Peripheral Neuropathies

What are the disease-based classifications of PN injuries?

• Pathology based - According to primarily affected area, in order of increased severity of PN injury.

  • Myelinopathies

  • Axonopathies

  • Neuronopathies

What are Myelinopathies?

• Segmental demyelination or Schwann cell damage.

What are Axonopathies?

• Axon disintegration, Wallerian or distal axonal degeneration.

What are Neuronopathies?

• Cell body originating problem (AHC, Brainstem nuclei involvement)

What are the details of Myelinopathies? (part 1)

• Myelin sheath or Schwann cells destroyed; no primary axon problem

• Immune etiology or local compression ischemia

• Gradual or sudden

• Symmetric or diffuse loss

• Myelin phagocytosed & denuded axon acts to stimulate remyelination

• Recovery is favorable

What are the details of Myelinopathies? (part 2)

• Multiple episodes produce “Onion Bulb” cross sections from repeated process

• Typically occurs with acquired immune-mediated inflammatory conditions

  • Guillain-Barre Syndrome

  • Diphtheria (Post-infectious PN damage, can lead to muscle weakness/sensory changes)

• With chronic demyelinating diseases axon involvement often occurring

What are the details of Axonopathies? (Part 1)

• Acute or traumatic injury that disrupts the axon

• Form of axonal disintegration occurs is called Wallerian degeneration

• Complete (distal axon degeneration) or incomplete (axon damage) transection of the nerve; both lead to Wallerian deg.

• Proceeds rapidly, in a few weeks

What are the details of Axonopathies? (Part 2)

• The result of chronic disease or long-term insult

• Develops slowly & progresses back toward the cell body - “Dying Back”

• Recovery is slower & less favorable than in case of Wallerian degeneration

• Symmetric distal involvement

• Common with toxins

• (Distal axonal degeneration)

What is muscle denervation & Reinnervation? (Panopto/book)

What are the Clinical Signs of PN injury?

• Localized, if a single nerve!

• Sensory loss/impairment

• Persistent weakness

• Distorted motor &/or sensory involvement

• Hyporeflexia or Areflexia

• Ataxia (sensory) or Tremor

• Postural deformities due to muscle imbalance

• Pain

What are the forms of Pain? (Definitions?/finish card)

• Nociceptive pain (chronic & acute): nerve damage detected by nociceptors.

• Non-nociceptive pain- neuropathic pain

  • Paresthesia: Abnormal sensation (tingling/numbness/pins & needles)

  • Dysesthesia: Unpleasant abnormal sensation (burning/electric shocks, unpleasant tingling)

  • Allodynia: Pain caused by a stimulus that normally should NOT be painful. (light touch, gentle brushing/clothes rubbing skin)

  • Hyperalgesia: Increased pain response to a stimulus that is normally painful.

What are the Etiological classification of neuropathies?

• Acquired forms

  • Mononeuropathies: Single nerve

  • Multiple mononeuropathies: Diffuse, Asymmetric

  • Polyneuropathies: Diffuse, typically bilateral & symmetric

• Hereditary forms

  • Most are Polyneuropathies

What are the most common Neuropathies?

• Diabetic polyneuropathy

  • Distal symmetric most common with mixed sensory & motor loss (large nerve fibers first). Pain/symptoms start distally & moves proximally. (my note)

• Alcoholic neuropathy

  • Mixed sensory & motor, distal axonopathy

• Hereditary

  • Charcot-Marie-Tooth (Most Common)

• Guillan-Barre Syndrome

  • Rapidly evolving acquired peripheral polyneuropathy

What is Charcot-Marie-Tooth (CMT)?

• AKA Hereditary motor & sensory neuropathy type 1 is most common

• Incurable, but not life threatening

• 3 types at least

• Caused by mutations in neuronal proteins, forming the myelin sheath. But some affects the axon.

• Typically present in childhood or early adulthood

• Not a progressive disorder, may stop developing by age of 35-40 yr

• Affects about one in 2,500 people

Charcot-Marie-Tooth (CMT) at later stages?

• Appears distally & symmetrically in LE, slow distal muscle wasting

• Foot drop, reduced endurance, fatigue, affect walking

• Paresthesia, involving toes or soles, muffled sensation, stocking pattern

• Loss of DTR beginning distally

• Involve repetitive de- & remyelination (onion bulbs), until axonopathy develops

• Later UE functions are affected

• (Left picture: also known as Stork leg deformity)

What is Guillain-Barre Syndrome?

• Life-threatening acquired polyneuropathy

• Most common form- Acute inflammatory demyelinating polyradiculoneuropathy

• “Ascending paralysis”- Begins with distal symmetric weakness, rapidly moves proximally, involving spinal & cranial nerves

• Considered a Autoimmune-mediated disorder

• 2/3 of cases preceded by Flu-like illness,, nearly all within previous 30 days

What’s the pathology of Guillain-Barre Syndrome?

• More than one cause

  • Viral infections:

    • pneumonia, Varicella-zoster, mumps, HIV, Mononucleosis, ZIKA (infection from mosquito), cytomegalovirus, COVID

  • Campylobacteria

  • Reaction to vaccination

• Initial infection develops antibodies that become a target for immune system attack

• Primary lesion is segmental demyelination of peripheral nerves (both motor & sensory) & spinal nerve roots with inflammatory cell infiltration

What is the clinical aspect of Guillain-Barre Syndrome?

• Begins with weakness, choking, SOB, or with abnormal sensation

• No fever, but may be after fever

• Rapidly ascending symmetric weakness & distal sensory impairments (lesser extent)

• Early loss of DTRs

• Facial symmetric weakness

• Elevation of CSF protein

• Cardiac abnormalities, such as tachycardia, arrhythmias, labile(unstable/changing) blood pressure

• Death rate now 2-5% due to good respiratory & cardiac support in critical phase

What are the complications of Guillain-Barre Syndrome?

• “Classic” presentation of GBS development: 4 weeks or less, then recovery begins 2-4 weeks after progression stops

• 20% may have significant residual complications

  • Loss of muscle strength

  • Residual sensory impairments (less than motor & mostly distal)

  • Mild pain (neuropathic)

  • Slower nerve conduction

  • Fatigue, reduced endurance

  • residual cardiac problems

Whats the treatment for Guillain-Barre Syndrome?

• Low-load & low repetition gradual strengthening exercises

• No maximal voluntary contractions within a year since onset

• Strong chance of spontaneous recovery

• Anyone in acute condition admitted to hospital, as symptoms can quickly worsen & can be fatal if untreated.

• Plasmapheresis or immunoglobulin infusion used as treatment

• Gamma immunoglobulins high-dose, administered intravenously, 0.4g/day for 5 days

• Can be placed on respirator when respiratory function drops to 1.0-1.4L

• Recovery favorable, recureent form 10% only