3._Disorders_of_the_PNS

Report
DISORDERS OF THE
PERIPHERAL NERVOUS
SYSTEM
Prepared by:
Dr. Sarwer Jamal Al-Bajalan
M.B.Ch.B, F.I.B.M.S(Neurology)
2014
Disorders Of The Peripheral
Nervous System
○ Introduction and clinical approach
○ Acquired polyneuropathies(PNP)
○ Hereditary neuropathies
○ Mononeuritis Multiplex
○ Mononeuropathies
Peripheral neuropathy:
Introductionand clinical approach
General considerations
 Peripheral neuropathy or polyneuropathy:
diffuse peripheral nerve lesion, often symmetrical

Mononeuropathy—lesion of a single nerve (i.e.,
median, femoral, or abducens). Often
entrapment or trauma

Mononeuritis multiplex—focal involvement of two
or more individual nerves, often asymmetric
Types and causes of peripheral neuropathy
Polyneuropathy:
clinical manifestations
Age of onset varies, for example
○ Childhood—CMT
○ Adulthood—Diabetes
○ Older adult—Paraproteinemia
Acuity of onset
○ Acute—AIDP, porphyria, toxic, tick paralysis, diphtheria, vasculitis
○ Chronic—B12 deficiency, paraproteinemia, diabetes, most other causes
Symptoms
○ Motor symptoms—distal weakness predominates in most neuropathies. Diffi culty
opening jars, tripping over feet
○ Sensory symptoms—may be
• positive (tingling, burning) or
• negative (numbness).
○ Autonomic symptoms—orthostatic lightheadedness, gastroparesis, sweating
abnorma ities, erectile dysfunction, tachycardia
Positive Sensory symptoms
○ Paresthesia — spontaneous abnormal sensations,
which are not unduly painful
○ Dysesthesia — painful paresthesia
○ Allodynia — painful sensation resulting from a
nonpainful stimulus, such as stroking, high sounds
○ Hyperesthesia — increased sensitivity to a stimulus
○ Hyperalgesia
stimulus
— increased sensitivity to a painful
Signs of PNP
Large-fiber neuropathy
• Loss of vibration and position sense
• Diminished or absent reflexes
• Positive Romberg sign
• Pseudoathetosis
Small-fiber neuropathy
• Loss of pain and temperature sensation
• Reflexes may be normal.
Autonomic dysfunction
• Miosis
• Orthostatic hypotension (BP supine and erect after 3 minutes)
Cutaneous sensory loss in a stocking-glove distribution
Foot deformities such as pes cavus, pes planus, or hammertoes may indicate a
hereditary neuropathy.
Nerve thickening may be seen in CMT, leprosy, Refsum disease, amyloidosis, or
HNPP.
Investigations in PNP

EMG and ENG
o Can distinguish polyneuropathy from polyradiculopathy or
plexopathy
o Can identify mononeuropathy and mononeuritis multiplex
o Can distinguish axonal and demyelinating neuropathies
o Can identify subclinical sensory or motor involvement

Blood tests
○ I) 75 gram 2 hour oral GTT, B12, TSH, SPEP, immunofixation,
ESR, renal and liver function tests
○ II) ANA, dsDNA, anti-Ro, anti-La, HIV, Lyme
○ III) Others…

CSF examination; (AIDP/CIDP)

Nerve biopsy: sural, radial, superficial peroneal(vasculitis)
Investigation of peripheral neuropathy
Acquired polyneuropathies
 Diabetic
neuropathies
 Guillain–Barre syndrome (GBS)

Chronic demyelinating polyneuropathy
 Chronic
axonal polyneuropathy
 Brachial plexopathy
 Lumbosacral plexopathy
 Spinal Root Lesions
Diabetic neuropathies
Commonest cause of neuropathy worldwide.
o 8% have neuropathy at diagnosis;
o 50% after 25 years.
Diagnosis
o Diabetes = fasting glucose >126, 2 hr postprandial glucose of 200 mg/dL
o Impaired fasting glucose = fasting glucose 100–125 mg/dL
o Impaired glucose tolerance = 2 hr postprandial glucose 140–199 mg/dL
Classification of diabetic neuropathies:
o
o
o
o
o
Diabetic polyneuropathy
Diabetic neuropathic cachexia
Diabetic amyotrophy
Diabetic cranial neuropathies
Diabetic mononeuropathies
Diabetic polyneuropathy
 Length dependent, painful sensory > motor
neuropathy
 Autonomic dysfunction is common.

NCS:
 Show length-dependent axonal polyneuropathy.
 May be normal if only small fibers involved.

Rx :
 Foot care,
 Control of hyperglycemia, and
 Medications for neuropathic pain (i.e., gabapentin,
nortriptyline, duloxetine, pregabain).
Diabetic amyotrophy
Clinical manifestations
 Abrupt onset of severe pain in backs, hips, and thighs followed by
weakness and wasting of proximal muscles > distal muscles
 Usually unilateral, but may progress to be bilateral
 Associated with weight loss
D Dx : Vasculitis, malignant infiltration
Investigations
 NCS(ENG) usually show distal sensorimotor polyneuropathy
 Needle EMG shows denervation in proximal lower extremity muscles
including paraspinals
 Consider MRI to rule out structural or infi trative process causing
radiculopathy or plexopathy
Management
 Spontaneous recovery over 1–3 years
 Methylprednisolone (1g iv tiw x 1, then qweek x 3, then q2 weeks x 4)
may speed recovery
 IVIG reported to be beneficial as well
Diabetic amyotrophy
Diabetic cranial neuropathies
○ Oculomotor (III) palsy — pupil sparing
○ Abducens (VI) palsy
Diabetic mononeuropathies


DM patients are prone to entrapment syndromes.
Surgery should be considered if motor involvement, but
results may not be as good as in nondiabetics.
○ Median at the wris(CTS)
○ Ulnar at the elbow
○ Common peroneal at the fibular neck
Guillain–Barre syndrome (GBS)
1. Acute inflammatory demyelinating
polyradiculoneuropathy (AIDP)
Epidemiology:
 The most common cause of acute neuromuscular
weakness.
 Annual incidence 1–2 /100,000
 Two-thirds are preceded by a GI or upper respiratory tract
infection (Campylobacter jejuni, CMV, EBV, haemophilus
influenzae, mycoplasma).
Pathogenesis
There is a predominantly cell-mediated inflammatory
response directed at the myelin protein of spinal roots,
peripheral and extra-axial cranial nerves, possibly triggered
by molecular mimicry between epitopes found in
the cell walls of some microorganisms and gangliosides
in the Schwann cell and axonal membranes. The resulting
release of inflammatory cytokines blocks nerve conduction
and is followed by a complement-mediated
destruction of the myelin sheath and the associated
axon
Clinical features









Neurologic symptoms begin 5 days to 3 weeks after antecedent event.
Ascending weakness. Proximal weakness may occur as well because
of root demyelination
Early loss of reflexes
Paresthesias common. Actual sensory loss is variable.
Progressive over days to weeks, nadir by 4 weeks
Often associated with back pain
Involvement of cranial nerves can cause facial and bulbar weakness.
Up to 25% have respiratory involvement requiring mechanical
ventilation.
Autonomic dysfunction (hypotension, hypertension, cardiac arrhythmia)
Diagnostic studies
NCS:
May be normal early in the course of the disease
 Prolongation of F-responses,
 Prolongation of motor latencies, and
 Prolongation of motor conduction velocities.
 Conduction block correlates with degree of weakness.
CSF:
 Elevation of protein (may be normal first 10 days).
 Little or no CSF pleocytosis, unless associated with HIV or
Lyme.
Management
 IVIG 0.4 g/kg/day x 5 days
 Plasma exchange (2–5 exchanges, depending on the severity of the disease)
 No benefit from corticosteroids
 Supportive measures
○
○
○
○
○
○
Follow vital capacity (VC) and negative inspiratory force (NIF
Transfer patient to the I CU and consider elective intubation IF:

fVC <20 mL/kg (1.5 L for an average adult) or

NIF is worse than –30 cm H2O,
Do not wait for O2 saturation or PO2 to drop.
Swallowing assessment
Cardiac monitoring in all patients who are severely affected, at least until they start to improve.
Treat neuropathic pain
○
○
○
(gabapentin, pregabalin, or tramadol).
Avoid tricyclic antidepressants early, which may lower threshold for arrhythmia.
DVT prophylaxis
Bowel regimen for constipation
Physical therapy to prevent contractures and speed recovery of function
Prognosis

Overall, 80% of patients recover completely within 3–6 months.

Untreated, about 35% of patients have residual weakness,
atrophy, hyporeflexia, and facial weakness.

Partial recovery followed by relapse occur in <10% of patients.

Recurrence after full recovery is 2%.

Mortality is 4 %.

Poor outcome associated with
○
○
○
○
Older age
Preceding diarrheal illness
Rapid deterioration and severe weakness
Electrically inexcitable nerves and muscle wasting (axonal loss)
Other Variants of GBS
2. Acute motor axonal neuropathy (AMAN)
○ Little or no demyelination
○ Often associated with Campylobacter jejuni infection
○ A subset of patients will recover rapidly
3. Acute motor sensory axonal neuropathy (AMSAN)
○ Little or no demyelination
○ Poorer prognosis than AIDP and AMAN
3. Miller Fisher syndrome
○
○
○
○
Ophthalmoplegia
Ataxia
Areflexia
Associated with GQ1b antibody
4. Acute sensory neuropathy
6. Acute pandysautonomia
Chronic polyneuropathy

A chronic symmetrical polyneuropathy, evolving over
months or years, is the most frequently seen form of
neuropathy.

In about 30% of patients no cause can be established,
even after thorough investigation.

These patients usually have a mild axonal neuropathy
which, whilst causing unpleasant symptoms, does not
lead to motor disability.

Therefore, if a patient with what seems to be an idiopathic
polyneuropathy progresses to significant disability, further
thought needs to be given to finding a specific cause
(usually inflammatory or genetic).
Chronic Demyelinating Polyneuropathy

This type of chronic polyneuropathy is often :
Hereditary or Immune -mediated (including those
caused by abnormal paraproteins).

Causes:
○
○
○
○
○
○
○
○
Hereditary
CIDP
Lymphoma
Osteoclastic myeloma
IgM paraproteinaemia
Arsenic toxicity
Amiodarone toxicity
Diphtheria
Heriditary Demyelinating Polyneuropathy

Many inherited disorders cause demyelinating peripheral
neuropathies and one of the best known is Charcot–Marie–
Tooth disease (CMT).

This neuropathy produces:
○ Distal wasting (‘inverted champagne bottle’ or ‘stork’ legs),
○ Often with pes cavus, and
○ Predominantly motor clinical involvement.
○ In 70–80% the cause is duplication of the PMP-22 gene on
chromosome 17 (autosomal dominant CMT type 1)
○ Similar phenotypes are produced by mutations in other
genes with differing modes of inheritance
CMT
Pes cavus,
Inverted champagne bottole,
Samll muscle atrophy
Hereditary peripheral neuropathies
Hereditary demyelinating neuropathies
Chronic Inflammatory Demyelinating
Polyradiculopathy (CIDP)
 Presents with a relapsing or progressive generalised neuropathy.
 Sensory, motor or autonomic nerves can be involved but the signs are
predominantly motor;
 A variant causes only motor involvement (multifocal motor neuropathy,
MMN).
 RX
Immunosuppressive treatment:






Corticosteroids ,
Methotrexate or
Cyclophosphamide , or
Plasma exchange
Intravenous immunoglobulin, IVIG
MMN is best treated by IVIG.
 Some 10% of patients with acquired demyelinating polyneuropathy have
an abnormal serum paraprotein, sometimes associated with a
lymphoproliferative malignancy.
Treatment flowchart for CIDP
Chronic axonal polyneuropathy

This is the most common type of chronic polyneuropathy.

Where the cause can be found, it is usually a disorder
affecting axonal metabolism and transport, either
acquired (drugs and toxins) or genetically determined
○
○
○
○
○
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○
○
Metabolic/endocrine diseases (including diabetes)
Alcohol
Drugs and toxins
Vitamin deficiency
Hereditary
IgG paraproteinaemia
Paraneoplastic
Primary amyloidosis
Brachial plexopathy
Trauma usually damages either the upper or the lower parts of the brachial
plexus, according to the mechanics of the injury.
 The clinical features depend upon the anatomical site of the damage .


Causes of Lower Brachial Plexopathy:
○ Infiltration from breast or apical lung tumours (Pancoast tumour).
○ Therapeutic irradiation
○ Thoracic outlet syndrome: which may be accompanied by circulatory changes in the
arm due to subclavian artery compression.
Brachial plexus anatomy:
L, lateral; M, medial; P, posterior
Neuralgic Amyotrophy

An acute brachial plexopathy of probable inflammatory
origin.

In this syndrome, a period of very severe shoulder pain
precedes the appearance of a patchy upper brachial
plexus lesion.

Often affecting the long thoracic nerve which produces
winging of the scapula.

Recovery occurs over months and is usually complete.
Lumbosacral plexopathy
May be caused by:

Neoplastic infiltration or

Compression by retroperitoneal haematomas in patients
with a coagulopathy.

A small vessel vasculopathy can produce a lumbar
plexopathy, especially in elderly patients when it may be
the presenting feature of;
○ Type 2 diabetes mellitus (‘diabetic amyotrophy’) or
○ A vasculitis.
Spinal Root Lesions

Compression at or near their spinal exit foramina by
prolapsed intervertebral discs or degenerative spinal
disease.

Infiltration by spinal and paraspinal tumour masses and

Inflammatory or infective processes.

The clinical features include:
○
○
○
○
Muscle weakness and wasting and
Dermatomal sensory loss with
Reflex changes that reflect the pattern of roots involved.
Pain in the muscles whose innervating motor roots are involved.
Mononeuritis Multiplex

Lesions of multiple nerve roots, peripheral nerves or cranial nerves.

It is due either to involvement of the vasa nervorum or to malignant
infiltration of the nerves.

The clinical expression of a very widespread multifocal neuropathy
may become confluent so that the clinical picture eventually
resembles a polyneuropathy.

In this case neurophysiology may be required to identify the multifocal
nature of the problem.
Causes of Mononeuritis Multiplex
Infections:
○
○
○
○
○
○
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Lyme disease
Leprosy
Acute viral hepatitis A
Hepatitis B
Hepatitis C
Acute parvovirus B-19 infection
Herpes simplex virus infection
AIDS and HIV infection
Rheumatological:
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Wegener granulomatosis
Henoch-Schönlein syndrome
Sjögren syndrome
Behçet’s disease
Temporal (giant cell) arteritis
Systemic lupus erythematosus
Rheumatoid arthritis
Polyarteritis nodosa
Scleroderma
Chronic:
○
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Diabetes mellitus
Amyloidosis[8]
Neurosarcoidosis[36, 37]
Cancer -related:
○
○
○
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Chronic graft versus host disease
(GVHD)
Direct tumor invasion with intraneural
spread of Lymphoma
B-cell leukemia
carcinoid tumor
Paraneoplastic – Small cell lung
cancer
Hematologic:
○
○
○
○
○
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Churg-Strauss syndrome
Hypereosinophilia
Cryoglobulinemia
Hypereosinophilia
Atopy-related peripheral neuritis
Idiopathic thrombocytopenic purpura
Miscellaneous:
○
○
○
○
Amphetamine angiitis
Gasoline sniffing
Genetic disorder; Tangier disease.
Multiple compression neuropathies.
Mononeuropathies
Facial mononeuropathy (Bell palsy)
 Weakness: Upper and lower face, inability to close the eye, mouth drawn to the




affected side.
Patients often describe the face as ‘numb’, but there is no objective somatosensory
loss.
Loss of direct & consensual corneal reflex on the affected side.
Decreased tearing, hyperacusis, and loss of taste to the anterior two thirds of the
tongue may be present.
Onset is sudden, usually over hours.
EMG/NCV are rarely necessary to make the diagnosis, but can be used to determine prognosis.
DDx: Herpes zoster, HIV, Lyme, facial tumor, sarcoidosis & neuro-brucellosis.
Rx
 Artificial tears, protective goggles, eye patch at night
 Prednisone 40–60 mg/d for a week ; speeds recovery if started within 72 hrs.
 Anti-virals probably not beneficial?? ( Acyclovior 400x5 for 10 days)
Prognosis

some recovery within 3
weeks(85%).
Complete recovery(75%)

Poor recovery predicted if:

 Complete paralysis,
 Older age
 Comorbidity; DM , HTN
 Hyperacusis
 Loss of taste
for > 1wk
 Reto-auricular pain
 Axonal loss

Aberrant re-innervation may occur
during recovery, producing unwanted
facial movements such as eye closure
when the mouth is moved, or ‘crocodile
tears’ (tearing during salivation).
Rt LMN VII palsy
Hemifacial spasm

Usually presents after middle age with intermittent twitching
around one eye, spreading ipsilaterally over months or years to
affect other parts of the facial muscles.

The spasms are exacerbated by talking or eating, or when the
patient is under stress.

The cause is probably an aberrant arterial loop irritating the
nerve just outside the pons.

The facial nerve should be imaged to exclude a structural
lesion, especially in a young patient.

Treatment
o Drug is not effective.
o Botulinum toxin (repeated every 3 months).
o Microvascular decompression.
Trigeminal Nerve Lesions

Isolated trigeminal sensory neuropathy is rare. It causes
unilateral facial sensory loss and is associated in some
patients with;
oscleroderma,
oSjögren’s syndrome or
oother connective tissue disorder.

Trigeminal neuralgia do not have sensory loss on
examination unless there have been operative procedures on
the nerve.

Herpes Zoster (most frequently in the ophthalmic division)
and is followed in about one-third of patients by postherpetic
neuralgia).
Herpes Zoster Ophthalmicus
Entrapment neuropathy

Focal compression or entrapment is the usual cause of mononeuropathy.

The pressure damages the myelin sheath  slowing NCS.

Sustained or severe pressure  axonal loss  loss of sensory AP
distal to the site of compression.
Causes:
 Acromegaly ,
 Hypothyroidism ,
 Pregnancy
 Diabetes
 Osteophytes
 HNPP(hereditary neuropathy with liability to pressure palsies)
- multiple recurrent entrapment neuropathies,
- especially at unusual sites
- autosomal dominant
Symptoms and signs in common Entrapment Neuropathies
Median at wrist (CTS)
Ulnar at elbow
Meralgaia Paraesthetica
Differential diagnosis by pattern of symptoms
Pattern 1:

Symmetrical proximal and distal weakness with sensory loss. (Consider CIDP, vasculitis.)
Pattern 2:

Symmetrical distal weakness with sensory loss. (Consider diabetes, drugs and toxins, hereditary
neuropathies, amyloidosis, paraproteinemia.)
Pattern 3:

Asymmetric distal weakness and numbness. (Consider vasculitic neuropathy, HNPP, infectious
neuropathy, multifocal trauma or entrapment.)
Pattern 4:

Asymmetric distal or proximal weakness without sensor loss. (Consider multifocal motor neuropathy,
motor neuron disease, inclusion body myositis.)
Pattern 5:

Asymmetric proximal and distal weakness with sensory loss. (Consider polyradiculopathy or plexopathy,
ma ignant infi ltration, brachial neuritis, HNPP.)
Pattern 6:

Symmetric small fiber sensory neuropathy without weakness. (Consider diabetes, Fabry disease,
amyloidosis, HIV.)
Pattern 7:

Symmetric small and large fiber sensory neuropathy without weakness. (Consider diabetes, drugs, toxins,
paraproteinemia.)
Pattern 8:

Marked proprioceptive sensory loss. (Consider paraneoplastic, B6 toxicity, Sjogren, HIV.)
Pattern 9:

Autonomic predominant. (Consider autoimmune, amyloidosis, diabetes, AIDP.)
Pattern 10:

Neuropathy with cranial nerve involvement. (Consider Lyme, HIV, AIDP, sarcoidosis, malignant infiltration,
Tangier disease, trichloroethylene toxicity, anti-Gd1b neuropathy.)

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