Peripheral Nerve Diseases Prof. Dr. Ece AYDOĞ Physical Medicine and Rehabilitation

Learning objectives: be able to define parts of peripheral nervous system be able to describe injuries in the peripheral nervous system (neuropraxia, aksonotmezis, nörotmezis,) be able to describe clinical signs of peripheral neuropathy (somatic and autonomic) be able to classify peripheral neuropathy according to the causes 5.5 be able to describe diagnosis, pharmacological and nonpharmacological treatment approaches for peripheral neuropathy.

Peripheral Nervous System (PNS) The function of the PNS is to carry impulses to and from to central nervous system These impulses regulate motor, sensory and automotic activities The peripheral nervous system is comprised of structures which lie outside the pial membrane of the brainstem and spinal cord and can be divided into cranial, spinal and autonomic componenets.

The structure of the NERVE CELL and AXON

Peripheral Nervous System

Structure of a Peripheral Nerve 􀁻 Endoneurium – loose connective tissue that surrounds axons 􀁺 Perineurium – coarse connective tissue that bundles fibers into fascicles 􀁺 Epineurium – tough fibrous sheath around a nerve

PNS in the Nervous System

Receptor Classification by Stimulus Type 􀁻 Mechanoreceptors – respond to touch, pressure, vibration, stretch, and itch 􀁻 Thermoreceptors – sensitive to changes in temperature 􀁻 Photoreceptors – respond to light energy (e.g., retina) 􀁻 Chemoreceptors – respond to chemicals (e.g., smell, taste, changes in blood chemistry) 􀁻 Nociceptors – sensitive to pain causing stimuli 8

The somatic system consists of 12 pairs of cranial nerves 31 pairs of spinal nerves: 8 cervical (C1-C8) 12 thoracic (T1-T12) 5 Lumbar (L1-L5) 5 Sacral (S1-S5) 1 Coccygeal (C0)

Spinal Nerves: Roots 􀁻 Each spinal nerve connects to the spinal cord via two medial roots 􀁻 Ventral roots arise from the anterior horn and contain motor (efferent) fibers 􀁻 Dorsal roots arise from sensory neurons in the dorsal root ganglion and contain sensory (afferent) fibers

Nerve Plexuses All ventral rami except T2-T12 form interlacing nerve networks called plexuses Plexuses are found in the cervical, brachial, lumbar, and sacral regions Each resulting branch of a plexus contains fibers from several spinal nerves Each muscle receives a nerve supply from more than one spinal nerve Damage to one spinal segment cannot completely paralyze a muscle

Brachial Plexus Formed by C5-C8 and T1 (C4 and T2 may also contribute to this plexus) It gives rise to the nerves that innervate the upper limb

Lumbar Plexus Arises from L1-L4 and innervates the thigh, abdominal wall, and psoas muscle The major nerves are the Femoral nerves for anterior thigh muscles Obturator nerves for adductors muscles

Sacral Plexus Arises from L4-S4 and serves the buttock, lower limb, pelvic structures, and the perineum (pudendal nerve) The major nerve is the sciatic, the longest and thickest nerve of the body tibial common fibular (peroneal)

Dermatomes A dermatome is the area of skin innervated by the cutaneous branches of a single spinal nerve All spinal nerves except C1 participate in dermatomes

Pathologies of peripheral nerves Nerves (Seddon and Sunderland Classification) Neurapraxia Axonotmesis Neurotmesis

Total conduction failure (neurapraxia) No function Recovers spontaneously over days or weeks (when the cause is resolved) Results of spontaneous recovery are almost always good 18

Neurapraxia 19

Interruption of axons (axonotmesis) No function New axon grows from cell body (spontaneously) 20

Axonotmesis Nerve may regenerate from injured location away from the cell body Regeneration: 1 mm per day (approx. 1 inch per month) Results of spontaneous recovery are good to moderate depending on distance 21

Axonotmesis Type 2 Neurotmesis Type 3 Type 4 Type 5

Interruption of nerve trunk (neurotmesis) No function Does not regenerate spontaneously Irreversible, grafting is required

Axonotmesis Type 2 Neurotmesis Type 3 Type 4 Type 5 24

Peripheral Neuropathy Mode of Onset Acute Subacute Chronic

Peripheral Neuropathy Acute: (A few days-4 weeks) Guillain-Barre Syndrome (GBS) Traumatic Vasculitis Herpes Zoster Diphtheria Porphyria Toxic (Thallium)

Peripheral Neuropathy Sub-acute: (Devolop over weeks) Symmetric..Sensory-motor Toxic Nutritional (Alcohol) Paraneoplastic (Sensory neuronopathy) Asymmetric...Motor-sensory Vasculitis Diabetic amyotrophy

Peripheral Neuropathy Chronic:(Devolop over months, years) 1-Acquired Diabetic distal sensory neuropathy Leprosy Autoimmune neuropathies Para-Neoplastic Others ( uremia….)

Peripheral Neuropathy 2-Hereditary HMSN ( Charcot-Marie-Tooth ) Refsum’s disease Hypertrophic polyneuropathy (Dejerine-Sottas disease)

Causes 1. Nutritional, metabolic and toxic neuropathies; the most common causes are diabetes mellitus and alcoholism Vitamin deficiencies, Renal failure, Chronic liver disease, Drugs (e.g. vincristine), Heavy metals, Toxins (e.g. diptheria), Chemicals (e.g. Hexane, glue) Diabetes - distal symmetric, autonomic and focal or multifocal asymmetric presentations

2-Inflammatory neuropathies Infectious - shingles (VZV), leprosy Vasculitic - polyarteritis, SLE Guillain-Barré Chronic inflammatory demyelinating polyradiculopathy

3. Hereditary neuropathies Hereditary sensory, motor and autonomic neuropathies Leukodystrophies Porphyria

4. Miscellaneous neuropathies Amyloid Paraneoplastic Compression

Mononeuropathies Median nerve- Carpal tunnel Syndrome Ulnar nerve-Cubital tunnel syndrome Radial nerve- Spiral oluk tuzak Posterior interosseous neuropathy Toracicus longus nerve-Serratus anterior Winging scapula Common Peroneal nerve-Fibula head Lateral femoral cutaneous nerve-Meralgia paresthetica Tibial nerve-Tarsal tunnel syndrome

Plexopathies Brachial plexus-Erb palsy, Klumpke palsy, Personage-Turner syndrome (idiopathic brachial neuritis) Lumbosacral plexus

Polyneuropathies Diabetic neuropathies Polyneuropathy (Sensory loss and distal weakness) Autonomic neuropathy (Postural hypotension, impotence, nocturnal diarrhoea) Mononeuropathy (Diabetic amytrophy)

Polyneuropathies Guillain-Barre Syndrome (GBS): Acute inflammatory demyelination polyradiculopathy

Peripheral Neuropathy Symptomatology-Motor Weakness: Lower motor-neuron type hypotonia & hyporeflexia fasiculation wasting (chronic) distal distribution

Peripheral Neuropathy Symptomatology-Motor Wasting & Deformities: Chronic > 3 months duration Kypho-scoliosis Pes cavus – Clawing of hands & feet Hereditary Motor-Sensory Neuropathy 40

Peripheral Neuropathy Symptomatology-Sensory Sensory Changes: Hyposthesia Parastheasia Dysthesia Allodynia Hyperalgesia 41

Peripheral Neuropathy Symptomatology-Sensory Distribution of sensory changes: gloves & stocking root or nerve distribution 42

Peripheral Neuropathy Symptomatology-Autonomic Autonomic manifestations: Anhydrosis Postural Hypotension Bladder Atonia…incontinence Gut Atonia….diarrhea Sexual dysfunction

History Time course (acute, subacute, chronic, episodic) Negative: numbness Postive: tingling, pain Weakness and loss of function Balance Postural dizziness DM Medication Social, toxins, diet Family history

Examination/Evaluation Observation of skin color, integrity, temperature Presence of pressure points or ulceration Strength testing ROM/flexibility testing Neurological testing Reflexes Sensation Proprioception Balance/coordination Foot wear assessment

Diagnosis A strong clinical suspicion will suffice to make a clinical diagnosis. To support the diagnosis some investigatios are necessary these include: Electromyography Nerve biopsy Nerve conduction studies Magnetic resonance imaging Computed tomography

Special Investigation Nerve conduction studies Motor conduction velocity Sensory conduction velocity Demyelination: Marked slowing of conduction velocity (30% at least reduced) with progressive reduction of amplitude. Axonal change: Reduced amplitude or absence of response to stimulation with mild slowing of conduction velocity Localized compression of nerve: Slowing conduction in region of block e.g. Over the elbow when ulnar nerve is compressed there.

Special Investigation Electromyography (EMG) A fine needle is inserted into the muscle and the recorded activity displayed on an oscilloscope. Primarily of value in muscle disease but can also give indirect evidence of a neropathic process. If chronic denervation has occured, re-innervation may be present with long duration high amplitude motor unit potentials.

Special Investigation Nerve biopsy In neuropathies of uncertain cause, light and electron microscopy examination occasionally help diagnosis. The sural nerve is usually chosen for biopsy.

Treatment Non pharmacological Patient education Maintaining optional weight Avoiding exposure to toxins Eating a balanced diet Correcting nutritional deficiencies Avoiding alchohol consumption Exercise Quitting smoking

Pharmacological First line treatments Second-line treatments Antidepressants (i.e., tricyclic antidepressants and dual reuptake inhibitors of both serotonin and norepinephrine) Calcium channel α2-δ ligands (i.e., gabapentin and pregabalin) Topical lidocaine Second-line treatments - Opioid analgesics and tramadol Third-line treatments -Antiepileptic and antidepressant medications, mexiletine, N-methyl-d-aspartate receptor antagonists, and topical capsaicin

Physical Therapy and Rehabilitation  Aerobic conditioning  Progressive flexibility/stretching exercises  Progressive strengthening exercises  Balance/coordination  Gait training  Alternative Monochromatic infrared Vibrating insoles Tai chi

Aerobic Conditioning

Flexibility Exercises Assessment from trunk to feet Goal is to normalize muscle length to allow for normal mechanics with movement

Strengthening Exercises Initial focus is on core, hip, knee, and ankle strengthening Progress into functional activities

Balance Exercises

Adaptive Devices • Prophylactic measures (eg. pressure sores) • Orthotics • Assistive devices • Walking aids • Wheelchairs • Environmental modifications

Surgical Options • Tendon transfers, releases • Procedures for pain relief (eg. ablation, implants) • Joint stabilization • Nerve repair, grafts