EVALUATION AND MANAGEMENT OF PERIPHERAL NEUROPATHY

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EVALUATION AND MANAGEMENT OF PERIPHERAL NEUROPATHY

• NAYEEM KARIM, DO
• Diplomate, American Board of Psychiatry and
  Neurology
• October 27, 2012

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OBJECTIVES

• PERIPHERAL NEUROANOTOMY NEUROPHYSIOLOGY
• CLINICAL FEATURES
• PHYSICAL EXAM FEATURES
• DIAGNOSTIC APPROACH
• ELECTRODIAGNOSTIC EVALUATION
• TREATMENT OPTIONS

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GBS IN KIDS

• Most common cause of acute flaccid paralysis in
  childhood, affecting 1 in 100,000 children each
  year.
• Several forms besides acute inflammatory
  demyelinating polyradiculoneuropathy (AIDP),
  including Miller Fisher syndrome, acute motor and
  sensory axonal neuropathy (AMSAN), and acute
  sensory axonal neuropathy (ASAN).

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• Ascending weakness is the hallmark of GBS, but
  pain may be the initial manifestation in almost
  half of affected children.
• Ataxia and cranial nerve findings are more
  frequent than in adults with this syndrome.

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• The most common serious complications are
  weakness of the respiratory muscles and autonomic
  instability.
• Pneumonia, respiratory distress syndrome,
  septicemia, pressure sores, and pulmonary embolus
  are also important complications.

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• In general, the outcome of GBS is more favorable
  in children than adults.
• The recovery period is longer than the duration
  of the acute illness, often weeks to months, with
  a median estimated recovery time of 7 months.

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CASE STUDIES

• Seven children with GBS treated with IVIg
  compared to eight children treated with
  plasmapheresis alone had similar clinical
  results. However, the need for admission to PICU
  and duration of ICU stay were lower in the IVIg
  group. IVIg recommended as initial therapy for
  pediatric GBS, because it was equally as
  effective as plasmapheresis and associated with
  fewer complications.
• (J Child Neurol. 1997 Sep)

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AMERICAN ACADEMY OF NEUROLOGY

• Both IVIg and plasma exchange are class B
  treatment option recommendations for children
  with severe GBS.

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PERIPHERAL NEUROANATOMY

• Cranial Nerves
• Spinal nerve roots
• Dorsal root ganglia
• Peripheral nerve trunks branches
• Peripheral autonomic nervous system

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Brachial Plexus
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LUMBAR PLEXUS
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Structure of Peripheral Nerves
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A Typical Neuron Overview

• Dentrites
• Cell Body
• Axon
• Terminal

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Action Potential Stages Overview
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Saltatory Conduction
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PATHOPHYSIOLOGY
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WALLERIAN DEGENERATION
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CLINICAL HISTORY

• PMHx infection, cancer, connective tissue,
  vascular, endocrine
• Medications
• Trauma
• Drugs, ETOH, exposure to heavy metals/ solvents/
  toxins
• HIV risk factors
• Foreign Travel
• Diet (nutrition)
• Vitamin Use
• Family History

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CLINICAL FEATURES OF SMALL FIBER NEUROPATHIES

• Small fiber burning/ lancinating pain, aching,
  dysesthesias, allodynia, paresthesias,
  hyperesthesia
• In chronic Axonal Neuropathies, the longer axons
  are affected first, resulting in symptoms that
  begin in the LE. Slow insidious progression,
  sensory symptoms precede motor symptoms, pain is
  often a predominant component. Primarily
  affecting the small unmyelinated fibers
  (Spinothalamic Tracts)
• As the syndrome progresses, mild weakness of the
  distal extremities and numbness may extend
  proximally
• Classic stocking and glove distribution of
  sensory loss
• Autonomic involvement

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Small-fiber Neuropathies

• Leprosy
• Diabetes
• Alcoholic Neuropathy
• Amyloidosis
• AIDS
• Hereditary

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Neuropathies with Autonomic Involvement

• Diabetic Polyneuropathy
• Amyloidosis
• Porphyria
• Paraneoplastic Syndromes
• GBS (Acute panautonomic neuropathy)
• HIV/ AIDS

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Neuropathies with Cranial Nerve Involvement

• Diabetes
• GBS (Miller-Fisher syndrome)
• HIV
• Lyme
• Sarcoidosis

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Clinical Features of Large Fiber Neuropathies

• Large fiber myelinated fibers (Posterior
  Columns) decreased VS proprioception, motor
  related complaints secondary to reduced
  proprioception. Imbalance, tripping, gait
  instability, weakness, loss of grip strength,
  difficulty climbing stairs, getting out of chair
• Demyelinating Neuropathies affects
  predominantly motor nerve fibers. So weakness
  rather than sensory loss is typically one of the
  earlier findings. Eventually complain of
  dysesthesias distally in the legs or arms.
  Clinical course is variable. On exam distal
  muscles are predominantly affected.

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3 TYPES OF PERIPHERAL NEUROPATHY

• Mononeuropathy symptoms and signs related to
  the particular nerve
• Polyneuropathies trouble turning keys in locks,
  having to use both hands to start ignition in
  car, weakness of feet/ ankles resulting in foot
  drop or ankle sprains
• Mononeuropathy Multiplex

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Neuropathic Pain Descriptors

• Burning
• Electricity
• Jabbing
• Broken Glass
• Spasms
• Icy Cold
• Unpleasant Paresthesia

• Squeezing
• Deep Aching
• Sharp
• Cramping
• Sunburn
• Frostbite
• Dysesthesias
• Intense Itching

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NEUROLOGIC EXAM

• General Physical Exam orthostatic hypotension,
  respiratory rate, vital capacity, organomegaly,
  skin lesions
• Cranial Nerves
• Fundoscopic
• Pattern of Weakness
• Pattern of Sensory Loss stocking/ glove, focal,
  dermatomal/ nerve root distribution
• Type of Sensory Loss pain and temp vs light
  touch and proprioception

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Neurologic Exam

• DTRs reduced/ absent (axonal vs demyelinating)
• Musculoskeletal Exam pes cavus, claw toes,
  hammer toes, high arches, foot drop,
  kyphoscoliosis, peroneal muscular atrophy,
  wasting of distal extremities
• Coordination gait ataxia, romberg,
  incoordination secondary to proprioceptive loss

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Common Mononeuropathies

• Median at the Wrist (CTS)
• Ulnar at the Elbow (Cubital Tunnel Syndrome)
• Facial (Bells Palsy)
• Radial at the Spinal Groove (Wrist Drop)

• Sciatic in the Thigh
• Peroneal at Fibular Head (Foot Drop)
• Lateral Femoral Cutaneous
• Femoral
• Spinal Accessory

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Mononeuritis Multiplex Differential Diagnosis

• Churg-Strauss
• Diabetes
• HIV
• Ischemia
• Sarcoidosis
• Rheumatoid Arthritis
• Neoplastic Infiltration

• CMV
• Giant Cell Arteritis
• Leprosy
• SLE
• Vasculitis
• Trauma
• Polyarteritis Nodosa

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Peripheral Neuropathies Etiologies

• Alcohol abuse
• Endocrine DM, Hypo T4
• Nutritional Thiamine, Pyridoxine, B12, Vitamin E
• Metabolic Uremia, Liver Disease
• Inflammatory GBS, CIDP, MMM, AMAN, AMSAN,
  Sarcoidosis, Critical illness Polyneuropathy

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• Connective Tissue Lupus, RA, Sjogrens Syndrome,
  PAN
• Infectious Diseases HIV, Lyme, Hepatitis,
  Leprosy
• Hematalogic Paraproteinemia (MGUS),
  Cryoglobulinemia, Porphyria, Amyloidosis,
  Multiple Myeloma, Leukemia, Waldenstroms
  macroglobulinemia
• Paraneoplastic

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Inherited Neurogenetic Diseases

• Giant axonal neuropathy
• Familial dysautonomia syndromes
• Spinocerebellar ataxias
• Dentatorubral-pallidoluysian atrophy
• Ataxia with vitamin E deficiency
• Abetalipoproteinemia
• Hereditary Neuropathy with Predilection to
  Pressure Palsies

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INBORN ERRORS OF METABOLISM

• Mitochondrial disorders
• MELAS, MERRF, Leigh disease, Kearns-Sayre
  syndrome
• Peroxisomal disorders
• Refsum disease, Adrenoleukodystrophy
• Lysosomal storage diseases
• Krabbes disease, Metachromatic leukodystophy,
  Niemann-Pick type C
• Leukodystrophies
• Alexander, Canavan, Pelizaeus-Merzbacher

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DRUG INDUCED NEUROPATHIES

• AXONAL
• Vincristine
• Taxol
• Colchicine
• Isoniazid
• Pyridoxine
• Dapsone
• Dilantin

• DEMYELINATING
• Amiodarone
• Chloroquine
• Gold

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Drug Induced Neuropathies

• Statins
• Nitrofurantoin
• Cisplatin
• Thalidomide
• Ara-C

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DIFFERENTIAL BY CLINICAL COURSE
Acute onset (within days) Subacute (wks to mnths) Chronic Course
Ischemic Toxins/ meds Endocrine
GBS Nutritional Hereditary
Acute Int. Porphyria Metabolic Metabolic Diseases
Critical illness polyneuropathy Paraneoplastic
Connective tissue Infection
Traumatic
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Subtypes of CMT Neuropathies
Disease Name Pathology Inheritance Prop. of CMT
CMT1 Abnormal myelin AD 50
CMT2 Axonopathy AD 20-40
Intermediate form Combination AD Rare
CMT4 Myelinopathy or Axonopathy AR Rare
CMTX Axonopathy with myelin changes XLD 10-20
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CLINICAL FEATURES OF CHARCOT-MARIE TOOTH DISEASE
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CLINICAL FEATURES OF CHARCOT-MARIE TOOTH DISEASE
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Charcot-Marie Tooth
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Peripheral Neuropathy Questionnaire

• Family Member
• (Circle yes or no)
  
  
  
• High arches YES
  NO
• Curled toes
  YES NO
• Soak feet
  YES NO
• Twist ankles easily YES
  NO
• Use of cane/crutches YES
  NO
• Foot surgery YES
  NO
• Casting of feet as a child YES
  NO
• Corrective shoes
  YES NO
• Cramps
  YES NO
• Skinny legs
  YES NO
• Numbness of feet/hands YES
  NO
• Difficulty buying shoes YES
  NO
• Burning of feet YES
  NO
• Painful feet
  YES NO

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NEUROPATHOLGY OF CMT
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• NORMAL ONION BULB
• FORMATION

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Hereditary Motor and Sensory Neuropathy
Type Inheritance Onset Neuro-pathy
HMSN1 (CMT1) AD 17 Childhood D
HMSN2 (CMT2) AD 1p Second decade Axonal
HMSN3 (Dejerine-Sottas) AR 1q or 17p Infancy D
HMSN4 (Rousy-Levy) AD Infancy D
HMSN5 (Refsum) AR Childhood D
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Hereditary Neuropathy with Autonomic Features
Type Inheri- tance Onset Pathology
HSAN1 AD 2nd decade DRG neurons
HSAN2 AR Infancy Absence of myelinated fibers
HSAN3 AR Birth Absence of myelinated fibers
HSAN4 AR Birth Absence of DRG neurons
Friedreich ataxia AR Before age 20 Loss of large myelinated fibers
Ataxia telangiectasia AR Before age 5 Loss of large unmyelinated fibers
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LABORATORY EVALUATION

• CBC, CMP
• HgA1c, TSH, ESR, SPEP, ANA
• Rheumatologic Screen
• HIV testing
• ACE level
• Paraneoplastic Panel
• 24hr urine for heavy metals
• CSF analysis

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ADDITIONAL TESTING

• EMG/ NCS
• Sural Nerve Biopsy
• Skin Punch Biopsy (Immunoflourescence of epidural
  nerve density)

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NERVE CONDUCTION STUDIES
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NERVE CONDUCTION STUDIES

• AMPLITUDE size of the response after the muscle
  / nerve is stimulated. Often corresponds to
  axonal injury.
• LATENCY time interval from nerve stimulation to
  recorded response. Corresponds to demyelinating
  injury.

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• NERVE CONDUCTION VELOCITY (m/s) Distance (m) /
  Time (s)
• (Proximal latency Distal latency) /
• (distance between proximal distal site)
• 8.5 ms 3.5 ms/ 23cm 46m/s

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Polyneuropathy Treatment

• Proper diet, strict blood glucose control
• Correction of hormone deficiency / over secretion
• Parenteral B12
• Removal of toxins
• Corticosteroids
• Genetic counseling for familial neuropathy

• Vitamin supplementation
• Immunosuppression
• Plasma exchange
• Intravenous IgG
• Treatment of HIV, infection, lyme, leprosy
• Physical therapy / orthotics

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Treatment of Neuropathic Pain

• NSAIDs
• Antidepressants (cymbalta, elavil, pamelor)
• Anticonvulsives (neurontin, lyrica, lamictal)

• Topical neuropathic creams
• Epidural spinal cord stimulation
• Anodyne therapy
• SSRIs

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Neroupathic Pain

• Pregabalin
• Dosage range 25 mg to 900 mg per day
• Effective for pain, sleep, and mood
• Side effects dizziness, somnolence, and weight
  gain
• Gabapentin
• Dosage range 100 mg to 4800 mg per day
• Effective for shooting and burning pain,
  allodynia, hypesthesia, and sleep
• Side effects drowsiness, fatigue, imbalance,
  cognitive issues

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• TOPICAL PAIN CREAMS
• ANTI-INFLAMMATORY CREAMS
• (Ketorolac, Diclofenac, Cyclobenzaprine,
  Baclofen)
• NEUROPATHIC PAIN CREAMS
• (Gabapentin, Imipramine, Amitriptyline)
• COMBINATION PAIN CREAMS
• (Baclofen, Diclofenac, Gabapentin, Lidocaine,
  Nifedipine)

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THANKS

• Abd-Allah SA. IVIg as therapy for pediatric GBS.
  J Child Neurol. 1997.
• Bracker MD. The Numb Arm and Hand. Am Fam
  Physician 1995 103-16.
• Donofrio P. Peripheral Neuropathy Diagnosis and
  Treatment, ACNS Annual Course in Clinical EEG
  and Electrophysiology 2008.
• Hughes RAC. Practice parameter immunotherapy for
  GBS. Neurology 2003.
• Maria B. GBS. Current Management in Child
  Neurology 2005 630-633.
• McLeod JG. Investigation of Peripheral
  Neuropathy. J Neurol Neurosurg Psychiatry 1995
  274-83.
• Poncelet A. An Algorithm for the Evaluation of
  Peripheral Neuropathy, American Family Physician
  1998.
• Thomas PK, Ochoa J. Symptomology and
  Differential Diagnosis of Peripheral Neuropathy
  1993 749-74.