Peripheral Neuropathy Rebecca Meyerson, MD Neurology SMDC

Peripheral Nervous System Motor peripheral nerves: neuron in the anterior horn of the spinal cord, axon extends peripherally to the skin Sensory peripheral nerves: neuron in the dorsal root ganglia, axon extending peripherally to the skin surface Pathology of the peripheral nerve may take place at any place along its pathway, and any peripheral nerve lesion must first be localized. Anterior horn cell Spinal nerve root Nerve plexus Nerve (certain places are prone to compression or injury) Neuromuscular junction Muscle

Differentiating upper motor neuron and lower motor neuron lesions UMN lesion LMN lesion Muscle bulk Preserved Atrophy Muscle tone Spastic Flaccid Spontaneous movements None Fasciculation's Reflexes Increased Absent Babinski reflex Present

Peripheral Nerves Contain: Motor nerve fibers Sensory nerve fibers Large myelinated fibers: vibration, proprioception, light touch Small unmyelinated fibers: pain and temperature Autonomic nerve fibers

Nerve injury Compressive injury Vascular insult Axonal damage Metabolic disruption of axonal transport Ion channel dysfunction Demyelination Infiltrative process

Differentiating Clinical Features Radiculopathy Radiating pain in a nerve root distribution Weakness Decreased DTR Decreased sensation Often associated with back and neck pain, and muscle stiffness Aggravated by sneeze, cough, valsalva maneuver, neck/trunk movement Plexopathy Does not fit nicely into a root or nerve pattern Is typically unilateral Mononeuropathy Single nerve involved Mononeuropathy multiplex Multiple single nerves involved Polyneuropathy Chronic and insidious onset Length dependent pattern

Cervical Radiculopathies

Lumbar Radiculopathies L5 and S1 nerve root compression most common Pain radiates in the distribution of the nerve root

Mononeuropathies of the upper extremities Median neuropathy Ulnar neuropathy Radial neuropathy

Median neuropathy Vulnerable at the carpal tunnel Most common, most common neuro prob in pregnancy Pain severe at night Pain thumb, index and middle finger, split sensory loss 4th digit Motor usually confined to abductor pollicis brevis

Ulnar neuropathy Injury usually occurs at the elbow May occur from repeated and trivial trauma (resting elbow) Tardy ulnar palsy occurs after a childhood fracture of the supracondylar humerus Sensory loss medial aspect hand and forearm, medial 2 fingers Weakness of intrinsic hand muscles

Radial neuropathy

Radial neuropathy Damaged in the axilla by incorrect use of a crutch, causing weakness of all the radial nerve innervated muscles – triceps, wrist extensors, finger extensors and brachoradialis. Classic appearance – wrist drop and finger extension weakness. Sensory loss occurs on the dorsum of the hand Injury of the radial nerve in the medial aspect of the arm results in the Saturday night palsy. Occurs when inebriated or heavily sedated patients go to sleep with their arm hanging over the back of a chair or over the edge of the bed.

Peroneal neuropathy Nerve in leg most often damaged, usually by compression at the fibular neck where protected only by skin and fascia Weakness of dorsiflexion (foot drop) and eversion of the foot. (Distinction between peroneal and L5 root lesion – L5 affects dorsiflexion and inversion) Sensory loss occurs in the lower anterolateral leg and on to the dorsum of the foot in a triangular area.

Assessment of UE strength

Assessment of UE Strength

UE Radiculopathies

Sensory deficit in UE Mononeuropathies

Assessment of LE Strength

LE Radiculopathies

Electrodiagnostic studies

Electrodiagnostic studies

Clinical features of polyneuropathies Motor symptoms – weak, atrophy, diminished reflexes Sensory symptoms – loss of small fiber (pain temperature), loss of large fiber (vibration, propriception, light touch) Gain of abnormal sensation: allodynia, hyperalgesia, paresthesias Autonomic symptoms – orthostatic hypotension, impotence, gastroparesis, altered sweating response Orthopedic abnormalities – high arched feet and hammer toes suggests a long standing condition

Neurological clinical evaluation of polyneuropathy Sensory: evaluate at least one test of both large and small fiber modalities ie: vibration and pain Motor: assess muscle tone, visual inspection for fasciculations and atrophy, in addition to muscle srength Reflexes Gait: inability to walk on heels early sign of distal weakness Romberg: evaluates distal large fiber sensation

Clinical evaluation cont Electrodiagnostic studies (NCS/EMG) Extablish extent and involvement of nerve pathology Distinguish primary axonal or demyelinating process Will not tell you anything about small fiber dysfunction Nerve biopsy

Causes of polyneuropathy Diabetes, alcohol, hypothyroidism, uremia, amyloidosis, medications, B 12 deficiency, B1 deficiency, B6 deficiency or toxicity, arsenic, lead, HIV, hepatitis, leprosy, lyme, polyarteritis nodosum, lupus, sjogrens, chronic inflammatory demyelinating polyneuropathy, guillian barre syndrome, paraneoplastic, charcot marie tooth, diptheria, thallium, porphyoria, acrylamide, gold salts, methotrexae, nitrofurantoin………………………

Schema to tease out etiology of polyneuropathies Timing: chronic vs acute Modalities affected (large fiber, small fiber, motor, sensory) Distribution (symmetric, asymmetric, focal, multiple focal nerves) Nature of primary pathology (axonal vs demyelinating

Metabolic causes of polyneuropathy Diabetes: most common cause of neuropathy Occurs from a combination of metabolic and vascular abnormalities due to hyperglycemia Severity of diabetic neuropathy correlates with the severity of hyperlipidemia and hypertension No treatment to reverse pathology Management: optimize blood glucose control, foot care, and symptomatic treatment of neuropathic pain

Metabolic etiologies Diabetes: typically cause symmetric sensorimotor axonal neuropathy Other presentations: sensorimotor demyelination prominent autonomic involvement mononeuropathy-especially carpal tunnel syndrome, truncal radiculopathies, cranial neuropathies (CN3) Mononeuropathy multiplex: results in simultaneous dysfunction of several peripheral nerves, due to ischemic infarction of the vasa nervorum Diabetic amyotrophy (ischemic infarction of the lumbosacral plexus) Uremia: symmetric sensorimotor axonal neuropathy Hypothyroidism: sensorimotor neuropathy, entrapment neuropathy (carpal tunnel syndrome)

Nutritional etiologies of polyneuropathies B12 deficiency: sensorimotor axonopathy, myelopathy involving the posterior columns B6 deficiency or toxicity: myelopathy and axonal sensorimotor neuropathy Thiamine deficiency: (wernickes-korsakoff syndrome), axonal sensorimotor neuropathy, can be rapid onset and progression. (thiamine needed for metabolism carbohydrates/amino acids) Copper deficiency: axonal sensorimotor axonopathy, myelopathy Zinc toxicity: due to induced copper deficiency, axonal sensorimotor neuopathy, myelopathy with posterior column (sensory ataxia) Vitamin E deficiency: axonal sensorimotor neuropathy, myelopathy

Infectious etiologies of polyneuropathies HIV Distal symmetric sensori>motor neuropathy Inflammatory polyneuritis of buillian barre type at the time of seroconversion Lyme disease Multifocal spinal root or cranial nerve (often facial nerve palsy) Demyelinating and axonal neuropathy often with multiple nerve root involvement Hepatitis C and cryoglobulinemia: vasculitis associated Painful, asymmetric sensorimotor polyneuropathy or multiple mononeuropathies Diptheria: Toxin mediated sensorimotor neuropathy Prominent autonomic disurbance

Toxic etiologies of polyneuropathies Alcohol: slowly progressive, distal, painful, symmetric sensorimotor axonal neuropathy. Nutritional factors likely contribute Lead toxicity: motor predominant, often presents with radial nerve associated wrist drop Arsenic toxicity: motor predominant sensorimotor demyelinating>axonal neuropathy. Can mimic guillian barre Multiple medications: nitrofurantoin, vincristine, amiodarone, phenytoin: usually produce a sensorimotor axonal neuropathy

Inflammatory/immune mediated etiologies of polyneuropathy Vasculitis: systemic lupus erythematosis, sjogrens, polyarterosis nodosum, wegeners granulomatosis, microscopic polyangiitis, rheumatoid arthritis Painful mononeuropathies or mononeuropathy multiplex Acute or subacute onset Paraprotinemic neuropathy: Monoclonal gammaopathy, excessive amounts of abnormal immunoglobulin produced by a single clone of plasma cell Several distinct peripheral neuropathy syndromes Symmetric polyneuropathy, (mononeuritis multiplex, mononeuropathy), demyelinating>axonal

Inflammatory/immune mediated etiologies of polyneuropathy CIDP (chronic inflammatory demyelinating polyradiculoneuropathy) Acquired neuropathy due to immune mediated demyelination Chronic progressive or relapsing-remitting neuropathy Symmetric sensorimotor neuropathy with predominant motor symptoms, demyelinating changes on EMG Subacute weakness proximally and distally variable sensory loss, areflexia Left untreated: continuously progressive or relapsing remitting course Treatment: corticoids, IVIG, plasma exchange

Hereditary etiologies of polyneuropathy Hereditary sensory motor neuropathy (HSMN) = charcot marie tooth (many genetic disorders identified, with distinct clinical syndromes) Genetic defect of axonal and myelin proteins Onset of symptoms is insidious and progression is indolent, often onset in childhood/adolenscence or early adulthood, progresses gradually throughout adult life Significant motor involvement, striking atrophy of the muscles of the foot, calf and hands Hereditary Sensory Motor Neuropathy HSMN-1 Demyelinating polyneuropathy Autosomal dominant pattern Striking atrophy calves (stork legs) Large fiber sensory loss with marked reduction in vibratory perception and proprioception

Distal symmetric polyneuropathy Pattern seen with most metabolic, toxic and nutritional etiologies Axonal predominant Length dependent (symptoms begin in the feet and progress rostrally), the stocking-glove pattern. The offending agent affects protein synthesis in the cell body of the peripheral nerve and then impairs axonal transport Dysfunction first occurs in the distal portions of the longest axons, thus in the most distal portions of the extremities Small diameter axons are most susceptible to metabolic injury because of their small size and lack of reserve Initial symptoms typically include autonomic dysfunction and small fiber sensory modalities, including loss of pain and temperature Clinical presentation: numbness, paresthesias, burning discomfort Loss sensation distal LE, later loss of achilles reflex and weakness intrinsic foot muscles

Distal symmetric polyneuropathy Examples Diabetes Alcohol Nutritional deficiencies Medications

Symmetric or asymmetric demyelinating polyneuropathy Demyelinating more than axonal involvement Numbness and weakness in a length dependent fashion Clinically: sensory loss in feet, and weakness (footdrop) Examples: Hereditary sensory motor neuropathies CIDP

Multifocal axonal neuropathy (mononeuropathy multiplex) Individual nerves are affected in a patchy fashion (ie: left median nruopathy, then right peroneal neuropathy) Underlying pathology ischemic infarction of the vasa nervorum Painful and cause profound weakness Prognosis for recovery is good assuming the underlying disease can be suppressed Examples: Vasculitis Diabetes

Acute polyneuropathies Guillian Barre syndrome (acute inflammatory demyelinating polyradiculoneuropathy): Rapidly progressive Motor predominence Diffuse polyradiculoneuropathy Clinical presentation: Nearly symmetric, rapidly ascending motor weakness often with associated paresthesias Often striking autonomic involvement (resting tachycardia, fluctuations in blood pressure)

Guillian-Barre syndrome cont Often follows a systemic infection Campylobacor jejuni infection Weakness reaches its nadir within the first 2 weeks, may require intubation and respiratory suppport Rate of recovery is accelerated by plasma exchange or IVIG

Other acute neuropathies Neurotoxins: Medications – acute onset symmetric neuropathy Toxic exposures – heavy metals Vasculitic neuropathies – especially if multiorgan involvement, multifocality, or severe pain

Acute motor weakness Disorders of neuromuscular transmission and muscle should be considered if rapidly progressing weakness without sensory findings

General principles of treatment of neuropathies Patient education and counseling, genetic counseling Withdrawal of medications suspected, or toxic exposure Correction of nutritional and vitamin deficiencies Treatment of alcoholism Blood glucose control in diabetics Specific drug therapies: chelating agents in lead neuropathy, prednisone in CIDP, plasmapheresis or IVIG for GBS Pain control: gabapentin, carbamazepine, other anticonvulsants, tricyclics, transcutaneous electrical nerve stimulation Meticulous foot care Orthotic devices and splints Surgical correction of entrapment neuropathies Physical and occupational therapy