Week 7

Question 1

neural centers responsible for movement control

Answer 1

1. Lower Motor Neurons:
   these neurons send their axons directly to skeletal muscles, causing them to contract and produce movement. Theyre found in spinal cord and teh brainstem
2. upper motor neurons: they control the activity of local circuit neurons and x-motor neurons (a type of lower motor neuron). found in the brain particularly in the motor cortex
3. local circuit neurons: these neurons are located in the spinal cord or in the motor nuclei of teh brainstem cranial nerves. they regulate teh activity of lower motor neurons. They play a crucial role in coordinating and refining motor commands from the upper motor neurons.
4. cerebellum and basal ganglia: these structures regulate the activity of upper motor neurons. The cerebellum is involved in the coordination, precision, and timing of movements. the basal ganglia involved in the intitation and regulation of voluntary movements. cerebellum and the basal ganglia do not have direct acceess to local circuit neurons or lower motor neurons but influence movement control indirectly through upper motor neurons. \

Summary
Lower Motor Neurons: Directly control muscle contractions.

Upper Motor Neurons: Control lower motor neurons and local circuit neurons.

Local Circuit Neurons: Coordinate motor commands within the spinal cord and brainstem.

Cerebellum and Basal Ganglia: Regulate upper motor neurons to ensure smooth and coordinated movements.

Question 2

what are teh 2 types of LMNs

Answer 2

1. x-motor neurons; these are the primary type of LMN that directly innervates the skeletal muscle fibres, causing muscle contraction
2. y-motor neurons: these neurons control the sensitivity of muscle spindles which are sensory receptors within the muscle that detect changes in muscle length.

Pathways:
- Spinal cord to msucles: axons from motor neurons located in the spinal cord travel to muscles via the ventral roots and peipheral nerves.

-brainstem to muscles: lower motor neurons in the brainstem are located in the motor nuclei, and their axons travel to muscles via cranial nerves.

Role in movement:
-final common path: all comands fro movement, whether reflexive or voluntary, are ultimately conveyed to muscles by lower motor neurons.

Question 3

Motor neuron - muscle relationship

Answer 3

1. Innervation by lower motor neurons: Each lower motor neuron innervates muscle fibres within a single muscle. This means that a single motor neuron controls multiple muscle fibres in one spefific muscle.
2. Branching of motor axons: individual motor axons branch within the muscle to form connections (synapses) with many muscle fibres. this branching allows one motor neuron to control multiple muscle fibres simultaneously.
3. single innervation of muscle fibers: eahc muscle fiber is innervated by only one single x-motor neuron. this ensures that each muscle fiber receives a clear and direct signal from its corresponding motor neuron.
4. action potential and muscle activation: when an action potential ( a nerve impulse) is generated in the axon of a motor neuron, it reaches the threshold and activates all the muscle fibers it innervates. this means that the signal from the motor neuron causes all the connected muscle fibers to contract simultaneously

Question 4

motor unit

Answer 4

a motor unit consists of a single motor neuron and all the skeletal muscle fibers it innervates.

1. Distribution of muscle fibers: the muscle fibers innervated by a single motor neuron are typically distributed over a relatively wide area within the muscle. this distribution ensures that the contractile force is spread evenly across the muscle.
2. Ensuring Effective Contraction:
   This wide distribution also ensures that local damage to motor neurons or their axons will not have a significant effect on overall muscle contraction. If some fibers are damaged, others can still function, maintaining muscle performance.
3. Activation and Force Production:
   Activation of one motor unit corresponds to the smallest amount of force the muscle can produce. When a motor neuron generates an action potential, it activates all the muscle fibers it innervates, causing them to contract simultaneously.

Question 5

Motor Neuron – Muscle Relationship

Answer 5

1. Motor Neuron Pool:
   All motor neurons that innervate a single muscle are collectively called the motor neuron pool for that muscle. These neurons are grouped together in one cluster within the spinal cord or brainstem.
2. Lateral Motor Neuron Pool: The motor neuron pools that innervate the distal parts of the extremities (such as fingers and toes) are located farthest from the midline of the spinal cord. This is referred to as the lateral motor neuron pool.

Question 6

upper motor neurons UMNS

Answer 6

1. Location: upper motor neurons have their cell bodies located in the cerebral cortex or brainstem.
2. Function in the cortex:
   -initiation of voluntary movements: upper motor neurons in the cortex are essential for initiating voluntary movements.

-complex movements: they are crucial for executing complex spatiotemporal sequences of skilled movements, such as playing as muscical instruments or typing.

3. Axonal connections:
   - Synapse with local circuit neurons: The axons of upper motor neurons primarily synapse with local circuit neurons in the spinal cord or brainstem.

-Direct Synapse with Lower Motor Neurons: In rare cases, particularly for distal muscles (like those in the fingers and toes), upper motor neurons can synapse directly with lower motor neurons.

4. function in the brainstem:
   - Regulation of Muscle Tone: Upper motor neurons in the brainstem help regulate muscle tone.

-Control of Posture and Balance: They are involved in controlling posture and balance in response to various sensory inputs, including vestibular (balance), auditory (hearing), visual (sight), and somatic (body) sensory inputs

Question 7

Spinal Reflex

Answer 7

A spinal reflex is an ivoluntary response to the activation of sensory receptor that is mediated through spinal pathwasy. this means that the response occurs without conscious thought and is processed at the level of spinal cord.

Question 8

Traditional View of Reflexes

Answer 8

Hard-Wired: Reflexes were once perceived as “hard-wired,” meaning that a given stimulus would always produce the same response. This view suggested that reflexes were fixed and unchangeable.

Question 9

Modern View of Reflexes

Answer 9

Modifiable: The current understanding is that even the simplest reflexes are highly modifiable. This means that the response to a stimulus can change based on various factors.

Reflex Modulation: Reflex responses are now seen as dependent on the context or task being performed. For example, the same stimulus might produce different reflex responses depending on the situation or the individual’s state.

Question 10

Reflexes and Voluntary Motor Commands

Answer 10

Reflexes are not isolated from voluntary motor commands. Instead, they are integrated with voluntary movements to produce coordinated and adaptive responses. This integration allows for more flexible and appropriate reactions to different stimuli

Question 11

Spinal reflex arc

Answer 11

a spina reflex arc is the neural pathway that mediates a reflex action. It involves the following components:

Receptor: Detects the stimulus (e.g., a stretch receptor in a muscle).

Sensory Neuron: Transmits the sensory information to the spinal cord.

Integration Center: Located in the spinal cord, where the sensory neuron synapses with a motor neuron or interneuron.

Motor Neuron: Carries the motor command from the spinal cord to the effector.

Effector: The muscle or gland that responds to the motor command (e.g., muscle contraction).

Question 12

Monosynaptic Reflex Pathway

Answer 12

A monosynaptic reflex involves a single synapse between a sensory neuron and a motor neuron.
Example: The patellar (knee-jerk) reflex.
Process:

A stretch receptor in the quadriceps muscle detects a stretch.

The sensory neuron transmits the signal to the spinal cord.

The sensory neuron directly synapses with a motor neuron.

The motor neuron sends a signal to the quadriceps muscle, causing it to contract.

Question 13

sensory systems controlling reflexes muscle spindles

Answer 13

muscle spindles: are sensory receptors within the muscle that detect changes in muscle length and the rate of change in length. they play crucial role in the regulation of muscle contraction and reflexes.

extrafusal muscle fibres are the true force producing fibers of the muscle. they are responsible for generating the force needed for muscle contraction and movement

intrafusal muscle fibres: These fibers are part of the sensory organ known as muscle spindles. They are not involved in producing force but are essential for sensing muscle stretch. Intrafusal fibers keep the sensory elements of the muscle spindle stretched, allowing them to maintain sensitivity to changes in muscle length, regardless of the overall muscle length. This ensures that the muscle spindle can detect even small changes in muscle stretch and provide feedback to the nervous system.

Question 14

sensory systems controlling reflexes muscle spindles

Answer 14

there is
1. muscle spindles
-extrafusal muscle fibers
-intrafusal muscle fibers

2. sensory endings
   -primary endings ( group Ia afferents): these show rapidly adapting responses to chnages in muscle length and provide information about the velocity of the movement

-secondary endings (group II afferents): these produce sustained responses to muscle length, providing information about the extent of muscle stretch

3. motor neurons
   - y-motor neurons: these neurons activate intrafusal muscle fibers and by changing their tension, significantly impact the sensitivity of muscle spindles

-x-motor neurons: these neurons activate extrafusal (force-producing) muscle fibers

Question 15

co-activation of x and y motor neurons

Answer 15

muscle spindles are sensory receptors that respond to muscle stretch. they play a crucial role in detecting changes in muscle length and providing feedback to the nervous system.

when a muscle contracts, it shortens rather than stretches. this could potentially reduce the sensitivity of muscle spindles to chnages in muscle length.

the co-activatio mechanism of x-motor and y- motor neurons: the x motor neurons activate extrafusal muscle fibers, which are the true force producing fibers of the muscle. when x motor neurons fire, they cause the muscle to contract. while y -motor neurons activate intrafusal muscle fibers within the muscle spindles by adjusting the tension of the intrafusal fibers, y-motor neurons ensure that the muscle spindles remain senistive to stretch even when the muscle is contracting.

the co-activation of x and y motor neurons ensures that muscle spindles can continue to provide accurate sensory feedback about muscle length and stretch during muscle contraction. this allows for precise control of muscle movements ad helps maintain muslce tone and posture.

Question 16

functions of spinal reflexes

Answer 16

1. rapid response to preturbations;
   spinal reflexes allow for very fast initiation of corrective responses following an unexpected perturbation. examples include: stretch flex which helps maintain muscle length and posture by contratcing the muscle in response to a stretch. another example includes cutaneous reflex which involved responses to stimuli on the skin, such as the withdrawal reflex. another exmaple is flexor withdrawal reflex which causes a limb to withdraw from a painful stimulus, like pulling your hand away from a hot object.
2. contribution to motor control and movement adjustments: the spinal reflexes take care of the details of movement execution, allowing higher control centers in the brain to focus on more complex tasks. they help adjust movements and maintain balance and posture without conscious effort.

Question 17

Reflexes modulation according to task

Answer 17

reflexes are not just simple, automatic responses; they can be highly organised and modulated based on the context and task being performed.

example of reflex modulation:
1. excitatory reflex response: when one arm experiences a perturbation (unexpected force or movement) i cna cuase an excitatory reflex response in the contralateral elbow extensor muscle. this happens when the contralateral limb is used to prevent the body from moving forward by grasping a table. the reflex helps stabilise teh body by activating the muscle needed to counteract the perturbation.

2. inhibitory reflex response: the smae perturbation cna produce an inhibitory response in the muscle when the contralateral hand is holding a filled cup. in this case, the reflex prevents the muscle from contratcing to avoid spilling the contents of the cup.

Question 18

Normal Function of Motor Neurons: Gain of Myotatic or Stretch Reflex

Answer 18

Stretch or Myotatic Reflex:
Definition: The stretch or myotatic reflex, also known as the “deep tendon,” “knee-jerk,” or “patellar” reflex, is a muscle contraction in response to muscle stretching. This reflex is mediated by muscle spindle afferents.
Monosynaptic Reflex: It is a monosynaptic reflex, meaning it involves a single synapse between a sensory neuron and a motor neuron. This reflex is usually accompanied by reciprocal inhibition of antagonist muscles, ensuring smooth and coordinated movement.

Biological Function:
Maintain Muscle Length: The primary function of the stretch reflex is to maintain the muscle at a desired length. When a muscle is stretched, the reflex causes it to contract, bringing it back to its original length.
Muscle Tone: Normally, muscles are always under some degree of stretch. This reflex circuit is responsible for maintaining a steady level of muscle tension, known as muscle tone

Gain of the Myotatic Reflex:
Definition: The gain of the myotatic reflex refers to the amount of muscle force generated in response to a given stretch of the muscle spindle. Higher gain means a stronger muscle contraction in response to the same amount of stretch.

Question 19

Normal function of motor neurons
Gain of myotatic or stretch reflex

Answer 19

The gain of stretch reflex depends on
* excitability of α-motor neurons
* sensitivity of muscle spindles regulated by
γ-motor neurons

The level of γ-motor neuron activity referred to as γ bias can be adjusted by upper motor neuron pathways as well by local circuitry.

Upper motor neurons are able to switch reflexes
off when not needed

Question 20

Proprioception
Golgi tendon organs (GTO)

Answer 20

Golgi tendon organs are formed by
branches of group Ib afferents
distributed among collagen fibres that
form tendons. They provide information
about muscle tension

GTOs are arranged in series with a
small number (10-20) of extrafusal
muscle fibres. Population of afferents
provide accurate sample of tension
which exists in a whole muscle.

Question 21

Golgi Tendon Organs: A Negative Feedback System to Regulate Muscle Tension

Answer 21

The Golgi tendon organ (GTO) circuit is a negative feedback system designed to regulate muscle tension. The GTO contacts Ib inhibitory interneurons in local circuits within the spinal cord.

Function:
-Regulation of Muscle Tension: The GTO circuit counteracts small changes in muscle tension by increasing or decreasing the inhibition of α-motor neurons. This helps maintain a steady level of muscle force.

-Counteracting Fatigue: The GTO control system helps maintain a steady level of force, counteracting effects that diminish muscle force, such as fatigue.

-Protective Role: At large forces, the GTO plays a protective role by preventing excessive muscle tension that could lead to injury.

Modulatory Inputs:
-Sources of Input: Ib inhibitory interneurons receive modulatory synaptic inputs from various sources, including upper motor neurons, joint receptors, muscle spindles, and cutaneous receptors. This allows the GTO circuit to integrate information from multiple sources to regulate muscle tension effectively.

Question 22

Diseases affecting motor system -
sites of pathology

Answer 22

1. primary muscle diseases (myopathies)
2. disease of the neuromuscular junction
3. peripheral neuropathies (axon and myelin)
4. motor neuron diseases (cell body)

Question 23

consequences of dimiished deescending control of spinal motor neurons

Answer 23

UMNS: UMNS provide excitatory input essential for the initiation of voluntary movements. the majority of inputs from UMNS that control spinal reflexs are inhibitory. this means they suppress reflexes when they are not needed, ensuring that reflex actions are appropritae and context-specific

Exaggerated Reflexes: when there is reduction in descending input from UMNS to spinal interneurons it results in an exaggerated and unrestricted flow of excitation reaching teh motor neurons. this cn alead to hyperactive reflexs beacuse the inhibitory contril is diminished. To compensate for the reduction in functional actviation of the spinal cord, the intrinsic excitability of motor neurons may increase. this means that motor neurons become more easily excitable, further ontributing to exaggerated reflex responses.

Question 24

Signs and Symptoms of Upper Motor Neuron (UMN) Dysfunction

Answer 24

Due to disinhibition of spinal reflex:
1. hyperreflexia: exaggerated reflexes due to teh loss of inhibitory control from the upper motor neurons.

2. spasticity: muscular hypertonicity with increased tendon reflexes.
3. rigifity; increased muscle tone leading to resistance to passive movement throughout the range of motion in both directions. Rigidity is not a typicla sign of UMN damage but rather results from dysregulation of UMN function originating from basal ganglia.
4. clasp-knife phenomenon: a manifestation of corticospinal spasticity where tehre is a sudden release of resistaance to passive flexion/extension, typically near the end of the range of joint movement.
5. clonus: Muscular spasm involving a series of brisk, repeated rhythmic, monophasic (unidirectional) contractions and relaxations of a group of muscles.
6. Myoclonus: Very rapid, shock-like contractions of a group of muscles, which are irregular in rhythm and amplitude.
7. contracture - a permanent structural shortening of a muscle or joint usually in
   response to prolonged hypertonic spasticity producing deformity
8. Babinski sign - reversal of cutaneous flexor reflex

Due to lost voluntary control:
1. loss of dexterity
2. slowness, and clumsiness

Question 25

Babinski sign in children

Answer 25

Infants will also show an extensor response. A baby's smaller toes will fan out and his big toe will dorsiflex slowly. This happens because the corticospinal pathways that run from the brain down the spinal cord are not fully myelinated at this age, so the reflex is not inhibited by the cerebral cortex. The extensor response disappears and gives way to the flexor response around 12 to 24 months of age.

Question 26

Signs and symptoms of LMN degeneration

Answer 26

-weakned reflexes -flaccidity -muscle cramps - fasciculation (a brief spontaneous contraction affecting a small number of muscle fibres, involuntary contraction of muscle fibres often seen as flickering of movement under the skin - muscle wasting

Question 27

Motor neuron epidemiology

Answer 27

each day in australia 2 people are diagnosed with MND highe rin males than females 90-95% sporadic 5-10% inherited average life expectancy is 27 months , 10% surviving longer than 10 years

Question 28

ALS amyotrophic lateral scleorosis ALS also known as Lou Gehrig's disease, clinical presentations

Answer 28

-typical LMN signs ( weakness, wasting, fasciculation) -typical UMN signs ( spasticity, hyperrflexia, babinski signs) -ALS has been traditionally viewed at a disease affecting the motor system usually with no compromise of cognitive abilities. typically not affected is -cerebellar function -sensory function -oculomotor function -autonomic nervous system -bowel and bladder sunction -sexual function and sexuality -cognitive ability

Question 29

ALS causes

Answer 29

-sporadic 90-95% -aetiology not known - it takes 9-15 month for someone to be diagnosed with ALS from the time they first begand to notice symptoms posisble environmental and lifetsyle risk factors syspected to have an effect: -exposure to hevay metals, solvents, agriculture chemicals -smoking in post menopausal women, but not among men -professinal high impact sports -military service

Question 30

Amyotrophic Lateral Sclerosis (ALS) and Chronic Traumatic Encephalopathy (CTE)

Answer 30

ALS affects both upper and lower motor neurons, leading to muscle weakness, atrophy, and spasticity. the degenration of UMN in the braina nd spinal cord results in the loss of voluntary muscle control CTE is a neurodegenrative disease ofetn resulting from repeated head injuries. it has been proposed as teh underlying reason or the correct diagnosis for some ALS cases observed among professional athletes and military veterans. CTE patients typically exhibit signs of dementia and behavioral probleems, which are not common in ALS. motor isgns in CTE more closely resemble parkinson's syndrome rather than ALS.

Question 31

Amyotrophic lateral sclerosis ALS causes

Answer 31

-genetic 5-10% Major gene mutations * SOD1 encodes synthesis of CuZn-superoxide dismutase (binds copper and zinc ions and destroys free superoxide radicals in the body). * C9ORF72 (Chromosome 9 open reading frame 72). The protein C9ORF72 is found in many regions of the brain, in the cytoplasm of neurons as well as in presynaptic terminals. It is the most common mutation identified that is associated with familial frontotemporal dementia (FTD) and/or ALS. * DCTN1 encodes dynactin. Its role is implied in both FTD and ALS. * TARDBP gene encoding TDP-43 protein. It is transcriptional repressor. Associated with several neurodegenerative disorders including frontotemporal lobar degeneration and ALS.

Question 32

ALS treatment

Answer 32

Amyotrophic Lateral Sclerosis (ALS) currently has no cure, so the primary goal of therapy is to improve the quality of life for patients. Here are some of the treatments available: 1. Riluzole: which block TTX-sensitive sodium channels and decreases glutamate release. it delays teh onset of vetilator-dependence in some patience and prolongs overall survival by 2-3 months 2. Edaravone (Radicava, Radicut, Xavron): it has antioxidant properties and is typically administered intravenously. effective within 2 years of dissease onset, 3. AMX0035 (Relyvrio, Albrioza): which is made up of TUDCA and PB, TUDCA increases the threshold for cell death by blocking key cell death pathways, while PB reduces stress on the endoplasmic reticulum.

Question 33

ALS symptomatic treatment

Answer 33

* Spasticity – Baclofen, Diazepam, stretching-exercise * Fasciculations – Lorazepam; decrease caffeine and nicotine intake * Respiratory insufficiency – noninvasive positive pressure ventilation * Dysphagia – percutaneous endoscopic gastrostomy (PEG) feeding tube * Sialorrhoea (hypersalivation) – anticholinergics, scopalamine * Pain – NSAIDs (Nonsteroidal Anti-inflammatory Drugs) * Depression – SSRIs (Selective Serotonin Reuptake Inhibitors), Tricyclic antidepressants

Question 34

Progressive bulbar palsy

Answer 34

Progressive bulbar palsy primarily affects motor neurons in brainstem. Symptoms include * Pharyngeal muscle weakness (involved with swallowing), weak jaw and facial muscles, progressive loss of speech, and tongue muscle atrophy. * Patients are at increased risk of choking and aspiration pneumonia, which is caused by the passage of liquids and food through the vocal folds and into the lower airways and lungs. * Limb weakness with both lower and upper motor neuron signs is often evident but less prominent. * Patients have outbursts of laughing or crying (emotional lability). * In about 25 percent of patients with ALS, early symptoms begin with bulbar involvement. * Life expectance between 6 months and 3 years from diagnosis.

Question 35

Pseudobulbar palsy

Answer 35

Pseudobulbar palsy shares many symptoms of progressive bulbar palsy, but is characterized by selective degeneration of upper motor neurons that transmit signals to the lower motor neurons in the brain stem. Symptoms include * Affected individuals have progressive loss of the ability to speak, chew, and swallow. * Progressive weakness in facial muscles. * Patients may develop a gravelly voice and an increased gag reflex. * The tongue may become immobile and unable to protrude from the mouth. * Individuals may have outbursts of laughing or crying.

Question 36

Primary lateral sclerosis (PLS)

Answer 36

Primary lateral sclerosis (PLS) affects the upper motor neurons of the arms, legs, and face. * The disorder often affects legs first, followed by the body trunk, arms and hands, and, finally, the bulbar muscles. * PLS is more common in men than in women. * The symptoms progress gradually over years, leading to progressive stiffness and clumsiness of the affected muscles. * The disorder is not fatal but may affect quality of life. * PLS is sometimes considered a variant of ALS, but the major difference is the sparing of lower motor neurons, the slow rate of disease progression, and normal lifespan.

Question 37

Lathyrism

Answer 37

Early symptoms include: * walking difficulties * unbearable cramps * leg weakness Pyramidal tract involvement is characterised by: * motor weakness * increased tone * a lurching scissoring gait caused by involvement of the thigh extensors and adductors, and gastrocnemius * Babainski’s sign * very brisk, exaggerated often clonic tendon reflexes * spastic paralysis develops, which becomes irreversible

Question 38

Progressive muscular atrophy (PMA) LMN (nonhereditary)

Answer 38

Progressive (spinal) muscular atrophy is marked by slow but progressive degeneration of only the lower motor neurons first described by Aran in 1850. Sometimes referred to as Adult Progressive Spinal Muscular Atrophy AranDuchenne type (not to be confused with Duchenne Muscular Dystrophy, which is completely different hereditary disease of skeletal muscle). Diagnosed by exclusion, mostly affects men, onset earlier than in other MNDs. About half of patients will live for more than 5 years from diagnosis. Weakness is typically seen first in the hands and then spreads into the lower body, where it can be severe. Other symptoms may include * muscle wasting, fasciculations, and muscle cramps, * loss of dexterity, * the trunk muscles and respiration may become affected, * exposure to cold can worsen symptoms, * the disease develops into ALS in many instances, * bulbar signs.

Question 39

Spinal muscular atrophy (SMA) LMN (hereditary)

Answer 39

Spinal muscular atrophy (SMA) is a hereditary disease affecting the lower motor neurons. It is an autosomal recessive disorder caused by defects in the gene SMN1, which makes a protein that is important for the survival of motor neurons – the SMN* protein. The muscle weakness is often more severe in the trunk and upper leg and arm muscles than in muscles of the hands and feet. SMA in children can be further classified into several variants, based on ages of onset, severity, and progression of symptoms, however, all of them are caused by defects in the SMN1 gene.

Question 40

Post-polio syndrome (PPS)

Answer 40

Poliomyelitis (Polio) is an acute contagious viral disease spreading through human faecal matter. It may cause severe damage of motor neurons, but strictly speaking is not a motor neuron disease due to its broad effects. Some forms of it may cause paralyses (temporarily or permanently). Post-polio syndrome (PPS) is a condition that can strike polio survivors decades after their recovery from poliomyelitis. After acute polio, the surviving motor neurons expand the amount of muscle that each controls. PPS and Post-Polio Muscular Atrophy (PPMA) are thought to occur when the surviving motor neurons are lost in the aging process or through injury or illness. It is suggested that PPS is latent weakness among muscles previously affected by poliomyelitis and not a new MND. Symptoms are similar to progressive muscular atrophy and appear most often among muscle groups affected by the initial disease. Doctors estimate that 25 to 50 percent of survivors of paralytic poliomyelitis usually develop PPS. PPS usually is not life threatening.

Question 41

what do we mean by disease of PNS

Answer 41

there is 1. Cell body: neuropathy disease like -anterior horn cell disorders: motor neuron diseases -sensory neuropathy: sensory ganglioopathy 2. peripheral process: peripheral neuropathy -axonopathies -myelinopathies

Question 42

Histopathologically 3 basic patterns

Answer 42

1. Wallerian degenration: reaction to axonal transection including myelin 2. distal axonal degenrations: degenration of axon and myelin develops firsts in the most distal parts of the axon, then the axon "dies back" 3. segmental demyelination: breakdown and loss of myelin over few segments, axon remains intact

Question 43

Distal axonal degeneration

Answer 43

* Causes characteristic distal "stocking-glove" sensory loss and muscle weakness. * Neurofilaments and organelles accumulate in the degenerating axon * Eventually the axon becomes atrophic and breaks down. ▪ Early unmyelinated axons ▪ Advanced disease myelinated axons * Histologically resembles Wallerian degeneration * Observed in many clinically important neuropathies ▪ Drugs, industrial poisons, solvents and metabolic disorders

Question 44

Segmental demyelination

Answer 44

* Causes conduction block or decreased conduction velocity * Deficit develop quickly but outcome is more favourable than axonal or Wallerian degeneration * Remyelinating is quicker than axonal regeneration * In many cases demyelination leads to axonal loss * Focal mononeuropathies and generalised neuropathies * Clinically – Acquired segmental demyelinating polyneuropathy – Hereditary polyneuropathy

Question 45

nerve conduction stduy

Answer 45

axonal= low demyelinating=slow

Question 46

clinically the 3 relevant questions are

Answer 46

1. where is the lesion? -what modalities are injured -are the fibers attached large/small; myelinated/unmyelinated -whether th einjury is axonal, demyelinating or both? 2. what is the cause? * Inflammatory and immune-mediated -Guillain Barre Syndrome -Chronic inflammatory demyelinating polyneuropathy * Vasculitis - Ischemic injury * Hereditary - Charoct-Marie-Tooth disease * Toxic -Drugs, environmental and industrial toxins * Autoimmune diseases - RA, Mixed connective tissue diseases * Infections - Leprosy, Diphtheria, Lyme disease, HIV, Herpes zoster * Malignancy-associated 3. cna it be treated?

Question 47

Axonopathies versus myelinopathies

Answer 47

Axonopathies ▪ Majority due to toxic, metabolic and endocrine causes ▪ Legs are more often affected ▪ NCS: reduced action potential ▪ EMG: signs of denervation (acute, chronic) and reinnervation Myelinopathies ▪ Often acquired immune mediated but some hereditary ▪ Hypertrophic nerves, global areflexia, weakness without wasting; >motor deficit ▪ NCS: slow conduction velocity and prolonged distal motor latency ▪ EMG: reduced recruitment without much denervation

Question 48

How do we then sort through the causes?

Answer 48

* Distribution: cna be asymmetry or symmetric Asymmetry: -Mononeuropathy -Mononeuritis multiplex – e.g. vasculitis Symmetric (glove/stocking) - Polyneuropathy * Duration: Ask if the disease is acute, subacute or chronic ▪ Most polyneuropathies are chronic ▪ Acute polyneuropathies: eg GBS, vasculitis ▪ Relapses and remissions: eg Intermittent toxin exposure * Deficits If predominant motor fibers think of: ▪ GBS ▪ Lead toxicity ▪ Charcot-Marie-Tooth disease If pure sensory/ severe proprioceptive deficit, think of sensory neuronopathy: ▪ Carcinoma (paraneoplastic) ▪ Vitamin B6 toxicity If autonomic nerves involved (small fiber) think of: ▪ Diabetes ▪ Amyloid ▪ Drugs like vincristine, ddI, ddC * Disease process * The vast majority are axonal * Demyelination a key finding because its causes are relatively few * If demyelination is uniform the cause is likely hereditary ▪ Charcot-Marie Tooth type I * If otherwise unremarkable chronic sensorimotor axonal polyneuropathy… exclude ▪ Alcohol, DM, Thyroid, Vit B12 deficiency, Monoclonal gammopathy * Developmental Clues: – Orthopedic deformities (feet, spine) – Long duration – Indolent progression – Few “positive” symptoms – Examine/question the family members! * Drugs: -Axonopathies: ▪ Cancer drugs (Vincristine) ▪ Antibiotics (Isoniazid) ▪ Cardiac medications (Amiodarone) -Myelinopathies: ▪ Environmental toxins ▪Arsenics ▪Lead ▪Glue sniffing

Question 49

clinical and laboratory investigations

Answer 49

* Special autonomic studies ▪ Cardiovascular autonomic reflexes * Heart rate response to deep breathing; * Heart rate and blood pressure in response to Valsalva manoeuvre ▪ Sudomotor function tests * Sympathetic skin responses * Quantitative sudomotor axon reflex test * Sweat testing * Electrodiagnostic studies * Laboratory investigations ▪ Nerve, muscle and/or skin biopsies ▪ Vitamin B12, FBC, ESR, Thyroid function, Blood chemistry, liver and renal functions ▪ Screen for DM ▪ Serum and protein electrophoresis with immunofixation ▪ Autoantibodies and testing for infections (HIV) ▪ Imaging ▪ Lumbar puncture and CSF investigation

Question 50

treatments

Answer 50

-treatment of underlying disease: * GB: IVIg * DM: control glycaemic state * HIV: anti-retroviral treatment -pain management : -supportive therapy : * Various physical therapies * Occupational therapy: orthosis, bracing, aids to ambulation, foot care

Answer 51

* What systems are involved? Motor, sensory, or autonomic * What is the distribution? Only distal versus proximal and distal Focal/asymmetrical versus symmetrical * What is the nature of sensory involvement? Temperature or burning or stabbing pain (eg small fibre) Vibration or proprioception (eg large fibres) * What is the temporal evolution? Acute (<4 weeks); subacute (4-8 weeks); Chronic (>8 weeks) * Is there any family history? * Are there any associated medical conditions? Cancer, diabetes, autoimmune disease, infections, medications, drugs, toxins * Is there any evidence of upper motor neuron involvement?