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Polyneuropathies Mononeuropathies Motoneuron diseases. Zsuzsanna Arányi. Peripheral nerve. Motor, sensory and autonomic fibers Fiber types according to diameter: A fibers- 1-17 μ m in diameter; myelinated motor and sensory fibers B fibers- 1-3 μ m in diameter; myelinated autonomic fibers

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Polyneuropathies mononeuropathies motoneuron diseases

PolyneuropathiesMononeuropathiesMotoneuron diseases

Zsuzsanna Arányi

Peripheral nerve
Peripheral nerve

  • Motor, sensory and autonomic fibers

  • Fiber types according to diameter:

  • A fibers- 1-17 μm in diameter; myelinated motor and sensory fibers

  • B fibers- 1-3 μm in diameter; myelinated autonomic fibers

  • C fibers- 0.3-1.3 μm in diameter; non-myelinated autonomic and pain fibers

Types of peripheral nerve damage
Types of peripheral nerve damage


  • Slowed conduction: no symptoms

  • Conduction block: weakness and sensory loss, but no atrophy

    Axonal damage (axonotmesis)

  • Degeneration of axons distal to the lesion (denervation)

  • Weakness, sensory loss, atrophy


  • Damage to axons and epineurium

  • Weakness, sensory loss, atrophy

  • No regeneration without nerve suture

Nerve regeneration reinnervation
Nerve regeneration – reinnervation



axon regeneration

Collateral reinnervation

(in case of partial nerve


2-12 weeks

1 mm/day

Intact basal

lamina/endoneuriumis needed

Starts within 4-6 weeks


  • Generalised disease of the peripheral nervous system (nerve roots and peripheral nerves)

  • Usually the longest nerves are affected first

    • Symptoms start on the toes, feet

  • Usually the symptom of an underlying systemic disease

    • Search for etiology!

Classification of polyneuropathies
Classification of polyneuropathies

  • Clinical presentation

    • Symmetric

    • Asymmetric

  • Time course

    • Acute

    • Chronic

  • Etiology

  • Pathology

    • Axonal

    • Demyelinative

    • Small-fiber

Clinical forms of polyneuropathies
Clinical forms of polyneuropathies

  • Chronic, symmetric, distal and predominantly sensory polyneuropathies

  • Mononeuropathy multiplex

  • Purely motor or sensory polyneuropathies

  • Autonomic polyneuropathies

  • Acute polyneuropathies

Typical symptoms of polyneuropathies
Typical symptoms of polyneuropathies

  • Chronic course

  • Symmetric, distal paraesthesia, pain and hypaesthesia in stocking – glove distribution; feet are affected first

  • Allodynia

  • Depressed or absent tendon reflexes

  • Distally pronounced muscle weakness, with wasting, fasciculation

  • Gait disorder

    • Sensory ataxia

    • Weakness

  • Autonomic dysfunction (reduced sweating, tachycardia, urinary disturbances, gastroparesis etc.)

Typical complaints of patients with polyneuropathies
Typical complaints of patients with polyneuropathies

  • Tingling, pin-prick, numbness, burning or cold sensation, burning pain (especially during the night)

  • ‘Ants crawling on my legs’

  • ‘As if I had tight boots on’

  • ‘As if I were walking on a duvet’

  • ‘As if I had stockings on when really not’

  • ‘As if my skin were thick on my soles’

  • Unstable gait, ‘dizziness’

  • Loss of dexterity of the hands: ‘I drop objects’

Causes of polyneuropathy
Causes of polyneuropathy

  • Metabolic-endocrine disturbances: diabetes mellitus, uremia etc.

  • Vitamin deficiencies: vitamin B1 -alcoholism, malabsorption, malnutrition, vitamin B12

  • Toxic causes: heavy metals, industrial solvents, drugs, alcohol

  • Dysimmune polyneuropathies

    • With manifestation only in the peripheral nervous system: acute inflammatory demyelinative polyneuropathy (Guillain-Barré syndrome), chronic inflammatory demyelinative polyneuropathy (CIDP), multifocal motor neuropathy (MMN)

    • Systemic diseases: vasculitis (polyarteritis nodosa, SLE etc.), paraproteinaemias

    • Paraneoplasia

  • Infectious: lepra, Lyme-disease, HIV

  • Hereditary: Charcot-Marie-Tooth disease etc.

  • Other: critical illness polyneuropathy, small-fiber neuropathy

  • Idiopathic

Investigation of polyneuropathies
Investigation of polyneuropathies


  • Blood tests: We, blood count, glucose, hepatic and renal function

  • Vitamin B12

  • Thyroid function

  • Se electrophoresis, autoanti-bodies, cryoglobulin

  • Serological examinations (HIV, Lyme, HCV)

  • Search for tumors

  • CSF

  • Toxicological investigations

  • Sural nerve biopsy

  • Genetic tests

Treatment of polyneuropathies
Treatment of polyneuropathies

  • Treat the cause!

  • Immune therapy

    • plasmapheresis: Guillain-Barré syndrome, CIDP

    • immunoglobulins: MMN, Guillain-Barré syndrome, CIDP

    • corticosteroids: CIDP, systemic vasculitis

  • Symptomatic treatment of paraesthesias and neuropathic pain

    • antiepileptic medications (carbamazepine, gabapentin, pregabalin)

    • tricyclic antidepressants (amitriptilin, clomipramin)

    • SNRI antidepressants (duloxetin, venlafaxin)

  • Vitamin B1: alcoholism, malabsorption, malnutrition

Polyneuropathies associated with diabetes mellitus
Polyneuropathies associated with diabetes mellitus

  • Distal symmetric sensory polyneuropathy

  • Mononeuropathies- carpal tunnel syndrome, ulnar nerve lesion

  • Cranial nerve lesions- oculomotor nerve palsy

  • Autonomic neuropathy- sexual and urinary disturbance, gastroparesis and diarrhoea etc.

  • Diabetic amyotrophy- painful, asymmetric, proximal weakness (plexopathy?)

  • Radiculopathy- lumbar, thoraco-abdominal

Diabetic chronic distal symmetric sensory polyneuropathy
Diabetic chronic distal symmetric sensory polyneuropathy

  • The most common form of diabetic neuropathy

    • Prevalence among diabetic patients: 20-60%

    • Present at the diagnosis of diabetes in 20% of patients

    • May be the only manifestation of impaired glucose tolerance

  • Severity is usually proportional to the duration and severity of hyperglycemia

  • Prevalence increases with age and duration of diabetes

  • Small fibers (pain, temperature, light touch) are preferentially affected →painful diabetic neuropathy in about 20-35%

  • Autonomic dysfunction

  • Trophic alterations →diabetic foot

Small fiber neuropathy skin biopsy
Small fiber neuropathy- skin biopsy

NormalSmall fiber neuropathy

Epidermal nerve fibers (arrow): anti PGP 9.5 antibodies

Fibrous tissue and basal lamina: anti collagen IV antibodies

Symptoms of sensory diabetic neuropathy i
Symptoms of sensory diabetic neuropathy I.

  • Length-dependent: first symptoms on the toes and feet

  • Later stocking-gloves distribution

  • Usually doesn’t go above the knees and elbows

  • If symptoms appear on the hands first → carpal tunnel syndrome

  • Areflexia

  • Trophic changes

Symptoms of sensory diabetic neuropathy ii
Symptoms of sensory diabetic neuropathy II.

  • Positive sensory symptoms:

    • burning pain (pronounced during the night)

    • hyperesthesia, allodynia

    • paresthesia

  • Negative sensory symptoms:

    • hypesthesia (loss of sensation)

Diabetic foot
Diabetic foot

  • Related to diabetic sensory neuropathy and peripheral artery disease

  • Diabetic foot ulcers precede 85% of non-traumatic lower limb amputations

  • Life-time prevalence of foot ulcers is 15% in diabetic patients

Guillain barr syndrome
Guillain-Barré syndrome

  • Acute immunmodulated poly-radiculo-neuro-pathy

  • Pathology: perivascular lymphocyte-macrophage infiltration in the peripheral nervous system leading to macrophage mediated segmental demyelination

  • Incidence: 1.5-2.0/100 000/year

  • In most cases preceded by an infection (upper respiratory tract infection, diarrhoea)

  • Infectious agents associated with Guillain-Barré syndrome: CMV, EBV, HIV, Campylobacter jejuni, Mycoplasma pneumoniae

    • The infectious agent is usually unidentified

Guillain barr syndrome symptoms
Guillain-Barré syndrome- symptoms

  • Acute, symmetric ascending flaccid paralysis

    • Variable severity

  • Respiratory insufficiency

  • Bilateral facial palsy

  • Ascending numbness to a lesser degree

  • Radicular pain

  • Areflexia

  • Autonomic symptoms- tachycardia, cardiovascular instability

Guillain barr syndrome time course
Guillain-Barré syndrome- time course

  • Symptoms evolve over 1-2 weeks

  • Plateau is reached within 2-3 weeks

  • Spontaneous recovery within a few months

  • Good prognosis

    • Prognosis is determined mainly by complications of being bed-bound (infection, thrombosis etc.)

Guillain barr syndrome diagnosis
Guillain-Barré syndrome- diagnosis

Normal neurography Segmental demyelination

Conduction block Temporal dispersion

Guillain barr syndrome diagnosis and treatment
Guillain-Barré syndrome- diagnosis and treatment

  • Diagnosis

    • Clinical symptoms

    • Electroneurography- confirms segmental demyelination

    • Cerebrospinal fluid examination: elevated protein content with normal cell count (starting from the 2nd week)

  • Treatment

    • Plasmapheresis, immunoglobulin (IVIG)

    • Supportive treatment!

Chronic inflammatory demyelinative polyneuropathy cidp
Chronic inflammatory demyelinative polyneuropathy (CIDP)

  • Autoimmune disease

  • Prevalence: 1-2/100 000

  • Course:

    • chronic monophasic (15%)

    • chronic relapsing-remitting (34%)

    • step-wise progressive (34%)

    • continuously progressive (15%)

  • Symptoms: proximal and distal motor and sensory symptoms, cranial symptoms (not a length-dependent neuropathy)

  • Rarely associated with central nervous system demyelination (3%)

Diagnosis of cidp
Diagnosis of CIDP

  • ENG/EMG: segmental (non-uniform) demyelination

  • CSF: protein >45 mg/dl, cell count <10

  • Histology (biopsy): not obligatory, may be normal

    • chronic demyelination-remyelination may lead to Schwann-cell proliferation (‘onion bulb’ formation)

    • infiltration of inflammatory cells

  • MRI: hypertrophy of peripheral nerves and nerve roots, contrast enhancement

Cidp nerve biopsy
CIDP- nerve biopsy

‘onion bulbs’

Cidp mri

Hypertrophied trigeminal nerves

Cidp treatment
CIDP treatment

  • IVIG

    • 2 g/kg bw in 2-5 days, monthly for 3 months

    • maintanance treatment

  • Corticosteroids

    • methylprednisolon 1 mg/kg bw, later gradual reduction

  • Plasmapheresis

Mononeuropathies causes
Mononeuropathies- causes

  • Trauma

    • cutting, laceration and stretching of the nerve

  • Compression

    • often iatrogenic

  • Tunnel syndromes

  • Ischemia

Localisation of focal nerve lesions
Localisation of focal nerve lesions

  • A partial proximal nerve lesion may selectively affect only one nerve fascicle → clinically the lesion appears more distal

  • The longer axons are more sensitive to compression → distal symptoms are more pronounced

Distal median nerve damage carpal tunnel syndrome
Distal median nerve damage: carpal tunnel syndrome

  • Incidence: 200-500/100 000/year, 3 times more common in women

  • Symptoms:

    • Painful paraesthesia of the hand during the night, pain in the whole arm

    • First the dominant hand is affected, but bilateral involvement in most cases

    • Advanced symptoms: sensory loss on digits 1-3, thenar atrophy and weakness

  • Causes: idiopathic, overuse, change of tunnel anatomy (fracture, arthrosis, oedema etc.), diabetes

  • Treatment:

    • Splinting of the hand during the night

    • Surgery

Proximal median nerve damage
Proximal median nerve damage


1. Weakness of all median nerve muscles ‘oath hand’


2. Weakness of flexion of the distal phalanx of digit 1-2 no sensory loss

Ulnar nerve lesion at the elbow two types
Ulnar nerve lesion at the elbow- two types



  • Retroepicondylar lesion (more common)

    • Compression, elbow fracture, arthrosis, diabetes

  • Real cubital tunnel syndrome

Ulnar nerve lesion
Ulnar nerve lesion

  • Numbness of digit 4-5 and ulnar edge of the hand

  • Atrophy and weakness of hypothenar, interosseus muscles and adductor pollicis muscle

  • Tinel-sign at the elbow

  • Claw hand

Radial nerve lesion on the upper arm
Radial nerve lesion on the upper arm

  • ‘Saturday night palsy’: nerve compression during sleep

    • common in alcoholics

  • Symptoms: weakness of wrist and finger extension (wrist drop); triceps is normal;loss of sensation on the dorsal-radial aspect of the hand

Radial nerve lesion on the forearm
Radial nerve lesion on the forearm

  • Weakness of finger extension (‘finger drop’), extension of the wrist is only sightly weak, oftens starts on digit 4-5 → may be confused with ulnar nerve lesion

  • No sensory loss

  • Causes: supinator tunnel syndrome due to overuse

Peroneal nerve damage at the fibular head
Peroneal nerve damage at the fibular head

  • Foot drop, steppage gate

  • Supination (inversion) and plantarflexion is normal

  • Sensory loss on the lateral aspect of the leg and dorsal aspect of the foot

  • Causes: compression

    • During sleep, in coma

    • During surgery

    • Cast

    • Crossed legs

    • Squatting (strawberry pickers)

    • Peroneal tunnel syndrome?

Motoneuron diseases
Motoneuron diseases

  • Progressive loss/degeneration of motoneurons

    • Weakness

    • Atrophy

    • No sensory or autonomic symptoms

  • Two major types:

    • Amyotrophic lateralsclerosis (ALS): both upper and lower motoneurons are affected

    • Spinal muscular atrophies / lower motoneuron syndromes

Polyneuropathies mononeuropathies motoneuron diseases

First described by Jean Martin Charcot in 1874

  • Incidence: 2 / 100 000 / year

  • Prevalence: 6 / 100 000

‘Lou Gehrig’s disease’

Als clinical forms
ALS- Clinical forms

  • Sporadic ALS

    • Classic ALS

    • Progressive muscular atrophy (PMA)

    • Primary lateralsclerosis

    • Progressive bulbar paralysis

    • Progressive pseudobulbar palsy

  • Familial ALS (5-10%)

    • Autosome dominant

      • SOD1 mutations

      • No SOD1 mutations

    • Autosome recessive

      • SOD1 mutation

      • Chronic juvenile ALS

    • X-linked

  • Frontotemporal dementia+ ALS (ubiquitin positive)



atrophy (PMA)




Classic ALS




Bulbar onset






Als symptoms and course
ALS- symptoms and course

  • Mixed signs of upper and lower motor neuron lesion

    • Atrophy, fasciculation, cramps

    • Spasticity, increased reflexes, Babinski

  • Relentlessly and quickly progressive

  • Average survival: 2-5 years

    • Cause of death: respiratory insufficiency

Als clinical syndromes at onset
ALS- Clinical syndromes at onset

  • Asymmetric small hand muscle atrophy and weakness (segmental distribution)- 60-85%

    • Diff. dg.: radiculopathy, ulnar nerve lesion

  • Proximal arm muscle atrophy and weakness (‘flail’ arm)

    • Diff. dg.: radiculopathy

  • Bulbar onset- 15-40%

    • Dysarthria and dysphagia

    • Diff. dg.: myasthenia gravis, pseudobulbar paresis

  • Spastic paraparesis

    • Diff. dg: spinal disease

Als treatment
ALS- treatment

  • No cure

  • Only drug approved for ALS: riluzol (inhibits the presynaptic release of glutamate), survival on riluzol increases by 3-6 months

  • Supportive treatment:

    • Muscle relaxants

    • Antidepressants, anxiolytic drugs

    • PEG in case of severe dysphagia

    • Assistive devices

    • Ventilation??? (moral issue)

Riluzol trials

Infantile and juvenile spinal muscular atrophies sma i iii
Infantile and juvenile spinal muscular atrophies (SMA I-III)

  • 1 / 6-20 000 live births

  • Autosome recessive

  • In 95% of patients the mutation is found in the SMN (survival motoneuron) gene (chr. 5)

Infantile and juvenile spinal muscular atrophies sma i iii1
Infantile and juvenile spinal muscular atrophies (SMA I-III)

  • SMA I: Werdnig-Hoffmann disease. Symptoms are present at birth- ‘floppy baby’. Death within 1-2 years.

  • SMA II.: Intermediate form

  • SMA III: Kugelberg-Welander disease

    • Symptoms start at age 12-15 years: proximal, symmetric weakness in the legs

    • Progression is variable

    • Differential diagnosis: muscle dystrophies

    • Dg.: EMG (chronic neurogenic findings), genetic testing

Adult onset spinal muscular atrophies lower motoneuron diseases
Adult onset spinal muscular atrophies / lower motoneuron diseases

SMA IV: 'adult onset' proximal spinal muscular atrophy

  • Onset: 20-40 years of age

  • Inheritance: 70% AR, 30% AD

  • Gene is unknown

  • Symptoms: very slowly progressive limb girdle weakness and atrophy. May be asymmetric, the quadriceps muscle is very often affected. No bulbar involvement.

  • Differential diagnosis: muscle dystrophies, ALS

Adult onset spinal muscular atrophies lower motoneuron diseases1
Adult onset spinal muscular atrophies / lower motoneuron diseases

dSMA V: 'adult onset' distal spinal muscular atrophy

  • Onset: 20-40 years of age

  • Inheritance : AD

  • Gene is unknown

  • Symptoms : slowly progressive distal weakness and atrophy

  • Differential diagnosis: polyneuropathies

Adult onset spinal muscular atrophies lower motoneuron diseases2
Adult onset spinal muscular atrophies / lower motoneuron diseases

Benign focal amyotrophy

  • Usually sporadic

  • More common in men

  • Starts in young adulthood, slow progression over a few years, then stagnation

  • Symptoms: small hand atrophy on one side

  • Differential diagnosis: ALS, ulnar nerve lesion