What are glial cells?
Refers to every neuronal cell besides neurons
What are the main patterns of neuronal injury?
- Acute injury –> red neurons
- Subacute/chronic injury –> degeneration, neuron loss/disappearance (Alzheimer’s disease)
- Axonal reaction –> cut close to neuron cell body
- Axonal spheroids –> ?
- Inculsions –> viral or degenerative
What is the structure & function of Oligodendrocytes?
Function: Produce myelin.
Structure: Contain darker chromatin than astrocytes and are smaller than astrocytes.
What is the structure & function of Ependymal cells?
Function: Make CSF
Structure: Line the ventricles (choroid plexus), have cilia for fluid movement and microvilli for absorption
When do Red Neurons occur?
- Acute injuries (infarction)
- Loss of blood flow
- Dying neurons
When do Cowdry Bodies occur?
Herpesvirus
When do Negri Bodies occur?
Rabies virus
When do Neurofibrillary Tangles occur?
Degenerative disease (Alzheimer’s disease)
When do Lewy Bodies occur?
Parkinson’s disease
What is the normal structure of astrocytes?
- Long star-like processes
- Open chromatin pattern
- Larger than oligodendrocytes
What is the function of astrocytes?
- React to injury
- Establish/maintain the blood brain barrier
- Provide structure for CNS
- Provide food (glycogen and lactate) for cells in CNS
- Can proliferate
Define Gliosis.
Proliferation of astrocytes.
(Equivalent to scar formation in the brain)
What is a Gemistocytic astrocyte?
Increased size and increased number of astrocytes as a result of injury.
What are the two types of inclusion bodies discussed in class?
Rosenthal fibers & Corpora amylacea
What are Rosenthal fibers?
Injurious processes that contain proteins, seen in many diseases (not very specific)
What is Corpora amylacea?
- Pearl like, lamellated, collections of glycosaminoglycans
- Part of the normal aging process, not pathological
What is the normal structure of microglia?
- Twisting cells that look squished or bent
- elongated long nuclei
What is the function of microglia?
- MACROPHAGES OF THE BRAIN!
- Proliferate
- Phagocytose intruders
- Form nodules around dead cells, bacteria, or foreign substances
When do ependymal cells acquire inclusions?
Cytomegalovirus (CMV)
What are neuronal storage disease?
Autosomal recessive enzyme deficiencies that result in accumulation of enzyme substrate (sphingolipids, mucopolysaccharides, or mucolipids) within neuronal lysosomes.
What do neuronal storage diseases lead to?
- Loss of cognitive function
- Possibly seizures
- Ballooned neurons
What enzymes are deficient in Neuronal Ceroid Lipofuscinoses?
Enzymes involved in protein modification/degratdation
What is the result of enzyme deficiency in Neuronal Ceroid Lipofuscinoses?
Lipofuscin accumulates within neurons —> leads to neuronal dysfunction
What are some symptoms of Neuronal Ceroid Lipofuscinoses?
- Blindness
- Mental and motor deterioration
- Seizures
When is the onset of Neuronal Ceroid Lipofuscinoses?
Ranges from Childhood to Adulthood
What enzyme is deficient in Tay-Sachs?
Hexosaminidase A
What is the result of enzyme deficiency in Tay-Sachs?
Accumulation of ganglioside in all tissues
What are the symptoms of Tay-Sachs?
Nervous system shows the most symptoms.
- Developmental delay
- “Cherry-red” spot in retina
- Paralysis
- Loss of neurologic function
- Death within several years
When is the onset of Tay-Sachs?
Usually begins in early Infancy
What are Leukodystrophies?
Mostly autosomal recessive diseases that affect white matter.
Characterized by myelin abnormalities/affecting oligodendrocytes that involve lysosomal or peroxismal enzymes.
What do Leukodystrophies lead to?
Deterioration of motor skills, spastiity, hypotonia, ataxia
What enzyme is deficient in Krabbe disease?
Galactosylceramidase enzyme
What is the result of enzyme deficiency in Krabbe disease?
- Accumulation of glactocerebroside that is converted to galactosylsphingosine –> which is TOXIC to oligodendrocytes.
- Loss of myelin and oligodendrocytes in the CNS and PNS.
What type of cells is characteristic of Krabbe disease?
“Globoid cells” = fat macrophages in the brain
(eat dead material and toxic oligodendrocytes)
What are the symptoms of Krabbe disease?
Rapidly progressive muscle weakness and stiffness
When is onset of Krabbe disease?
3-6 months
What are the clinical features of Thiamine Deficiency (Vit B1)?
- Chronic alcoholism
- Classic Triad: Confusion, Ophthalmoplefia, and Ataxia in Wernicke Encephalopathy
- Memory disturbances and confabulation in Korsakoff Syndrome
What are the histologic findings seen in Thiamine Deficiency (Vit B1)?
- Wernicke Encephalopathy: Hemorrhage and necrosis in mammillary bodies and walls of 3rd/4th ventricles
- Korsakoff Syndrome: Cystic spaces, hemosiderin-laden macrophages in mammillary bodies and ventricle walls with thalamic lesions
What are the two conditions associated with Thiamine Deficiency (Vit B1)?
- Wernicke Encephalopathy (acute & reversible)
- Korsakoff Syndrome (prolonged & mostly irreversible)
What are the clinical features of Cobalamin Deficiency (Vit B12)?
- Anemia
- Lower extremity numbness, ataxia, weakness
- Paraplegia
What are the histological features of Cobalamin Deficiency (Vit B12)?
- Myelin gets damaged –> Swells up!
- Swelling of myelin layers, vacuolization
- Subacute combined degeneration of spinal cord due to deficient myelin (ascending & descending tracts involved)
What are the clinical features of Carbon Monoxide Poisoning?
- Confusion
- Disorientation
- Delirium
- Pink discoloration of skin/tissues (usually on autopsy)
What are the histological features of Carbon Monoxide Poisoning?
- Demyelination of white matter tracts
- Particularly affects cortex (layers III/V), hippocampus, Purkinje cells
How does Carbon Monoxide cause injury?
Injury due to hypoxia!
-Higher affinity CO displaces O2 on hemoglobin
What are the clinical features of Methanol Toxicity?
- Blindness
- Suicide attempt
What are the histological features of Methanol Toxicity?
- Preferentially affects retina
- Degeneration of ganglion cells
How much Methanol can cause blindness?
10 mL
How much Methanol could potentially cause death?
30 mL - 100 mL
What are the clinical features of Ethanol Toxicity?
- Truncal ataxia
- Unsteady gait
- Nystagmus (uncoordinated eye movements)
- Trouble maintaining balance
What are the histological features of Ethanol Toxicity?
- Preferentially affects cerebellum
- Cerebellar atrophy -Loss of granule cells
- Loss of Purkinje cells
- Bergmann gliosis (proliferation of astrocytes (“scarring”) where purkinje cells should be)
What is the cause of Guillian-Barre Syndrome?
- Inflammatory Neuropathy
- acute inflammatory (immune-mediated) demyelinating polyradiculoneuropathy
What is the clinical course of Guillian-Barre Syndrome?
- 2/3rds of cases start with acute flu-like illness
- then rapid onset weakness, symmetric, with loss of deep tendon reflexes and some sensation
- progresses to acute ascending paralysis with immune-mediated demylination that resolves over time with remyelination
- Elevated CSF protein without lymphocytes -2-5% mortality due to respiratory paralysis, autonomic instability, cardiac arrest, complications of treatment
What are the histologic findings of Guillian-Barre Syndrome?
- Inflammation around venules/nerves
- Lymphocytes, macrophages, and plasma cells widely distributed thorughout the PNS
- Macrophages are right next to the myelin sheath –> unwrapping
- Most intense demyelination in spinal and cranial nerve motor roots and adjacent nerves
What is the cause of Leprosy (Hansen Disease)?
- Mycobacterium leprae that causes Infectious Polyneuropathy (slowly progressive infection of skin and nerves)
- Transmitted through respiratory droplet
- 95% of world’s pop’n is immune, but it is endemic in poor tropical countries
What is the clinical course of Leprosy (Hansen Disease)?
- Tuberculoid Leprosy: dry, localized, scaly, skin lesions with nerve degeneration (less severe anaesthesia, ulcers, contractures)
- Lepromatous Leprosy: more severe widespread lesions in the skin, nerves, eyes, mouth, hands, feet, and testes that can turn in to nodules and fluid-filled vesicles
What is the bodies response in Leprosy (Hansen Disease)?
- Tuberculoid Leprosy: nice T-CELL RESPONSE to the bug with granuloma formation by macrophages
- Lepromatous Leprasy: body makes FOAMY HISTIOCYTES that are formed by macrophages (no granuloma formation)
What are the histological findings in Leprosy (Hansen Disease)?
- Obligate intracellular bacterium that is Acid-fast
- Does not gram stain
- Cell wall is waxy, which enables immune evasion
What is the cause of Varicella-Zoster Virus Infection?
- Common viral infection of the PNS caused by Herpes Virus 3 alpha
- Remains dormant in the sensory ganglia of the spinal cord and brainstem
- Eventually reactivates causing a painful, vesicular, dermatomal rash called shingles
What are the histological findings in Varicella-Zoster Virus Infections?
-Neuronal destruction with MULTINUCLEATED GIANT CELLS
What is the cause of Charcot-Marie-Tooth Disease, demyelinating type?
-Hereditary neuropathy caused by repetitive demyelination and remyelination
What are the histological findings in Charcot-Marie-Tooth Disease, demyelinating type?
Onion bulb formation around peripheral nerves
What is the clinical course in Charcot-Marie-Tooth Disease, demyelinating type?
- Loss of sensation and motor function of skin/muscles that surround the feet and lower leg
- Pain sensation remains intact
- High arches, hammer toes, muscle atrophy
- Can appear in childhood or early adulthood
- Normal life span
What are the three main patterns of peripheral nerve disease in adult-onset diabetes mellitus?
- Symmetric sensory and motor neuropathy involving distal nerves
- Autonomic neuropathy (bladder incontinence)
- Aysmmetric neuropathy (one-sided sensory and motor neuropathy)
What are the common MONOneuropathies associated with malignancies?
- Brachial plexopathy from lung neoplasms
- Obturator palsy from pelvic neoplasms
- Cranial nerve palsies from brain tumors
What are the common POLYneuropathies associated with malignancies?
- Small cell lung cancer
- Plasma cell malignancies (Polyneuropathy can occur as a PARANEOPLASTIC effect and produce antibodies that attack nerves)
What type of skull fracture is most common?
Linear (straight crack)
When do frontal hits often occur?
Patient was unconscious prior to falling.
When do occipital hits often occur?
When patient remains conscious during fall.
What is a depressed skull fracture?
- bone displaced inward
- comminuted (in pieces)
- can damage brain
What is a diastatic skull fracture?
- fracture that spans or crosses a suture
- causes suture to widen
What age patient usually obtains a diastatic skull fracture?
Usually children
What is a basal skull fracture?
- fracture to base of the skull
- very forceful
What often occurs in basal skull fractures?
- Distant hematomas
- CSF drainage
- Battle sign (bruising behind ear)
What is the definition of a concussion?
Altered consciousness from head injury due to change in momentum of head (e.g. head hits rigid surface).
-unkown mechanism
What are common symptoms of concussion?
- Amnesia
- Confusion
- Headache
- Visual disturbances
- Nausea & Vomitting
- Dizziness
How are concussions graded?
Grade 1: no LOC, lasts <15 min
Grade 2: no LOC, lasts >15 min
Grade 3: LOC
What is the typical clinical setting for an epidural hematoma?
Hit in temple with baseball.
- may have luccid period, then LOC
- neurosurgical emergency
What is the typical clinical setting for an subdural hematoma?
Elderly patient falls, seems okay after.
Acute: develop progressive numbness hours after.
Chronic: develop symptoms months after.
What is the typical clinical setting for a subarachnoid hematoma?
Patient states “Worst headache I have ever had,” after sustaining head contusion.
-neurosurgical emergency (ruptured berry aneurysms)
What is the typical clinical setting for a diffuse axonal injury?
Angular acceleration/deceleration
- “Shaken Baby” syndrome
- Boxing