AN APPROACH TO PERIPHERAL NEUROPATHY

AN APPROACH TO PERIPHERAL NEUROPATHY

Peter-Brian Andersson MBChB, DPhil.Goals: 1. Learn how basic science anatomy and physiology applies to understanding neuropathy.2. Learn the patterns of disease by which peripheral neuropathy presents clinically.

3. Learn a simple approach to diagnose peripheral neuropathy at the bedside.

Reading:

Cecil Essentials of Medicine, 7th Ed. 2007 p1146-51Further reading for reference:

Hughes, RAC 2008 Prac Neurol 8: 396-405

Hughes, RAC 2002 BMJ 324:466-9

Poncelet, AN 1998 Am Fam Phys 57:755-764

Donofrio, PD & Albers, JW.1990 Muscle & Nerve 13:889-903Lecture Notes: The Key Points.A useful approach to neurology clinical problem solving is to ask and answer the following questions in sequence: 1) Where is the lesion? 2) What is the cause of the lesion? 3) What is the treatment of the lesion? The approach is used in the seminar. Peripheral neuropathy is a common condition and encountered in a whole host of medical subspecialities, not just the neurology service, and the reason is because it has so many causes. Bedside Question 1. Where is the lesion?

The answer hinges on knowing the anatomy of peripheral nervous system and how injury causes symptoms and signs. The peripheral nervous system consists of root, plexus and peripheral nerve. Each of these potential localizations causes a signature clinical pattern which can be deduced at the bedside. Root injury (radiculopathy) produces motor and sensory deficits in a segmental distribution, plexus injury (plexopathy) in the distribution of its organizational anatomy and peripheral nerve injury in a particular nerve distribution. Setting radiculopathy and plexopathy aside, disease can either affect the nerve cell body, also called neuronopathy (which in the case of motor neurons is called motor neuron disease and for sensory neurons is called sensory ganglionopathy), or the peripheral process (which is by convention referred to as peripheral neuropathy). Peripheral nerve injury (peripheral neuropathy) results when nerves are diseased either:

1) focally (called mononeuropathy) like carpal tunnel syndrome, as may be seen in pregnancy with fluid retention, or 2) focally but multiply (called mononeuritis multiplex) for example in vasculitis, or 3) diffusely (called polyneuropathy) for example chronic ethanol toxicity. Recognizing these different patterns at the bedside is important because their causes and treatments are different. What determines the clinical presentation of neuropathy?The clinical effects of a peripheral neuropathy depend on: #1) whether the injury affects the axon or the myelin,

#2) what modalities are affected (motor, sensory or autonomic) and #3) what nerve fibers are affected (large fibers or small fibers). #1) Axonal neuropathy or Demyelinating neuropathy?Peripheral neuropathies can be divided histopathologically, electrodiagnostically and clinically depending on whether the injury is axonal or demyelinating. Wallerian degeneration is the name of a characteristic pathology after acute focal injury to peripheral nerve (eg. infarction or transection). Axonal degeneration goes hand in hand with reinnervation attempts by the regenerating nerve. Both have characteristic histopathologic (denervation atrophy, axon dropout for the former and regenerating sprouts for the latter), electrodiagnostic (reduced compound muscle action potential amplitude with reduced recruitment of muscle fibers on EMG for the former and large motor unit potentials on EMG for the latter) and clinical signs (weakness with atrophy) that permit diagnosis of this pattern of neuropathy. On the other hand the pattern of typical demyelinating neuropathies is characterized histopathologically by loss of myelin and onion bulb formation, electrodiagnostically by slowed conduction velocities (uniform in hereditary causes with rare exception and non-uniform in acquired), little or no signs of reinnervation on EMG, and clinically by weakness without wasting, a tendency for predominant motor over sensory deficits and generalized arreflexia. Peripheral nerves (e.g. the greater auricular) may even be palpably hypertrophic on examination.#2) What modalities are affected?For convenience motor, sensory and autonomic nerve injury can be considered to produce positive and negative effects as follows:

Loss of function NegativeAltered function Positive

Motor nervesWasting

Hyopotonia

Weakness

Hyporeflexia

Orthopedic deformityFasciculations

Cramps

Sensory

Large Fiber Vibration

Proprioception

Hyporeflexia

Sensory ataxiaParesthesias

Sensory

Small Fiber

Pain

TemperatureDysesthesias

Allodynia

Autonomic nerves SweatingHypotension

Urinary retension

Impotence

Vascular color changes Sweating

Hypertension

#3 Which fibers (large or small) are affected?

All motor fibers are large and myelinated, autonomic fibers are all small mostly unmyelinated and sensory fibers may be either large (proprioception and vibration and touch) or small (pain and temperature0.Bedside Question 2: What is the cause of the lesion?

There are a whole host of causes of peripheral neuropathy! A strategy to sort them out is essential to the clinician. Understanding the syndrome of peripheral neuropathy is a metaphor for much of the art of clinical medicine learning how to organize volumes of medical data and isolate and apply that which is pertinent. The need here is to have an approach at the bedside to sort through the many potential etiologies by a familiarity of pathophysiology, the patterns of disease presentation, and a knowledge of short lists of differential diagnoses for those patterns rather than tedious (and costly) shot gunning. Finding the etiology is also to answer the third question of clinical neurology, namely What is the treatment of the lesion? because in this syndrome the treatment is of the underlying cause and the symptoms (e.g. pain, orthstasis, ataxia and foot deformities).Here is a clinical approach to make an etiologic diagnosis: Use the 7 Ds:

1. What is the duration?

2. What is the distribution of the deficits?

3. What are the deficits (which fibers are involved)?

4. What is the disease pathology (axonal or demyelinating)?5. Is there an inherited (developmental) neuropathy?

6. Is there drug/toxin exposure?

Appended are some lists of differential diagnoses based on the above principles for questions 1, 2 and 4. THIS TABLE IS PROVIDED TO YOU FOR REFERENCE ONLY!1. DURATION OF NEUROPATHY? Most polyneuropathies are chronic i.e. months and years

For acute polyneuropathies think Guillain Barre syndrome

Vasculitis

Toxins and Drugs

Tick paralysis

Diphtheria

Porphyria

If relapses and remissions think

Intermittent toxin exposure

Chronic Inflammatory Demyelinating Polyneuropathy2. DISTRIBUTION OF NEUROPATHY DEFICITS? If predominant motor fibers think:

Motor neuron disease (motor neuronopathy) exclusively motor

Multifocal motor neuropathy exclusively motor

Acute Inflammatory Demyelinating Polyneuropathy (Guillain-Barre)

Chronic Inflammatory Demyelinating Polyneuropathy

Lead intoxication

Acute porphyria

Charcot-Marie-Tooth disease (HMSN)

If pure sensory/ severe proprioceptive deficit, think sensory neuronopathy:

Carcinoma (paraneoplastic)

Sjogrens syndrome

Drugs like Cisplatinum, styrene, B6 toxicity

HIV

Friedrichs ataxia

If autonomic nerves involved (small fiber) think:

Diabetes

Amyloid

Drugs like Vincristine, ddI, ddC

HIV

Hereditary Sensory Autonomic Neuropathy (HSAN)

Guillain-Barre

Acute porphyria

4. DISEASE PATHOLOGY?

If demyelination and uniform, cause is hereditary. Think of:

Charcot-Marie-Tooth disease (HMSN)

Hereditary Neuropathy with Liability to Pressure Palsy

Rarer myelin disorders like adreno- and metachromatic leukodystrophy

Friedrichs ataxia

If demyelination is non uniform the cause is acquired. Think of:

Acute Inflammatory Demyelinating Polyneuropathy

Chronic Inflammatory Demyelinating Polyneuropathy

Monoclonal gammopathy

Acute arsenic poisoning

Friedrichs ataxia

Axonal polyneuropathies are by far more common than demyelinating forms. If otherwise unremarkable however length dependent, chronic, sensory more than motor axonal polyneuropathy without associated toxin, drug or disease consider cryptogenic sensory axonal polyneuropathy. Exclude treatable diseases with the following five laboratory tests (no need for antibody panels!): TSH (for hypothyroidism), HBA1c (for diabetes), B12 and methylmalonic acid (for B12 deficiency), serum protein electrophoresis with immunofixation (for monoclonal gammopathy) and creatinine (for uremia).

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