Peripheral Nerve Diseases Prof. Dr. Ece AYDOĞ 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

Peripheral Nervous System Divisions Somatic System –Motor –Sensory Autonomic System –Sympathetic –Para-Sympathetic

Somatic Nervous System - controls skeletal muscle as well as external sensory organs. Somatic Nervous System - controls skeletal muscle as well as external sensory organs. –Sensory Nervous System - sends information to the CNS from internal organs or from external stimuli. -- Motor Nervous System - carries information from the CNS to organs, muscles, and glands. Autonomic Nervous System - controls involuntary muscles, such as smooth and cardiac muscle. Sympathetic - controls activities that increase energy expenditures. Parasympathetic - controls activities that conserve energy expenditures.

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

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

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) NeurapraxiaAxonotmesisNeurotmesis

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

Neurapraxia

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

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

Type 2 Type 3 Type 4 Type 5 Axonotmesis Neurotmesis

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

Type 2 Type 3 Type 4 Type 5 Axonotmesis Neurotmesis

Clinical Manifestations of Neuropathy Some combination of motor, sensory and sometimes autonomic deficits – –Motor symptoms: weakness – –Sensory - most neuropathies present with slowly progressing, symmetrical sensory loss, often "stocking/glove" distribution

Clinical manifestations of neuropathy -Loss of deep tendon reflexes - lesion anywhere in reflex arc -Autonomic - postural hypotension, anhidrosis, weak bowel and bladder sphincters, impotence, unreactive pupils -Some neuropathies, especially vasculitis - multiple nerves involved asymmetrically - mononeuropathy multiplex

Peripheral Neuropathy Mode of Onset AcuteSubacuteChronic

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: 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 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 LeukodystrophiesPorphyria

4. Miscellaneous neuropathies Amyloid Paraneoplastic Compression

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

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

Peripheral Neuropathy Symptomatology-Sensory Sensory Changes: Sensory Changes:  Hyposthesia ParastheasiaDysthesiaAllodyniaHyperalgesia

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

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

Peripheral Neuropathies “ clinical types” diagnosis PolyneuropathyMononeuropathy Mononeuritis Multiplex (Multiple Mononeuropathy) Plexopathy

Diagnosis A strong clinical suspicion will suffice to make a clinical diagnosis. To support the diagnosis some investigatios are necessary these include: 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

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 Gait (foot drop, stepage, unsteady Romberg positive) Cranial Nerves (retinopathy; facial, bulbar, or neck weakness, tonic pupils) Limbs Pseudoathetosis, Pes cavus, Clawing, Wasting, fasiculation Flaccidity, palpable nerves Distal weakness (radiculopathy) Reduced or absent DTRs Glove loss, allodynia (Small or large fibre) Systemic rash, BP

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 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 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 Methyl cobalamin Alpha lipoic acid Vit B complex TCACarbamazepineGabapentinLamotriginePhenytoin Opioid analgesice Tramadol

Physical Therapy and Rehabilitation Modalities for pain relief (heat, cold, TNS biofeedback) Therapeutic exercise OCCUPATIONAL ADL vocational (re-)training PSYCHO-SOCIAL family counselling vocational and avocational

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

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

Mononeuropathies 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

Clinical features Initial sensory (numbness- dull pain) for days Progressive ascending paralysis over days- 3weeks: May involve respiratory, facial and extraocular muscles Autonomic dysfunction Plateau for weeks Progressive good recovery in > 80% over few months

Management of GBS Medical Emergency Close monitoring in the early phase –Swallowing ( NG feeding) –Respiration: VC > 1.5 litre –BP and heart rhythm LP: cytoalbominologic dissociation Plasmapheresis/IVIG in 1 st 2-3 weeks Physiotherapy