DISEASESOF THE PERIPHERAL NERVE

1. DISEASES
OF THE
PERIPHERAL NERVE
MUKESH SAH, MD
UNITED KINGDOM

2. MOTOR UNIT

3. Stepwise approach to the diagnosis of
peripheral nervous system disorders
Does a medical disorder or neurotoxin exposure account for the
neuropathy?
Is the disorder familial?
Axonal versus demyelinating?
What is the temporal profile?
Which fibers are involved?
What is the spatial distribution?
Does the patient have a peripheral nervous system disorder?

4. Stepwise approach to the diagnosis of
peripheral nervous system disorders
Is a specific etiology suggested?
YES
Confirmatory Studies
(laboratory tests, selected tissue
biopsies)
NO
Screening Laboratory Studies
(based on clinical and electrophysiologic
classification of the neuropathy)

5. Stepwise approach to the diagnosis of
peripheral nervous system disorders
Etiologic Diagnosis Established (+/- 80%)
Cryptogenic Neuropathy (+/- 20%)

6. Peripheral nervous system
disorders: spatial patterns
FOCAL MULTIFOCAL
(ASYMMETRIC)
DIFFUSE
(SYMMETRIC)
Mononeuropathy
Monoradiculopathy
Brachial plexopathy
Lumbosacral plexopathy
Motor neuronopathy
Dorsal root ganglionopathy
Multiple mononeuropathies
Polyradiculopathy
Motor neuropathy
Motor neuronopathy
Polyneuropathy
Dorsal root ganglionopathy
Motor neuronopathy

7. Pattern of Nerve Fiber Type
Involvement
Sensory
Motor
Autonomic
Large-caliber
◦Motor fibers
◦Type A-αand A-
βsensory afferents
Small-caliber
◦A-δand C fibers

8. TEMPORAL PROFILE
ACUTE
◦Days to weeks
SUBACUTE
◦6 weeks to 6 months
CHRONIC
◦6 months to years
Monophasic
Progressive
◦Uniform or stepwise
Relapsing, remitting

9. AXONAL
vs
DEMYELINATING
Axonal
◦ Causes are abundant
Demyelinating
◦ Suggests just a few
etiologies
◦ Segmental (multifocal) or
uniformly slow

10. FAMILY HISTORY
Approximately 40% are hereditary neuropathies:
◦ Long-standing inherited neuropathies may produce
characteristic deformities of the foot (pes cavus) and spine
(kyphoscoliosis)
◦ Typical hereditary motor-sensory neuropathy has little in
the way of positive sensory symptoms
◦ Clinical and electrodiagnostic examination of family
members, even when asymptomatic, may reveal
polyneuropathy

11. The under-recognition of hereditary
neuropathies may be attributed to:
Failure to elicit an adequate family history
The occurrence of de novo mutations (e.g., peripheral
myelin protein-22 gene duplication associated with CMT-
1A)
Recessive and x-linked inheritance patterns
The fact that neuropathy may remain asymptomatic for
decades

12. Medical Comorbidity,
Medications, and Toxins
Diabetes mellitus
Connective tissue
disease
Underlying malignancy
Infection
Malnutrition
Megavitaminosis
Exposure to drugs,
alcohol, and toxins

13. ROLE OF LABORATORY
TESTING
Most patients with peripheral neuropathy, whether acute
or chronic, should have a:
◦ Complete blood count
◦ Serum electrolytes
◦ Renal and liver function studies
◦ Screening for diabetes mellitus
◦ Fasting blood glucose
◦ Hemoglobin AIc

14. ROLE OF LABORATORY
TESTING
For patients with chronic sensorimotor
polyneuropathies, they should be screened for:
◦Paraproteinemia with:
◦Serum immunofixation
◦Immunoelectrophoresis

15. ROLE OF NERVE BIOPSY
Sural nerve
Superficial peroneal nerve
Radial sensory nerve
Yields a diagnosis in 27% of cases and provides
useful information in a further 37%
Moderately involved nerve is preferable

16. ROLE OF NERVE BIOPSY
Primary indication:
◦To identify potentially treatable neuropathies in
undiagnosed progressive acute or subacute
asymmetric and, less commonly, symmetric
sensorimotor polyneuropathies
May confirm a diagnosis of leprosy, if skin biopsy is
not diagnostic

17. PITFALLS IN THE EVALUATION OF
PERIPHERAL NEUROPATHY
False-positive diagnosis of peripheral neuropathy:
lumbosacral polyradiculopathy
Not all distal weakness is due to peripheral
neuropathy
Amyotrophic Lateral Sclerosis
Failure to consider age

18. PITFALLS IN THE EVALUATION OF
PERIPHERAL NEUROPATHY
Distinction between Acute Central and Peripheral
Nervous System Disorders
Erroneous Diagnosis of Chronic Inflammatory
Demyelinating Polyneuropathy
Diagnosis of Peripheral Neuropathy is Correct, but
the Cause is Falsely Attributed
False-Negative Diagnosis of Peripheral Neuropathy

19. Approach to the Management and
Follow-up of Patients with Peripheral
Neuropathy
Therapeutic approaches
◦Those that alter the natural history of the
disease
◦Symptomatic psychotherapies
◦Rehabilitative therapies to limit disability

20. Disease-modifying therapy in
treatable neuropathies
Plasmapheresis
IVIg
Corticosteroids
Cytotoxics (e.g.,
cyclophosphamide)
Endocrine treatment
Vitamin replacement
Interferon – α
Antimicrobials
Radiation/surgery

21. Neuropathies
Facial Nerve Paralysis
Brachial Plexus Injury
Inflammatory
Neuropathies
Hereditary Neuropathies
Friedreich’s Ataxia
Giant Axonal
Neuropathy
Infantile Neuroaxonal
Dystrophy
Metabolic
Neuropathies
Toxic Neuropathies

22. Guillain - Barré
Syndrome

23. Guillain - Barré Syndrome
(GBS)
A number of related immune polyneuropathies that cause
acute generalized weakness
Affects individuals of all races and ages
An acute viral syndrome or other infectious illness occurs 1
– 4 weeks prior to the onset of GBS
Most common viral trigger is CMV
Most common infection preceding GBS is Campylobacter
jejuni

24. Pathophysiology of GBS
There is endoneurial inflammation
predominantly affecting the nerve
roots, and an immune-mediated attack
directed against components of the
myelin sheath or nerve axon

25. Clinical Features
Weakness
◦Always bilateral, but some degree of
asymmetry is common
Reduced or absent deep tendon reflexes
Cytoalbuminologic dissociation

26. GBS Variants
Axonal Forms
◦ Acute motor-sensory axonal
neuropathy
◦ Acute motor axonal neuropathy
Miller-Fisher syndrome
Pure motor GBS
Pure sensory GBS
Pure dysautonomia
Pharyngeal-cervical-brachial
weakness
Paraparetic variant
Ataxic with or without
ophthalmoplegia
Acral paresthesias with abducens
palsies
Acral paresthesias with peroneal
palsies
Facial diplegia with paresthesias

27. Treatment
Supportive care
Immune therapy
◦IVIg

28. Thank you