Diseases of peripheral nervous system. Myasthenic, myopatic

Diseases of peripheral nervous
system.
Myasthenic, myopatic, myotonic
syndrome.
M. Týblová, J. Böhm
Department of Neurology 1st Faculty of Medicine
Peripheral nervous system (PNS)
Motor neuron - root -plexus
– nerve – neuromuscular
junction
Characteristics of peripheral
paresis
• Flaccid muscle weakness (paresis or plegia)
according to innervation area
• Diminished (hyporeflexia) or extinct (areflexia)
proprioceptive reflexes
• Muscle atrophy, hypotrophy
• Reduced muscle tone (hypotonia)
• Fasciculations are present, but no pyramidal
irritative signs
• Also sensory disturbances may be present,
according to corresponding area (area nervorum,
radiculorum)
1. Anterior horns of spinal cord
• Lesion of the second motor neuron:
SMA (spinal muscular atrophy), poliomyelitis
• Motor neuron disease – ALS (amyotrophic lateral
sclerosis)
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Amyotropthic lateral sclerosis ALS
• Neurodegenerative disease with progressive loss of
motor neurons in anterior horns of spinal cord, loss of
nuclei of cranial nerves in bulbar area and also with
affliction of motor corticospinal tract
• Typically combination of disturbance of both central and
peripheral motor neuron
• Onset: cca 5th- 6th decade
• Average survival rate is 2 – 4,5 years
• Cause of death – failure of respiratory muscles, bulbar
syndrome with aspiration, quadriplegia
ALS - etiology
• ?????
• Excitatory toxins ( glutamate), oxidative stress, disturbance of
Ca II+ homeostasis, proinflammatory cytokines, autoimmune
mechanisms
• genetic factors – familiar form is in ca.10%, hereditary
occurence (AD, AR, X bound)
The result is apoptosis (managed extinction) of motor neurons
Amyotrophic lateral sclerosis ALS
The first symptoms: affliction of te limbs (upper
limbs 50- 60%), weakness, atrophy, DK 25-30% (spasms, weakness) or bulbar symptoms (20 –
30%). Respiratory failure occurs only rarely.
Clinical picture – combination of peripheral
(fasciculation, atrophy) amd central symtpoms
(hyperreflexia, pyramidal irritative signs)
Diagnosis: EMG examination
Treatment: Riluzol (Rilutec)
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ALS symptoms
2. Radicular syndromes
Anterior rooot – motor
functions
Posterior root – sensory
functions
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Causes of radicular and spinal
compression
• Spondylosis, prolase of intervertebral disc,
degenerative changes – osteophytes, listesis
• Tumour, primary tumors, metastasis
•
•
•
•
•
Infection acute (herpes, borrelia), tbc
Hematoma, AVM
Trauma
Cyst arachnoid, syringomyelia
Polyradiculoneuritis
Medial prolapse
Lateral prolapse
Subarachnoid space
Dural sac
L4
L5
L4
L5
L5
L5
Charakteristics of radicular
syndrome
• Irritative signs:
- paresthesias, dysesthesias, hyperesthesias,
pain
- fasciculation
• Destructive signs:
- motoric deficit, hypotrophy, atrophy
- sensory deficit - hypesthesia, anesthesia
- diminished or extinct rr.
Clinical symptoms of herniation of lumbar prolappse
výhřezu
Herniation on the level
pain
sensory f.
motor f.
trophic state
reflexes
Normal
rr.L2-S2+
only
Throu
gh SI
hip
lat.
thigh,
calf
Lat. calf
Fingers1-3
L4/5
L5/S1
Throu
gh
SI hip
poster
lat.
thigh,
calf,
heel
Dorsum of
calf, laterally
from heel to
little finger
Extension
of instep,
thumb,
disturbed
walking on
the heel
Tibialis
anterior
Flexion of
instep and
of big toe.
Disturbed
walking on
toes
Gastrocnemius,soleus
Femoro
tibio
posterior
r. low to 0
(FTP 0)
R. of
Achilles
tendon: low
to 0
L5-S2low-0
3. Plexus brachialis
Affliction of brachial plexus (BP)
• Paresis of upper type
– especially roots C5, C6
= „healthy arm on the sick shoulder“
• Paresis of lower type
- Roots C7, C8
= „sick arm on the healthy shoulder“
• Complex paresis
- Often as an avulsion of brachial plexus
= Monoparesis of upper limb
Affliction of lumbosacral plexus
• Lesion of lumbar plexus
= mainly affection of femoral nerve
- disturbed movement in the knee and in the
hip
• Lesion of sacral plexus
= mainly lesion of ischiadic n. (tibial n. +
fibular n.) – disturbed movement especially in
the ankle
4. Neuropathy
• Neuropraxia – functional affliction
• Axonothmesis – damaged nerve but preserved sheath
• Neurothmesis – completely damaged nerve
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
Mononeuropathy
Polyneuropathy (PN)
Mononeuropathy –
Median n. (C5-8,Th1)
= carpal tunnel
syndrome
• Entrapment syndrome
• Paresthesia of 1st-3rd finger on
the palm side
• Often occurs during the night,
forces to shake the upper limb
• Later, also motor dysfunction
may be present – flexion of the
Ist-IIIrd finger
Ulnar nerve (C8,Th1)
Claw-like hand
• Entrapment syndrome – most
frequently in cubital tunnel
• Paresthesias and hypesthesias of
the 5th and lat. side of the 4th finger
palm and dorsum of hand
• Weakening of m. interossei and
adduction of the thumb = claw-like
hand
Radial n. ( C5-8, Th1)
dropping hand and fingers,
Fallhand
•
•
•
Compression or trauma in the area of
axilla and the neck of humerus
Disturbed sensory f. in the area of
dorsum of the hand
Weakening of extensors of the wrist =
syndrome of the „swan neck“
Fibular nerve
• Paresthesias of lateral side of the lower
leg, dorsum of the leg, milder
paresthesias also on the fingers
• Weakening of the dorsal flexion of the
leg
,,foot drop“
Femoral n. (L2-L4)
• Disturbance of „locking“ the knee
(especially when walking on the
rough terrain, upstairs etc.).
• Paresthesias and disturbance of
sensory f. in the innervation area
5. Polyneuropathy

Multiple lesion of nerves

Symptoms are mostly symmetrical, maximum is
in the acral area, more on lower limb
(predominant lesion of long nerves – contrary to
myopathy)

Main causes: metabolic (diabetes, thyroid
dysfunction, hypovitaminosis B12), toxic
(alcohol, chemoteraphy), inflammation
(polyradiculoneuritis)
Polyneuropathy – according
to symptoms:
sensory (hypesthesia, paresthesia,
dysesthesia, allodynia, pallhypesthesia)
motor (diminished or even extinct
proprioceptive reflexes, muscle
hypotrophy, flaccid paresis)
Mixed, sensory-motor
autonomní
Polyneuropathy classification
According to the course of disease:
• Acute (up to 4 weeks) – acute
polyradiculoneuritis AIDP
• Subacute (ca. up to 8 weeks) - metabolic
• Chronic - chronic polyradiculoneuritis
(CIDP), hereditary (HSMN)
Polyneuropathy classification
According to lesion of neural structure
• Demyelinating- inflammatory (AIDP)
• Axonal (more frequent) - toxic, metabolic
(alcohol, chemotherapy, diabetes)
Polyneuropathy clasiffication
According to etiology
• Congenital - HSMN
HSMN IA – duplication of gene 17p 11.2
• Acquired – see further
Polyneuropathy - diagnosis
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


Neurological examination ( distal hypo- or even
areflexia, sensory disturbances - hypesthesia,
reduced tuning fork, proprioception, ´motor
disturbances)
EMG : neural conduction – conduction studies
Biochemical examonation ( bloodv – thyroid gland, ELFO,
B12, glycemia, liquor – inflammation, higher level of
proteins)
Biopsy of nerve
Acute polyradiculoneuritis =AIDP
(Guillain – Barré syndrome)
• Multifocal autoimmune inflammatory demyelinatng
lesion of the sheath of peripheral nerves
(polyneuropathy) and roots of spinal cord
• More often around 40th year of age, more in men
• Seasonal occurence – spring, autumn
• Mortality 2-5%
The course of AIDP
• Typical course:
- 2-4 weeks before onset: may be vaccination,
gravidity, surgery, intestinal (camphylobacter jejuni)
and respiratory infection (mycoplasma pneumonie)
- Development of symptoms to 2-4 weeks
- plateau 2-4 weeks
- Gradual improvement of condition up to 6 – 12
months
Clinical picture of AIDP
• 3. main clinical symptoms:
- diffuse weakness, more on lower limbs (relat.
sym.)
- paresthesias of limbs in glove and sock shape
- areflexia
• Lesion of cranial nerves (diplegia of facial n., oculomotor
disturbances and bulbar symptoms
• Autonomic dysfunction – tachycardia, postural hypotension
• Lesions of CNS and cerebellum
• Event. also sphincter dysfunction in 1/3 of cases
• Respiratory insufficiency – 60% pac. need JIP hospitalization
Diagnosis of AIDP
• EMG: multifocal dymelinating lesion of nerves and roots
according to conduction study, blocks in neural conduction
• Liquor – proteinocytologic dissociation (elevated protein)
• Dif.dg.: myositis, borreliosis, lymphoproliferative disorders,
acute toxic polyneuropathy, MS, botulis, paraneoplastic
syndrome
Treatment of AIDP
- In milder forms: only symptomatic
- Severe forms with paresthesias in the
trunk and respiratory dysfunction →
UPV, probe, PF 2-7x, IVIG (0,4 g/kg),
corticoids
- Intensive rehabilitation
Disorders of neuromuscular
junction
Myasthenic syndrome
• Muscle weakness and fatigue depending
on physical effort, more in the evening
• Normal neurological examination –
– without pain and sensory dysfunctions
– Normal or only slightly reduced reflexes
– Normal muscle tone and trophic condition
Classification of disorders of
neuromuscular transmission
•
Autoimmune – presynaptic: Lambert – Eaton
- postsynaptic: MG
– presynaptic: botulism, post
- postsynaptická: post medication
• Congenital – presynaptic: (synthesis of Ach, deficit
•
Toxic
•
of vesicules, production of vesicules,
release of Ach)
•
•
- basal memrane: deficit of Ach
- postsynaptic: kinetics of Ach, slow-
•
channel sy, fast-channel sy, interaction of
with Achr, deficit of Achr
Ach
Myasthenia gravis
• Postsynaptic dysfunction of neuromuscular
transmission, antigens against acetylcholin
receptor (Achr)
• Prevalence 5-70/100 000 (relatively rare disease)
• Onset of disease ca. 20th-30th year of age
(women : men 2 : 1) and around 60th-80th year
(men : women 2 : 1 )
• Relation to thymus – folicular hyperplasia in
young patients, 10-15% of patients with MG suffer
from thymoma
Myasthenia gravis symptoms
• Muscle weakness – ocular, masticatory,
swallowing, respiratory and limb muscles
• Fluctuation of symptomatology (worse in
the evening, after physical exertion)
• Cave ! – myasthenic crisis x cholinergic
crisis - ARO, UPV – life threatening!
Examination in MG
•Medical history and neurological examination + loading tests
Examination in MG
• EMG – repetitive stimulation
- decrease of amplitude
(decrement)
• Achr, MuSK
• CT or MRI of mediastinum to exclude thymoma (again
with contrast agent)
• Dif.dg. examination:
- MRI of the brain, lumbar punctue (RS)
- brainstem stroke (doppler of carotid arteries)
- hormones of thyroid gland
- tumor markers
- EMG, muscle enzymes, muscle biopsy
(neuromuscular disease)
Therapy of MG
•
•
•
•
•
Inhibitors of cholinesterase
Corticoids
Immunosupressive therapy
IVIG, PF
thymectomy
• symptomatic treatment and regimen
measures
Myopathy - definition
• Myopathies are diseases with various causes
and affect primarily skeletal muscles, more
precisely cells of these muscles
• Altered metabolism, structure and function of
muscle cell
• Various etiology – congenital, acquired
Myopathic syndromes – clinical
picture
 Characteristics:
- Muscle weakness (proximal muscles, symmetricaly)
- Hypotonia, hypotrophy, pseudohypertrophy
- Trendelenburg gait, Gower´s sign („walking up“ own
body from squatting position
Gower´s sign - problematic elevation of the limbs
above horizontal line
 Neurological picture:
- Reduced or extinct reflexes (however, they may be
normal as well)
- No sensory disturbance, may be pain
Myopathy - symptoms
Myopathy EMG
Myopathy biopsy
Myopathy
– summary of diagnosis
•
•
•
•
Medical history and clinical picture
Neurological examination, muscle tests
EMG
Muscle enzymes, CK, Myoglobin, LDH
•
•
•
•
Biopsy of muscle
genetic examination (X-linked Becker´s myopathy)
cave ! Cardial muscle – ECG, ECHO, cardio
spirometry – respiratory muscles
Myopathy - clasiffication
1. Genetically determined myopathy
- Dystrophy
- Deposition of glycogen and lipids
- Congenital myopathies associated
with structural abnormalities
2. Acquired myopathies
- Inflammatory (autoimmunne, infectious)
- Metabolic
- Toxic (e.g. caused by drugs)
Duchenne´s myopathy (DMD)
• The most frequent myopathy – 1 : 3 500 neonates (boys)
• Deficit of specific muscle protein dystrophin
(dystrophinopathy)
• Only boys are affected – X-linked disease, women are
carriers
• Clinical manifestation 3rd- 5th year
• Dg.: marked elevation of muscle enzymes, EMG, genetic ex.
DMD
• Early symptoms: difficulties with walking up and
down from stairs, falls without evident cause
• Increased volume of muscles
especially of calves – also
early characteristic sign
• Further: progressive
deterioration of standing up
from lying and sitting position
DMD- clinical manifestation
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


Immobilization occurs in various age –
most, but most of children lose ability of
walking in the age from 7 to 13 years
After immobilization – rapid development
of fixed skeletal deformities and
progressive skoliosis
Patients die mostly before or around 20th
year due to respiratory isufficiency (90%)
Heart is often affected but asympomatic –
cardial insufficiency is the cause of death
only in 10% children
Becker´s muscle dystrophy

Another frequent cause of muscular disease in boys
but with relatively milder course – patients remain
mobile after 20th year of age

This disease is caused by the same gene and
protein – but there is no deficit, only
dysfunction
Other muscular dystrophies
Congenital myopathies
associated with structural
abnormalities
Central core disease
Nemaline rod myopathy
Muscle biopsy shows characteristic signs
of brightening of cell centres
Glykogenosis and disorders of
lipid metabolism
Acquired myopathies
2a, inflammatory myopathy
Polymositis, dermatomyositis – AI etiology
2b, myopathy with endocrine or metabolic etiology
Hyper- a hypothyreosis, hyperparathyreosis (hypercalcemia), Cushing´s
syndrome, hypokalemia
2c, Toxic and drug-induced myopathies
Alcoholic myopathy - acute and chronic, corticoid-induced myopathy,
Myopathy induced by treatment with statins
Myotonia
• Hand grip is
accompanied by
prolonged
contraction and slow
relaxation
Myotonia
• Disorder of de-contraction (relaxation of the
muscle)
• EMG – after input of the needle signs of resting
activity – „dive bomber“
1) Myothonia congenita Thomson, Becker
(channelopathies – Cl channel)
2) Myotonic dystrophy
Myotonic dystrophy
- clinical manifestation
 Multiorgan disturbance with variable onset time of
symptoms in various systems
 The most prominent manifestation is evident on
skeletal muscles (myopathy + myotonia, cramps),
cardial conduction system, brain, smooth muscles
and eye lens (cataracts)
 Endocrine disorder
• Thanks for your attention.
Mononeuropatie a radikulopatie pro
studenty 4. ročníku 1.LF UK
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