Lecture 11 Flashcards
(39 cards)
What are the two major functional elements of peripheral nerves, and how do they relate to conduction velocity and sensory modalities?
Functional elements: Axonal processes and their myelin sheaths (made by Schwann cells)
Axonal diameter and myelin thickness correlate with conduction velocity
These features help distinguish axon types responsible for different functions:
Light touch: Transmitted by thickly myelinated, large-diameter axons → Fast conduction
Temperature sensation: Transmitted by thin, unmyelinated axons → Slow conduction
What are the key differences between axonal and demyelinating peripheral neuropathies?
Axonal Neuropathies:
Caused by direct axon injury
Leads to distal axon degeneration
Associated with secondary myelin loss (a.k.a. Wallerian degeneration)
Demyelinating Neuropathies:
Damage to Schwann cells or myelin
Axons are relatively spared
Causes slowed nerve conduction velocity
Demyelination occurs at random individual internodes → called segmental demyelination
what is Guillain Barre syndrome
collection of clinical syndromes that manifests as an acute inflammatory polyradiculoneuropathy with weakness and diminished reflexes
- rare and severe disease, occurs after acute infectious procedure, usually it initially effects the peripheral NS, and we see paralysis in the lower body area that moves towards the upper limb and face, gradually the patient will loose all their reflexes and goes through complete body paralysis.
it is life threatening and needs timely treatment and supportive care.
chronic inflammatory demyelinating polyneuropathy (CIDP)
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a long-term autoimmune disorder that affects the peripheral nerves.
It involves chronic inflammation that damages the myelin sheath (the protective covering of nerves), leading to demyelination.
The exact cause is unknown, but it’s believed to be due to the immune system mistakenly attacking the myelin.
It develops gradually over at least 8 weeks (unlike Guillain-Barré syndrome, which is more rapid).
diabetic neuropathy
person w diabetes -> serve forms of nervous system damage
- impaired sensation or pain in the feet or hands, slowed digestion of food in the stomach.
classification of diabetic neuropathy
symmetric polyneuropathy
autonomic neuropahty
polyradiculopathy
mononeuropathy
what is myasthenia gravis
autoimmune disorder affecting the myoneural junction, weakness of the voluntary muscles.
- due to presence of antibodies to acetylcholine receptors at the neuromuscular junction
- impaired transmission of impulses across the myoneural junction
- voluntary muscle weakness
etiology and pathogenesis of Myasthenia graves
Normal muscle activation:
When a nerve impulse reaches the nerve ending, it releases a chemical called acetylcholine (ACh). ACh travels across the neuromuscular junction (the gap between the nerve and muscle) and binds to ACh receptors on the muscle. This activates the muscle and causes it to contract.
In Myasthenia Gravis (MG):
Chronic inflammation leads to structural changes in the neuromuscular junction that make nerve-to-muscle communication less effective. These changes include:
* Flattening of the junctional folds (which reduces surface area for receptors),
* Fewer ACh receptors (around 66% decrease),
* Wider gap between nerve and muscle,
* Disruption in the placement of ACh receptors and acetylcholinesterase (the enzyme that breaks down ACh).
All these changes weaken signal transmission and contribute to muscle weakness in MG.
symptoms
ocular symptoms
bulbar symptoms
weakness of jaw muscles
dysphonia
Lambert eaton myasthenic syndrome (LEMS)
disorde rof neuromuscular junction where antibodies are made against presynaptic voltage gated calcium channels
symptoms are muscle weakness fatigue and autonomic dysfunction
autoimmune disease - hard cases are associated with small cell lung cancer
IgG self reactive to calcium ion channels in presynaptic neuron
Miscellaneous Neuromuscular Junction Disorders
Congenital Myasthenic Syndromes (CMS):
A group of inherited (genetic) disorders.
Caused by mutations affecting proteins at the neuromuscular junction.
Problem areas:
Presynaptic (acetylcholine release),
Synaptic (ACh movement across the gap),
Postsynaptic (muscle response to ACh).
Symptoms may resemble myasthenia gravis or Lambert-Eaton syndrome.
Some types respond to acetylcholinesterase inhibitors (which increase ACh levels).
Infections Affecting Neuromuscular Transmission:
Certain bacteria release toxins that block nerve-muscle communication:
Clostridium tetani → causes tetanus.
Clostridium botulinum → causes botulism.
Both produce potent neurotoxins that impair muscle contraction.
Inherited Disorders of Skeletal Muscle
Types of Genetic Muscle Disorders:
Muscular Dystrophies:
Inherited.
Muscles weaken over time (progressive).
Patients usually appear normal at birth.
Congenital Muscular Dystrophies:
Early onset (starts in infancy).
Progressive muscle weakness.
Some also affect the central nervous system (CNS).
Congenital Myopathies:
Another group of inherited muscle diseases, usually not mentioned in detail here.
Dystrophinopathies: Duchenne and Becker Muscular Dystrophy
Caused by mutations in the dystrophin gene.
Most common type of muscular dystrophy.
Two main types:
Duchenne Muscular Dystrophy (DMD):
Severe and fatal.
Affects about 1 in 3500 male births.
Symptoms begin early and worsen rapidly.
Becker Muscular Dystrophy (BMD):
Milder and slower progression compared to DMD.
Duchenne Muscular Dystrophy (DMD) – Clinical Features
Early Symptoms:
Clumsiness
Can’t keep up with peers (due to muscle weakness)
Pattern of Weakness:
Starts in pelvic girdle
Then spreads to shoulder girdle
Key Physical Sign:
Pseudohypertrophy (enlarged calf muscles—not true muscle growth, but fat/fibrosis)
Cardiac Issues:
Heart muscle damage and fibrosis
Can cause heart failure and arrhythmias
May be fatal
Cognitive Problems:
No clear brain abnormalities
But cognitive impairment is sometimes seen
In some, may be as severe as mental retardation
Blood Test Findings:
High serum creatine kinase (CK) from birth
Levels stay high in childhood, then drop as muscle mass is lost
Cause of Death:
Respiratory failure
Pneumonia
Heart failure (cardiac decompensation)
Myotonic Dystrophy
Key Symptom:
Myotonia = Delayed muscle relaxation after contraction
Example: Trouble letting go after a handshake
Other Common Complaints:
Muscle stiffness
Weakness
Genetics:
Autosomal dominant inheritance
>95% of cases due to mutation in the DMPK gene
Genetic Mutation Details:
Caused by abnormal CTG repeat expansion
Normal: <30 repeats
Severe cases: Thousands of repeats
Acquired Skeletal Muscle Disorders
Polymyositis
Type: Autoimmune
Key Features:
↑ MHC class I expression on muscle fibers
Endomysial inflammation (inside muscle fascicles)
Infiltration by CD8+ T cells
Effect:
Causes muscle fiber damage (necrosis)
Followed by muscle regeneration
2. Dermatomyositis
**Most common inflammatory muscle disease in children
Adults: Often linked to paraneoplastic syndromes (cancer-related)
Cause: Autoimmune mechanism suspected
Note: Affects both skin and muscle
schwannomas
Schwannomas are benign, encapsulated tumors made of Schwann cells (classified as WHO Grade I). They grow eccentrically (off to the side) from the nerve they originate from.
They contain two types of tissue patterns:
* Antoni A areas:
* Densely packed cells arranged in bundles (fascicles)
* Show characteristic Verocay bodies (rows of aligned nuclei with acellular spaces in between)
* Antoni B areas:
* Loosely arranged, less dense cells
* Prone to cystic degeneration
Neurofibromatosis
Neurofibromatosis is a genetic disorder that causes tumors to grow on nerve tissue. These tumors can appear anywhere in the nervous system—including the brain, spinal cord, and peripheral nerves.
* It is usually diagnosed in childhood or early adulthood.
* Most tumors are benign, but some can become malignant (cancerous).
* Symptoms are often mild, but complications can include:
* Hearing loss
* Learning difficulties
* Heart and blood vessel problems
* Vision loss
* Severe pain
schwannomas symptoms
Acoustic schwannomas (also called vestibular schwannomas) grow on the nerve of the inner ear, which can lead to damage and irritation of the nerve fibers. This often causes ear-related symptoms like hearing loss, tinnitus (ringing), or balance issues.
If a schwannoma affects other nerves, symptoms will depend on which nerve is involved.
The intensity of symptoms can vary from person to person.
Peripheral Nerve Tumors
Malignant Peripheral Nerve Sheath Tumors (MPNST)
Type: Malignant tumor in adults
Origin:
From Schwann cells
May clearly arise from a peripheral nerve
Often Develop From:
Plexiform neurofibroma
Association with NF1 (Neurofibromatosis Type 1):
~50% of MPNST cases occur in NF1 patients
3–10% of all NF1 patients develop MPNST in their lifetime
2. Traumatic Neuroma
Type: Non-neoplastic (not a true tumor)
Cause: Previous nerve injury
Mechanism:
Nerve injury → axon transection
Triggers regeneration → axon sprouts and elongates
Leads to disorganized nerve growth at injury site
Cerebral Edema
Definition:
Buildup of excess fluid in the brain tissue (parenchyma)
Types (Often Occur Together):
- Vasogenic Edema
Cause: Breakdown of blood-brain barrier (BBB)
Fluid moves from blood vessels → brain extracellular space
Can be:
Localized (e.g., in inflammation or tumors)
Generalized
2. Cytotoxic Edema
Cause: Injury to neurons and glial cells
Leads to intracellular fluid buildup
Seen in:
Hypoxic-ischemic injury
Toxin exposure
Hydrocephalus
Hydrocephalus – Summary Notes
Definition:
Excess accumulation of CSF in the ventricular system of the brain.
Normal CSF Flow:
Made by choroid plexus (inside ventricles)
Circulates through ventricular system
Flows through foramina of Luschka and Magendie into the subarachnoid space
Absorbed by arachnoid granulations
Causes of Hydrocephalus:
Most common:
Impaired CSF flow or absorption
Rare:
Overproduction of CSF (e.g., choroid plexus tumors)
Effects:
If blockage is localized, only part of the ventricles enlarge (not all)
Brain Herniation
Cause:
Increased volume inside skull (tissue + fluid) → raised intracranial pressure (ICP)
Anatomy:
Skull has rigid partitions made of dura mater:
Falx cerebri
Tentorium cerebelli
What Happens:
Brain tissue pushes against or moves past these dural folds (called herniation)
Consequences:
Compression (“pinching”) of brain tissue and blood vessels
Leads to reduced blood flow → tissue infarction (damage)
Causes more swelling → worsens herniation cycle
Types of Brain Herniation
Subfalcine (Cingulate) Herniation
One side of the cerebral hemisphere expands unevenly
The cingulate gyrus is pushed under the falx cerebri (a dural fold)
Can compress the anterior cerebral artery (risk of stroke)
Transtentorial (Uncal) Herniation
The inner part of the temporal lobe (uncus) is pushed against the edge of the tentorium cerebelli
Can compress brain structures near the tentorium
Tonsillar Herniation
The cerebellar tonsils move down through the foramen magnum
Very dangerous because it compresses the brainstem
Can disrupt vital respiratory and cardiac centers in the medulla
Life-threatening
Cerebrovascular Diseases: Hypoxia, Ischemia, and Infarction
Brain’s Oxygen Dependence
Brain = only 2% of body weight but:
Gets 15% of resting cardiac output
Uses 20% of total body oxygen
Why? Brain can’t store oxygen or glucose, so it needs constant blood flow.
🩸 Cerebral Blood Flow: Autoregulation
The brain regulates its own blood flow to stay stable, even if systemic blood pressure or intracranial pressure changes.
Achieved through vascular resistance adjustment (like vasodilation or constriction).
🛑 Two Ways the Brain Can Be Deprived of Oxygen (Hypoxia):
- Functional Hypoxia
Oxygen is available in the blood, but the brain can’t use it properly
Cause Example
Low oxygen in the air High altitude
Blood can’t carry oxygen well Anemia, CO poisoning
Cells can’t use oxygen Cyanide poisoning - Ischemia
Blood (and thus oxygen) can’t reach brain tissue
Can be transient (e.g. TIA) or permanent (e.g. stroke)
