromosome 4) characterized by expanded trinucleotide repeats (CAG) in the huntingtin gene
- Hunt 4 food (chromosome 4)
- food = Cats, Armadillos, Giraffes (CAG trinucleotide repeat)
Huntington Disease - presentation
chorea that can progress to dementia and depression
average age of presentation is 40 years
suicide is a common cause of death
Normal pressure hydrocephalus
Increased CSF resulting in dilated ventricles
can cause dementia in adults ; usually idiopathic
Presents as a triad - “wet, wobbly, and wacky”
- urinary incontinence
- gait instability
- dementia
Normal pressure hydrocephalus - presentaton
Presents as a triad - “wet, wobbly, and wacky”
- urinary incontinence
- gait instability
- dementia
Normal pressure hydrocephalus - treatment
lumbar puncture improves symptoms
treatment is ventriculoperitoneal shunting
Spongiform encephalopathy
degenerative disease due to prion protein
prion protein normally expressed in CNS neurons in an α-helical configuration (PrPc)
- disease arises w/ conversion to a ß-pleated conformation (PrPsc)
- conversion can be sporadic, inherited (familial forms of disease) or transmitted
Pathologic protein is not degradable and converts normal protein into the pathologic form –> vicious cycle resulting in damage to neurons and glial cells characterized by intracellular vacuoles (Spongy degeneration)
Spongiform encephalopathy - most common type
Creutzfeldt-Jakob disease
- usually sporadic; rarely can arise due to exposure to prion-infected human tissue (ie human growth hormone or corneal transplant)
- presents as rapidly progressive dementia associated with ataxia (cerebellar involvement) and startle myoclonus
- periodic sharp waves seen on EEG
- results in death, usually < 1 year
- Variant CJD - special form associated with exposure to bovine spongiform encephalopathy (“mad cow disease”)
Creutzfeldt-Jakob disease - presentation
- presents as rapidly progressive dementia associated with ataxia (cerebellar involvement) and startle myoclonus
- periodic sharp waves seen on EEG
- results in death, usually < 1 year
Variant CJD
special form of disease associated with exposure to bovine spongiform encephalopathy (hence the ‘mad cow disease’)
spongiform enceaphlopathy - inheritable form
Familial fatal insomnia
characterized by severe insomnia and an exaggerated startle response
CNS Tumors - statistics
50% metastatic
50% primary
CNS metastatic tumors
metastatic tumors characteristic present as multiple well-circumscribed lesion at the gray-white junction
lung, breast and kidney are common sources
CNS primary tumors
classified according to cell type of origin
In adults, primary tumors are usually supratentorial (area above the tentorium cerebelli)
- most common are glioblastoma multiforme, meningioma, and schwannoma
In children, primary tumors are usually infratentorial
- most common are pilocytic astrocytoma, ependymoma, and medulloblastoma
locally destructive, but rarely metastatize
CNS Primary tumors - most common tumors in adults?
Usually supratentorial (area above the tentorium cerebelli)
most common are glioblastoma multiforme, meningioma, and schwannoma
CNS Primary tumors - most common tumors in children?
Usually infratentorial
most common are pilocytic astrocytoma, ependymoma, and medulloblastoma
Glioblastoma multiforme (GBE)
- Malignant, high grade tumor of astrocytes
- most common primary malignant CNS tumor in adults
- usually arises in cerebral hemisphere; characteristicsally crosses the corpus callosum (‘butterfly lesion’)
- characterized by regions of necrosis surrounded by tumor cells (pseudopalisading) and endothelial cell proliferation
- tumor cells are GFAP positive (Glial fibrillary acidic protein - an intermediate filament encoded by astrocytes)
- poor prognosis
Glioblastoma multiforme (GBM)
usually arises in cerebral hemisphere; characteristicsally crosses the corpus callosum (‘butterfly lesion’)
Glioblastoma multiforme - IHC or IF staining
tumor cells are GFAP positive (Glial fibrillary acidic protein - an intermediate filament encoded by astrocytes)
Meningioma
Benign tumor of arachnoid cells
most common benign CNS tumor in adults
- more commonly seen in women; rare in children
may present as seizures; tumor compresses, but does not invade the cortex
imaging reveals a round mass attached to the dura
histology shows a whorled pattern; psammoma bodies may be present
Meningioma - histology
a whorled pattern
psammoma bodies (concentric lamellated calcified structures) may be present
Schwannoma
Benign tumor of Schwann cells
involves cranial or spinal nerves
- within the cranium, most frequently involves CN7 at the cerbellopontine angle (presents as loss of hearing and tinnitus)
tumor cells are S-100 positive
bilateral tumors seen in neurofibromatosis type 2
Schwannoma - histological staining
S-100 positive
Oligodendroglioma
Malignant tumor of oligodendrocytes
imaging reveals a calcified tumor in the white matter, usually involving tnt lobe; may present with seizures
‘Fried-egg’ appearance of cells on biopsy
Oligodendroglioma - Malignant tumor of oligodendrocytes
imaging reveals a calcified tumor in the white matter, usually involving tnt lobe; may present with seizures
‘Fried-egg’ appearance of cells on biopsy
Pilocystic astrocytoma
Benign tumor of astrocytes
most common CNS tumor in children; usually arises in cerebellum
imaging reveals a cystic lesion with a murale nodule
Biopsy showsn Rosenthal fibers (thick eosinophilic processes of astrocytes) and eosinophilic granular bodies; tumor cells are GFAP positive
GFAP positive staining via IHC
GFAP on astrocytes
Could be pilocytic astrocytoma or glioblastoma multiforme. Need additional info to diagnose
Rosenthal fibers
thick eosinophilic processes of astrocytes
associated with pilocystic astrocytoma
Medulloblastoma
Malignant tumor derived from granular cells of cerebellum (neuroectoderm)
usually arises in children
histology reveals small, round blue cells
- Homer-Wright rosettes may be present
poor prognosis - tumor grows rapidly and spreads via CSF
- metastasis to the cauda equina is termed ‘drop metastasis’
Ependymoma
Malignant tumor of ependymal cells – usually seen in children
most commonly arises in the 4th ventricle; may be present with hydrocephalus
Perivascular pseudorosettes are a characteristic finding on biopsy
Perivascular pseudorosettes
most often seen in ependymoma (can also see in medulloblastoma, PNET, central neurocytomas, and glioblastomas)
Craniopharyngioma
Tumor that arises from epithelial remnants of Rathke’s pouch
Presents as a supratentorial mass in a child or young adult
- may compress the optic chiasm leading bilateral hemianopsia
Calcifications are commonly seen on imaging (derived from ‘tooth-like’ tissue)
benign, but tends to recur after resection
