#1013 Approaching Neuropathies

January 18 to 21

Steven M. Nash, MDAssistant Professor of Clinical NeurologyDepartment of NeurologyThe Ohio University Medical Center

Isabelle Periquet, MDAssistant Professor of NeurologyDepartment of NeurologyThe Ohio University Medical Center

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Steven M. Nash, MDAssistant Professor of Clinical Neurology

Department of NeurologyThe Ohio University Medical Center

Profile Profile

Mr. Winkleman• 67 year old male

Symptoms• Falling down frequently• Unexplained weight loss• Low back, hip, and leg pain• Tingling in right side of trunk• Right foot drop

Mr. Winkleman• 67 year old male

Symptoms• Falling down frequently• Unexplained weight loss• Low back, hip, and leg pain• Tingling in right side of trunk• Right foot drop 2

Profile Profile

Mr. WinklemanEvaluation• Weakness in multiple muscle groups - Asymmetrical from side to side• Less severe sensory loss• EMG showed active, asymmetrical sensory motor polyneuropathy• Sural nerve biopsy revealed vasculitic neuropathyDiagnosis: Vasculitic neuropathy

Mr. WinklemanEvaluation• Weakness in multiple muscle groups - Asymmetrical from side to side• Less severe sensory loss• EMG showed active, asymmetrical sensory motor polyneuropathy• Sural nerve biopsy revealed vasculitic neuropathyDiagnosis: Vasculitic neuropathy 2A

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Key PointsKey Points

• Neuropathies may present in many different ways

• Neuropathy is a result of some other pathology

• Treatment requires identification and removal of the underlying cause

• Work-up includes a careful history and physical exam, blood work, and EMG

• Neuropathies may present in many different ways

• Neuropathy is a result of some other pathology

• Treatment requires identification and removal of the underlying cause

• Work-up includes a careful history and physical exam, blood work, and EMG

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Neuropathies Neuropathies

• Mononeuropathy (including radiculopathy, plexopathy)

• Multiple mononeuropathies

• Neuronopathy

• Axonal polyneuropathy

• Demyelinating polyneuropathy

• Mononeuropathy (including radiculopathy, plexopathy)

• Multiple mononeuropathies

• Neuronopathy

• Axonal polyneuropathy

• Demyelinating polyneuropathy

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Peripheral Motor Neurons Peripheral Motor Neurons

• Cell bodies located in anterior horn of spinal cord or in brainstem nuclei

• Axons myelinated

• Axons terminate on skeletal muscle fibers

• Cell bodies located in anterior horn of spinal cord or in brainstem nuclei

• Axons myelinated

• Axons terminate on skeletal muscle fibers

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Peripheral Motor Neurons Peripheral Motor Neurons

• Cell bodies in dorsal root ganglia (pseudounipolar)

• Both myelinated (proprioception) and unmyelinated (pain/temperature) axons

• Terminate in sensory receptors

• Cell bodies in dorsal root ganglia (pseudounipolar)

• Both myelinated (proprioception) and unmyelinated (pain/temperature) axons

• Terminate in sensory receptors

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PeripheralAutonomic Neurons

PeripheralAutonomic Neurons

• Cell bodies (second order neurons) in spinal cord nuclei. Axons terminate on third order neurons in autonomic ganglia• Axons are unmyelinated (slow)

• Axons of third order neurons terminate in glands and smooth muscle

• Cell bodies (second order neurons) in spinal cord nuclei. Axons terminate on third order neurons in autonomic ganglia• Axons are unmyelinated (slow)

• Axons of third order neurons terminate in glands and smooth muscle 8

Symptoms of Neuropathy Symptoms of Neuropathy

• Numbness

• Imbalance

• Burning, stinging pain dysesthesia)

• Insomnia

• Depression

• Weakness

• Numbness

• Imbalance

• Burning, stinging pain dysesthesia)

• Insomnia

• Depression

• Weakness9

Signs of Neuropathy Signs of Neuropathy

• Loss of position and vibration sensitivity

• Pain and temperature loss

• Romberg sign

• Weakness and loss of reflexes

• Trophic changes of skin, hair loss, decrease / increase of sweating

• Loss of position and vibration sensitivity

• Pain and temperature loss

• Romberg sign

• Weakness and loss of reflexes

• Trophic changes of skin, hair loss, decrease / increase of sweating

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Common Causesof Neuropathy

Common Causesof Neuropathy

• Diabetes• Alcohol abuse

• Diabetes• Alcohol abuse

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Presentations ofDiabetic Neuropathy

Presentations ofDiabetic Neuropathy

• Mononeuropathy (including cranial nerves, lumbosacral plexus)

• Multiple mononeuropathies

• Distal sensorimotor polyneuropathy

• Mononeuropathy (including cranial nerves, lumbosacral plexus)

• Multiple mononeuropathies

• Distal sensorimotor polyneuropathy

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Alcoholic Neuropathies Alcoholic Neuropathies

• Direct toxic effect

• Secondary nutritional effects (vitamin deficiencies)

• Direct toxic effect

• Secondary nutritional effects (vitamin deficiencies)

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Uncommon Causesof Neuropathy

Uncommon Causesof Neuropathy

• Nutritional (vitamin deficiencies)

• Guillain-Barre syndrome

• Toxic (drugs, hexacarbons, heavy metals)• Hereditary• Rheumatologic disease• Amyloid

• Nutritional (vitamin deficiencies)

• Guillain-Barre syndrome

• Toxic (drugs, hexacarbons, heavy metals)• Hereditary• Rheumatologic disease• Amyloid 14

Other Uncommon Causes Other Uncommon Causes

• Paraneoplastic (Anti-Hu)

• Infection

• Systemic disease (uremia, hypothyroid, etc)

• Tumors (Especially in neurofibromatosis, type1)

• Paraneoplastic (Anti-Hu)

• Infection

• Systemic disease (uremia, hypothyroid, etc)

• Tumors (Especially in neurofibromatosis, type1)

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Guillain-Barre SyndromeGuillain-Barre Syndrome

• “Ascending paralysis”, loss of reflexes

• Elevated CSF protein, normal cell count

• Slowing on nerve conduction studies

• Diagnosis often requires high index of suspicion

• Most recover with prompt care

• Plasmapheresis / IVIg both speed recovery

• “Ascending paralysis”, loss of reflexes

• Elevated CSF protein, normal cell count

• Slowing on nerve conduction studies

• Diagnosis often requires high index of suspicion

• Most recover with prompt care

• Plasmapheresis / IVIg both speed recovery

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Neuropathy Due toVasculitis

Neuropathy Due toVasculitis

• May be isolated to peripheral nerves

• Sometimes associated with rheumatologic diseases• Multiple mononeuropathies• Requires nerve biopsy for definite diagnosis• Treated with corticosteroids; cyclophosphamide often required

• May be isolated to peripheral nerves

• Sometimes associated with rheumatologic diseases• Multiple mononeuropathies• Requires nerve biopsy for definite diagnosis• Treated with corticosteroids; cyclophosphamide often required 17

Blood Work in Work-upof Neuropathy PatientsBlood Work in Work-upof Neuropathy Patients

• Glucose, BUN, creatinine, liver enzymes, TSH, ESR, hemoglobin A1C, serum protein electrophoresis

• ANA, RF, ANCA in selected patients• Gene testing in selected patients

• Antibody testing in selected patients

• Glucose, BUN, creatinine, liver enzymes, TSH, ESR, hemoglobin A1C, serum protein electrophoresis

• ANA, RF, ANCA in selected patients• Gene testing in selected patients

• Antibody testing in selected patients

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Antibody Testingin Polyneuropathies

Antibody Testingin Polyneuropathies

• Anti-Hu useful in sensory neuronopathies

• Anti-GM1 only for motor neuropathies in the absence of conduction block on NCS

• Anti-MAG, anti-sulfatide not helpful for diagnosis or treatment

• Anti-Hu useful in sensory neuronopathies

• Anti-GM1 only for motor neuropathies in the absence of conduction block on NCS

• Anti-MAG, anti-sulfatide not helpful for diagnosis or treatment

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Electromyography / NerveConduction Studies

Electromyography / NerveConduction Studies

• Used to evaluate function of the large, myelinated peripheral nerve fibers

• All patients with clinical evidence of polyneuropathy should be studied to determine distribution, type (axonal vs. demyelinating), severity, and activity

• Used to evaluate function of the large, myelinated peripheral nerve fibers

• All patients with clinical evidence of polyneuropathy should be studied to determine distribution, type (axonal vs. demyelinating), severity, and activity

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ConclusionsConclusions

• Neuropathies may present in many different ways

• Neuropathy is a result of some other pathology

• Treatment requires identification and removal of underlying cause

• Work-up includes a careful history and physical exam, blood work, and EMG

• Neuropathies may present in many different ways

• Neuropathy is a result of some other pathology

• Treatment requires identification and removal of underlying cause

• Work-up includes a careful history and physical exam, blood work, and EMG

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Summary Summary

Mr. WinklemanTreatment• IV corticosteroids• Tapering dose of oral Prednisone• Six months of oral Cytoxan• Physical therapy• Not back to baseline, but improving• Re-gained some weight

Prognosis: Good

Mr. WinklemanTreatment• IV corticosteroids• Tapering dose of oral Prednisone• Six months of oral Cytoxan• Physical therapy• Not back to baseline, but improving• Re-gained some weight

Prognosis: Good 22

Isabelle Periquet, MDDirector, Peripheral Neuropathy Center

Assistant Professor of NeurologyDepartment of Neurology

The Ohio University Medical Center 23

Profile Profile

Mrs. Blanton

• 57 year old female

Symptoms• 8 year history of burning foot pain• Tingling sensations

Mrs. Blanton

• 57 year old female

Symptoms• 8 year history of burning foot pain• Tingling sensations

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Profile Profile

Mrs. Blanton

Evaluation• Strength preserved• Reflexes preserved• Sensory testing: - Normal vibration, position and light touch sensation - Diminished pin sensation• Normal EMG

Diagnosis: ?

Mrs. Blanton

Evaluation• Strength preserved• Reflexes preserved• Sensory testing: - Normal vibration, position and light touch sensation - Diminished pin sensation• Normal EMG

Diagnosis: ? 24 A

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EvaluationEvaluation

• Is this a neuropathy or is it something else?

• How can I confirm a diagnosis of neuropathy?

• What laboratory tests are needed to evaluate for a cause?

• How do I treat this patient?

• Is this a neuropathy or is it something else?

• How can I confirm a diagnosis of neuropathy?

• What laboratory tests are needed to evaluate for a cause?

• How do I treat this patient?26

Painful Sensory NeuropathyProspective Evaluation Using Skin Biopsy

Painful Sensory NeuropathyProspective Evaluation Using Skin Biopsy

• 140 consecutively referred patients

• Inclusion criteria - Pain in the extremities as a primary complaint - No significant weakness

- No identified cause

• 140 consecutively referred patients

• Inclusion criteria - Pain in the extremities as a primary complaint - No significant weakness

- No identified cause

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Evaluation: EMG / NCSEvaluation: EMG / NCS

114 Patients

EMG / NCS

Abnormal Normal 60/114 (53%) 54/114 (47%)

QST AUTO

Skin Biopsy

114 Patients

EMG / NCS

Abnormal Normal 60/114 (53%) 54/114 (47%)

QST AUTO

Skin Biopsy28

Evaluation: QSTEvaluation: QST

• Computerized method of determining vibration threshold (large fiber function) and temperature threshold (small fiber function)

• QST was abnormal in 72% of patients with normal EMGs

• Computerized method of determining vibration threshold (large fiber function) and temperature threshold (small fiber function)

• QST was abnormal in 72% of patients with normal EMGs

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Evaluation: Autonomic TestingEvaluation: Autonomic Testing

• Battery of tests evaluating sweat function (QSART), heart rate and blood pressure responses to deep breathing, valsalva and tilt

• QSART was abnormal in 59% of patients with normal EMG’s

• Battery of tests evaluating sweat function (QSART), heart rate and blood pressure responses to deep breathing, valsalva and tilt

• QSART was abnormal in 59% of patients with normal EMG’s

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Evaluation: Blood StudiesEvaluation: Blood Studies

• Routine blood studies - CBC, lytes, ESR, BUN, Cr, Ca++, LFTs, TSH, HgbA1C, B12 (MMA, HC), chol, TG

• Immune / infectious blood studies - HIV, FTA, ANA, ENA, RF, IEP with IF - Nerve antibodies (GM1, MAG, SGPG, Hu, sulfatide)

• DNA - PMP22 mutations, FAP (met 30)

• Routine blood studies - CBC, lytes, ESR, BUN, Cr, Ca++, LFTs, TSH, HgbA1C, B12 (MMA, HC), chol, TG

• Immune / infectious blood studies - HIV, FTA, ANA, ENA, RF, IEP with IF - Nerve antibodies (GM1, MAG, SGPG, Hu, sulfatide)

• DNA - PMP22 mutations, FAP (met 30)

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Differential DiagnosisDifferential Diagnosis

• Large Fiber Sensory Neuropathy - Hereditary 5 - Connective tissue disease 3 (Sjogren’s, MCTD) - Monoclonal gammopathy 2 - Amyloidosis 2 - Cancer (CML) 1 - Vasculitis (non-systemic) 1 - Ganglionitis 1 - Old GBS 1 - Drug-induced (Taxol) 1 - Creutzfeld-Jacob disease 1 - Idiopathic 42

• Large Fiber Sensory Neuropathy - Hereditary 5 - Connective tissue disease 3 (Sjogren’s, MCTD) - Monoclonal gammopathy 2 - Amyloidosis 2 - Cancer (CML) 1 - Vasculitis (non-systemic) 1 - Ganglionitis 1 - Old GBS 1 - Drug-induced (Taxol) 1 - Creutzfeld-Jacob disease 1 - Idiopathic 42 33

Differential DiagnosisDifferential Diagnosis

• Small Fiber Sensory Neuropathy - Hereditary 1 - Monoclonal gammopathy 1 - PROMM 1 - Idiopathic 41

• Need also to consider - diabetes, AIDS, uremia, porphyria, Tangier Fabry

• Small Fiber Sensory Neuropathy - Hereditary 1 - Monoclonal gammopathy 1 - PROMM 1 - Idiopathic 41

• Need also to consider - diabetes, AIDS, uremia, porphyria, Tangier Fabry

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TreatmentTreatment

• Non-Pharmacologic Measures - TENS - Immersion in cold / warm water - Application of creams (Lidocaine cream) - Massage - Dorsal column stimulation

• Non-Pharmacologic Measures - TENS - Immersion in cold / warm water - Application of creams (Lidocaine cream) - Massage - Dorsal column stimulation

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TreatmentTreatment

• Tricylic antidepressants (amitriptyline, nortriptyline, desipramine)• Anticonvulsants (carbamazepine, phenytoin, gabapentin, clonazepam, lamotrigine, topiramate)• Antiarrythmics (mexiletine, lidocaine drip)• SRIs (fluoxetine, paroxetine, ventrafaxine)• Opiates• Others (tramadol, baclofen, transdermal / intrathecal clonidine)

• Tricylic antidepressants (amitriptyline, nortriptyline, desipramine)• Anticonvulsants (carbamazepine, phenytoin, gabapentin, clonazepam, lamotrigine, topiramate)• Antiarrythmics (mexiletine, lidocaine drip)• SRIs (fluoxetine, paroxetine, ventrafaxine)• Opiates• Others (tramadol, baclofen, transdermal / intrathecal clonidine)

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Questions on this subject?Questions on this subject?

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#1014 Ulcer Disease Update

January 25 to 28

Hagop S. Mekhjian, MDProfessor of Internal MedicineDivision of Digestive DiseasesMedical Director, OSU HospitalsThe Ohio University Medical Center

E. Christopher Ellison, MDZollinger Professor of Surgery and Interim Chair, Department of SurgeryThe Ohio University Medical Center

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