Week 8 Flashcards
Neuromuscular disease (31 cards)
Neuromuscular Disorders: Sites of Primary Injury
Neuromuscular disorder are a family of conidtions affecting motor system, causing muscle weakness and atrophy (loss of muscle tissue)
- Cell Bodies of Peripheral Nerves/ or u can say Motor neurons:
Example: Motor neuron diseases such as amyotrophic lateral sclerosis (ALS). - Peripheral nerves: conditions like Guillain Barre syndrome and diabetic neuropathy
- Neuromuscular Junction:
Example: Myasthenia gravis, an autoimmune disorder that affects the communication between nerves and muscles at the neuromuscular junction. - Skeletal Muscle:
Examples: Inflammatory myopathies and muscular dystrophies, which directly affect the muscle tissue
Motor System Injury:
Motor system injury:
- Muscle Atrophy: Injury anywhere from the motor neuron to the muscle typically results in muscle atrophy, which is the wasting away or reduction in muscle mass.
- Peripheral Nerve Disorders: These disorders can cause muscle atrophy and may also lead to distal sensory or autonomic function loss, such as in sensorimotor neuropathies.
Tendon reflexes:
1. Reduced Reflexes: Tendon reflexes are generally reduced in most peripheral nervous system (PNS) diseases.
- Exaggerated Reflexes: Reflexes may be exaggerated when corticospinal tracts are also involved.
Exceptions:
Hypertrophy/Pseudohypertrophy: In some neuromuscular disorders, hypertrophy (increase in muscle size) or pseudohypertrophy (appearance of increased muscle size due to fat and connective tissue) may occur instead of atrophy
Motor System Injury and Muscle Deficits
Cerebral CNS lesions:
- Contralateral Deficit: Lesions in the cerebral central nervous system (CNS), such as those caused by a stroke or brain tumor, typically result in deficits in multiple muscle groups on the opposite side (contralateral) of the body.
- Higher Cortical Functions: These lesions often affect higher cortical functions, leading to a range of neurological symptoms.
Cord CNS lesions:
- Localized Impact: Lesions in the spinal cord usually affect muscle groups at and below the level of the lesion, leading to localized deficits.
Neuromuscular Disorders:
Bilateral Deficits: -Neuromuscular disorders often produce bilateral deficits, meaning they affect both sides of the body. These deficits may be generalized but often predominate in certain muscle groups.
Motor System Injury and Muscle Deficits
Localized Peripheral Nerve Lesions:
-Ipsilateral Impact: These lesions affect focal muscle groups on the same side (ipsilateral) of the body. For example, brachial plexopathy impacts the muscles innervated by the brachial plexus.
Neuromuscular Disorders:
-Bilateral and Broadly Distributed Deficits: These disorders often produce deficits on both sides of the body (bilateral) and are broadly distributed. Examples include polyneuropathy and myopathy.
Symptoms:Dependence on Nerve Fiber Type and Severity of Damage: The symptoms experienced depend on the type of nerve fibers affected and the severity of the damage. For instance, motor nerve damage can lead to muscle weakness and atrophy, while sensory nerve damage can cause numbness and pain.
Amyotrophic Lateral Sclerosis (ALS)
ALS Overview:
ALS is a motor neuron disease that affects both lower motor neurons (LMNs) and upper motor neurons (UMNs).
It leads to the degeneration of corticospinal tracts, resulting in muscle weakness, atrophy, hyperreflexia (overreactive body response), and spasticity, includes repiratory failure
Key Features:
Death of LMNs and UMNs: This results in denervation (loss of nerve supply) and muscular atrophy.
Symptoms: Common symptoms include muscle weakness, fasciculations (muscle twitches), hyperreflexia (exaggerated reflexes), and spasticity (muscle stiffness).
Respiratory Compromise: ALS often leads to respiratory muscle weakness, increasing the risk of pulmonary infections, which can be fatal.
Genetics:
Sporadic vs Familial: Approximately 90% of ALS cases are sporadic, while 10% are familial.
Genetic Mutations: Common mutations associated with ALS include SOD1, C9orf72, TDP43, and FUS.
Association with Other Conditions:
Frontotemporal Lobar Degeneration (FTLD): ALS is sometimes associated with FTLD, which can lead to cognitive impairment.
Other Disorders Affecting Motor Neurons in the Spinal Cord and/or Brainstem
- Spinal Muscular Atrophies (SMAs):
Nature: Hereditary disorders.
Impact: These conditions lead to the degeneration of motor neurons in the spinal cord and brainstem, resulting in muscle atrophy and weakness.
- Poliomyelitis:
Nature: Acquired, infectious, viral disease.
Impact: Poliomyelitis affects motor neurons in the spinal cord and brainstem, leading to muscle atrophy and weakness. It is caused by the poliovirus.
Types of Peripheral Nerve Injury
- Axonal Injury:
Description: Direct injury to the axon.
Consequences: Axonal degeneration and secondary myelin loss.
Regeneration: Regeneration occurs through axonal regrowth and subsequent remyelination.
Outcome: This process leads to a decrease in axonal density.
Examaple: diabetic neuropathy
- Demyelinating Injury:
Description: Direct injury to Schwann cells or myelin, with relative sparing of the axon.
Outcome: This results in normal axonal density but affects the myelin sheath.
example: guillain -barre syndrome
- Mixed Injury:
Description: Involves both axonal and demyelinating components.
Frequency: Mixed injuries are frequent and can present a combination of the above characteristics.
symtoms: include muscle atrophy, sensory loss, and tendon reflex
Peripheral Neuropathies: Topographical Patterns
Polyneuropathies:
Symmetrical: Affect both sides of the body equally.
Distal Onset: Symptoms typically begin in the extremities, such as the hands and feet, and progress proximally.
“Stocking-and-Glove” Distribution: This pattern describes the areas affected, resembling the distribution of stockings and gloves.
Examples: Toxic or metabolic neuropathies, such as those caused by diabetes or exposure to toxins.
- Mononeuritis Multiplex:
Random Distribution: Affects multiple individual nerves in a random pattern.
Example: Vasculitis, an inflammation of blood vessels that can damage nerves.
3.Mononeuropathy:
Single Nerve: Affects a single nerve.
Example: Trauma, such as carpal tunnel syndrome, where a specific nerve is compressed or injured.
what are common causes of neurogenic muscle atrophy?
- acquired polyneuropathies ( e.g. diabietes, vitamin dediciency, alcohol, drugs)
- Hereditary polyneuropathies (e.g., Charcot-Marie-Tooth disease)
-Nerve damage (e.g., trauma, carpal tunnel syndrome)
-Spinal cord injury
-Poliomyelitis
-Amyotrophic lateral sclerosis (ALS)
-Guillain-Barré syndrome
Why is diabetic neuropathy significant and what are its features?
mechanism: hyperglycemia causes direct nerve injury and microvascular damage (ishcemia)
symptoms: stocking and glove sensory loss, motor weakness, and autonomic dysfunction
significance: most common cuase of peipheral neuropathy (axonal + demyelinating).
features: Sensory, motor, and autonomic manifestations due to direct neural injury and microangiopathy.
histology: mixed axonal and demyelinating damage.
Describe Guillain-Barré syndrome (GBS)
Immune-mediated peripheral neuropathy with demyelinating and axonal forms.
Triggered by infections, often presenting with ascending muscle weakness.
Risk of respiratory failure and involves lymphocyte/macrophage infiltration in nerves (polyradiculoneuritis)
it is charcaterised by ascending paralysis (from legs upward), risk of respiratory failure
histology: demyelination with inflammatory infiltrates.
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), what are its characteristics?
Chronic acquired inflammatory peripheral neuropathy.
Symmetrical sensorimotor symptoms lasting ≥ 2 months.
Immune-mediated, with a relapsing-remitting or progressive course.
Associated with immune disorders and features onion bulb formation from Schwann cell proliferation.
What are some causes of toxic and vasculitic neuropathy?
Toxic causes: Drugs like isoniazid (necessitates vitamin supplementation), alcohol (CNS and PNS toxin).
Vasculitic causes: Systemic vasculitides (e.g., mononeuritis multiplex).
what are the neurological impacts of leprosy?
Infectious disease caused by Mycobacterium leprae and M. lepromatosis.
Chronic infection leads to nerve damage and granulomatous reactions rich in T cells.
Tuberculoid variant presents with nerve-centered granulomas.
What is a traumatic neuroma, and how is it treated?
Non-neoplastic lesion from nerve injury.
Characterized by disorderly regeneration of nerve fibers and fibrosis.
Presents as a small, painful nodule; curative treatment is complete excision.
What are the features and risk factors of Morton’s neuroma?
painful condition in the ball of the foot with “pebble” sensation.
Caused by nerve entrapment or perineural fibrous thickening.
Risk factors include ill-fitting shoes, repetitive trauma, and foot deformities.
Describe the types and features of peripheral nerve tumors.
Generally refers to peripheral nerve sheath tumors, mostly benign but can become malignant.
Schwannomas: sporadic or hereditary (NF2).
Neurofibromas: sporadic or hereditary (NF1).
What are the clinical features and mechanisms of Myasthenia Gravis? how does it affect tehe neuromuscular junction?
Mechanism: Autoimmune disease with antibodies against ACh receptors, leading to impaired receptor binding and degradation.
Features: Ptosis (drooping eyelids), diplopia(double vision), generalized weakness, fluctuating symptoms, and fatigability.
histology: loss of AChR on muscle biopsy
therapies: anticholinesterase drugs,a nd immunosuppressants
What are some other disorders of the neuromuscular junction?
Lambert-Eaton syndrome: Autoantibodies destroy presynaptic calcium channels → impaired ACh release.
Tetanus: Clostridium tetani exotoxin → spastic paralysis.
Botulism: Clostridium botulinum toxin → flaccid paralysis.
Differentiate between slow-twitch and fast-twitch muscle fibers.
Slow-twitch: Found in postural muscles (e.g., back, soleus).
Fast-twitch: Found in muscles requiring rapid movement (e.g., extraocular muscles, triceps brachii).
Characteristics of Slow-Twitch Fibers
Location: Higher proportion in postural muscles (e.g., back muscles, soleus).
Capillary Density: High.
Energy Use: More ATP per contraction cycle.
Characteristics of Fast-Twitch Fiber
Location: Higher proportion in extraocular muscles, triceps brachii.
Capillary Density: Low.
Energy Use: Less ATP per contraction cycle.
Muscle Biopsy
Haematoxylin & Eosin Stain: Identifies normal and pathological fibers.
ATPase at pH 4.6 Stain:
Normal: Distinguishes fiber types (Type I dark, Type IIa lightest, Type IIb intermediate).
Abnormal: Fiber type grouping indicates reinnervation.
Features of Chronic Myopathy
Necrotic Fibers: Signs of cell death.
Regenerative Fibers: Indicative of repair.
Fibrosis and Fat Replacement: Sign of degeneration surpassing repair.
5. Example Stains: Haematoxylin & Eosin remain pivotal in histopathology.
