Neuropathy Flashcards
notes
mononeuropathy
multiplex - isolated , but more than one.
connective tissue disease - e.g sacrodosis
polyneuropathy - disease of mu;tiple periphearal nerves
tend t be bilateral , symmetrical , motor and sensory impact.
distal part loses function first - proximal part spared in early times , as progress damage spreads t proximal part
aeitolgy - is it linked to cancer etc , cause
radiculopathy - compression of nerve root
pain along nerve - weakness , sensory lost , dysfuntion of what the nerve innervates.
doral plus vebtral roye form spinal nerv.
motor neurone d - with cns - cortex to
amytrophic musclar atropy - upper , lower , brainstem motr neurones impacted — whole thing affected
PLS - Primary laterl SCLEROSIS - damage to brainstem neurones
Muscular dystrophy - motor neurones in spinal cord damage.
nerve damage
compression
damage to myelin - central & peripheral mylein are the same.
central neurones - less myelin vs peripheral
peripheral - whole series of shwann cells wrapping around peripheral nerve - thick covering - the outer layer has a cytoplasm which contains nuclues
central - oligodenendrocyte - many branches - single layer - cover given by OLigodendrocytes are sparse vs cshwann cells - so in the case of muscular sytropy - so impacts on central nervous system vs peripheral
classification
- Transient block - damage to myelin sheath ,
- Axonotmesis - damage to axon
- Neurootmesis - damage to axon , endoneurtum , perineuritum , epineuritum
( can be entire axon )
progressively it gets worse.
segemental demyeination - segments of myelin gone.
axonal demyelination - myelin sheath in tact , but problem with the axon itself
Wallerian degeneration -
axoplasmic flow - directly connected to cell body.
Nerve vs Neurone ?
Nerve - collection of neurones
Neurone - single neurone.
What is a Spinal nerve made out of ?
Structure
Ventral & Dorsal route join together to form spinal nerve.
Spinal nerve - part of peripheral NS.
Structure -
epineurium - sheath surrounding spinal nerve
Contains :
0 BV - Veins , Arteries
0 fascicle - clusters of bundles of neurone.
o each
fascicle
surrounded
by
perineurium
0 Neurones - contained in fascicle - either myelinated / unmyelinated
( endoneurium - surrounds this )
Parts of the neurone ?
0 Axon
0 Cell body - ( Soma) -( if this is damage - neurone cannot regenerate )
0 Dendrites
0 Terminal bulbs - (if this is damaged regeneration can occur. )
neurotransmitter released from here.
Why don’t most CNS fibres regenerate while PNS fibres can ?
0 Oligodendocytes which surround CNS fibres - inhibit regeneration ( shwann cells cover PNS fibres - so dont have this problem. Shwann cells actually assist in regeneration.)
0 Clean up is slow ( faster in PNS by macrophages)
0 environment not very optimal
Time is important - need to clean up damage - to allow the fibres that can regenerate to regenerate.
Classification of Nerve injury ?
Neuropraxia - myelin sheath damage - demyelination ( reversible conduction block )
0 can happen as a result of compression - axon ,endoneurium ( surrounds neurone intact ) but myelin sheath compressed .
e.g radial nerve compression. (wrist drop )
Axonotmesis - Demyelination + Axon loss
Axon and corresponding segment of myelin sheath loss - but endoneurium still intact so it can grow back.
( However , distal end - terminal bulb will undergo Wallerian degeneration )- commoly seen in crash inhries - fractures.
Neurotmesis - Demyelination , Axon loss + ( one or all of following - endoneurium , perineurium , epineurium damage )
IF DAMAGED
o endoneurium - can grow back / fair growth.
o perineurium - poor regrowth o epineurium - no growth
What is Wallerian degeneration ?
Damage to neurone interrupts connection to cell body - or damages cell body itself.
Part of axon is disconnected from the soma of neuron.
Disconnected portion degenerates & debris is cleared aided by glial cells.
CNS - causes
0 Tumour
0 Haemorrhage
0 head injury with shearing of fibres.
Types of Neuropathies ?
- Mononeuropathy
Mononeuropathy mutiplex
WHAT IS IT ?
CAUSES?
EXAMPLES
Mononeuropathies - damage to single peripheral nerve - sensory disturbances ( paranthesia , numbness , pain ) & weakness in one isolated area - supplied by the peripheral nerve.
CAUSES -
TRAUMA
- compression
- violent muscular activity / overextension of joint.
0 Compression —–>1. entrapment neuropathy - narrows passageways , nerve compressed e.g carpal tunnel syndrome.
- Compression - by tumour , cast , crutches , prolonged cramped postures —–> nerve compression syndrome - can cause paralysis.
- compression - by hemorrhage.
Compression can be : o transient (eg, caused by an activity) o fixed (eg, caused by a mass or anatomic abnormality).
Mononeuropathy multiplex / Mononeuritis Multiplex - damage to more than two isolated peripheral nerve .
o Sensory
disturbance
& weakness
in more than
2 isolated
areas -
corresponding
to peripheral
nerves.
CAUSES -
0 Connective tissue disorders
o polyarteritis nodosa,
o systemic lupus
erythematosus [SLE],
o other types of
vasculitis,
o Sjögren syndrome,
o rheumatoid arthritis
0 Sarcoidosis
0 Metabolic disorders
o diabetes,
o amyloidosis)
0 Infectious disorders (eg, Lyme disease, HIV infection, leprosy)
neuropathy - can either be sensry , motor or mixed.
o sensory - sensory disturbance - no weakness
o motor - weakness , no sensory D.
EX. of mononeuropathy
- Carpal tunnel syndrome - compression of median nerve.
Peroneal nerve palsy - compression of peroneal / fibular nerve against fibular neck.
(FOOTDROP)
Radial nerve palsy - compression of radial nerve against humerus.
(WRIST DROP - weakness of wrist & finger extensors ) - C7 radiculopathy - compression of C7 nerve root can cause similar symptoms
Ulnar nerve Palsy - compressed under medial condyle - cubital tunnel syndrome . ( SENSORY DEFICIT IN 5TH , 4TH DIGIT - WEAKEND / ATROPHIEDINTEROSSEUS MUSCLE OF HAND - found by metatarsal bones - help control fingers )
POLYNEUROPAHTY - extensive involvement of many nerves.
RADICULOPATHY - damage due to compression of spina nerve root. -radiating pain , weakness , sensory disturbance down dermatome.
Types of Neuropathies ?
0 Polyneuropathy
- Pattern of presentation
- causes
- things to consider
Extensive involvement of many nerves
Bilateral , symmetrical
CAUSES
0 damage to myelin sheath - demyelination - infectious causes
0 Damage to BV supplying nerve - causes nerve infarction
(Chronic arteriosclerotic ischemia, vasculitis, infections, hypercoagulable states )
0 Axon damage - can be symmetric or asymmetric
CAUSES
0 Nutritonal deficiences - B12 , B6 , E
0 Alcohol
0 Infection
Common
causes of symmetric
o Diabetes mellitus
o Chronic renal insufficiency
o Adverse effects of chemotherapy drugs (eg, vinca alkaloids)
THINGS TO CONSIDER
- can affect;
- sensory vs motor vs autonomic
- distribution of nerve injury - stocking glove syndrome
- nerve compartment affected - BV , Myelin or Axon]
- Pattern of inheritance - acquired vs congenital
- Cause
What is the Stocking glove syndrome ?
- Peripheral neuropathy.
Early stages of peripheral neuropathy -
sensory disturbances , muscle weakness - present distally at first ———————–> as disease progresses it moves proximally.
Types of Motor neurone disease ?
ALS - Amyotrophic Lateral Sclerosis
A - No
myo - muscle
Trophic - nourishment
( NO MUSCLE NOURISHMENT)
Neurogenerative disorder - damage to neurones - upper , lower & brainstem motorneurones ( ALL THREE )
- upper motor neurone - from brain to spinal cord
- lower motor - spinal cord / brainstem to sketetal m. - cause movement
DAMAGE HERE - IS MORE DISABLING WEAKNESS VS UPPER
Motor neurone stop working —-> neurone & muscle atrophies
progressive weakening of muscles
( start to lose hand and arm fuction ————-> difficulty walking, speaking —————–> difficulty breathing )
0 respiratory failure often cause of death - death usually 3 -5 yrs after diagnosis.
CAUSES
O Accumulation of dysfunctional proteins in neurones ( cell body )————————-> degeneration of neurone —— muscles die / atrophy due to no activation ——> impair function.
SYMPTOMS
Early
- asymmetricc hand weakness - dropping objects
- cramping of upper extremities
- dysarthria , dysphagia , dysphonia
Intermediate
- Atrophy ——————-> can’t ambulate ( walk without any assistance ) ————> wheelchair use.
Late
- respiratory weakness —–> dyspnea ——> respiratory infection
- recurrent cough , fever , chill , pneumonia
-
What is Progressive muscular atrophy ?
Subtype of Motor neurone disease
- only affects mainly Lower motor neurones - Slow , progressive damage .
no UMN signs (but most people will progress to showing these ) - prognosis better than ALS
SYMPTOMS
0 Weakness in hands ——————-> spreads into the lower body- can be severe.
0 muscle wasting (shrinking),
0 clumsy hand movements, twitches, and muscle cramps.
0 Torso muscles and breathing may be affected.
*Exposure to cold can worsen symptoms.
What is Primary Lateral Sclerosis ?
Affects only upper motor neurone ( supply hands , legs , face )
- neurodegenerative disease - progressive stiffness & weakness
SYMPTOMS
PAINLESS
- slow & difficult movement in hands , legs ,face
caused by spasticity - spasm
Legs first —————–> torso ————–> arms & hands ——-> muscles used for swallowing , speaking , chewing in face (less common).
difficult to walk , speak , fine hand coordination.
( distal to proximal )
Progresses more slowly than ALS.
if they develop LMN symptoms - diagnosis change to ALS.
What is Spinal musclar atrophy (SMA) ?
Affects LMN only.
most common cause of genetic infant mortalilty .
alpha LMN (responsible for innervation of voluntary skeletal muscle ) from spinal cord (anterior horn ) die prematurely - ( LMN can die or the whole LM nerve )
————> motor unit ( neurone / nerve + muscle fibre ) - stops working———————–>
IF ENOUGH MUSCLE FIBRES STOP WORKING
muscles weakness & flaccid -low tone paralysis ———————> Muscle atrophies ( lack of innervation ).
0 Fasciculations (Spontaneous involuntary muscle contraction ) — If a lot of muscle fibres affected
0 Diminished reflexes - deep tendon reflexes
CHRONIC SYMPTOMS
0 Scoliosis - poor support of spine
0 extremely thin limbs - muscle wasting.
Difference btw Upper motor neurone damage vs lower motor neurone ?
UMN - Increased muscle tone & spasticity (spasm )
LMN - Muscle weakness ——-> Flaccid / low - tone paralysis ——–> Muscle atrophy
Types of SMA - spinal musclar atrophy ?
TYPES
0 Type 1a - congenital - before birth
(MOST SEVERE)
- mothers might notice reduced fetal movement
0 Type 1b -infantile
Normal at birth ———————> low muscle tone (hypotonia ) few weeks after
(MOST COMMON ) - normally don’t survive after a few years.
o progressive weakness - worse proximally than distally - more obvious in legs
( ex - worse in the top part of leg than bottom or the top part of arm vs bottom ) - DIFFICULT TO SIT UP
- difficulty talking milk , swallowing their own secretions e.g saliva - weakness in muscle responsible for sucking , chewing , swallowing.
o can cause aspiration
0 Weakness in chest wall all , diaphragm
o cause breathing difficulties.
Type II
Type III
Type IV
(these are progressively milder - IV - mildest , with later age of onset.)
Why are there different subtypes of SMA ?
Subtype / severity determined by the number of copies of SMN 2.
- Reason
SMN proteins needed for development of alpha LMN.
Two types of SMN genes than encode for protein - SM1 & 2 .
SM1- 1 is more functional - produces more viable proteins .
SMN -2 - produces non - functional + functional proteins.
SMA patients - have no copy of SMN-1
( SO THE MORE COPIES OF SMN 2 - THE MORE FUNCTIONAL PROTEINS PRODUCED – the less severe SMA is )
Why does muscular dystrophy etc. affect either CNS or the PNS but not the other - only one ?
CNS - oligodendrocyte ( has many branches) - covers the neurone in single layer - so cover given is
sparse
vs PNS - Schwann cells wrap around axon multiple times ( thick covering )
so in the case of muscular dystrophy - demyelination will affect the CNS more
How does the structure of CNS & PNS neurones affect the impact of allergic recation etc. on their neurones ?
CNS & PNS neurones - 30 % Protein , 70 % lipid
CNS & PNS - have similar lipids
but proteins have important differences.
differences in proteins - means an allergic reaction in one against proteins - may not affect the other.
However , lipids similar - so will affect both.
What is Distal axonopathy ?
Degneration of axon / myelin begins at most distal part of axon - moves distally to proximally ———————— if it persists then axon dies back. – Stocking & glove .
CAUSES
Stagnation in Axoplasmic flow - so organelles & neurofillaments remain in degenerated part of axon ( cannot get back to cell body ) —- eventually axon becomes atrophic , breaks down.
0 Dysfunction in cell body means metabollic demands of neurone cant be met —–> distal part will be affected first (furthest away)
(THIS IS ALSO WHY LARGE AXONS - MOST SEVERELY AFFECTED - HIGHER METABOLLIC DEMAND )
0 Can be caused:
- drugs and industrial poisons :
o pesticides, o acrylamide, o organic phosphates, o industrial solvents
AXOPLASMIC TRANSPORT
- cellular process moves organelles e,g mitochondria , vesicles , proteins etc - from neuronal cell body to distal end via axoplasm (axon cytoplasm ).
Responsible for transport of molecules destined for degradation back to cell body to be degraded by lysozymes.
What is Segmental Demyelination ?
Breakdown & loss of myelin over a few segments
Axon remain intact & no change to neuronal body.
CONSQUENCES
0 Loss of saltatory conduction —————–> decreased conduction velocity and conduction block.
Deficts happen rapidly - but reversible as schwann cells make new mylein.
However , many cases - demyelination leads to axons & permanent deficits.
