peripheral neuropathy - rochester, ny of neuropathy • sensory –large fiber loss (vibration,...

Peripheral Neuropathy

Ralph F. Józefowicz, MD

PN: Definition

• A general term for any disorder affecting

the peripheral nerves.

Symptoms of Neuropathy

• Sensory:

– Dysesthesias in distal extremities

– Pain

– Numbness (stocking-glove)

• Motor:

– Distal>proximal weakness

• Autonomic:

– Orthostatic hypotension

– Impotence

Signs of Neuropathy

• Sensory– Large fiber loss (vibration, proprioception)

– Small fiber loss (pain, temperature)

• Motor– Weakness (distal>proximal, extensor>flexor)

– Muscle atrophy

– Flaccid tone

• Reflexes: absent or reduced

• Autonomic: orthostatic hypotension

Classification of Neuropathy

• Etiology

• Distribution

• Pathology

• Modality

Etiology of Neuropathy

• Hereditary

• Toxic/metabolic

– Drugs

– Toxins

• 2° to systemic disease

• Autoimmune

Hereditary

• Charcot-Marie-Tooth disease (HSMN I&II)

• Dejerine-Sottas disease (HSMN III)

• Refsum’s disease (HSMN IV)

Drugs

• Amiodarone

• cis-platinum

• Dapsone

• INH

• Phenytoin

• Pyridoxine

• Vincristine

• Nitrofurantoin

• ddI

• ddC

Toxins

• Heavy metals

– Hg, Pb, Zn, As

• Ethanol

• Organophosphates

Systemic Diseases

• Diabetes mellitus

• Uremia

• Porphyria

• Pernicious anemia

• Amyloidosis

• Hypothyroidism

• Carcinoma

• Lymphoma

• Multiple myeloma

• Cryoglobulinemia

• Monoclonal gammopathy

• Vasculitis (SLE, RA, PAN)

• Sarcoidosis

• Infection

Diabetes Mellitus

• Symmetric neuropathies

– Sensory>motor polyneuropathy

– Autonomic neuropathy

• Asymmetric neuropathies

– Mononeuropathy multiplex

– Cranial neuropathy

– Truncal radiculopathy

– Amyotrophy

– Entrapment neuropathy

Infections

• Leprosy

• Syphilis

• HIV

• Diphtheria

Autoimmune

• Guillain-Barré syndrome (AIDP)

• Chronic inflammatory demyelinating

polyneuropathy (CIDP)

Distribution

• Symmetrical generalized

– Polyneuropathy

(stocking-glove, dying back neuropathy)

• Multifocal

– Mononeuropathy multiplex

• Focal

– Entrapment neuropathy

Pathology

• Axonopathy: most polyneuropathies

• Myelinopathy: GBS, CIDP

• Neuronopathy

– Somatic motor: ALS

– Somatic sensory: carcinoma, Sjögren's

– Autonomic: hereditary dysautonomia

Modality

• Motor

• Sensory

• Autonomic

• Mixed

Etiology of Peripheral NeuropathiesDANG THERAPIST

• Diabetes

• Alcohol

• Nutritional

• Guillain-Barré

• Toxic

• Hematologic

• Endocrine

• Rheumatologic

• Amyloid

• Porphyria

• Infectious

• Sarcoid

• Tumor

Diagnostic Studies

• Nerve conduction study

• Electromyography

• Serum studies

• Urine studies

• Nerve biopsy

Nerve Conduction Study

• Demyelinating lesions:

– Slowed conduction velocities

– Prolonged terminal latencies

– Dispersion of evoked CMAP

– Conduction block

• Axonal lesions:

– Reduced amplitudes of CMAP and SNAP

Electromyography

• Axonal lesions:

– Acute denervation: fibrillation potentials

positive waves

– Chronic denervation: large, prolonged CMAP

reduced recruitment

• Demyelinating lesions:

– Reduced recruitment

Serum Studies

• CBC

• Chemistry profile

• T4, TSH

• Vitamin B12 assay

• ESR

• ANA

• Rheumatoid factor

• SPEP

• SIEP

• RPR

• HIV

Urine Studies

• Heavy metal screen

• Porphobilinogen

Nerve Biopsy

(Sural Nerve)

• Only helpful in screening for

– Vasculitis

– Amyloid

– Sarcoid

– Leprosy

Normal Sural NerveTrichrome Stain

Chronic Axonal NeuropathyTrichrome Stain

VasculitisH&E Stain

CIDPToluidine Blue Stain

Demyelinating NeuropathyTeased Nerve Fiber Preparation

Treatment of Neuropathies

• Specific treatment

• Treatment of immune-mediated neuropathies

• Symptomatic treatment

Treatment of Immune Mediated

Neuropathies

• Corticosteroids

• Immunosuppressive drugs

– Azathioprine

– Cyclophosphamide

– Mycophenolate

• Plasmapheresis

• IVIg

Symptomatic Treatment

• Tricyclic compounds– Amitriptyline

– Nortriptyline

– Duloxetine

• Anticonvulsants

– Gabapentin

– Pregabilin

• Topicals

– Capsaicin

– Lidocaine patch

Case 1

A 23-year-old, right-handed college student and summer waitress was well until one month ago when she developed tingling in both hands, primarily in the thumb, second and third digits, and worse on the right. It frequently awoke her from sleep. She occasionally noted pain in her right forearm. She denied any hand weakness. No history of neck pain.

She started to work as a waitress 2 months ago. She had no tingling when waiting on tables or when mowing the lawn but developed the tingling afterwards.

Case 1 – PMH

Past Medical History: Herniated lumbar disk following a fall; s/p right L5 laminectomy

Medications: Oral contraceptives

Family History: Unremarkable

Case 1 – Examination

Physical Examination:

• P=108/min; BP=110/80 mm Hg

• Neck ROM full

• Tinel sign negative bilaterally

• Phalen sign positive bilaterally

Neurologic Examination:

• Motor exam: Slight weakness of the right APB muscle

• Sensory exam: normal, including hands and feet

• MSR: 3+ bilaterally, including ankle jerks

• Romberg: negative

Case 1 – Nerve Conductions

Nerve Terminal

latency

Amplitude Conduction

Velocity

R median

motor

7.0 msec 3.9 mV 59 m/sec

L median motor 6.2 msec 6.6 mV 55 m/sec

Normal <4.2 msec >10 mV >50 m/sec

R median

sensory

5.0 msec 8.4 μV

L median

sensory

5.3 msec 7.2 μV

Normal <3.6 msec >20 μV

Case 1 – Laboratory

• T4 23.5 μg/dl

• Free T4 9.68 units

• TSH <0.1 mIU/L

Diagnosis?

Carpal Tunnel Syndrome

• Median nerve compression at the wrist

• Motor: APB muscle weakness

• Sensory: digits 1, 2, 3, lateral digit 4

• Pain: wrist, median hand, forearm

• Tinel and Phalen signs

• EMG and nerve conduction study

• Treatment: wrist splints and surgery

The Carpal Tunnel

Case 2

A 56-year-old mechanical engineer was referred for evaluation of numb toes that came on gradually and painlessly 12 years ago. The numbness is most pronounced when he is trying to fall asleep and is made worse by cold weather; warm weather improves the sensation in his feet. He has decreased sensation on the soles of his feet when he is stepping on the pedals in his car. Walking barefoot produces intense pain. The numbness has progressed to involve the distal feet.

He denies weakness in his feet, walking difficulty, bowel or bladder difficulty, sexual dysfunction, or back or neck pain.

Case 2 – PMH

Past Medical History: Hypertension, meralgia

paresthetica, s/p appendectomy

Medications: captopril, potassium, aspirin

Habits: occasional EtOH, no tobacco

Family History: unremarkable

Case 2 – ExaminationPhysical examination:

• P=60/min, BP=160/100 mm Hg

• Moderately obese, lipoma over right lateral hip

• Neck and back ROM intact; SLR negative

Neurologic examination:

• Motor: atrophy of EDB muscles in both feet; unable

to fully cock up his toes

• Sensory: reduced pin sensation in toes; absent

vibration and position sense in feet

• Reflexes: absent ankle jerks

Case 2 – Laboratory

• NCS demyelinating neuropathy

• ANA ≥1:640, speckled

• Anti DS-DNA <10

• RF Negative

• SPEP Normal pattern

• Immunofixation Monoclonal IgM lambda protein

Diagnosis?

Distal Polyneuropathy

• Symmetric, distal sensory>motor

• “Stocking – glove” neuropathy

• “Dying back” neuropathy

• Pathology: usually mixed axonal and

demyelinating features

• Various etiologies, including DM,

nutritional deficiency, toxins, metabolic

Case 3

A 70-year-old woman developed numbness in her feet and upper back pain. The following month she developed a left Bell's palsy that was treated with a seven day course of prednisone. She then developed progressive numbness and pain in her feet and hands in a stocking-glove distribution. Distal weakness developed after this. She was treated with amitriptyline which helped the pain but not the numbness or weakness. Over the past two weeks her weakness worsened to the point that she had difficulty walking because of bilateral foot drop. She was therefore admitted for further evaluation.

Case 3 – PMH

Past Medical History: Hypertension

Medications: HCTZ, nifedipine, ranitidine, ASA

Case 3 – Examination

Physical Examination:

• P=84/min; BP=140/82 mm Hg; T=37°C

• Grade 2/6 SEM present

Neurologic Examination:

• Motor: unable to stand on heels or toes; grade 4 weakness in biceps, wrist extensors and flexors, finger flexors and psoas muscles; grade 2 weakness in interossei and dorsi and plantar flexor muscles

• Sensory: light touch, temperature and pin reduced in a stocking-glove distribution; vibration and position sense absent at the toes;

• Reflexes: UE 2+; knees 1+; ankles absent

• Gait: bilateral steppage

Case 3 – Laboratory

• CBC WBC=11.0/mm3; Hct=37%

• ESR 90 mm/hr

• ClCr 42 ml/min

• ANA 1:160, homogeneous

• RF Negative

• Anti DS-DNA Negative

• Anti RNP Negative

• Anti SM Negative

• Anti SSA Negative

• Anti SSB Negative

Case 3 – Additional Labs

• NCS Demyelinating neuropathy

• Sural nerve biopsy Vasculitis

Diagnosis?

Vasculitic Neuropathy

• Due to infarction of vasa nervorum

• Usually asymmetric

• Involves peripheral nerves, roots, plexi

• Typically painful

• Etiology: vasculitis, DM

Case 4

A 63-year-old school bus driver noted tingling and

numbness in her limbs two months ago. The tingling

first began in her left arm and leg. Her gait is unsteady

and she fell 3 times. She has exquisite pain in her feet

when she steps on a sharp object. She also feels that

her lower limbs are weak.

Case 4 - PMH

Past Medical History:

• s/p cervical laminectomy in 1994 for severe spinal stenosis

• s/p left 6th nerve palsy one year ago with resolution

• Stage 2 endometrial cancer in 2001, s/p surgery, pelvic irradiation and chemotherapy (carboplatin / paclitaxel)

• Hypothyroidism

Medications: diltiazem, l-thyroxine, ASA

Case 4 - Examination

Physical Examination:

• P=76/min, BP=142/80 mm Hg

• Neck ROM reduced in all directions

Neurologic Examination:

• Motor: Essentially normal

• Sensory: Absent vibration in hands and feet, position sense in toes, pin and temperature reduced distal to mid forearms and calves and at umbilicus

• Coordination: ataxia with heel-to-shin testing

• Reflexes: MSR absent, plantar responses flexor

• Romberg unsteady, wide based gait

Case 4 – Laboratory

• NCS: Large fiber sensory demyelinating neuropathy

• CSF: 4 WBC, glucose 56 mg/dL, protein 116 mg/dL

Diagnosis?

Guillain-Barré Syndrome

• Large-fiber demyelinating neuropathy

• Motor, sensory and autonomic nerves

• Post-infectious and monophasic

• Etiology: molecular mimicry

• CSF: elevated protein, no cells

• Treatment: plasmapheresis or IVIg

• NO STEROIDS!