Neuro Pathology

Question 1

Diseases of Peripheral Nerves

Answer 1

Peripheral nerve injury

• Axonal Neuropathies —problems with axons
• Demyelinating Neuropathies —problems with myelin covering axons
• Neuronopathies — problems with neurons

Question 2

Types of Peripheral Neuropathies

Answer 2

Mononeuropathies

• Polyneuropathies — multiple nerves in a symmetric fashion
• Mononeuritis multiplex — several nerves in a haphazard fashion
• Polyradiculoneuropathies — affect nerve roots and peripheral nerves; Symptoms in proximal and distal parts of the body

Question 3

Neuronal Diseases of the Neuromuscular Junction

Answer 3

> Antibody mediated

• Myasthenia Gravis
• Lambert-Eaton Myasthenic Syndrome

> Congenital
Caused by toxins

Question 4

Diseases of Skeletal Muscle

Answer 4

Skeletal Muscle Atrophy
Neurogenic and myopathic changes
Inflammatory myopathies
Toxic myopathies
Inherited diseases of skeletal muscle — muscular dystrophies

Question 5

Peripheral Nerve Sheath Tumors

Answer 5

Schwannomas 
Neurofibromas
Malignant Peripheral Nerve Sheath Tumors
Neurofibromatosis Type 1 and Type 2
- Type 1 is most common

Question 6

Neuropathy with Systemic Autoimmune Diseases

Answer 6

Rheumatoid arthritis Sjögren’s
SLE
Distal sensory or sensorimotor polyneuropathies

Question 7

Problems in the CNS come from

Answer 7

Malformations
Injury
Trauma —brain trauma, spinal cord injury
Cerebrovascular disease —hypoxia, ischemia, and infarction
Hypertensive cerebrovascular disease — hemorrhage
Infections
Demyelinating Diseases
Neurodegenerative
Genetic, Metabolic
Toxic and Acquired Metabolic Diseases
Tumors

Question 8

MYASTHENIA GRAVIS

Answer 8

Chronic autoimmune disorder causing peripheral neuropathy

• Circulating antibodies against the nicotinic ACh receptor (specifically the muscle-specific receptor tyrosine kinase) — impair neuromuscular transmission

More common in females

 SYMPTOMS 
Muscle fatigability — not strong enough to support body
- Diplopia
- Dysarthria
- Dysphagia
- Limb weakness
- Shortness of breath
- Ptosis —can affect one or both eyes
- Pale skin to cyanotic 
- SOB 
-sleepiness/dizziness 
-lower BP 
-headache 

Diagnostic Tests
- Serum acetylcholine receptor antibody analysis

A drooping eyelid is the most frequent early sign of myasthenia gravis

Question 9

Botulism

Answer 9

Disease of neuromuscular junction caused by TOXIN

Clostridium botulinum — neurotoxin
o Blocks receptors, causing permanent paralysis in the whole body, including the
respiratory system

• Botox acts by blocking the release of acetylcholine receptors — temporary paralysis

Question 10

Diseases of Skeletal Muscle/Myopathies

Answer 10

Skeletal Muscle atrophy — many disorders

Loss of innervation

Neurogenic and Myopathic changes

Inflammatory

Toxic — recreational drugs, statins, chloroquine, and alcohol

Congenital

Myopathy is very common with use of statins

Question 11

NEUROFIBROMATOSIS Type 1

NF type 1

Answer 11

Common autosomal dominant disorder

• Peripheral Nerve Sheath Tumor
• Mutation gene on chromosome 17
• Associated nonneoplastic tumors
• Neurofibromas, gliomas, hamartomas
• Malignant tumors
• Cutaneous hyperpigmented macules**
• Brown red spots of the eye ( Lisch Nodules)**

Question 12

GUILLAIN-BARRE SYNDROME

Answer 12

Acute Inflammatory Demyelinating Polyneuropathy
- Inflammation of peripheral nerves
- Demyelination, damage to axons
o Lose myelin, which damages the axons
- Life threatening respiratory paralysis
- Ascending paralysis — loss of pain sensation
- Weakness
- Often preceded by a virus
o 2/3of cases are preceded by an acute influenza like illness
o Cytomegalovirus, Epstein Barr, Mycoplasma

Diagnostic Test: CSF reveals elevated protein count with normal cell count

TXT:

• Plasmapheresis (plasma exchange)
• High dosage immunoglobulin therapy
• Corticosteroids

Question 13

Infectious Neuropathies

Answer 13

Shingles
Leprosy
Diphtheria
Varicella-zoster

Question 14

Leprosy (Hansen Disease)

Answer 14

Mycobacterium leprae

• Infection
• Polyneuropathy
• Large traumatic ulcers

Question 15

Lyme Disease

Answer 15

Late stages

• Polyradioculoneuropathy
• Unilateral or bilateral facial nerve palsies

Question 16

HIV/AIDS

Answer 16

Peripheral neuropathy

• Poorly understood
• Immune deregulation
• Mononeuritis multiplex

Question 17

Diphtheria

Answer 17

peripheral nerve dysfunction, diphtheria exotoxin

Question 18

Diabetic Neuropathy

Answer 18

o most common cause or peripheral neuropathy

o Metabolic and secondary vascular changes

o Damage and loss of peripheral nerve fibers (neurons and Schwann cells)

o Ischemic damage of the nerves
- Without circulation, the nerves get damaged

o Major effect is on the small unmyelinated nerve fibers that modulate autonomic
function and thermal and pain perceptions

o Impact on wound healing and ulcerations

Question 19

Uremic neuropathy

Answer 19

Renal failure
o Muscle cramps, diminished deep tendon reflexes
o Axonal degeneration
o Regeneration and recovery are common after dialysis
- Patients in stage 3 or 4 may not be ready for dialysis

Question 20

Other Metabolic, Hormonal, and Nutritional Neuropathies

Answer 20

Thyroid dysfunction —hypothyroidism

Vit B12 deficiency = pernicious anemia, the only anemia with neurological symptoms
o Damage to long tracts in the spinal cord and peripheral nerves
o Neurological symptoms, peripheral neuropathy, and problems with gait

Question 21

Neuropathies Caused by Physical Forces

Answer 21

• Trauma
• Lacerations
• Compression

o Carpal Tunnel Syndrome — median nerve at the level of the wrist

Question 22

Inherited Peripheral Neuropathies

Answer 22

o Genetically diverse disorders
o Charcot- Marie-Tooth disease
o Hereditary Motor Neuropathies
o Hereditary sensory neuropathies
o Familial amyloidosis

Question 23

Shaken Baby Syndrome

Answer 23

Brain hitting the back and front of skull

• Babies are more fragile, and the shaking can create hemorrhage
• The brain hits against the bone, causing the internal hemorrhage

Question 24

Trauma and Neuronal Damage

Answer 24

Location and extension determine prognosis
- Blunt trauma — brain injury at the original point of contact and on the opposite side of
the brain
o Trauma occurs at one point, but affects two points in the brain
- Rapid displacement of the head and brain can tear axons, severe, irreversible neurologic
damage
- Traumatic tearing of blood vessels — epidural or subdural hematoma
- Skull fractures
- Parenchymal Injuries — concussion
- Direct Parenchymal Injury — contusions and lacerations
- Sudden impacts that result in violent posterior or lateral hyperextension of the neck
may avulse the pons from the medulla or the medulla from the cervical cord — instant
death

Question 25

Traumatic Vascular Injury

Answer 25

Direct trauma and disruption of the vessel wall, hemorrhage - Epidural (arterial) - Subdural (venous) - Subarachnoid - Intraparenchymal - Combination

Question 26

Brain Trauma Sequelae

Answer 26

Post-traumatic hydrocephalus Chronic traumatic encephalopathy — dementia that develops after repeated head trauma Post-traumatic epilepsy

Question 27

Guideline on antibiotic prophylaxis for dental patients at risk for infection

Answer 27

For valve replacement, valve repair, history of bacterial endocarditis, unrepaired cyanotic heart defects or repaired within 6 months, history of heart transplant with history of valvulopathy - NOT for hydrocephalus VA shunts!! o But may still need prophylaxis depending on the immune status

Question 28

Hydrocephalus

Answer 28

- CSF accumulation - Widening of brain ventricles - Pressure - Genetic abnormalities - Developmental disorders like spina bifida/neural tube defects - Intraventricular hemmorage - Meningitis, tumors, traumatic head injury TXT: surgery-shunt diverts the flow of CSF to another part of the body such as the abdominal cavity (VP), heart (VA), or around the lung where the CSF can drain and be absorbed

Question 29

Ischemic Stroke

Answer 29

syndrome, not a disease - It is caused by a transient or permanent critical reduction in cerebral blood flow due to arterial occlusion or stenosis - Identification of the underlying mechanisms and etiologies is important so that appropriate therapy can be initiated to decrease the risk of recurrent stroke

Question 30

Global Cerebral Ischemia

Answer 30

- Generalized reduction of cerebral perfusion - Cardiac arrest, shock, and severe hypotension - Severity depends on location and extent - Survival varies

Question 31

Focal Cerebral Ischemia

Answer 31

Localized area — arterial occlusion or hyporperfusion - Size, location, shape of the infarct, and extent of tissue damage - Major source of collateral flow is the circle of Willis

Question 32

Occlusive Vascular Disease

Answer 32

- Embolism — from a distant source o Atrial fibrillation, MI, valvular diseases o Atheromatous plaques — carotid arteries o Cardiac surgery o Emboli form other material — tumor, fat, air - In situ thrombosis o Commonly associated with atherosclerosis and plaque rupture o Hypertension and Diabetes - Inflammatory processes o Infectious vasculitis — syphilis and TB, immunosuppression, and opportunistic infection — CMV encephalitis

Question 33

STROKE definition

Answer 33

clinical designation that applies to Hypoxia, Ischemia, Infarction, Hypertensive Cerebrovascular disease, and Intracranial Hemorrhage Acute neurologic deficit caused by cerebrovascular etiology - Hemorrhagic stroke or ischemic stroke - In ischemic stroke, patients do not exhibit GI symptoms - Test — CT scan hemorrhage - Vascular rupture with bleeding - Bleeding extended in anticoagulated patients - Mortality is high

Question 34

risk factor most commonly associated with | lobar hemorrhages is...

Answer 34

Cerebral amyloid angiopathy (CAA)

Question 35

The most important effects of hypertension on the brain include:

Answer 35

o Lacunar infarcts o Slit hemorrhages o Hypertensive encephalopathy o Massive hypertensive intracerebral hemorrhage

Question 36

Demyelinating Diseases

Answer 36

Multiple Sclerosis Neuromyelitis Optica Acute Disseminated Encephalomyelitis Acute Hemorrhagic Encephalomyelitis

Question 37

Acquired v. Critical Role Demyelinating diseases

Answer 37

Acquired conditions — preferential damage to myelin with relative preservation of axons Critical role — myelin nerve conduction - Widespread and severe neurologic deficits

Question 38

Multiple Sclerosis

Answer 38

Autoimmune in which the immune system destroys myelin, resulting in slowing of conduction and exposure of axons which may lead to permanent loss of the axon and subsequent loss of nerve function Related to genetic predisposition - An environmental trigger than causes an immune attack - Thus get loss of myelin and nerve damage Clinical course - relapsing and remitting episodes Key diagnostic factors - Visual disturbance in one eye - Peculiar sensory phenomena Other diagnostic factors - Female, age 20-40 - foot dragging or slapping, - leg cramping - fatigue - urinary frequency - bowel dysfunction, - - spasticity/increased muscle tone - increased deep tendon reflexes - imbalance/incoordination-

Question 39

Orofacial Manifestations of MS

Answer 39

- Intermittent facial numbness - Facial palsy or spasm - Paroxysmal pain syndromes (neuropathic) o High-frequency episodes of shock-like or lancinating pain o Trigeminal neuralgia (1-5% of patients) - Mild dysarthria - Lhermitte sign - Monocular visual disturbances

Question 40

Neurodegenerative Diseases

Answer 40

- Alzheimer Disease - Parkinson Disease - Multiple System Atrophy - Huntington Disease - Spinocerebellar Disease — ataxias - Amyotrophic Lateral Sclerosis (ALS)

Question 41

Huntington Disease

Answer 41

Autosomal dominant - Progressive movement disorders and dementia - Degeneration of neurons - Hyperkinetic, dystonic movements, all parts of the body (chorea) - Progressive and fatal - Key diagnostic factors o Positive family history of Huntington disease, known expansion of the CAG repeat length at the N-terminal end of the huntingtin gene, impaired work or school performance, personality change, irritability and impulsivity, chorea, twitching or restlessness, loss of coordination, deficit in fine motor coordination, slowed rapid (saccadic) eye movement

Question 42

Amyotrophic Lateral Sclerosis (ALS)

Answer 42

Progressive disorder - Loss of upper motor neurons in the cerebral cortex and lower motor neurons in the spinal cord and brainstem - Toxin protein accumulation - Denervation of muscles — weakness - Slightly affects more men - Symptoms o Asymmetric weakness of the hands, difficulty in performing fine motor tasks o Cramping and spasticity of the arms and legs (extremities) o After — respiratory muscles  severe pulmonary infections o Abnormalities in swallowing and phonation

Question 43

Seizure classification

Answer 43

Partial — seizure activity starts in one area of the brain o Simple — retain awareness o Complex — altered awareness and behavior - Generalized — seizure involves whole brain and consciousness is affected o Tonic clonic — “grand mal” or convulsions o Absence — “petit mal” or staring fit o Atonic/tonic — “drop attack” o Myoclonic — sudden muscle jerks

Question 44

Neuronal Reaction to Injury

Answer 44

* Acute (e.g. trauma; lack of oxygen or glucose) * Chronic (e.g. degeneration; accumulation of products) Neuronal death occurs either by necrosis (unplanned) or apoptosis (programmed cell death)

Question 45

Acute neuronal injury

Answer 45

``` (“red neurons”) - Evident by 12-24 hrs after irreversible injury - Changes: • Neuronal body • Nucleus • Nucleolus • Nissl substance • Cytoplasm ```

Question 46

Chronic or Subacute neuronal injury

Answer 46

Subacute and chronic neuronal injury (“degeneration”) - Slow(er) process - Changes: • Cell loss (initially difficult to detect) • Often selective functional area • Cell could be apoptotic • Reactive gliosis (indicator of cell injury, regardless the etiology)

Question 47

Reactive gliosis

Answer 47

process that defends the body, but it’s also a good indicator of cell injury for us to look at - Doesn’t occur unless there’s injury - Occurs regardless of etiology Gliosis refers to the glia (astrocytes and oligodendrocytes, but NOT microglia) - Microglia are NOT glia! They come from somewhere else! - Not schwann cells either because we’re in the CNS