DISEASES

OF PERIPHERAL NERVE
ALTHEA PURZUELO-TAMPOS, M.D.

Peripheral nerve

 PERIPHERAL NEUROPATHY
Abnormalities that affect the peripheral nervous
system
Site: nerve cell bodies, nerve roots, nerve trunks, or
terminal branches
Pathology: axon, myelin sheath, connective tissues,
vascular tissues

Pathologic reactions of Peripheral Nerves

Wallerian degeneration destruction of myelin
sheath and axon distal to the site of disruption of
an axon
Segmental demyelination

Focal degeneration of myelin sheath with sparing of the

axon

Axonal degeneration

Degeneration of myelin sheath secondary to axonal

damage from distal to proximal
dying-back phenomenon

Chromatolysis / axonal reaction changes in nerve

cell body that are due to axonal reaction

 Three main types of nerve fibers:

1.Group A fibers
Largest fibers, 1-2 m
Conduction rate: 5 100 m/sec
Myelinated, has both sensory and motor functions
Found in somatic nerves

2.Group B fibers
1-3 m diameter
Conduction velocities 3 14 m/sec
Found solely in preganglionic autonomic nerves

3.Group C fibers
Smallest fibers, <1 m
Unmyelinated, conduction rate: 2 m/sec
Found in cutaneous and visceral nerves

 Degeneration of peripheral nerves:

Early phase 1st 3 5 days after damage
Axons swell, myelin sheath begins to form bead-like structures, and series of
enlargements (round, fatty fragments) appear

Late phase 8 32nd day

gradual disappearance of myelin, increase in Schwann cells and macrophages

 Regeneration of peripheral nerves:

Formation of outgrowths or sprouts of axon near the cut tip

Rapid proliferation of Schwann cells
Neuroma / Pseudoneuroma tumor-like swelling in larger gaps (>3mm)
Doctrine of neurotropism ability of the axon to grow into peripheral stump
and form a new axon
Rate of growth of regenerating nerve 1 to 4 mm/day

 Terms:
Neuronopathy
Radiculopathy
Polyradiculopathy
Polyradiculoneuropathy
Plexopathy/plexitis
Mononeuropathy
Polyneuropathy
Mononeuritis multiplex
Axonal neuropathy
Demyelinating neuropathy
Entrapment neuropathy

Symptomatology of Peripheral Nerve Disease

Impairment of motor function
Axonal polyneuropathy GBS, nutritional, metabolic
Generalized paralysis GBS, diphtheria, toxic
Bibrachial motor neuron diseases, inflammatory-demyelinating
polyneuropathies, paraneoplastic
Paraparesis inflam of cauda equina, cytomegalovirus, herpes
simplex infecions
Bifacial GBS, connective tissue diseases
Atrophy 90 to 120 days; reduces volume by 75 to 80%

Tendon reflexes:
Generally lost or diminished but lesser in small fiber neuropathy

 Sensory loss
Escutcheon pattern of sensory loss
Sensory ganglionopathy
Universal sensory loss

Paresthesias, Pain and Dysesthesias

Allodynia
Hyperpathia vs Hyperesthesia
Causalgia

Sensory Ataxia and Tremor

Pseudoataxia

 Deformity and trophic changes

Talipes equinus
Claw foot / le pied en griffe
Charcot joint

Autonomic dysfunction
Anhidrosis
Orthostatic hypotension

Fasciculations, Cramps and Spasms

myokimia

Peripheral Neuropathies

Negative signs:
1.
2.
3.
4.
5.
6.

Muscle wasting
Muscle weakness
Sensory loss
Sensory ataxia
Areflexia
Autonomic dysfunction

Positive signs:

1. Fasciculations
2. Muscle cramps / pain on
exercise
3. Paresthesia
4. Dysesthesia
5. Hyperalgesia/Hyperesthe
sia

Approach to patient with PN

1.
2.
3.

Establish the existence of PNS disease

Determine its nature and possibilities of treatment
Laboratories:
1.
2.
3.
4.

4.

EMG
NCV
Biochemical tests
CSF examination

5. Nerve and muscle biopsy

6. Measure Ig and anti-neural
antibodies
7. Genetic testing

Determine the course

1.
2.
3.

Acute
Subacute
Chronic

Goals of management of Peripheral Neuropathy

I.
manage underlying condition or cause
- imunosuppressants, plasmapheresis, lifestyle modification

II.

repair damage
- mechanical aids
- Braces, orthopedic shoes, mechanical ventilator

III.

provide symptom relief

A. Medications that may help provide pain relief:
1. Pain relievers acetaminophen, NSAIDS
2. Antiepileptic gabapentin, carbamazepine, phenytoin
3. Lidocaine patch
4. Tricyclic antidepressants amitriptyline, desipramine,
imipramine
5. Opioid analgesics - Oxycodone or codeine
6. Capsaicin
B. Surgery

Syndrome of Acute Motor

Paralysis with variable
disturbance of sensory and
autonomic function

Guillain-Barre Syndrome
Most common acute neuropathy
1-2 / 100,000 population / year
Most patients are healthy and active prior to onset
Usually sporadic although epidemics do occur
Age of onset:
Any age
Average: 40 yrs old (50-74 y/o)
Rare over 80 yrs or less than 2 yrs of age

 Course of the disease:

Progresses over a period less than 4 wks
(3-4 wks)
Chronic form (CIDP) - > 8 wks
Most patients reaches maximal deficit within 2 weeks of onset
Recovery occurs over the ensuing weeks to months

 About 2/3 of all GBS patients describe an infectious syndrome within 4 weeks
prior to the onset of neuropathic symptoms
Common infectious syndrome reported:
Upper respiratory tract infections (40%)
Diarrhea (15-20%)

Most common enteric organism C. jejuni

Symptoms:

Symmetric ascending weakness involving proximal and distal muscles

Paresthesias and muscle pain may be presenting complaints
Sensory impairment is usually minimal

Signs:

Deep tendon reflexes are lost early

Cranial nerves, particularly facial nerves are commonly affected
Respiratory failure (30%)
Autonomic nerve involvement:

Fluctuations of BP
Cardiac arrhythmias
Bowel and bladder dysfunctions

Diagnostic Criteria for Guillain-Barre Syndrome

(Asbury, et al)

Features required for diagnosis:

1.
2.
3.
4.

Progressive muscle weakness with areflexia

Features that are supportive of the diagnosis:

Symmetric progression less than 4 wks
Autonomic features
Cranial nerve involvement
Absence of fever

Diagnostic Criteria for Guillain-Barre Syndrome

CSF findings
Elevated protein without cells (albuminocytological
dissociation)
CSF protein peaks within 4 6 weeks but may be normal
early

Electrodiagnostic findings
Suggestive of demyelination: prolonged distal latencies
and abnormalities in F-wave responses or mild slowing of
conduction velocities

 Variants of GBS:

Regional:

Fisher syndrome: ophthalmoplegia, ataxia, areflexia

Cervico-brachial-pharyngeal: difficulty in swallowing with neck and proximal arm
weakness, may be associated with ptosis
Oculopharyngeal weakness
Predominant paraperesis
Bilateral facial or abducens weakness with distal paresthesias
Ophthalmoplegia with GQ1b autoantibodies

 Variants of GBS:

Functional:

Generalized ataxia without dysarthria or nystagmus

Pure sensory
Pandysautonomia
Pure motor / Acute Motor Axonal Neuropathy (AMAN)
Acute Motor-Sensory Axonal Neuropathy (AMSAN)

 Recent Classification:
1. Acute inflammatory demyelinating
polyradiculoneuropathy (AIDP)
2. Acute motor and sensory axonal neuropathy
(AMSAN)
3. Acute motor axonal neuropathy (AMAN)
4. Chronic Inflammatory Demyeinative
Polyneuropathy (CIDP)

 Acute Axonal Form:

Characterized by widespread and severe axonal
degeneration
Muscle atrophy appears early within weeks
Numerous electrically inexcitable motor and signs of
extensive denervation
Antibodies to GM1
Recovery is prolonged but incomplete

 Laboratory findings:
CSF Examination

Normal pressure
Few lymphocytes
Protein is normal in few weeks but peaks in 4 6 weeks
Presence of Ig M antimyelin antiboies

EMG / NCV
Decrease in amplitude of muscle action potentials
Slowed conduction velocity
Conduction block in motor nerves

 Pathologic findings:
Increased lymphocytic infiltrates along endoneural
perivascular area
Segmental demyelination
Wallerian degeneration
Pathogenesis and etiology
Cell-mediated immunologic reaction directed at
peripheral nerves

Treatment
General Medical care:
Admitted to monitor respiratory, autonomic and motor
functions
Respiratory assistance
If FVC < 15 ml/kg

High dose corticosteroid therapy - controversial

Treatment
Human immunoglobulin
0.4 g/kg iv qd x 5 days (total dose: 2 g); start with slow infusion rate,
increase rate of infusion as tolerated
Side effects:
Headache, renal failure

Plasmapheresis
4-6 exchanges over 8 to 10 days = total of 200-250 ml/kg plasma is
removed

Heparin
5000 U sq, q 12
Deep vein thrombosis prophylaxis

 Prognosis:
3 5% do not survive
Majority recover with mild motor / sensory deficit
10% have pronounced residual deficits
If axons are damaged recovery is 6-18 mos or longer
5-10 % will have recurrences

CIDP (Chronic Inflammatory Demyelinating

Polyradiculoneuropathy) and CRIP (Chronic Relapsing
Inflammatory Polyradiculoneuropathy) Syndromes
Autoimmune disorder

Similarities between GBS and CIDP

Widespread polyradiculoneuropathies
Cytoalbuminologic dissociation of CSF increased

protein concentrations with few or no cells

Decreased conduction velocity and partial
conduction block in motor nerves
Multifocal perivenous inflammatory infiltrates

Differentiated from GBS by:

1. Prolonged and relapsing course
2. Enlargement of nerves
3. Responsiveness to corticosteroids
Laboratory features:

Increased CSF protein 75 to 250 mg/dl

Rarely papilledema and pseudotumor cerebri syndrome in very high CSF protein
Increased CSF gamma globulin fraction
Mild lymphocytic pleocytosis
Nerve biopsy demyelination with interstitial and perivascular infiltrates of inflammatory
cells

 Treatment ;

steroids prednisone 60 to 80 mg/day

Immunosuppressants
IV Ig - 2 g/kg x 4 to 5 days

 Herpes Zoster
affects individual nerve roots / trunks producing pain and sensory
loss, motor functions are usually spared
Vesicles erupt 4-5 days after onset of severe localized pain
Postherpetic neuralgia
Treatment anti-viral agents, pain relievers

Diphtheritic neuropathy
Corynebacterium diphtheriae inhibits myelin synthesis of
Schwann cells
Neuropathy (20%) occurs 4 8 wks after infection; fatal due to
respiratory involvement
Blurred vision, nasal speech (1st 2 wks)
Cause of death diphtheritic myocarditis

Hereditary Motor Sensory

Neuropathies

I.

HMSN (PERONEAL MUSCULAR ATROPHY, CHARCOTMARIE-TOOTH DISEASE TYPE I & TYPE II)
Autosomal dominant w/ almost complete
penetrance / recessive gene on chromosome 1 or
17 / x-linked dominant or recessive
Duplication of gene for peripheral myelin protein
(PMP22) on chromosome 17
Age of onset: any age but obvious signs and
symptoms usually occur at 10 20 yrs of age
Prevalence: 1 / 2500 1 / 4000

HMSN I

HMSN II

Mean Conduction decreased - less than 38

velocity
m/sec

Normal / near normal

Amplitudes of
Reduced
sensory and action
potentials

Reduced

Genetics

Duplication of PMP 22
gene autosomal
dominant

Mutation forconnexin -32

gene = X-linked
transmission

Age of onset

First decade

Second decade

Hallmark
Genetic transmission
Complete symmetry
Very slow progression
Loss of myelin disproportionate to axons

Other features:
Slowed nerve conduction velocity (10 20 m/s)
Pathology peripheral segmental demyelination and dorsal column degeneration

Clinical features:
Difficulty in running, frequent weakness, sprains
of ankles, stumbling and slapping of feet
Kyphoscoliosis
Weakness of extensor hallucis, digitorum longus,
peronei and intrinsic feet muscles lead to:

pied en griffe high arches and hammertoes

Pes cavus
Foot drop atrophy of calf muscles
Champagne glass or stork-like legs

 Clinical features (cont):

Impaired motor, vibration and joint position sense
Tremors (occasional)
Paresthesias, cramps, sensory loss
Atrophy of muscles - Claw foot and hand

Differential diagnosis:
Distal muscular dystrophies
Friedrichs ataxias
Roussy-Levy syndrome
Adult onset CIDP

Pathologic findings:
Depletion of axons, myelin sheaths, sensory and
motor fibers
Nerves may be enlarged with onion bulb
formations of Schwann cells and fibroblasts
Prognosis: good
Treatment:
No specific treatment
Regular exercise
Light braces or shoes with springs
Arthrodoses to stabilize ankles

II.

HEREDITARY NEUROPATHY WITH PRESSURE PALSIES

Multiple recurrent focal neuropathies and plexopathies often

provoked by compression
Dominant trait
Deletion of PMP22 gene at half normal level
Usually non-painful
often with underlying chronic but slowly progressive mild
demyelinating sensorimotor neuropathy
Nerve biopsy (+) localized nerve sheath thickening with
duplication of myelin lamellae (tomaculae)
EMG mild slowing of conduction of distal sensory and motor
nerves

III. HMSN III OF DYCK (HYPERTROPHIC PERIPHERAL

NEUROPATHY OF INFANCY, DEJERINE-SOTTAS DISEASE)

Autosomal recessive
Onset: early childhood or infancy
Walking is delayed in onset and progressively impaired
Pain and paresthesias in the feet are early symptoms followed
by symmetrical weakness and wasting of distal extremities
All sensory modalities are impaired
Areflexia

 Other Manifestations:
1.Kyphoscoliosis
2.Deformities of hands and feet
3.Miotic, unreactive pupils
4.Nystagmus
5.Deafness
6.Hypertrophy of nerves
7.Severe motor deficit
7. Severe sensory deficit (pseudoataxia / pseudoathetosis)

 NCV markedly reduced (10 m/s)

Pathology segmental demyelination
Thickening of nerves onion bulb
Mononeuritis multiplex

CSF protein persistently increased

Prognosis:
Poor ; wheelchair bound at early age

Treatment:
Symptomatic

PREDOMINANTLY SENSORY
NEUROPATHIES

 Hereditary Sensory and Autonomic Neuropathy Type I

(HSAN I) / Mutilating Hereditary (Dominant)
Polyneuropathy in Adults
Rare; autosomal dominant
Begins with subtle loss of pain and temperature
sensation in the feet later of the fingers
Calluses, later blistering, ulceration of feet
Osteomyelitis and osteolysis
Shooting pain and sensory loss
Mild muscle weakness
Hypo/areflexia
Loss of sweating

 Pathology slowly progressive sensory distal axonal

degeneration and segmental demyelination affecting nonmyelinated and small myelinated fibers
Loss of function of enzyme serine palmitoyltransferease
rate limiting step in biosynthesis of sphingolipids
Sensory nerve conduction absent or slowed
Prognosis - good

 Recessive Mutilating Sensory Polyneuropathy of

Childhood
Autosomal recessive
Onset: infancy and early childhood
Walking is delayed
Ataxia
Ulceration of tips of toes and fingers
Areflexia
Impaired sensory modalities
Disruption of nerve growth factors

 HSN II (Morvans syndrome, Infantile Syringomyelia,

Congenital SN)
Rare; autosomal recessive
Distal sensory deficit
Onset: infancy

HSN IV (Congenital SN w/ anhydrosis / Congenital

Insensitivity to Pain)
- Rare; autosomal recessive
- Onset infancy
- High fever due to absence of sweating mechanisms
- mental retardation
- short stature
- insensitivity to pain
- Absence of neurons in dorsal root ganglia, Lissauers
tract and decreased size of descending tract of CN V
- Prognosis - poor

 HSN with Familial Dysautonomia

(Riley-Day Synd)
Rare; autosomal recessive
Jewish families
Congenital absence of autonomic and dorsal root ganglia sensory neurons
Autonomic neuropathy (fluctuating body temperature, no tears, postural hypotension, dry
mouth, impaired taste sensation w/ strikingly smooth tongue, poor suck, failure to thrive
episodes of pneumonia)
Loss of pain and temperature sense with preservation of pressure and tactile sense
Absent reflexes

Motor functions slightly affected

Corneal ulceration, fixed pupils, blotchiness of skin,
excessive sweating, difficulty in swallowing,
esophageal and intestinal dilatation, emotional
instability, recurrent vomiting, stunted growth
Histopath: diminished myelinated and unmyelinated
fibers, and sympathetic and parasympathetic ganglion
cells
Prognosis poor (die at age 15) due to autonomic
dysfunction

 Hereditary Areflexic Dystasia (Rousy-Levy Syndrome)

CMT3
Autosomal dominant
Mutation of myelin protein gene
Onset: infancy / from birth
Sensory ataxia
Pes cavus and areflexia
Some degree of sensory loss: vibratory and position
Atrophy of muscles of legs and postural tremors
Relatively benign

INHERITED POLYNEUROTAPHIES
WITH RECOGNIZED
METABOLIC DISORDER

 Inherited (Familial Amyloidosis, FA) Amyloid

Neuropathies
Pathology: deposition of amyloid around nerve fibers or
covering of nerves & microvascular deposition of
amyloid leading to vasculitic neuropathy
Small diameter fiber damage producing pain and
temperature loss and autonomic neuropathy
2 main types:
1. Familial amyloidosis (FA)
2. Primary (non-familial) systemic amyloidosis (AL)

 Non-familial systemic amyloidosis

Generalized symmetrical sensorimotor neuropathy w/ serious autonomic involvement

Multiple myeloma
Diagnosis - biopsy of sural nerve, rectum / gum
Death cardiac or renal involvement by amyloid

Familial amyloid polyneuropathy

1.

Autosomal dominant
Males = females
4 types:
Portuguese (Andrade) type - Unpleasant, progressive and fatal neuropathy;
starts from legs in the 3rd decade and runs its course for 10 or more years

Numbness, paresthesias, pain in lower extremities

Mild weakness and areflexia
Sensory loss (pseudosyringomyelic pattern)
Autonomic involvement loss of pupillary light reflexes and miosis, anhydrosis,
vasomotor paralysis with orthostatic hypotension, alternating diarrhea and
constipation, impotence

 Difficulty in walking
Cranial nerve involvement (facial weakness and
numbness, loss of taste) may occur late
Cardiac enlargement and irregular cardiac
rhythm
Anemia
Behavior abnormalities, cerebellar ataxia,
bilateral corticospinal signs, nephrotic
syndrome, uremia
CSF normal or increased protein
Africa, France, Brazil, Japan, Sweden

2.

Familial amyloidosis with carpal tunnel syndrome (Swiss Type)

Milder, starts from arms w/ Carpal tunnel-like

synd
Atrophic muscle weakness in distribution of
median nerve
vitreous opacities
Generalized neuropathy starting at 4th and 5th
decade., w/ minimal autonomic involvement
Mutation of protein transthyretin (TTR)
German origin

3.

Iowa type onset 30 yrs

Amyloid deposits in testes, adrenal glands, kidneys

Fairly severe sensorymotor neuropathy
Mutated apolipoprotein A1

4. Cranial neuropathy with corneal lattice dystrophy

and facial palsies

Finnish type
Onset 3rd decade
5th decade facial nerves are affected
Excessive skin folds in face, facial diparesis, dysarthria,
spasticity, loss of posterior column function, amyloid
deposits from gelsolin protein

Lipoprotein Disorders and Peripheral

Neuropathy

Cerebral Lipoidosis deposition of abnormal lipids in

the brain
Diagnosis: NCV & nerve biopsy
2 types:
1.

Metachromatic Leukodystrophy deficiency of arysulfatase A

-

2.

widespread demyelination of brain

Intrellectual impairment
Prognosis poor

Krabbes Disease deficiency of galactosylceramide beta-galactosidase

-

accumulation of galactocerebroside in brain and PN

Fatal w/in 1-2 years of onset

Neuropathy due to Glycoprotein

deficiency

1.

Bassen-Kornzweig Synd (A-betalipoproteinaemia)

autosomal recessive
- accumulation of triglycerides in intestinal mucosa &
impaired absorption of fat soluble vitamins
- Steatorrhea often precedes weak and unsteady gait
- Onset: 2 y/o areflexia
- Vibratory and position sense loss
- Developmental delay

Cerebellar signs (progressive ataxia, titubation of

head, dysarthtria
Peripheral neuropathy (impaired posture sense, loss
of pain and temperature sense)
Ophthalmoparesis
Retinitis pigmentosa
Muscle weakness
Babinski sign

- Laboratory extremely low serum cholesterol,

acanthocytosis
- Complications: cardiac enlargement and congestive
failure
- Neuropathologic findings: demyelination of peripheral
nerves and degeneration of nerve cells in spinal gray
matter and cerebellar cortex
- Management high doses of fat-soluble vitamins. &
dietary fat restrictions
- Prognosis may live to middle age

2.

Tangier Disease (High-Density Lipoprotein Deficiency)

- autosomal recessive
- Gene mutation inhibits function of ATP cassette
transporter protein
- Cholesterol deposition in tonsils
- Swollen yellow-orange tonsils producing difficulty of
breathing and swallowing
- Impaired pain and temperature sense sometimes
limited to face and upper extremities
(pseudosyringomyelia)

- Laboratory absent serum high-density lipoproteins

& low cholesterol and high triglyceride serum levels
- Fat-laden macrophages in bone marrow
- Neuropathy progresses slowly
- Treatment: dietary restrictions of fats

3.

Refsums Dse (Hereditary Ataxic Neuro., Phytanic Acid

Storage Dse) HMSN IV
Autosomal recessive
Deficiency of phytanoyl-coenzyme A (CoA)
Inability to break down phytanic acids
Onset late adulthood, adolescence, early adult life
Retinitis pigmentosa, night blindness, pupillary
abnormalities, cataracts, constricted visual fields
Neurogenic deafness
Progressive peripheral neuropathy, all sensations are
reduced
Ataxia
Ichthyosis

 Diagnosis: increased phytanic acid in blood

(normal 0.3) of patients with chronic peripheral
neuropathy
Treatment low phytol diet
Cause of death cardiac involvement

4.

Fabrys Disease (Anderson-Fabry dse., Angiokeratoma

Corporis Diffusum,)

-Galactosidase A Deficiency
X-linked recessive
Lipid deposition in all tissues and body fluids
Deposition of glycolipid (ceramide trihexodase) in
nerves and cells of spinal ganglia and anterior and
intermediolateral horns of spinal cord
Heterozygous women (10%) have later onset and
milder neuropathic symptoms than men
Initial Symptom: pain-severe burning type, followed
by paresthesias of palms and soles

 Telangiectasia of lower trunk and upper legs

Impairment of renal function and cerebral and cardiac
infarction
Dark red macules and papules over trunk and limbs,
some cluster around thigh and lower limbs and around
umbilicus
Treatment: anticonvulsants for pain, enzyme
replacement therapy
Cause of death renal failure

 Acute Intermittent Porphyria

Defect in uroporhyrinogen-1 synthetase
Autosomal dominant
Incidence 1.5/100,000
severe colicky abdominal pain w/ vomiting, abnormal
behavior, severe ascending neuropathy, rapidly
ascending flaccid paralysis, cranial nerve palsies,
autonomic involvement, deep red color of urine
Diagnosis determination of erythrocyte
urobilinogen-1 synthetase

 Other metabolic dysfunctions

Evidence of SIADH, salt-losing nephropathy
Liver damage

Treatment IV glucose @ 10 20 g/h, haematin 4

mg/kg/12 h, Chlorpromazines
Prognosis poor; 25-50% mortality
Recovery at 6-8 wks; slow & incomplete

Drugs precipitating attacks of porphyria

Alcohol

Levodopa

Barbiturates

Meprobamate

Carbamazepine

Methosuximide

Chloramphenicol

Methyldopa

Chlordiazepoxide

Estrogens

Dichloralphenazone

Pentazocine

Ergotamine derivatives

Phenytoin

Griseofulvin

Sulphonamides

Imipramin

Tolbutamide

SYNDROME OF CHRONIC SENSORY

MOTOR POLYNEUROPATHY

 Alcoholic Peripheral Neuropathy

Severe pain in the feet w/ marked hypersensitivity to
light touch / other stimuli
Painless motor neuropathy
Treatment alcohol withdrawal, Vit B

Neuro of Chronic Renal Failure

Due to uremia
Generalized mild painful sensorimotor neuro
Restless leg syndrome

Leprosy (Hansens Dse)

generalized skin involvement and nerve damage due
to Schwann cell involvement by Mycobacterium
leprae
India, Central Africa, South America, Florida, Texas,
Louisiana, Gulf of Mexico
Stages:
1.

2.

Indeterminate leprosy - patchy skin lesions affecting cutaneous nerves

(depigmented and anesthetic patches)
Tuberculoid leprosy circumscribed epithelioid granuloma involving cutaneous
and subcutaneous nerves resulting to hypopigmented patch with superficial
numbness and sensory loss

3.

Underlying subcutaneous sensory nerves may

enlarge
Ulnar, median, peroneal, posterior auricular,
facial nerves
May lead to sensorimotor deficit

Lepromatous leprosy diffuse infiltration of bacilli to skin, ciliary bodies, testes,

lymph nodes, nerves

Symmetrical pattern of pain and temperature

loss, involving pinnae of ears, nose, dorsal
surfaces of hands, elbows, forearms, and
feet, anterolateral aspects of legs =
temperature-dependent pattern

4.
-

Impaired motor function and loss of sweating

Preserved tendon reflexes
Infections, trophic changes and loss of tissue
Dimorphous leprosy has both tuberculoid and
lepromatous characteristics
diagnosis nerve biopsy
Treatment Dapsone, Rifampicin and Clofazimine
Thalidomide

ASYMETRICAL AND MULTIFOCAL

POLYNEUROPATHIES
(MONONEUROPATHY, MONONEURITIS
MULTIPLEX)

VASCULITIC Neuropathies

 Sarcoidosis
Chronic generalized granulomatous disorder
Pulmonary problems w/ peripheral nerve lesions in 5 % (bilateral
or recurrent attacks of Bells palsy; sensorimotor neuropathy)
May affect CNS usually pituitary stalk diabetes insipidus , or
myelopathy
Painful small fiber sensory neuropathy

Rheumatoid Arthritis
1 5 % of patients with RA have vasculitic involvement of one or
more nerves
Small-vessel fibrinoid type with immunoglobulins on vessel walls

 Systemic lupus erythematosus

10% of patients with SLE have peripheral neuropathy
Symmetrical, progressive sensorimotor paralysis beginning at feet
and legs and extending to arms
Weakness and areflexia are prominent in some
Sensory deficit usually vibratory and position senses
Mechanisms of nerve damage;
Axonal degeneration
Chronic demyelinating pathology
Vasculitic injury from deposition of immune complexes

SYNDROME OF SUBACUTE
SENSORIMOTOR PARALYSIS FROM
PERIPHERAL NEUROPATHY

Toxic Neuropathies

 Arsenic
Pathology: axonal degeneration
Chronic: GI symptoms, anemia, polyneuropathy,
jaundice, brownish cutaneous pigmentation,
hyperkeratosis of palms and soles, Mees lines
Acute: severe GI symptoms, renal & hepatic failure,
encephalopathy, neuropathy
Treatment: gastric lavage, BAL

Thallium
Rapidly progressive painful sensory neuropathy, optic
atrophy, ophthalmoplegia, alopecia (15-30 days)
Treatment: potassium chloride

Lead

Colic, anemia, predominantly motor peripheral

neuropathy, encephalopathy basophilic stippling of
red cell precursors in bone marrow
Laboratory: copoporphyrin in urine, blood lead level
>70 g/dl
Treatment: penicillamine

Other metals
1.
2.
3.
4.

N-hexane
Methyl n-butyl ketone
Methyl bromide
Ethylene oxide

Drugs that could cause neuropathies

I. Antibiotics
1.
2.
3.
4.
5.

Metronidazole
Nitrofurantoin
Dapsone
Isoniazid
Chloramphenicol

II. Antineoplastic
1.
2.

Vinka alkaloids
cisplatin

III. Other drugs

1.
2.
3.
4.
5.
6.
7.

Phenytoin
Disulfiram
Hydrallazine
Penicillin
Cliquinol
Sodium cyanate
pyridoxine

 Diabetic Peripheral Neuropathy

50% of diabetics who have the disease for 20 yrs have neuropathy
Presenting symptom in maturity onset diabetes
Pathology: 1 axonal degeneration w/ 2 demyelination; proximal
vascular lesions; compression palsies
Forms:
Mild peripheral sensory neuropathy slight numbness of feet
and loss of ankle reflexes
Sensorimotor neuropathy distal sensory loss, generalized
areflexia, pain
Treatment amitriptyline, phenytoin, carbamazepine

Diabetic Peripheral Neuropathy

Forms (cont)
Autonomic neuropathy impotence, diarrhea, postural
hypotension, tachycardia, gastrointestinal stasis, pupillary
constriction, impaired autonomic response to
hypoglycemia; bad prognostic feature
Nerve compression palsies carpal tunnel synd, ulnar nerve
and peroneal nerve compression
Vascular nerve lesions recurrent and multiple extraoccular
nerve palsies and intercostal nerve vascular lesions

Diabetic Peripheral Neuropathy

Forms (cont)
Diabetic amyotrophy

Maturity onset diabetes; male

Onset sudden dramatic weight loss without obvious deterioration in diabetic
state

Excruciating pain from anterior thigh to medial maleolus in distribution of

femoral nerve; severe for
5-10 days

Rapidly progressive weakness of quadriceps; disappearance of knee jerk;

atrophy of thigh muscles

Recovery 6 18 mos

 Neuro associated Carcinoma (Oat cell CA)

Mild general sensory w/ minor motor
Due to chemotherapy or damage to dorsal root
ganglion

Ischemic Peripheral Neuropathy

- tingling paresthesias in the feet w/ blunted cutaneous
sensation of foot
- Cyanosis, loss of pulsations of peripheral vessels
- Onset 70-80 yrs

Mononeuropathy,
mononeuropathy
multiplex and plexopathy

 Motor, reflex and sensory changes confined to

the territory of a single nerve (mononeuropathy)
several individual nerves affected in a random manner
( mononeuropathy multiplex)
a plexus of nerves or part of a plexus, (plexopathy)
Pain overlying site of infarction or distally

 Brachial Plexus Neuropathies

Sensorimotor derangements
Etiology = compression e.g tumors
infections, usually viral
trauma arm is hyperabducted or shoulder is
violently separated from the neck
delayed results of radiotherapy
direct compression by adjacent skeletal anomalies
subcutaneous or intramuscular injections
ischemic lesion from subclavian artery /vein
thrombosis
inflammatory diseases related to lymphoma or
granulomas
idiopathic

 Lesions of entire brachial plexus

Paralysis of entire arm, complete sensory loss from shoulder
to medial side of middle third of upper arm
Loss of biceps, triceps, radial reflexes
Usual cause = vehicular trauma

 Upper brachial plexus paralysis

Distal 5th and 6th cervical root injury
Usual causes = forceful separation of head and shoulder during
difficult delivery (Erb-Duchenne palsy), pressure on
supraclavicular region, immune reactions to injections of foreign
serum, pressure on supraclavicular region during anesthesia,
idiopathic brachial plexitis
Muscles affected = biceps, deltoid, supinator longus,
supraspinatus and infraspinatus, and rhomboids
Arm hangs at the side, internally rotated and extended at the
elbow, movements are unaffected
Good prognosis but Erb-Duchenne palsy is usually permanent

 Lower brachial plexus paralysis

C7, C8, T1
Result from traction of abducted arm in a fall or during operation on
the axilla, compression of tumor from apex of lung (Pancoast
Syndrome), compression by cervical ribs, breech delivery (DejerineKlumpke paralysis)
Weakness and wasting of small muscles of the hand, clawhand
deformity
Sensory loss over ulnar border of hand and inner forearm
Horner syndrome

 Intraclavicular lesions involving cords of Brachial Plexus

Common causes = iatrogenic (damage to subclavian or axillary
vessels, anesthesia block of brachial plexus), dislocation of head of
humerus, direct axillary trauma, supraclavicular compression during
awkward positioning of the arm
Lesion of lateral cord
Musculocutaneous nerve and lateral root of median nerve
Weakness of flexion and pronation of forearm
Lesion of medial cord
Medial root of median nerve and ulnar nerve
Combined median and ulnar nerve palsy
Lesion of posterior cord
Weakness of deltoid muscle, extensors of the elbow, wrist and
fingers, sensory loss on outer surface of upper arm

 Thoracic Outlet Syndrome

Shoulder and arm pain, aching in character, felt over posterior
hemithorax, pectoral region and upper arm
Compression or spontaneous thrombosis of subclavian vein = dusky
discoloration, venous distention, edema of arm
Paget-Schotter Syndrome vein may become thrombosed after
prolonged exercise
Compression of subclavian artery
Ischemia of limb, digital gangrene and retrograde embilization
Unilateral Raynaud phenomenon, brittle nails, ulceration of
finger tips
Supraclavicular bruit

 Neurologic symptoms in thoracic outlet syndrome

Slight wasting and weakness of hypothenar, interosseous,
adductor pollicis, and deep flexor muscles of 4th and 5th fingers
Weakness of flexor muscles of forearm
Preserved tendon reflexes
Intermittent aching pain and/or numbness or tingling sensation of
ulnar side of forearm and hand
Sensory symptoms may be reproduced with firm pressure above
clavicle or traction of arm

Conventional tests for vascular compression

Adson test patient is seated with arm extended takes and holds
full breath, tilts head back and turns it to affected side
Wright maneuver abducts and externally rotates the arm, braces
shoulders and turns head to either side

 Diagnosis
Reduced amplitude of ulnar sensory potential on NCV
Large amplitude motor units on EMG
Brachial artery MR angiography arterial occlusion, aneurysm
Differential diagnosis
Carpal tunnel syndrome
Ulnar neuropathy or entrapment at the elbow
Cervical radiculopathy due to arthritis or disc disease
Brachial neuritis
Treatment
Local heat
Analgesics and muscle relaxants
Physical therapy / exercises
Surgery

 BRACHIAL MONONEUROPATHIES
LONG THORACIC NERVE OF BELL
C5,6,7
Supplies seratus anterior
Inability to raise arm over the head, winging of medial border
of scapula when outstretched arm is pushed against resistance
SUPRASCAPULAR NERVE
C5,6
Supraspinatus and infraspinatus muscles
Weakness of abduction and external rotation of arm

 AXILLARY NERVE
Posterior C5,6
Teres minor and deltoid muscles
Weakness of abduction of arm, wasting of deltoid muscle, slight impairment of
sensation on lateral aspect of shoulder

 RADIAL NERVE
Posterior cord, C5-8
Triceps, brachioradialis, supinator muscles, extensor muscles of wrist and fingers,
abductor of thumb
Paralysis of extension of elbow, wrist and fingers, and supination of forearm
Impaired sensation over posterior aspect of forearm radial aspect of dorsum of hand
Crutch palsy, lead intoxication

 ..

MEDIAN NERVE
C5-T1
Pronator of the forearm, long finger flexors, abductor and opponens muscles of thumb
and sensory to palmar aspect of hand
Inability to pronate the forearm or flex the hand in radial direction, paralysis of flexion
of index finger and terminal phalanx of thumb, weakness of flexion of other fingers,
weakness of opposition and abduction of thumb

 Carpal tunnel syndrome

Compression of median nerve at the wrist (transverse
carpal ligament)
Impairment of superficial sensation over palmar aspect
of thumb, index finger and middle finger, paresthesias
Phalen maneuver
Tinel sign
Treatment:
Splinting of wrist
Injection of hydrocortisone
surgical division of carpal ligament

 Pronator syndrome
Compression of the nerve at the elbow where the nerve
passes between two heads of pronator teres or just
behind bicipital aponeurosis
Forceful pronation of the arm produces aching pain,
weakness of abductor pollicis brevis and opponens
muscles, numbness of first 3 digits and palm

 ULNAR NERVE
C8 T1
Ulnar flexor of wrist, ulnar half of deep finger flexorsabductors and adductors of
fingers, adductor of thumb, and 3rd and 4th lumbricals, muscles of hypothenar
eminence
Claw hand deformity wasting of small hand muscles, hyperextension of fingers at
metacarpophalangeal joints and flexion at interphalangeal joints
Sensory loss over 5th finger, ulnar aspect of 4th finger and ulnar border of palm
Delayed (tardive) ulnar palsy

 LUMBOSACRAL PLEXUS LESIONS

T12 S3
Upper Lumbar Plexus Lesion
Weakness of flexion and adduction of thigh and extension of the
legs
sensory loss over anterior thigh and leg
Lower Plexus Lesion
Weakness of thigh, leg and foot muscles
loss of sensation over 1st and 2nd sacral segments
Entire Plexus
Paralysis of all leg muscles with atrophy
areflexia and anesthesia from the toes to perianal region

 ..

FEMORAL NERVE

L2-L4
Iliacus and psoas muscles
Anterior division pectineus and sartorius muscles, anteromedial surface of thigh
Posterior division quadriceps muscles, medial side of leg
Weakness of extension at knee, wasting of quadriceps muscles, failure of fixation of
knee, absent knee jerk
If more proximal weakness of hip flexion

 SCIATIC NERVE
L4, L5, S1, S2
Motor to hamstring muscles and all muscles below knee, sensory to posterior thigh,
posterior and lateral of leg, entire sole
Cannot flex knee, paralysis of all muscles below knee, weakness of gluteal muscles,
pain in buttock and posterior thigh
Sciatica disc compression L4-L5: pain in posterolateral thigh and leg, numbness over
inner foot, weakness of dorsi flexion of foot and toes

L5-S1: pain in posterior thigh and leg, numbness of

lateral foot, weakness of foot plantar flexion, loss
of ankle jerk

Problems in Diagnosis of
Chronic Polyneuropathies

Diagnosis of Early Chronic Polyneuropathy

Sensorimotor paralysis involving legs more than arms and
distal more than proximal

Diabetes
- occult neoplasia
HIV infection
- paraproteinemia
Connective tissue diseases - CIDP
Toxic neuropathies
- Vit. B deficiency / malnutrition

Purely or predominantly sensory polyneuropathy not caused

by diabetes
Carcinoma
- paraprotinemia
Sjogren syndrome
Primary and familial amyloidosis

Diagnosis of Late Chronic Polyneuropathy

Usually heredofamilial or sporadic mutations of genes
DNA testing is very helpful
Slowly progressive polyneuropathy with CNS degeneration
particularly cerebellar ataxia is most often hereditary

Diagnosis of Recurrent or Relapsing Polyneuropathy

CIDP
Tangier disease
GBS
Toxic neuropathies

- Refsum disease
- Porphyria
- Alcoholic-nutritional

Laboratory tests for the investigation of subacute and

chronic polyneuropathies (in addition to EMG/NCV)
Serum glucose, glucose tolerance test, glycosylated
hemoglobin A1C diabetes
Anti Hu antibody paraneoplastic neuropathies
Immunoelectrophoresis or immunofixation of serum and
urine paraproteinemic and amyloid polyneuropathies
Antimyelin-associated glycoprotein and antisulatide
antibodies chronic immune sensory neuropathies
Anti GM1 antibody multifocal motor conduction block

 Human immune deficiency virus antibody

Lyme antibody
Heavy metal concentrations in blood and tissue toxic
neuropathies
Blood urea nitrogen
Thyroid hormone
Sedimanetation rate, ANA, cryoglobulins, c-ANCA,
rheumatoid factor, and SSA-SSB Sjogren antibodies,
eosinophil count vasculitides
antiglandin antibodies sprue

 Vit B 12 and methyl malonic acid levels B12

deficiencies or nitrous oxide exposure
Serum carotene, Vit E, pyridoxine levels nutritional
deficiencies and vitamin excess
Genetic testing for Charcot-Marie-Tooth disease and
for hereditary liability to pressure palsy and brachial
plexopathy inherited neuropathies
Spinal fluid protein determination and cell content
chronic inflammatory demyelinating polyneuropathy,
neoplastic and granulomatous meningitis